Advisory Committee on Immunization Practices (ACIP) - September 19, 2025 – Day 2 of 2

Published 19 Sep 2025

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Advisory Committee on Immunization Practices (ACIP) - September 19, 2025 – Day 2 of 2

[Kevin Reed Grimes]

[0:00:10]
So, I was a hospital administrator in Cleveland. In Cleveland? Yes. Oh, cool. So, small town city of New Hampshire.
[Speaker 48]
Aww.
[Kevin Reed Grimes]
And I spent about seven or eight years as a staff member in the state legislature and made the report.
[Speaker 48]
Oh, how interesting.
[Kevin Reed Grimes]
So, I can put all that together here at the CDC.
[Speaker 48]
Yeah, that's cool. I was just in Maine for a story. It's such a nice, like, I was in, um, where was I? Mira and Tessa?
[Kevin Reed Grimes]
That was the one, yeah.
[Speaker 48]
Yeah, and I went to, um, Alabama? Did you go there?
[Kevin Reed Grimes]
Hallowell.
[Speaker 48]
Hallowell. Yeah, it was such a cute town and, like, once that restaurant that everybody used to go to there, I can't remember what it was called, but it was such a funny place. And, like, it was packed. It was like a Monday night. It was 5.30. And, like, I couldn't get in. And, like, I don't know. I just, like, I really liked the vibe.
[Kevin Reed Grimes]
It's a big state. Yeah.

[0:01:00]
It's a big state to explore.
[Speaker 48]
For sure. I met up with Nirav Shah.
[Kevin Reed Grimes]
Dr. Shah is an internet star from Maine.
[Speaker 48]
Do you think? Oh, how interesting. I didn't talk to him about that at all. Oh, that's fascinating.
[Kevin Reed Grimes]
He was, like, a celebrity during the book.
[Speaker 48]
He totally was. And even, like, we were walking around the city. He was doing, like, a year of teaching there. Just visiting. Yeah. And, like, people kept staring at him, honestly. They all did.
[Kevin Reed Grimes]
For sure. He has a problem.
[Speaker 48]
Yeah. I just realized he came from Banyan. Like, he's a hedgehog guy. But he also is a doctor.
[Kevin Reed Grimes]
A little bit of everything.
[Speaker 48]
I think that's, like, a good background. It's, like, I don't know. You just, like, think about things in a different way. It seems to, like, help him when it came to, like, public health.
[Kevin Reed Grimes]
For sure.
[Speaker 48]
He's, like, a good communicator.
[Kevin Reed Grimes]
He's a very good communicator.
[Speaker 48]
Yeah. I had no idea, though. Is he running for president?
[Kevin Reed Grimes]
Wait, is the current governor? She's not. So, Janet Wells, she is going out.
[Speaker 48]
Oh, I see.
[Kevin Reed Grimes]
She may run for U.S. Senate against Cecil Collins. And that's the world first if it was.

[0:02:01]
Okay. Yeah. So, Dr. Shah would be a lot of, like, Senate Democrats in the primary. And then there was Senator. Yeah. We're probably. Being primary is easy. So, we're, like, under either of that.
[Speaker 48]
Being primary is easy.
[Kevin Reed Grimes]
Yeah.
[Speaker 48]
That's very interesting.
[Kevin Reed Grimes]
Every year. Every year. When it's an open suit, that's when we see everybody running for it.
[Speaker 48]
Yeah.
[Kevin Reed Grimes]
Yeah. About 12 people running for Senate.
[Speaker 48]
Wow. Interesting. I saw a campaign ad for a guy who's running for, I think it's Congress. Yeah. He was really interesting. He was, like, a vet. And he was, like, a, I heard it was oysters or scallops or whatever he did. He was, like, I don't know. He just seemed, like, very Brazilian. And, like, do you know what that means?
[Kevin Reed Grimes]
I do.
[Speaker 48]
Yeah. Yeah. I just thought it felt fascinating.
[Kevin Reed Grimes]
Something different.
[Speaker 48]
Yeah, exactly. That's cool. So, do you grow up in California?
[Kevin Reed Grimes]
No, I'm from California.
[Speaker 48]
Oh, me too.
[Kevin Reed Grimes]
I'm from Santa Barbara County.
[Speaker 48]
Santa Barbara?

[0:03:00]
Oh, lovely. My parents live in Pasadena.
[Kevin Reed Grimes]
That's close.
[Speaker 48]
Yeah.
[Kevin Reed Grimes]
California's even bigger. Yeah. But I was in Maine at least. So, it feels like that.
[Speaker 48]
It's far apart from here.
[Kevin Reed Grimes]
So, in the western mountains of Maine, on the border of New Hampshire, there's a couple little towns. So, I grew up in California.
[Speaker 48]
That's cool. That's a fun way to say California. Did you go to camp there or something?
[Kevin Reed Grimes]
Yeah. That's what it was.
[Speaker 48]
Oh, fun.
[Kevin Reed Grimes]
Yeah, I know a lot of people there.
[Speaker 48]
Nice.
[Martin Kulldorff]

[0:08:52]
So, we will get the meeting started.

Meeting Start and Roll Call

We have many things on the agenda. We will start with the roll call.

[0:09:01]
And I ask you to just very briefly state your name and for members of the committee that you have no conflicts of interest.
[Mina]
Good morning, everyone. We'll start with the chair.
[Martin Kulldorff]
I'm Martin Kulldorff, no conflicts of interest.
[Dr. Robert Malone]
Robert Maluma, the sketchy microphone, has no conflicts of interest.
[Dr. Jason Goldman]
James Pagano, no conflicts.
[Kirk Milhoan]
Kirk Milhoan, no conflicts of interest.
[Hillary Blackburn]
Hilary Blackburn, no conflicts of interest.
[Kathy Stein]
Kathy Stein, no conflicts of interest.
[Joseph Hibblen]
Evelyn Griffin, no conflicts of interest.
[Raymond Pollack]
Raymond Pollack, no conflicts.
[Joseph Hibblen]
Joseph Hibblen, I have no conflicts of interest.
[Vicky Pebsworth]

[0:10:03]
Vicky Pebsworth, no conflicts.
[Joseph Hibblen]
Reza Flevi, no conflicts.
[Mina]
Thank you. And our ex-officio CMS?
[Dr. Cody Meissner]
Oh, you forgot me, Mina.
[Mina]
I'm sorry. I'm sorry.
[Dr. Cody Meissner]
Yes. Cody Meissner, I have no conflicts of interest. Thank you.
[Mina]
Thank you.
[Dr. Cody Meissner]
Andrew Johnson, Centers for Medicare and Medicaid Services.
[Mina]
Thank you. HRSA?
[Kevin Reed Grimes]
Kevin Reed, Grimes, HRSA.
[Mina]
Thank you. IHS?
[Uzo Chukwuma]
Good morning. Uzo Chukwuma, representing the Indian Health Service.
[Mina]
Thank you. NIH? Mike Carrillo, representing NIH. Thank you. And FDA? Tracy Beth Hoag, FDA. Thank you. And I'll move on to the liaisons. American Academy of Family Physicians, American Academy of Pediatrics, American Academy of Physician Associates, American College of Health Association, American College of Nurse Midwives, American College of Obstetricians and Gynecologists.
[Dr. Laura Morris]

[0:11:32]
I was just given the ability to speak. I don't think any liaisons have their microphones activated.
[Mina]
Okay, I'll start from the top. Okay, I'll start from the top. American Academy of Family Physicians.
[Dr. Laura Morris]
Hi, this is Dr. Laura Morris, representing AAFP. Thank you.
[Mina]
American Academy of Pediatrics, American Academy of Physician Associates, American College Health Association, American College of Nurse Midwives.

[0:12:17]
Carol Hayes, present. Thank you. American College of Obstetricians and Gynecologists, American College of Physicians.
[Dr. Jason Goldman]
Dr. Jason Goldman, present.
[Mina]
Thank you. I heard both American College of Obstetricians and College of Physicians. American Geriatric Society, America's Health Insurance Plans.
[Dr. Vishal Raskala]
Ken Schmader here for AGS.
[Mina]
Thank you. American Medical Association.
[Dr. Sandra Fryhofer]
Dr. Sandra Fryhofer, representing the American Medical Association.
[Mina]

[0:13:00]
Thank you. American Nurses Association. Barbara Resnick, representing the ANA. American Osteopathic Association. American Pharmacists Association. Dr. Kelly Good, representing the American Pharmacists Association. Association of Immunization Managers. Molly Howell, representing AIM. American Immunization Registry Association. Good morning. Rebecca Coyle, representing the American Immunization Registry Association. Association for Prevention, Teaching, and Research. Good morning. Christy Mulling Jaffel, representing APTR. Association of State and Territorial Health Officials. Dr. Susan Consagra, representing ASTHO. Biotechnology Innovation Organization.

[0:14:04]
Council of State and Territorial Epidemiologists.
[Nisa Shafi]
Dr. Christine Hahn, representing CSTE.
[Mina]
National Association of County and City Health Officials. Dr. Zadeh. Philis Arthur, representing BIO.
[Patricia Armstrong]
Thank you.
[Uzo Chukwuma]
Thank you.
[Kevin Reed Grimes]
And this is Dr. Judith Troy, representing National Association of County and City Health Officials.
[Mina]
Thank you.
[Dr. Reza Flevi]
Excuse me, Dr. Masoud Mahmoudi, Osteopathic Association. Mute button didn't work, sorry.
[Mina]
Okay. Thank you. I'll come back to... Oh, go ahead.
[Dr. Katie Scharf]
This is Dr. Lori Coyle, representing America's Health Insurance Plans. I also was muted. Thank you.
[Mina]
Okay. Thank you. And just checking. National Association of County and City Health Officials.
[Alejandra Gertman]
Yes. Hi, again. This is Dr. Judith Troy, representing the National Association of County and City Health Officials.

[0:15:03]
Thank you. Thank you.
[Mina]
I didn't hear. Thank you. Canadian National Advisory Committee on Immunization.
[Kevin Reed Grimes]
Matthew Tunis, present.
[Mina]
Thank you. Infectious Diseases Society of America. Flor Munoz, representing IDSA. Okay. International Society for Travel Medicine. National Association of Pediatric Nurse Practitioners. This is Dr. Stacey Buchanan, and she represents... Thank you. National Foundation for Infectious Diseases. This is Dr. Bob Hopkins, Medical Director of the National Foundation for Infectious Diseases. National Medical Association. Pharmaceutical Research and Manufacturers of America.
[Richard Su]
Yeah, good morning.
[Dr. Wafik Aldairi]
Michael Ibarra, Chief Medical Officer at Pharma.
[Richard Su]
Right.
[Mina]
Pediatric Infectious Diseases Society.
[Grant Paulson]

[0:16:00]
Grant Paulson with Pediatric Infectious Diseases Society. Thank you.
[Mina]
Thank you. Society for Adolescent Health and Medicine.
[Hillary Blackburn]
Good morning, everyone.
[Mina]
It's Amy Middleman, representing SAM. Society for Healthcare Epidemiology of America.
[Dr. Kupferwasser]
Dr. Prithi Murotra, representing SHEA. Present today, was also present yesterday, but unable to unmute.
[Mina]
Great. Thank you. I'll mark that. Appreciate it. Thank you, everyone.
[Martin Kulldorff]
Thank you for that.

Discussion on VFC Resolution for MRV Vaccine

Yesterday, we had a very interesting and stimulating and scientific discussion. I think it was obvious to everybody who was listening that this committee has enormous depth and knowledge about vaccines, about science, about clinical experience, taking care of patients, about public health. There is one thing, though, in which we are rookies. And with one exception, this was either our first ACIP meeting or our second.

[0:17:02]
And there are many technical issues that we might not grasp as of yet. And after yesterday's meeting, I was approached by one of the members about the second vote we had yesterday about the VFC resolution on the MRV vaccine. That maybe we thought that maybe didn't quite understand what was going on. And with the VFC, typically, the votes are the same to ensure that all children have the same coverage and the same responsibilities or resources to vaccines. For example, if you have two vaccines and one is good and one is not so good, we want all children to have equal access to the vaccine that's very good. So I think there has been some thought about what to do about these two conflicting votes.

Motion to Reconsider VFC Resolution on MRV

[Vicky Pebsworth]

[0:18:11]
Okay. Yes. I move to reconsider the VFC resolution on MRV considered by the committee yesterday.
[Martin Kulldorff]
Thank you. Do we have a second for that?
[Vicky Pebsworth]
I second.
[Martin Kulldorff]
Thank you. So what I think we have to do first, any other comments on that? So we do have the first vote to reconsider. And then if the vote is yes to reconsider, we will vote on that resolution a second time. So this first vote is just whether to vote a second time. So please state your name and conflict of interest and how your vote is.

Vote on Reconsideration of VFC Resolution

Dr. Levi, please.
[Vicky Pebsworth]

[0:19:00]
Vicki Pebsworth, no conflict of interest. Yes.
[Joseph Hibblen]
Joe Hibblen, no conflicts of interest. Yes, this should be reconsidered.
[Raymond Pollack]
Raymond Pollack, yes. No conflicts.
[Evelyn Griffin]
Evelyn Griffin, no conflicts. Yes.
[Kathy Stein]
Kathy Stein, no conflicts. Yes.
[Hillary Blackburn]
Hillary Blackburn, no conflicts. Yes.
[Kirk Milhoan]
Kirk Milhoan, no conflicts. Yes.
[Dr. Jason Goldman]
James Pagano, no conflicts. Yes.
[Dr. Robert Malone]
Robert Malone, no conflicts. Abstain.
[Martin Kulldorff]
And Dr. Meister?
[Dr. Cody Meissner]
No conflicts. Abstain.
[Martin Kulldorff]
So now we then have to vote on. Yes. I'm Martin Kulldorff, no conflicts of interest. I would. Yes. So now we have to vote on the actual VFC votes. And that is to approve the updated vaccines for children's resolution for prevention of measles, mumps, rubella, and varicella.

[0:20:07]
This was described to us yesterday. Do you have a motion? So the outcome of the vote to reconsider is that it passed. 10 votes in favor to abstain. And so do we have a motion?

Motion to Approve Updated VFC Resolution for MRV

Yeah. To approve the updated vaccines for children's resolution for prevention of measles, mumps, rubella, and varicella. Do we have a motion? Do we have a second? You need to say.
[Vicky Pebsworth]
Second the motion. Thank you so much.
[Martin Kulldorff]
I appreciate that. So now we will vote on to approve the updated vaccines for children's resolution for prevention of measles, mumps, rubella, and varicella. Please state your name, conflict of interest.

[0:21:01]
And yes.
[Dr. Jason Goldman]
Mr. Chair point of order.

Debate on Updated VFC Resolution for MRV

Will you allow for discussion and comment before you vote?
[Martin Kulldorff]
Yes, of course. May I speak.
[Dr. Jason Goldman]
Who's who's talking. Dr. Jason Goldman. American college of physicians.
[Martin Kulldorff]
Yes, please speak.
[Dr. Jason Goldman]
So I, by your own criteria yesterday, I'm willing to debate and discuss with you so the public can trust me when I say this. And I was very concerned about the vote that was taken yesterday because you had two conflicting votes that you're now reconsidering that had the exact same resolution. But the second one primarily affects those of lower socio economic levels. So either you, the vaccine presentation and the harm you were saying only is good for children. Who are lower socioeconomic level and should only get what you consider and the committee of harmful vaccine. Or would you consider that the second vote actually revealed the truth that you do not have the data or evidence to challenge the current standing and that there is no associated harm.

[0:22:08]
The second vote for the same recommendation is actually what should be valid for the entire population, that the risk is not a concern and there isn't harm to the MMRV. That was stated in the first vote because the second vote actually revealed the truth.
[Martin Kulldorff]
Thank you. I appreciate that comment. Any other comments?
[Dr. Reza Flevi]
Yeah, I think that the chair explained that there was an error in the interpretation of the votes. And I suggest that we spend the time today on actual debate and scientific debate and not trying to provoke a discussion that is, has no merit.
[Martin Kulldorff]
Thank you. Yeah. Any other comments? Joe Hibblen here.
[Joseph Hibblen]
As a committee, we discussed that the wording of the second vote, the second question was indeed confusing and not precise.

[0:23:05]
And considering the enormous amount of work that the CDC has done and the committee has done. As Mark Twain said, you know, if I had more time, I'd write a shorter letter. And part of this confusion I think was just simply that in much of it was in wording. And I appreciate the new clarity of the, of the question.
[Martin Kulldorff]
Thank you. Anybody else? So I think that discussions and debate is always very positive. So I thank everybody for that both yesterday, and I think we'll have made plenty of that today. So I think we can move forward to the vote then. So again, state your name, comfort of interest and your vote. Dr. Levi.
[Vicky Pebsworth]
Rates of levy.

Vote on Updated VFC Resolution for MRV

No conflict of interest. Yes. Vicki Pabstworth.

[0:24:00]
No conflict of interest. Yes. Joe Hibblen. No conflicts of interest. Yes.
[Joseph Hibblen]
Raymond Pollack. No conflicts of interest.
[Evelyn Griffin]
Evelyn Griffin. No conflicts of interest. I vote. Yes.
[Kathy Stein]
Kathy Stein. No conflicts of interest. Yes.
[Hillary Blackburn]
Hillary Blackburn. No conflicts. Abstain.
[Kirk Milhoan]
No conflicts of interest. Yes.
[Dr. Jason Goldman]
James Pagano. No conflicts. Yes.
[Dr. Robert Malone]
Robert Malone. No conflicts. Abstain.
[Dr. Cody Meissner]
Cody Meissner. No conflicts of interest. Abstain. And Martin Kulldorff. No conflicts of interest. Yes.
[Martin Kulldorff]
So thank you very much. We have nine voting.

[0:25:01]
Yes. And three abstain. So thank you for that. And I just want to stress that. What all this means is that every child, including every child in the vaccine. In the vaccine program, the FC program, vaccine for children program, will have access to be vaccinated against measles. They will have access to be vaccinated against mumps. They will have access to be vaccinated against rubella, which is German measles. And they will have access to be vaccinated against varicella, which is chickenpox. So this ensures that they all are sure to be able to be vaccinated to all these four very important diseases.

Hepatitis B Vaccine Discussion and Votes

So thank you very much. Yesterday, we had very good discussions about the hepatitis B vaccine.

[0:26:03]
And we will now proceed to do the votes for the hepatitis B vaccine. If we can get the motion on the screen. So the first vote is all pregnant women should be tested for hepatitis B infection.

Motion to Test All Pregnant Women for Hepatitis B

Do we have a motion?
[Dr. Arjun Srinivasan]
Motion.
[Martin Kulldorff]
Thank you. Do I have a second? Thank you. And again, we will please state your name, conflict of interest, and your vote.

[0:27:06]
And we can start from here this time.

Vote on Testing All Pregnant Women for Hepatitis B

Dr. Malone.
[Dr. Robert Malone]
Robert Malone, no conflicts of interest. Votes yes. James Pagano, no conflicts of interest.
[Kirk Milhoan]
Yes. Kirk Milhoan, no conflicts of interest. Yes.
[Hillary Blackburn]
Hillary Blackburn, no conflicts. Yes. Kathy Stein, no conflicts. Yes.
[Evelyn Griffin]
Evelyn Griffin, no conflicts. I vote yes.
[Joseph Hibblen]
Raymond Pollack, no conflicts. Yes. Joseph Hebelin, no conflicts of interest. Yes.
[Vicky Pebsworth]
Vicky Pepsworth, no conflicts of interest. Yes.
[Dr. Cody Meissner]
Retta Flevi, no conflicts of interest.
[Martin Kulldorff]
Yes. Dr. Meissner.
[Dr. Cody Meissner]
No conflicts of interest.

[0:28:01]
I vote yes.
[Martin Kulldorff]
State your name, please.
[Dr. Cody Meissner]
Cody Meissner. Sorry.
[Martin Kulldorff]
I'm Martin Kuldorff, no conflicts of interest. I vote yes. Is there a point of order? Yes.
[Carol Hayes]
Could there be some discussion about this very briefly?

Discussion on Wording of Hepatitis B Testing Recommendation

This is Carol Hayes with the American College of Nurse Midwives.
[Martin Kulldorff]
We did have a discussion of this yesterday. Well, I would just like to suggest that the wording... Okay.
[Carol Hayes]
I would just like to suggest that the wording be changed to SAHARE, that it includes the antigen test and not the antibody test, to make it more clear for clinicians.
[Martin Kulldorff]
So I think we have excellent colleagues at CDC, and they can phrase the exact language so that they accept proper tests.

[0:29:01]
I think that's a very good suggestion, and I think we can have the CDC colleagues to sort of fine tune that specification. So the number of votes here was 12 votes in favor. So thank you, everybody. The second vote...
[Vicky Pebsworth]
Dr. Pepsworth, did you have a comment here?

Discussion on Hepatitis B Vaccine Safety and Efficacy

Actually, I do, if it's all right. In light of a lot of the comments that were made by the public and others, I went back and reviewed some of the information that we were given yesterday. And CDC's presentation on slide 18 about global distribution of different vaccination policies showed that in 26 countries, the first dose of hepatitis B vaccine is given to at either two or three months in the mothers who are hep B negative.

[0:30:15]
So this includes most of Europe, England, France, Spain, Germany, Ireland, Norway, Denmark, Sweden, Iceland. CDC also reported that reactogenicity within the first week of life varied by study, and they presented data showing that systemic reactions in hepatitis B vaccinated children were in fact not rare. In fact, up to 5% were reported to have fever. 32% were drowsy and sleeping. 3% were categorized as severe. Irritability, fussiness, and crying was reported for 11% in the first 24 hours and 22% in the first five days of life.

[0:31:04]
These are not trivial reactions and reported in up to one third of births. In addition to the Yang study that I mentioned yesterday from 2016 showing that hepatitis B vaccine impaired behavior and neurogenesis, there was a 2013 study that I wish that we had been presented with by CELIC. It was published in the European Journal of Pediatrics titled Inflammatory Responses to Hepatitis B Vaccine in Healthy Full-Term Infants. It showed that 30% of infants developed significant elevations of C-reactive protein without clinical signs of sepsis, and they were negative for blood cultures. This suggests a robust inflammatory response is occurring during critical window of neurodevelopment, which would be involving neurogenesis and synaptic development.

[0:32:06]
So in light of this finding and CDC reports of up to a third of infants experiencing significant systemic adverse reactions, I personally think we should be erring on the side of caution and adopt a more prudent vaccination policy similar to what is used in most of Europe, which not only doesn't vaccinate low-risk newborns on the first day of life, they don't even vaccinate at one month, as we are considering. It is typically delayed until two to three months.
[Martin Kulldorff]
Thank you. Any other comments? Dr. Malone?
[Dr. Robert Malone]
Along the lines of differences in interpretation of information between what was presented and what is published, my understanding is that what was published or my interpretation is that what was presented relating to the findings of the Institute of Medicine were not entirely accurate through an error of omission.

[0:33:29]
My understanding is that the IOM report found that the 22 most commonly claimed serious harms for this product, all but one of which was found to be causative relationship. The studies had not been done to assess if it caused harm or didn't cause harm. To interpret that that implies the absence of data implies safety is, I think, a perversion.

[0:34:02]
We have widespread claims, case reports, case series suggesting that there are harms, and we have an IOM report indicating that they could not conclude statistically whether or not those were at merit. That does not mean that it's safe, which was the assertion, and I think that that gets right to the fundamentals of this. In my opinion, in intervention, in particular in pregnancy and in the newborn, the burden is to demonstrate safety, not to generate the statistics to demonstrate the converse non-safety. The default should be the assumption that there is no intervention in the infant and the pregnant woman with a vaccine unless there is definitive evidence of safety.

[0:35:09]
And the position that was taken, in my opinion, appears to be an inversion of that. And I respectfully disagree that the absence of data that statistically proves lack of safety does not mean that the product is safe.
[Martin Kulldorff]
Over. Thank you, Dr. Hubel. And if we can keep it brief because we have a very long agenda today, I would appreciate it.
[Joseph Hibblen]
Briefly, thank you, Mr. Chair.

Discussion on Hepatitis B Vaccine Dosing and Clinical Decision-Making

I'm a strong advocate in clinical decision-making, and I think that needs to be supported. And in order to support that, I believe that we need to clear up the question, which, as I read it, has a logical inconsistency.

[0:36:04]
The first part is that it says the dose should not be given until the child is one month old. And if that's an absolute that it should not be given, then there's no opportunity for decision-making. The second part says that there should be clinical decision-making. You can't have it both ways. You can't say it can't be given and then say it can be given if there's clinical decision-making.
[Martin Kulldorff]
If we changed it to not recommended, would that work?
[Joseph Hibblen]
Well, it says it's not recommended. And then it says, well, you can give it if you have clinical decision-making. So I would propose to modify the question to say the first dose of hepatitis B is not given until the child is one month old, except for when there is clinical decision-making.

[0:37:04]
As it's written now, it's a logical inconsistency. You can't say don't give it and then give an opportunity to give it. So I think it should have some modification is not given, except for the case of clinical decision-making.
[Raymond Pollack]
Point of order, Mr. Chairman.

Motion to Postpone Hepatitis B Vaccine Question Indefinitely

We're debating something already without having a motion on the floor. So I think you need to have a motion on the floor. Robert's Rules of Order. You need to have a motion on the floor. Open it up for discussion because I think there is going to be some debate as to whether any evidence at all was presented for what's being recommended.
[Martin Kulldorff]
Do we have a motion?
[Raymond Pollack]
Motion on the floor, then open it for discussion and then take a vote either to reword this or to discard it completely.
[Martin Kulldorff]
Thank you for that. I think I wasn't very clear. My apologies here.

[0:38:02]
I'd like to make a motion. Yes, please, Dr. Malone. I move to postpone the question indefinitely.
[Dr. Robert Malone]
I believe that there's enough ambiguity here and enough remaining discussion about safety, effectiveness, and timing that I believe that a vote today is premature.
[Raymond Pollack]
So that's my motion. That's a motion to table. Motion to table cannot be debated. We have to take a vote on a motion to table. If the motion to table succeeds, then the current guidelines would remain in place until this committee comes back with other recommendations.
[Martin Kulldorff]
We have a motion to table. I make a motion to table. I second that motion. So we're going to have a vote on whether to table this. And are there any discussions on this motion?

[0:39:00]
There's a motion to table. You have to take a vote. OK. So please state your name and your conflict of interest and your vote. Dr. Levi?

Vote on Motion to Postpone Hepatitis B Vaccine Question

Reza Flevi, no conflict of interest.
[Dr. Reza Flevi]
I support the motion. I think we need to go to a more robust policy like my colleague here just proposed. So what is your vote? Yes, I support to table.
[Vicky Pebsworth]
Vicki Pebsworth, no conflict of interest. I vote yes.
[Joseph Hibblen]
Joseph Hibbelen, I vote yes to table. We are more prudent when we are cautious and have full debate.
[Raymond Pollack]
Raven Pollack, no conflict, vote yes.
[Evelyn Griffin]
Evelyn Griffin, no conflict of interest. I vote yes.
[Kathy Stein]
Kathy Stein, no conflict of interest. I vote yes.
[Hillary Blackburn]
Hillary Blackburn, no conflict, yes.
[Kirk Milhoan]
Kurt Milhoan, no conflict of interest, yes.
[Martin Kulldorff]

[0:40:01]
James Pagano, no conflict, yes.
[Dr. Robert Malone]
Robert Malone, no conflict of interest, yes.
[Dr. Cody Meissner]
Dr. Meissner? Cody Meissner, no conflict of interest. And I vote strongly to table this question. I don't know if this is an opportunity, because there certainly are responses to comments that were made. And I would like to be sure I have a chance to state those.
[Martin Kulldorff]
Marty Kulldorff, no conflict of interest, no. So the motion passes, 11 yes, one no. And I think Dr. Meissner wanted to have a statement.

Discussion on Hepatitis B Vaccine Safety and Efficacy (Continued)

[Dr. Cody Meissner]
Thank you, Dr. Kulldorff. I'm not sure if you want to wait until we revisit this. But my comment is especially in response to Dr. Malone's thoughtful comments regarding this.

[0:41:05]
And I would just want to point out that it's very, very difficult to prove the absence of harm. It's simply not a practical objective. And I think the experience that we have accrued over administration of a dose of the vaccine in the first 12 to 24 hours is overwhelming. And the issues that were raised regarding irritability or restlessness, those are certainly not objective parameters that should be used to assess safety. Over.
[Martin Kulldorff]
Thank you. We did have some people who wanted to make comments on this before the decision was to table.

[0:42:02]
I don't know if they still would like to comment or if we can move forward with the agenda. Since this table, we're not going to make any votes on hepatitis B vaccine today. Dr. Stein.
[Kathy Stein]
I think we should be careful to make absolute statements about, yes, this is absolutely not harmful or no, this is not harmful. I think much of that is in the eyes of the parents and the children. And so I think we just need to be very careful about using absolute language and consider the full context of the literature and any patient experience that we have available to us. Thank you.
[Dr. Cody Meissner]
So, Dr. Meissner. Yes. Thank you, Dr. Calder. I wish to respond to that most recent comment. I think it's important for everyone to understand that no vaccine is 100 percent safe and no vaccine is 100 percent effective.

[0:43:09]
What's important for the provider before administering a vaccine is to think about that particular patient. And does the benefit of protection exceed any possible side effect from the vaccine? And when you apply that to a newborn hepatitis B vaccine, I don't think there's any question whatsoever that the benefit far outweighs any adverse side effect. Over.
[Martin Kulldorff]
We will have a discussion if people want to. But I would actually urge that we since we're not going to vote on this, that we leave it to a subsequent date. That was what we voted to table it. So I would urge everybody not to that we can do this later.

[0:44:02]
But I will allow anybody who wants to speak to do so. Dr. Munoz.
[Flor Munoz]
Yes. Good morning. Thank you so much for this opportunity again to speak about this. I am pleased with the decision to table. I think that it would be important when you consider this, that there has been 30 years of progress with prevention of hepatitis B disease and potentially cancer. And that, indeed, the discussion that has been brought up regarding safety is not based on evidence other than case reports and anecdotes. And I would urge for a proper process to be able to address any potential concerns that people might have. The committee can request additional studies.

[0:45:00]
I think that this decision to completely dismiss a very successful program is more harmful than beneficial at this point based on the data that has been provided. And just to comment on the previous vote, I was wondering what the point will be about it. The hepatitis B testing is routine standard of care already in prenatal care practice, obstetric practice. And it's something that is part of the care of women at this point. So what is the plan with that motion that was just voted on?
[Martin Kulldorff]
I think that currently the testing is in about 86, 87% of pregnant women. And it shows the methods that we think we should be closer to 100. Dr. Hopkins.

Discussion on Hepatitis B Vaccine Review Process

[Bob Hopkins]
Thank you, Dr. Kaldorff.

[0:46:01]
I just think if this issue is going to be revisited, it should undergo a full review by a work group, including the full evidence to recommendations framework, including the domains of equity and practical implementation. Thank you.
[Martin Kulldorff]
Thank you. Thank you for being very brief, Dr. Goldman.
[Dr. Jason Goldman]
I will also be brief as well, echoing Dr. Hopkins comments. But a question, Mr. Chair, can you please present and describe to the public and the committee what process you will be using in the future to vet this information, as has always been done for an extensive amount of time? The work groups would go through not only the evidence to recommend framework, but a grade process to rate the quality of the evidence to see if it is a trial that is powered correctly. If it has the correct evidence, if there's biases, there's conflict, if it's case report. Can you please explain what methodology the committee will be using in the future to discuss this?

[0:47:01]
If you have abandoned the evidence to recommend framework and grade process that the work groups have been using for many years, or if you are going to do that. I think it's important for the public to know how you are going to be vetting this data to make these presentations. As we have seen in the past two days, that it has not been through the work groups and the committee has been discussing things that typically is vetted through a work group process. So I applaud the committee for getting this one vote right by tabling to allow it to have further discussion. But please, if you could explain to all of us what this committee will be doing in the future. Thank you.
[Martin Kulldorff]
I hope we can come back to that if this vote comes back in a future meeting. I'm not skilled enough, I guess, to do a very quick response to that. So I apologize for that. Dr. Middleman.
[Amy Middleman]
Thank you for recognizing me. I just want to echo some of the comments, but I think it's not just related to hepatitis B.

[0:48:04]
I think some of the concerns that people have are echoing throughout all of the discussions that the committee is having. It is really important, as Dr. Meisner stated, to recognize that no intervention, not even Tylenol, not even amoxicillin, clearly not chemotherapy drugs. There's always some risk. There's a risk to walking across the street. And the committee's scientific challenge is to determine whether the benefits outweigh the risks. These questions have been vetted very clearly. It is very easy to get distracted by one study that says this or one study that does or does not say that. And I would urge the committee to use a methodical scientific method to weigh the risks and benefits appropriately using grade or evidence to recommendation. This is important for all vaccine decisions, and this is what I think some of us are really concerned about in terms of the absence of it.

[0:49:07]
So thank you very much.
[Martin Kulldorff]
Dr. Levi.
[Dr. Reza Flevi]
I appreciate the desire to keep scientific methods. And I just I have to say that one thing that puzzles me is that many of the speakers that push for the scientific approach are speaking very confidently, confidently in the absence of the gold standard evidence of robust long term clinical trials against placebo. And we all agree that those trials in these settings for this particular intervention do not exist. So I just suggest that if we want to keep a scientific approach, we should be scientific throughout all the steps of the decision making. And I think that too many times we hear very confident statements about safe and effective in the absence of that gold standard, especially in the context of vaccination.

[0:50:10]
So with all due respect, I just encourage all of us to be a little bit more humble and also recognize that many times we make decisions not following the gold standard.
[Martin Kulldorff]
The motion, this issue has been tabled and those who are still on the list who want to speak. I would encourage you to to come back if we if this issue is come up in the next previous meeting that you we would like to hear from you then. But at this point, we have tabled the motion and we're going to have to move forward with the agenda. Otherwise, Mr. Chair, for other things, Mr. Chair, Dr. Goldman, I think you already had a chance to speak once.
[Dr. Jason Goldman]
Very respectfully, though, we have to we have to move forward.

[0:51:00]
This speaks to process.
[Martin Kulldorff]
It is not currently a motion on the table for the hepatitis B vaccine.
[Dr. Jason Goldman]
Respectfully. Please stop unmuting me. That is disrespectful. You want debate and discussion, but you're muting people and silencing them. This speaks to the process. As Dr. Levy said, we need gold standard. I agree. That's what the work groups are for. Please provide to the public so they can have trust, faith and confidence in vaccination as to what process we are going to be using to properly vet and discuss all future vaccines. That is why the evidence to recommend framework was created so we would have a standard to be able to vet all vaccines. But that is not being used. So if you could kindly, respectfully tell the public how you are going to be analyzing all of these vaccine decisions so we can have confidence in this committee as previous. Thank you.
[Martin Kulldorff]

[0:52:01]
You made that comment before and I responded to that comment in a very nice and polite manner. We will not have agency updates. That is something that was on the agenda for yesterday.

Agency Updates: CDC

Again, I would like if the agencies can keep it fairly brief, that would be appreciated. We start with CDC.
[Uzo Chukwuma]
Good morning. Randy Limbago presenting for the National Center for Immunization and Respiratory Diseases from CDC. My updates this morning are about some of our response and preparedness activities. As of September 16, CDC has confirmed 1491 measles cases in 2025 in the U.S. from 42 jurisdictions. This is the highest number of measles cases reported since 1992.

[0:53:03]
86 of these cases have been associated with 38 outbreaks this year. And in comparison for last year, 69% of those cases were outbreak associated and only with 16 outbreaks. I also want to make you aware that the vast majority of measles introductions have been from U.S. citizens traveling abroad to areas with active measles infection and returning home, underscoring the importance of these domestic transmission events in measles outbreaks, especially when they return to under-vaccinated communities. That said, the overall risk of measles to the general U.S. population remains low, primarily due to the high population immunity and vaccine coverage for the general population.

[0:54:03]
We are also preparing for the 2025-2026 respiratory virus season. The bulk of our activities really focus on what we call the big three respiratory viruses, influenza, COVID-19, and respiratory syncytial virus. As we move into this season, flu and RSV activity remain low, while COVID activity is peaking in many areas across the country with elevated emergency department visits and hospitalizations nationally. We're seeing this through increasing positive laboratory tests for COVID-19, and we are seeing the highest number of emergency department visits in children 0-4 years old, and also increased visits among children aged 5-17 years old and adults 65 years of age and older.

[0:55:00]
Hospitalizations are elevated for adults 65 years and older. Because seasonal influenza, COVID-19, and RSV share modes of transmission, seasonal timing, and prevention strategies, CDC is taking a coordinated approach in preparing for these, and this includes aligning our programmatic work, our data systems, outreach efforts, and communication channels across all three of these pathogen areas. We are also continuing to monitor for other pathogens for respiratory diseases, including bacterial pathogens such as mycoplasma newinia, group A strep, and pertussis. I will cede to any other CDC updates.

Agency Updates: CDC (Ebola Outbreak)

[Chris Braden]
Yes, this is Chris Braden. I'm online. So my update has also to do with a significant outbreak response that the National Center for Emerging and Zoonotic Infectious Diseases is involved with right now.

[0:56:03]
On September 1st, CDC received reports from in-country sources regarding cases of suspected viral hemorrhagic fever in the Kasai province of the Democratic Republic of Congo, which was later to be confirmed as Ebola virus Zaire. The index case was a pregnant woman who was admitted to Gulope General Hospital on August 20th with symptoms including high fever, bloody diarrhea, hemorrhaging, vomiting, and weakness. The patient passed away from multi-organ failure on August 25th. Two healthcare providers treating this patient also became ill with similar symptoms and died. Genomic sequencing analysis from DRC's National Public Health Laboratory collected from patients are distinct from previous Ebola outbreaks, suggesting that a new spillover event from wildlife rather than a transmission from a previous outbreak in the province. The government of DRC swiftly recognized the probable case of viral hemorrhagic fever and confirmed the presence of Ebola in the Kasai province.

[0:57:08]
They quickly communicated with CDC, allowing the agency to rapidly establish an emergency response structure, respond to the outbreak. Of note, CDC has worked with DRC over 20 years. CDC established a country office in DRC in 2002 and currently is staffed with about 30 CDC experts on the ground, building labs, training staff, and strengthening core public health capabilities. The DRC Ministry of Health reported that there are now 37 confirmed cases as of September 15th, including 19 deaths among confirmed cases. Additional suspect cases have been identified for testing, but challenges in reporting, tracking, and case definition reduced the reliability of these numbers.

[0:58:01]
CDC is working to support the Ministry of Health in strengthening surveillance and case counting. As of September 15th, 944 contacts have been identified, underscoring the importance of further epidemiological support. Vaccination of health care workers and contacts of cases has begun on September 13th. As of September 15th, 369 vaccinations have been administered. All reported cases have been from Kasai province, and all confirmed cases are located in the Bulapes health zone. The true scope of the outbreak is likely larger than is currently known. No Ebola cases related to the outbreak have been reported outside of the Democratic Republic of Congo or in the United States. The anticipated risk of Ebola to the public in the United States is low.

[0:59:00]
Yesterday, CDC issued a health alert network health advisory to summarize recommendations for public health departments and clinicians in the United States related to case identification, testing, and biosafety considerations should there be an imported case. CDC headquarters is supporting the CDC DRC country office, assessing response needs, country, and providing support to DRC as they respond to this outbreak. CDC has provided two staff to the country office to the Kasai province to assist with outbreak response, and has deployed from headquarters two medical epidemiologists and a senior advisor who arrived in Kinshasa on Tuesday, September 16th. CDC is actively preparing to deploy additional CDC staff based on country needs. Likely areas of technical support will include laboratory testing, case surveillance and investigation, contact tracing, and infection and control measures.

[1:00:02]
Thank you.
[Martin Kulldorff]
I'm happy to answer any questions if you have.
[Dr. Robert Malone]
Can I ask a follow-up question?
[Martin Kulldorff]
Thank you.

Agency Updates: CMS

We move on to CMS. Thank you. I really like that brief update. You're my favorite.

Agency Updates: FDA

FDA, please.
[Tracy Beth Hoag]
I'll try to keep it brief. Tracy Beth Hoag, FDA. We had a few recent and potentially relevant regulatory actions and announcements. The four currently approved COVID-19 vaccines, MNEC spikes, spike vacs, Comirnaty, and Nuvaxovib are approved and indicated in adults 65 and older, and then those with risk factors above the age of 12. Risk factors for severe COVID-19 above the age of 12 for Nuvaxovib and MNEC spikes, above the age of five years for Comirnaty, and above the age of six months for spike vacs.

[1:01:07]
And then the prior EUAs for Novavax, Pfizer, and Moderna were revoked. For the currently approved formulations of the COVID-19 vaccines, there are three post-marketing commitments, including looking at persistence of spike protein and associated symptoms, as well as, most importantly, the randomized saline placebo-controlled trials to look for safety and efficacy of all of those vaccines. I think yesterday we saw a very interesting example of how real-world evidence can be misleading when we saw the association with hepatitis B vaccine given to newborns and the apparent protection against bronchopulmonary dysplasia, which, of course, as many of you pointed out, was likely an example of healthy vaccine bias.

[1:02:01]
So that's why we need the robust gold standard science, preferably randomized controlled trials, as we've all been discussing. And along those lines, we are also going to be requiring, we announced we'll be requiring randomized controlled trials for concomitant administration of different vaccines. And then in some interesting news, the Ixchic vaccine for chikungunya virus, this is a live attenuated vaccine, was recently suspended due to safety concerns. And so those are my announcements for now. Thanks.
[Martin Kulldorff]
Thank you. And HRSA, please.
[Kevin Reed Grimes]
Captain Grimes for HRSA.

Agency Updates: HRSA

No updates at this time. Thank you.
[Martin Kulldorff]
Thank you. AIHS, Indian Health Service.
[Wendy Lu]
Good morning.

Agency Updates: IHS

[Joseph Hibblen]
No updates from the Indian Health Service.
[Martin Kulldorff]

[1:03:01]
Thank you. NIH?

Agency Updates: NIH

[Joseph Hibblen]
No updates at this time from NIH.
[Martin Kulldorff]
Thank you. Thank you all. And that ends the agency updates. We will now move forward to the next vaccine on the agenda, which is the COVID-19 vaccines.

COVID-19 Vaccines: Introduction by Dr. Levi

And we will first have an introduction by Dr. Levi.
[Dr. Reza Flevi]
Thank you. I'm going to be trying to be brief and get the presentations going. So we were tasked with preparing the discussion today as a workgroup. Because of the circumstances, we had less time than desired. Okay. And we basically set for ourselves both immediate goals and longer-term goals. So the immediate goals were very much focused on the current meeting.

[1:04:02]
And we were tasked with thinking about the recently authorized products. And think about what populations and subgroups should be recommended what. And the options that we considered are either recommend, not recommend, or individual-based decision. And we're going to make a precise definition of what this is later today. We also felt that one of the things that we wanted to address with respect to this meeting is to really think about all the risks and uncertainties that we would like to suggest that there should be communicated more consistently with patients. And in particular, potential changes to the vaccine information statement that the workgroup found that its current state is not reflective of the true risks and uncertainties. We also considered, and we have medium-term goals.

[1:05:02]
We have an expansive terms of reference. And just for the record, the only debates that we had so far with the former leadership of the CDC were around the scope of the questions that we can ask. And we believe that ACIP and, as a result, the workgroup should really be able to ask and consider any potential information or knowledge that is relevant to vaccine policies, vaccination policies. That's our charter, and we believe that we need to pursue that and really have three focus clusters that are assigned to workgroup members based on their expertise. And the goal of each cluster is to summarize all the available knowledge for the discussion in the workgroup and highlight important issues and knowledge gaps. And, as a result, hopefully formulate policy options on broad vaccination-related issues for consideration by ACIP.

[1:06:02]
That's kind of how we see the long-term goals of this workgroup. I want to say something about values and conduct. Again, we, in the mindset that we need to leverage all the relevant published and unpublished scientific, clinical, and public health data, information, and knowledge, including experiences from the field. We are going to focus on personalized risk-benefit analysis, and we're going to very much stay away from the narratives or the statements about safe and effective. We don't believe that these are appropriate or scientific language to talk about the issues related to vaccination. And in terms of how we are going to conduct the workgroup, we believe strongly in debate with respect and also with communicating the workgroup's members' diverse positions and opinions with maximum transparency. And you're going to hear today three presentations of workgroup members.

[1:07:04]
The first one will be by Professor Eldari and Professor Cooperwasser on some safety uncertainties of COVID-19 vaccines. The second one will be by Professor Carlton about genomic or vaccine-induced myocarditis. And just speaking to the open debate and transparency, we are going to hear later in the afternoon from members in the workgroup, Professor Bernstein, Professor Miglis, and Professor Perlman, that will talk about the minority opinion of the workgroup. Again, we are going to make sure that there is debate and it's transparent, and that's kind of the way we believe we should conduct ourselves. I want to thank – I want to end by thanking my other – the other ACIP members that served with me on this workgroup, Dr. Pagano and Dr. Mellon.

[1:08:01]
And I cannot thank enough for all the external subject matter experts that participated in the workgroup discussions. It has been an honor for me to interact with them and a pleasure, and they all worked very, very hard on a very, very impossible timeline. And this is also an opportunity to thank our colleagues at the CDC and FDA that worked also their butts off, again, in some kind of an impossible timeline that was forced on us by the circumstances. And finally, I want to thank the two ex-officios that participated in the workgroup, Dr. Hogg and Dr. Johnson. Again, I look forward to hearing everybody today and have a good debate. Thank you.
[Martin Kulldorff]
Thank you for that, Dr. Oliva. We now have three presentations by Dr. Srinivasan from CDC.
[Dr. Arjun Srinivasan]

[1:09:03]
Good morning.

COVID-19 Epidemiology Update by Dr. Srinivasan

My name is Dr. Arjun Srinivasan. I'm the acting chief medical officer for CDC's National Center for Immunization and Respiratory Diseases. I'll begin today with updates to COVID-19 epidemiology. I'll note that, as yesterday, I am joined by subject matter experts on the line to respond to questions. And I will also note that I have been asked to move very fast, so buckle up. The data presented and discussed in this section will be data from the COVID-19 Associated Hospitalizations Surveillance Network, or COVID-NET. COVID-NET is one of three RESVNET platforms, in addition to RSVNET and FluServeNET, that collect data using similar methods and catchment areas on laboratory-confirmed COVID-19, RSV, and influenza-associated hospitalizations, respectively. It is a collaborative effort between CDC and state and local health departments who share data with CDC via cooperative agreements.

[1:10:01]
COVID-NET is a population-based surveillance system that collects and reports data for more than 300 acute care hospitals in 185 counties across 13 states. The COVID-NET catchment area includes about 10% of the U.S. population. COVID-NET collects and reports two types of data. The first type of data are population-based rates of COVID-19-associated hospitalizations. These include all hospitalizations that meet the COVID-NET case definition of a laboratory-confirmed SARS-CoV-2 positive test among hospitalized residents of the COVID-NET catchment area. COVID-NET collects and reports some data for all cases, including age, sex, race, ethnicity, site, and test and admission dates. The second type of data describe clinical characteristics of hospitalized patients, including outcomes, underlying conditions, treatments received, and discharge diagnoses. These data are obtained through detailed medical chart reviews of an anonymized site and age-stratified random sample of hospitalizations.

[1:11:06]
When presented in reports or presentations, clinical analyses are limited to hospitalizations due to COVID-19, the definition of which will be presented later. The primary purpose of COVID-NET is to monitor laboratory-confirmed COVID-19-associated hospitalizations among children and adults and deliver these data to decision-makers and the public in order to provide a broad and timely understanding of COVID-19 trends. COVID-19-associated hospitalization rates are updated weekly and are used to estimate and compare disease burden and respond to rising rates. Detailed clinical data, including underlying conditions, allow CDC to categorize hospitalizations that are due to COVID-19, better understand COVID-19-associated hospitalization trends and determine who is most at risk, track severity of illness, examine how many people hospitalized due to COVID-19 have underlying medical conditions, and provide insights into treatments used.

[1:12:07]
When defining COVID-19-associated hospitalization in COVID-NET, a case is counted if the person lives in the defined COVID-NET catchment area and tests positive for SARS-CoV-2 using a laboratory-based molecular antigen or serology test within 14 days before or during hospitalization. This definition is used to monitor overall trends in hospitalizations. The surveillance definition is a simple approach that works across hundreds of hospitals and is available in near real-time. Similar definitions are used to monitor hospitalizations for other pathogens like RSV and influenza in the U.S. and worldwide. This approach was developed by infectious disease experts, and the surveillance definition has met the balance needs of accuracy, speed, and broad coverage over COVID-NET's five-year existence. There has been sustained interest in determining whether hospitalizations among SARS-CoV-2 positive persons are with or for COVID-19-related illness.

[1:13:08]
During the early pandemic, with asymptomatic transmission, no immunity or vaccinations, and high rates of illness, hospitals screened every patient when they arrived at the hospital. The screening likely identified hospitalizations among SARS-CoV-2 positive asymptomatic patients or persons with COVID-19 illness who were hospitalized for other reasons, like surgery or labor and delivery. As a result, COVID-NET implemented an algorithm to track cases with COVID-9 identified as the likely primary reason for admission, hereafter referred to as hospitalizations due to COVID-19, using chief complaint and history of present illness. Data for all current and previous surveillance periods back to March 2020 are posted monthly on COVID-NET's public dashboard. It is our understanding that this topic was of interest to the committee. Of note, while widespread screening of every patient for COVID has largely stopped, COVID-NET continues to use the algorithm.

[1:14:07]
Before going further, we should describe some of the factors to consider when defining hospitalizations due to COVID-19. Regardless of the focus, identifying a singular cause of hospitalization can be difficult for several reasons. A positive SARS-CoV-2 test can influence the decision to admit a patient who has comorbidities or other conditions. Additionally, the presence of comorbidities or other conditions can influence the decision to admit a SARS-CoV-2 positive patient. Many data elements extracted from the medical record, medical chart, including SARS-CoV-2 testing, treatment, discharge diagnosis codes, and other data elements can misclassify hospitalizations with respect to whether or not they are due to COVID-19. For example, ICD-10-CM codes in the U.S. are designed for administrative and billing purposes, not surveillance, and may overcount or undercount cases. Additionally, the COVID-19 ICD code can be used just to indicate a positive SARS-CoV-2 test.

[1:15:05]
COVID-NET uses a rigorous and standardized process to determine whether sampled hospitalizations can be classified as being due to COVID-19. As mentioned, this approach relies on abstraction of the chief complaint in history of present illness at admission from the medical record. This slide describes the algorithm used to define hospitalizations where COVID-19 was the likely primary reason for admission. First, hospitalizations are classified as non-COVID-19 related if the history of present illness indicates obstetric care, such as labor and delivery, an inpatient surgery or procedure, a psychiatric admission, trauma, such as fracture or car crash, or newborns hospitalized at birth. For the remaining hospitalizations, if the chief complaint or history of present illness documents fever or respiratory illness, a COVID-19-like illness, or suspicion for COVID-19, the hospitalization is classified as having a COVID-19-related reason for admission.

[1:16:00]
A small subset of hospitalizations that do not clearly fit these categories are reviewed by two COVID-NET physicians with adjudication by a third if necessary. If the medical record indicates that the positive SARS-CoV-2 test results was an incidental finding or that the hospitalization was not related to COVID-19, such as for a localized infection or surgical complication, those hospitalizations are classified as not being related to COVID-19. This figure shows the percent of hospitalizations due to COVID-19 based on reason for admission over time by age group. Using the algorithm, 87% of hospitalizations among SARS-CoV-2 positive admissions identified by COVID-NET were due to COVID-19. Percentages have increased over time, likely because widespread screenings of asymptomatic patients are no longer occurring. The percent of COVID-NET hospitalizations due to COVID-19 was 89% for children, and the percent increased with age among adults.

[1:17:01]
Adults aged 65 years accounted for 70% of COVID-19-associated hospitalizations, of which 91% had COVID-19 as the likely reason for admission. As a collaborative surveillance system, COVID-NET must balance the burden of chart abstraction with the utility of clinical data. There are limitations to what can be collected and reported, as well as how and when. Because ICD-10 coding occurs after patient discharge, reporting can be delayed, and in some cases, final ICD-10 codes may be stored only in billing systems that are not accessible to abstractors. To address these challenges, COVID-NET surveillance officers also review each patient's discharge summary. This allows them to capture conditions that were not present on admission, but developed during the hospital stay. By combining discharge summaries with available ICD-10-CM codes, COVID-NET provides a fuller picture of the hospitalization and reduces some of the bias that comes from relying on billing codes alone for public health surveillance.

[1:18:01]
This chart walks through the percent of COVID-NET hospitalizations that are classified as either due to COVID-19, shown in the blue boxes, or with COVID-19, shown in the red boxes, using two approaches. On the left, COVID-NET hospitalizations are classified using ICD-10-CM codes and discharge diagnoses. On the right, they're classified using COVID-NET's reason for admission algorithm. We're using data from the 2023-24 season, as ICD-10-CM codes are not available for the ongoing 24-25 surveillance season. During this period, COVID-NET identified more than 66,000 hospitalizations among patients of all ages. Of those, 7,279 were sampled for abstraction of clinical data from the medical record. Starting in the boxes on the left, this flowchart examines the presence of the COVID-19 ICD code or sepsis or respiratory-related discharge diagnoses among all sampled COVID-NET hospitalization. Of them, 81% had a COVID-19 ICD-10 discharge diagnosis in any of the first nine coding positions, which capture both the principal diagnosis and the most important contributing diagnoses.

[1:19:12]
52% had a sepsis or respiratory-related discharge diagnosis, and 88% had either a COVID-19 ICD-10 code or a respiratory discharge diagnosis, as shown in the dark blue box on the left. And as shown in the red box on the left, 12% of cases had neither a COVID-19 ICD-10 code nor a sepsis or respiratory-related discharge diagnosis. Moving to the boxes on the right, this flowchart describes how COVID-NET defines hospitalizations due to COVID-19, applying the reason for admission algorithm to the same sampled hospitalizations. Of them, 85% had hospitalization due to COVID-19 based on reason for admission, as shown in the blue box on the right. Of those, 91% had either a COVID-19 ICD-10 code or a sepsis or respiratory diagnosis, the same criteria used in the flowchart on the left.

[1:20:08]
Of the remaining 15% who had a non-COVID-19 reason for admission, shown in the red box on the right, 64% also had a COVID-19 ICD-10 diagnosis code. In summary, the two approaches to classify hospitalizations as being due to COVID include identifying COVID-19 as the likely reason for admission or identified COVID-19-related discharge diagnoses. These two methods show very strong agreement with 88% of all hospitalizations having a COVID-19 ICD-M code or sepsis or respiratory diagnosis, and 85% identified as having COVID-19 as likely primary reason for admission. 92% of hospitalizations using COVID-NET's reason for admission approach had a COVID-19 ICD-10-CM code or sepsis or respiratory-related diagnosis.

[1:21:01]
COVID-19's reason for admission approach is more conservative than examining discharge diagnoses and, more importantly, can be completed in a timely manner. Given the similar findings, these results give us confidence that COVID-NET strikes the right balance in terms of timeliness, accuracy, and representedness of the population. This figure shows the rates of COVID-19-associated hospitalizations per 100,000 population by age group. These are cumulative rates and represent the cumulative risk of hospitalization by age group for the 12-month period of October 2024 through September 2025. As a reminder, these rates are based on the surveillance standard of a positive SARS-CoV-2 test among hospitalized residents of the surveillance attachment area. The cumulative rates for hospitalizations are highest among adults 65 to 74 and 75 years and older, as well as among infants less than six months of age. Unlike older adults, there has never been an approved vaccine products for infants less than six months.

[1:22:04]
Any immunity to reduce the risk of hospitalization would need to be provided through maternal vaccination. This figure shows the percent of hospitalizations due to COVID-19 that resulted in severe in-hospital outcomes by age group, including admission to the intensive care unit or ICU in tan and in-hospital death in red. A significant proportion of adults hospitalized due to COVID-19 experienced severe outcomes, with 15% of adults having been admitted to the ICU. In-hospital death is more common among adults 50 years of age and older. As noted in the yellow box on the bottom, 84% of all adults hospitalized due to COVID-19 who died in hospital were 50 years of age and older. Note that these are only in-hospital deaths. We know that COVID-19 associated deaths occur outside the hospital, including some that occur within 30 days of hospital discharge.

[1:23:02]
Note that different respiratory viruses affect different age groups differently, with the biggest collective impact at the extremes of age. This figure shows cumulative rates of laboratory-confirmed hospitalizations for COVID-19, influenza, and RSV. As you can see, RSV in yellow contributes to the highest burden of respiratory disease in children less than one on the left. But COVID-19 has an outsized impact on older adults. However, COVID-19 is not inconsequential in infants, with hospitalization rates comparable to rates of influenza hospitalization. As mentioned, this figure represents the cumulative rates of hospitalization since October 2024. Finally, it is important to note that the rates were in the context of a high-severity influenza season, with cumulative overall rates of influenza hospitalization the highest experience since the 2010-2011 season. On this slide, the larger figure shows cumulative rates of COVID-19 hospitalization by age group, with a focus on those less than 75.

[1:24:05]
The rates of hospitalizations among infants ages less than six months remain close to those among adults ages 65 to 74 years throughout the season. The rates have diverged in recent weeks, with rates increasing among infants at a faster slope compared to adults 65 to 74, with current cumulative rates of 223 and 194 per 100,000, respectively. The cumulative rates during this period among infants less than six months are 14% higher than adults age 65 to 74 years. The inset figure in the red box includes these same rates in addition to adults ages 75 years and older, indicated by the orange line. As background, this analysis on chronic conditions is an update to a peer-reviewed manuscript published in 2021. The results of that analysis inform the infographic pictured here, which summarizes the relative risk for hospitalization among persons with the specified conditions to those without.

[1:25:11]
The data sources for this analysis were threefold and include COVID-net data on the number of hospitalizations due to COVID-19 from October 2022 through September 23. Data on the prevalence of chronic conditions were from the Behavioral Risk Factor Surveillance System, or BRFSS, the largest continually conducted health survey system in the world, with hundreds of thousands of interviews among community-dwelling U.S. adults administered each year. Population data from the U.S. Census were provided by the National Center for Health Statistics. The methodology used for the analysis is complex, but in short, COVID-net was used to obtain weighted counts of persons hospitalized due to COVID-19 with and without underlying conditions. COVID-net data were limited to hospitalizations with COVID-19 as likely primary reason for admission, as previously described, and limited to community-dwelling adults, as BRFSS is only administered to community-dwelling adults age 18 years and older.

[1:26:12]
Weighted counts of community-dwelling adults with and without chronic diseases of interest in participating states were calculated using BRFSS data. Using state populations and statistical modeling, adjusted rate ratios of hospitalization rates with versus without chronic conditions were calculated. The chronic conditions examined were limited to those conditions included as part of the BRFSS interview and are listed here. This figure shows the prevalence of chronic conditions examined among adults admitted for COVID-19 in blue compared to the general population of the COVID-net states in gray. The prevalence of most chronic conditions among adults hospitalized due to COVID-19 was generally higher than the prevalence observed in the general population.

[1:27:09]
This chart shows the rate ratios of chronic conditions comparing adults hospitalized due to COVID-19 with the condition to those without by age group. Among adults, most chronic conditions examined increased the risk of being hospitalized due to COVID-19. The risk conferred by several conditions appeared to decline with age including coronary artery disease, diabetes, and obesity. This might be a consequence of an inability to adjust for comorbidities in the models or low population prevalence of some conditions in some age groups. For example, severe obesity is uncommon among adults age 75 years and older and COPD is uncommon among adults younger than 50 years of age. Additionally, this analysis shows risk for hospitalization due to COVID-19 increases with the number of chronic conditions and age.

[1:28:01]
Having multiple comorbid conditions in older age were the strongest risk factors for COVID-19 hospitalization among adults. As shown in the red box, adults with three or more underlying conditions are nearly six times more likely to be hospitalized due to COVID-19 compared to those with no underlying conditions. As shown in the blue box, hospitalization rates were 18.5 times as high among adults age greater than 75 years compared to adults age 18 to 49 years. Being age 75 years or more was the greatest risk factor examined in this analysis. This analysis has many strengths. The data are gathered from a robust COVID-19 hospitalization surveillance system. This allows us to compare underlying conditions using state level prevalence data and to examine how specific underlying conditions, the presence of multiple conditions and age groups contribute as risk factors for COVID hospitalization.

[1:29:00]
That said, there are limitations. Results are still preliminary and remain under review. As previously noted, this analysis is limited to community dwelling adults to align with the population from which we have BRFSS data on chronic conditions. The risk for hospitalization due to COVID-19 among children or among non-community dwelling adults like those who live in long-term care settings could not be examined and might be different from those presented. Some underlying conditions tend to co-occur such as diabetes and chronic kidney disease. Adjustments for some comorbidities such as adjusting for chronic kidney disease among persons with diabetes could not be made due to sparse data, especially in younger age groups. Additionally, this analysis was not able to look at differences in rate ratios across outcomes such as ICU admission or race and ethnicity categories due to sparse data. And I don't know if we want to pause here for questions, Martin, or Recep. Sorry, do you want to move on to the next presentations?

[1:30:01]
Yeah, please move on to the next presentation.
[Dr. Robert Malone]
Can we have the next presentation, please? You know, I object, Martin.

Q&A on COVID-19 Epidemiology and Testing

I've got some really concrete questions I'd like to ask. Could I have permission?
[Martin Kulldorff]
Please, Dr. Malone.
[Dr. Robert Malone]
So as I understand it, and this relates to information that was presented by the CDC to the subgroup, help me to understand there is significant overlap and challenge in the clinical diagnosis of COVID-19 as opposed to other, let's call them influenza-like illnesses. Is that true or false? Meaning that the symptoms of COVID-19 overlap with symptoms for other respiratory illnesses? Almost completely. I would say that's true. Okay, thank you. Number two, when I queried the CDC representative on the specificity and sensitivity of the testing being used, which is the other key leg of your whole data set, what she told me was sensitivity and specificity in this context were academic.

[1:31:11]
Now, as somebody trained in pathology, taught pathology for years, I object to that. My point is it's lovely that you created all this data, but the two underlying theses that underpin all your data are tenuous. And in the case of the diagnostic testing, as has been widely noted, the diagnostic testing for COVID has had significant problems with specificity and sensitivity, and that's not factored into the model. Is that true or false?
[Dr. Arjun Srinivasan]
Let me ask one of the subject matter experts to comment on sensitivity and specificity of the tests used in the model.
[Dr. Patton]
Thank you. This is the NCIRD SME room. The tests used in COVID-NET are the FDA-approved tests that are performed in hospitals and medical clinics across the country.

[1:32:07]
We do not perform testing as part of the COVID-NET surveillance. Those are all clinically tests that are done at the clinical discretion of the provider seeing the patients.
[Dr. Robert Malone]
Right. So what you're admitting or acknowledging is that all those tests have issues with sensitivity and specificity that will affect the interpretation of these data. True? True.
[Dr. Patton]
Hi. Any test that is performed clinically has sensitivity and specificity values. These are FDA-approved tests that are used to identify patients who test positive for SARS-CoV-2.
[Dr. Robert Malone]
But if they're only 80 percent specific, therefore, as one example, your underlying thesis about what is a COVID case or not a COVID case inherits a similar level of ambiguity.

[1:33:02]
True or false?
[Natalie Thornburg]
This is Natalie Thornburg, lab SME in NCIRD. FDA has, and I'm not speaking for FDA, but all of the tests that have been used in COVID-NET, again, have been received FDA approval through CDHR, and they have baseline specificity and sensitivity requirements. And the specificity has to be above 90 percent, I believe, and sensitivity similar.
[Martin Kulldorff]
Thank you. Dr. Srinivasan has actually three parts to his presentation. So the idea is to let him do all three parts before we have a question and answer. So if you have a question and answer, we are noting that on the list here, and we will do that in the order as you request them, but we will continue with the other two sections of his presentation before we take more questions and answers.

[1:34:06]
So please go ahead, Dr. Srinivasan. Thank you.
[Dr. Arjun Srinivasan]
All right, let's move on to COVID-19 vaccine implementation.

COVID-19 Vaccine Implementation Update by Dr. Srinivasan

Okay. Wrong one. All right. Before I discuss COVID-19 vaccination coverage, I thought it would be helpful to explain the sources of the data I will present. One of the data sources the Immunization Services Division uses to obtain data on vaccination coverage, like COVID-19 vaccination, and other information on immunization implementation, is the National Immunization Survey, or NIS.

[1:35:03]
The NIS is a random-digit dial cellular telephone survey of adults aged 18 years and older in the U.S., local jurisdictions, and associated territories. Data for children are reported by their parent or guardian. All responses are self-reported. The sample size is approximately 15,000 adults weekly or 60,000 adults monthly. Data are weighted to reflect the non-institutionalized U.S. population. This slide shows 2024-2025 COVID-19 vaccination coverage for at least one dose among adults 18 to 49 years, 50 to 64 years, and adults 65 years and older in the top dark blue line from September 2024 through April 2025. Vaccination coverage among older adults reached 44% for one or more doses, 25% for adults 50 to 64, and 14% for adults 18 to 49.

[1:36:34]
COVID-19 vaccination coverage increased for older adults between the 2023-2024 seasons and 24-25. The first graph is among adults 18 to 49 years. The second graph is among adults 50 to 64 years.

[1:37:01]
The third graph is among adults 65 to 74 years. And the final graph is among adults 75 years and older. For the first two age groups, you see the vaccination coverage was the same for the two seasons. For those 65 to 74 years of age, vaccination coverage rose almost 5 percentage points in the most recent season, while for adults 75 years and older, coverage improved by about 8 percentage points by the end of the 24-25 season. Note these differences are statistically significant in 65 to 74 and 75 and older age groups to less than 0.5. This slide shows COVID-19 vaccination coverage estimates for the pediatric population. Approximately 5.6% of children less than four years of age were up to date with COVID vaccination, according to current recommendations for that age group shown in light blue. In children 5 years and older, up to date is defined as receipt of at least one vaccination since August.

[1:38:01]
For children between 5 and 17 years of age, almost 16% have received at least one dose. Overall, approximately 13% of children between 6 months and 17 years of age were up to date with their COVID vaccinations at the end of April 2025. For immunocompromised adults age 18 years and older who received their first COVID vaccine dose in August or September of 2024, 8% were fully vaccinated with two doses by the end of March. When coverage is stratified by age, 16.6% of those in the 50 to 64 year age category were fully vaccinated, compared to 2.4% in the 18 to 49 year category, and only 0.8% in the 65 year and older category. In summary, COVID-19 vaccination coverage for older adults improved in 24-25 compared to the previous season.

[1:39:00]
Vaccination coverage for adults 18 to 64 years was similar between seasons. Approximately 13% of children between 6 months and 17 years of age were up to date with COVID vaccinations at the end of April 2025. This slide shows the place of vaccination for adults 18 years and older. This was asked among persons who reported receiving a 24-25 COVID-19 vaccination since August 2024 for an N of 9,359. These data were collected between April 1st and April 27th of 2025. The majority of adults, that is 67%, reported receiving their vaccine in a pharmacy or drugstore location. About 29% received their vaccine in a medical place, such as a doctor's office. About 4% received their vaccine in a non-medical place, such as the workplace. I'll now share data on vaccination in healthcare personnel collected through CDC's National Healthcare Safety Network, or NHSN.

[1:40:08]
NHSN is the nation's most widely used healthcare-associated infection tracking system and provides important process measures like healthcare personnel vaccination status. CMS-certified skilled nursing facilities and hospitals report COVID-19 and influenza vaccination data for healthcare personnel. Data collected through NHSN show that influenza vaccination rates in acute care hospital staff, the red triangles, and long-term care staff, the gray Xs, have remained fairly consistent from 2022, when NHSN first started collecting healthcare personnel vaccination data, through the most recent respiratory virus season, 2024-25. COVID vaccination coverage, however, continues to decline across seasons in both the acute care, blue boxes, and long-term care settings, the gray diamonds.

[1:41:05]
And we'll move on. Can we have the last presentation in this group, please? Yeah, yeah, I'll take a drink of water while that.

COVID-19 Vaccine Effectiveness Update by Dr. Srinivasan

I'll first review methods for vaccine effectiveness, or VE, then share some results on VE for children, maternal VE, and VE for adults. Note that some of these slides were previously shared at the June ACIP meeting. Today's presentation is a summary of the data, with additional methods information in the presentation, and additional methods and data included in backup slides available on the CDC's website. First, it's important to differentiate between data from randomized controlled trials and real-world evidence.

[1:42:03]
Randomized controlled trials are needed to demonstrate vaccine efficacy for licensure of new vaccines, and answers the question, does vaccination prevent disease under ideal and controlled conditions? That is, compared to a placebo or a different vaccine. Observational studies provide real-world evidence of vaccine effectiveness, or VE, and answers the question of whether vaccines protect against disease in the population. For COVID-19, vaccine effectiveness measures the benefit of current vaccination in a population with existing levels of protection due to prior infection, vaccination, or both. Importantly, efficacy and effectiveness are population-level estimates. If a vaccine has an effectiveness of 80%, it does not mean that the vaccine will only work 80% of the time. It does mean that in a vaccinated population, 80% fewer people will have the outcome of interest when they are exposed to the virus compared to the unvaccinated population.

[1:43:09]
VE can be measured using study designs across a spectrum from a case control to a cohort. In a case control study, controls are generally sampled from the same population that gave rise to the cases. The controls are meant to be similar to cases, usually by geography or other demographic characteristics, and give an estimate of the vaccine coverage in the population where the cases originated. On the other end of the spectrum, a cohort includes an eligible at-risk population that is followed to see who develops or does not develop disease. A test-negative design, or TND, takes pieces of both case control and cohort studies, and depending on the specific design characteristics, can be more akin to a case control or more akin to a cohort study. In a TND, controls can be sampled or include the entire eligible at-risk population.

[1:44:01]
For respiratory viruses, CDC and many other countries generally use a test-negative design to measure vaccine effectiveness. In the test-negative design, people who seek care for a respiratory illness are included. Cases are those who test positive for SARS-CoV-2, and controls are those who test negative. Controls in these studies are meant to represent the population from which the cases arose and give us an understanding of COVID-19 vaccine coverage among people seeking care for respiratory illness. We then compare vaccination status in cases and controls to determine vaccine effectiveness, or VE. If coverage is higher among controls than among cases, that indicates the vaccines are associated with protection against disease. Because both cases and controls are people seeking care for respiratory illness, we can reduce the impact of factors that can distort or confound the relationship between vaccination status and illness. Reducing the impact of or adjusting for factors like age and geography helps reveal the true relationship between vaccination status and illness.

[1:45:09]
There are strengths and limitations to all study designs. The test-negative design is meant to leverage strengths of both case control and cohort studies and also mitigate some potential limitations of these traditional designs. A test-negative design, like a case control study, starts at the diagnosis of the disease of interest, making it useful for rare outcomes, including many infectious diseases. Unlike a case control, however, the test-negative design controls for health-seeking behavior by selecting controls or respiratory symptoms from the same health facility as the cases. This feature also reduces cost and increases the speed of a test-negative design, allowing for results within the same season. Additionally, when a test-negative design is conducted in a hospitalized population, it helps mitigate healthy vaccine bias because both cases and controls are hospitalized for respiratory illness. Finally, test-negative designs that leverage the entire eligible at-risk population for controls, usually by using electronic health record data, allows for large sample sizes, increasing ability to assess outcomes stratified by important factors, such as age or time since vaccination.

[1:46:20]
Today I'll be sharing VE results from three CDC study platforms for children and adults. The first VE platform is the VISION network, a multi-site network of electronic health records at over 300 emergency departments and urgent care clinics and over 200 hospitals that includes both children and adults. VISION uses a test-negative design and includes eligible people of all ages with COVID-19-like illness and a clinical test result within 10 days before to 72 hours after their encounter. Cases are those with a positive NAT or antigen test for SARS-CoV-2 and no positive RSV or influenza test results.

[1:47:00]
Controls are those with a negative nucleic acid amplification test or NAT for SARS-CoV-2 and no positive NAT test for influenza or RSV, depending on age. Vaccination is documented by electronic health records and state and city registries. The second VE platform enrolls only children with enrollment at 26 pediatric hospitals in 20 states. The analysis I'll present today was designed to assess the effectiveness of COVID-19 vaccination in pregnant women for prevention of COVID-19-related hospitalizations in infants less than six months of age. The third platform included today is the IVY network, a multi-site VE platform in 26 hospitals in 20 U.S. states that, like VISION, uses a test-negative design. Unlike VISION, IVY uses an active enrollment design with patient interviews and nasal swabbing of enrollees. Participants included in analyses presented today were adults ages greater than 18 years hospitalized with COVID-19-like illness.

[1:48:07]
Cases have a SARS-CoV-2 positive NAT or antigen test, and controls were negative for SARS-CoV-2, influenza, and RSV by RT-PCR. Vaccination history is ascertained through electronic medical records, state and local vaccine registries, and plausible self-report, and specimens are collected for central testing and sequencing. How we've measured COVID-19 VE has changed by season. When COVID-19 vaccines were first released, we measured absolute VE, which compares the frequency of health outcomes in vaccinated versus unvaccinated people. During the bivalent era, however, we also measured relative VE, which compares the frequency of health outcomes in people who received one type of vaccine to people who received a different vaccine. For example, people who received a bivalent dose versus those who received only the original monovalent COVID-19 vaccine.

[1:49:01]
Generally, more recently, we have looked at seasonal vaccine effectiveness, which is similar to how annual flu VE is calculated. Seasonal VE compares people who received this season's COVID-19 vaccine to people who did not, regardless of past COVID-19 vaccination. This slide shows 2023-24 COVID-19 vaccine effectiveness against emergency department and urgent care encounters, including data through August 2024, which is when the 24-25 vaccines were released. Note that the referent group includes all individuals who did not receive a 23-24 COVID-19 vaccine. For those aged greater than five years, this includes unvaccinated persons, and persons who were vaccinated with greater than one original monovalent or bivalent COVID-19 doses. For those aged less than five years, both those in the referent group and those in the vaccinated group were required to have completed an initial series.

[1:50:07]
The 23-24 dose could have been part of the initial series or in addition to the initial series. In the top block, you see counts of encounters, cases, and time since dose for people who did not receive a 2023-24 COVID-19 by age group, nine months to four years, five to 17 years, and adults 18 and up. The middle block shows VE among those who received a 23-24 dose seven to 59 days earlier, and the bottom is VE among those who received the dose 60 to 299 days earlier. Note that there are not enough children vaccinated 60 to 299 days earlier with positive SARS-CoV-2 tests to split the 60 to 299 day block in children more granularly. You can see that VE is estimated to be as good or better among children as it was among adults.

[1:51:00]
This aligns with previous seasons showing generally comparable VE across age groups. This slide is similar to the previous one. They're now showing VE during the 24-25 season. Lower numbers of COVID cases in 24-25 compared to 23-24 and overall low COVID-19 vaccination coverage in children resulted in less statistical power during the season. So we were not able to estimate VE by time since dose for 24-25. Instead, we've shown overall VE for the seven to 179 days since receipt of a 24-25 COVID vaccine dose. You can see that as with 23-24, VE is the same or higher in children as in adults. This slide shows VE of receipt of a 23-24 COVID-19 vaccine during pregnancy for protection against emergency department urgent care visits by pregnancy status.

[1:52:08]
In the top block, you can see VE among women who are pregnant at the time of their COVID-like illness encounter. And in the bottom block, among non-pregnant women of the same age. Time since dose was similar across the two groups with confidence intervals for VE that entirely overlapped, showing that protection is similar among pregnant and non-pregnant women. This slide shows estimates of the effectiveness of maternal COVID-19 vaccine receipt for protection of COVID-19 associated hospitalization among infants from the overcoming COVID-19 network during 2022-23. Maternal VE for infants is particularly important because infants under six months of age are not eligible for COVID-19 vaccination and have higher rates of severe COVID-19 than older children and most adult age groups.

[1:53:01]
Vaccination of pregnant women is the only way to protect their infants from severe COVID-19. This analysis included mothers who received their last dose of a COVID-19 mRNA vaccine between the first day of pregnancy and 14 days before delivery. The comparison group was mothers who did not receive any COVID-19 vaccination either before or during pregnancy. As you can see, VE was highest in the youngest children at 54% during the first zero to two months of life and 35% during the first zero to five months of life. This mirrors pattern in older children and adults where VE drops with more time since dose. This slide shows VE against COVID-19 associated hospitalization among adults age 65 years and up without documented immunocompromising conditions in the vision and IV networks. The slide is laid out the same as the previous slides except instead of age groups, it shows vision adults in the top block and IV results in the bottom block for adults age 65 years and up.

[1:54:11]
VE was almost identical across the two networks providing reassurance of the results. During the seven to 179 days since the dose, the point estimate was 44% in vision and 46% in IV. VE started at 46% in vision and 42% in IV declining to 32% in vision and 40% in IV during the 120 to 179 days after vaccination. Though note that the confidence intervals for this time period are wider due to smaller numbers of both cases and controls vaccinated four to six months before their encounter. This slide shows VE against COVID-19 associated critical illness in vision and IV. Vision on the top defines critical illness as admission to intensive care or in-hospital death and estimates are shown by time since dose among those 65 years and up.

[1:55:07]
You can see that the point estimates do not change much over time even in the longest time since dose strata, 120 to 179 days since the dose, indicating relatively durable protection. This mirrors what we've seen in previous years. VE against the most severe outcome remains most durable over time with little evidence of waning in the longest time since dose period. In IV shown on the bottom, we have VE against three separate outcomes all shown for the seven to 179 days since a dose shown generally by increasing severity including acute respiratory failure, ICU admission or death, and invasive mechanical ventilation or death. Here again, we see indications of higher VE for the most severe outcomes at 70% for invasive mechanical ventilation or death.

[1:56:17]
Among adults age 65 years and up with immunocompromising conditions in vision and IV. Though IV did not have enough statistical power to estimate VE by time since dose in this group. In vision, VE appears to be increasing over time, which is something we've seen previously in adults with immunocompromising condition and is likely due to faster waning of infection induced immunity in the immunocompromised people, which would make the referent group, those who did not receive a 24, 25 vaccine have less protection over time since the summer surge, thereby appearing to increase VE. VE for the overall time period, 38% in vision and 36% in IV is close to VE in non immunocompromised adults, providing reassurance that the vaccine is working in immunocompromised adults.

[1:57:07]
For the respective year compared to no in season dose COVID-19 vaccination provided additional protection against COVID-19 associated emergency department and urgent care visits among children. Protection was similar across age groups. COVID-19 associated emergency department and urgent care visits among adults. COVID-19 associated hospitalizations among adults age greater than 65 years with and without immunocompromising conditions and COVID-19 associated critical illness among adults age greater than 65 years. Protection appeared to be higher and more durable against critical illness compared to less severe outcomes. VE should be interpreted as the added benefit of the 23, 24 or 24, 25 COVID-19 vaccination in a population with high levels of infection induced immunity vaccine induced immunity or both.

[1:58:00]
Prior SARS-CoV-2 infection contributes protection against future disease their protection wanes over time. An increase in SARS-CoV-2 circulation in the United States during late summer 2024 just before the 24, 25 COVID vaccines were approved and authorized may have resulted in higher population level immunity against JN1 lineage strains which could have resulted in lower measured VE than in a population with less recent infection. And I'd like to thank the numerous colleagues from CDC and collaborators within the vision, IV, and overcoming COVID-19 networks who contributed to the presentation.
[Martin Kulldorff]
Yes, so we will take the Q&A later. We'll move on directly to Dr. Su. Thank you.
[Dr. Su]
I'm sorry. So we're moving straight on to the my presentation.

Vaccine Safety Signal Detection and Evaluation by Dr. Su

[Martin Kulldorff]

[1:59:01]
Okay.
[Dr. Su]
Thank you. Sure. Here we go. Thank you. So good morning. The ISO was presented asked to present an overview of how vaccine safety signals are detected and evaluated. There we go. This presentation will first define some terms and describe conceptually how a safety signal is detected and evaluated. A real world example from the vaccine safety data link will then be used to illustrate how this process works in a CDC surveillance system.

[2:00:05]
An adverse event following immunization is defined as any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. This slide provides the definition of a signal. In brief, a signal is information that arises from one or multiple sources which suggests a new potentially causal association between an intervention and an event that is judged to be of sufficient likelihood to justify verificatory action. This figure illustrates the concept of signal detection and evaluation and begins with signal detection. Detection of a signal might occur through clinical observations such as case reports or through safety surveillance systems. If further assessment of initial information continues to suggest a potential association between the vaccine and the adverse event, the next step is to perform a hypothesis testing study that attempts to either verify or rule out the signal.

[2:01:14]
If the signal based upon evidence is verified as causally associated with vaccination, public health action or further studies might follow such as evaluation of biological mechanisms or prevention strategies. For context, CDC has four complementary systems that work together to detect and evaluate potential vaccine safety concerns. The following example comes from the vaccine safety data link or VSD. The next section of this presentation walks through an example of signal detection and evaluation. As a reminder, the VSD is a collaboration between CDC and several integrated healthcare organizations with a combined population of more than 15 million people.

[2:02:11]
The VSD conducts active surveillance using electronic medical record data to detect signals and can also evaluate signals using more robust study designs. The VSD uses data that was collected as part of routine healthcare activities and links together vaccination records, healthcare encounters, and patient characteristics into a common data model for use in epidemiologic analyses. The VSD uses rapid cycle analysis or RCA surveillance to monitor a limited set of pre-specified adverse events of special interest with potential cases of those events identified using ICD-10 codes for healthcare encounters.

[2:03:02]
The RCA method is designed to detect statistical signals or finding from an analysis in which a test statistic exceeds a specified statistical threshold. A statistical signal does not necessarily represent a vaccine safety problem and requires further assessment before conclusions can be drawn. Since 2020, VSD has performed RCA using a vaccinated concurrent comparator method. The vaccinated concurrent comparator method compares the incidence of an adverse event during a risk interval, such as 1 to 21 days post-vaccination, to the incidence during a control interval, such as 43 to 63 days post-vaccination. This method inherently adjusts for calendar time and also controls for age, sex, race, and VSD site.

[2:04:06]
Detection of statistical signals using the RCA concurrent comparator method is intended to be rapid but might have residual bias. When a statistical signal is detected, the VSD can evaluate the signal using a different method known as self-controlled case series. This method requires waiting for complete accrual of follow-up time but is less prone to bias. This slide shows a list of preselected adverse events of special interest for COVID-19 vaccines monitored by multiple U.S. federal vaccine safety systems. Non-hemorrhagic stroke, also called ischemic stroke, is an outcome that has been monitored by VSD for potential statistical signals since 2020.

[2:05:04]
VSD has monitored the risk of ischemic stroke following each dose of COVID-19 vaccine as additional doses were authorized and recommended over the last five years. A statistical signal for ischemic stroke was detected for the first time during 2022 through 2023. A statistical signal was also detected for the 2023-2024 vaccine formulation. This graph, previously presented at an ACIP meeting in 2023, shows how the initial VSD RCA statistical signal for ischemic stroke progressed over the course of the 2022-2023 season. The graph shows the time period from October 2022 to April 2023.

[2:06:01]
Sequential analyses were performed each week as data accumulated over the course of the season. As more people were vaccinated, post-vaccination follow-up time accrued. The gray line shows how the rate ratio estimate changed over time from a higher value that was statistically significant early in the season to a final value of 1.26 during the last week, which was no longer statistically significant. CDC and FDA worked together during 2023 to further evaluate and communicate about this signal to the ACIP and to the public, as shown by the FDA webpage on this slide. The VSD was the only vaccine safety system to signal for ischemic stroke. Other analyses in the U.S. and in other countries had not observed similar findings. The interpretation at the time was that the evidence did not support the existence of a safety concern.

[2:07:11]
The VSD RCA statistical signal for ischemic stroke in 2022 and 2023 was specifically detected among people aged 65 years and older following the Pfizer vaccine. Further assessment of data at the time also examined the effect of same-day administration with influenza vaccine. VSD RCA surveillance during 2023 through 2024 also detected statistical signals for ischemic stroke. However, these signals were for ischemic stroke following Moderna vaccine and Pfizer vaccine and were among age groups different from the 2022 to 2023 signal. These signals were presented to ACIP in 2024. To further evaluate these signals, VSD performed self-controlled case series analyses for both seasons.

[2:08:06]
These data have not been previously presented. This slide shows the self-controlled case series analysis for the 2022-2023 Pfizer vaccine, including subgroup analyses for people who received the COVID-19 vaccine with or without influenza vaccine on the same day. Age groups are shown by row and incident rate ratio for both 21 and 42-day risk intervals are shown in the columns on the right. There were no statistically significant increased risk for ischemic stroke for either separate or same-day administration in any of these analyses. Next slide, please.

[2:09:00]
Previous slide, please. Yeah, I think. Yes, thank you. This slide shows the self-controlled case series analysis for the 2023-2024 season for both the Pfizer and Moderna vaccines. Again, no statistically significant increased risk for ischemic stroke was identified for COVID-19 vaccine with or without same-day administration of influenza vaccine. FDA also performed a self-controlled case series analysis for the 2023-2024 season among Medicare beneficiaries aged 65 years and older who received COVID-19 vaccine. FDA also did not find evidence for increased risk of ischemic stroke following vaccination with vaccine from any of the manufacturers shown here.

[2:10:06]
In summary, the Vaccine Safety Datalink Rapid Cycle Analysis Surveillance monitored a list of pre-specified adverse events of special interest, including ischemic stroke. The VSD detected statistical signals for ischemic stroke after COVID-19 vaccines during 2022-2023 and 2023-2024. However, subsequent signal evaluation using self-controlled case series analyses in the VSD and in other data sources have not confirmed an increased risk of ischemic stroke. So, thank you for the opportunity to present, and back to you.
[Martin Kulldorff]
Thank you so much, and that was actually a little bit shorter than the assigned time, so I appreciate that. Thank you so much.

[2:11:00]
We are going to move forward, actually, with the next presentation directly, and we will have Q&As, but we will do that after all the presentations. So, please, Dr. Aldairi and Dr. Kupferwasser.
[Dr. Wafik Aldairi]
Yeah, Dr. Kupferwasser will lead off.

COVID-19 Vaccine Safety Uncertainties by Dr. Aldairi and Dr. Kupferwasser

Charlotte, you're on mute.
[Dr. Kupferwasser]
My apologies. We'll start that again.
[Martin Kulldorff]
Thank you.
[Dr. Kupferwasser]
So, Dr. Wafik, Aldairi, and myself will be summarizing four major areas related to terms of reference 6, 7, and 8. Next slide, please.

[2:12:00]
First, for immune changes, literature on both scientific and nonspecific immune effects was reviewed focusing on the cumulative short and long-term impact of repeated boosting. This is an area where data are still emerging. Second, on biodistribution, the clinical and scientific information was reviewed, both from the literature and from the FDA. Third, frame-shifting was tracked given its potential to alter protein products and downstream immune responses. And finally, for impurities, published and unpublished data about residual DNA in existing mRNA products was reviewed. Next slide. There is evidence that COVID vaccination, especially after multiple doses, is associated with a range of immune changes. One of the best documented findings is IgG4 class switching reported in a seminal study by Arang and colleagues. They showed that individuals receiving Pfizer's BNT162b2 mRNA vaccine developed anti-spike IgG4 antibodies and IgG4 switched memory B cells within six months of their second dose, with levels rising further after a third dose.

[2:13:18]
Importantly, these changes were linked to reduced antibody effector function consistent with IgG4's role in promoting immune tolerance. Other studies have reported the production of anti-idiotype antibodies and persistent alterations in IgG glycosylation patterns. These structural modifications can influence how antibodies interact with immune cells, tipping the balance toward either inflammation or tolerance. Beyond antibody changes, vaccination has also been linked to long-lasting shifts in cytokine profiles, with elevated inflammatory cytokines persisting for months. These immune alterations may contribute to an increased risk of recurrent or persistent infections in some individuals.

[2:14:04]
Finally, work from Akiko Iwasaki's lab at Yale has demonstrated cellular immune changes, including reductions in circulating memory and effector CD4 T cells, alongside increases in TNF-alpha positive CD8 T cells following vaccination. Next slide, please. These and other studies raise questions about the persistence of the immunological changes associated with mRNA vaccination, along with their long-term clinical significance and consequences. And because of the long-term changes in cytokine profiles and T cell ratios observed in vaccinated individuals, more research is needed to evaluate vaccine effects on shaping both innate and adaptive immunity over the long term. Next slide. For biodistribution, Pfizer did not use the actual spike mRNA product in their studies.

[2:15:00]
Instead, they substituted in a luciferase reporter mRNA packaged in the same lipid nanoparticles. This approach allowed them to track where the mRNA traveled in rodents. The studies showed that following intramuscular injection, most of the mRNA remained at the site of injection, but there was also notable levels detected in the liver. Despite the limitations of this approach, which can underestimate low-level or transient distributions to other tissues, it nevertheless showed that the vaccine components do not remain confined to the injection site. Next slide. For Moderna, no dedicated biodistribution study was performed with the COVID mRNA itself. Instead, data was provided from a surrogate product, a CMV mRNA, mRNA-1647, which used the same lipid nanoparticle formulation. In their rat study, after intramuscular injections, high levels of the mRNA were detected at the injection site, but also in multiple organs, such as the draining lymph nodes, spleen, eye, and liver.

[2:16:08]
Lower levels were also found across a wide range of tissues, including the heart, lungs, testes, and brain. Importantly, this study clearly showed that the mRNA can cross the blood-brain barrier. Next slide. Consistent with what was seen in animal studies, the vaccine mRNA and its spike protein have been detected in humans across multiple tissues, including blood, lymph nodes, the heart, and even the brain. These findings make it clear that the mRNA does not remain confined to the injection site. Importantly, persistence has been documented well beyond the initial hours or days, lasting weeks in some tissues, and in certain studies, detectable for many months. Next slide. To summarize the biodistribution data, it's important to note that neither Moderna nor Pfizer used their actual commercial mRNA vaccine products in the preclinical biodistribution studies.

[2:17:04]
Instead, they relied on surrogate construct packaged in same or similar lipid nanoparticles. Second, the results of those studies show that the mRNA and lipid nanoparticles were not confined to the injection site. Systemic distribution was observed with evidence that the mRNA can cross the blood-brain barrier. Consistent with these findings, studies in humans have confirmed that vaccine mRNA can be detected in multiple tissues, including lymph nodes, the heart, the central nervous system, and blood. Finally, persistence is not just short-term. In some reports, mRNA has been detected for weeks to months, and in certain cases, as long as 706 days post-vaccination. Taken together, these data highlight that biodistribution is broad and persistence is longer than initially expected, raising important questions and concerns for ongoing research and safety monitoring. Next slide.
[Dr. Wafik Aldairi]

[2:18:01]
Thank you, Dr. Kuperwasser. The workgroup focused on a couple of other areas that I will describe. The first is ribosomal frame-shifting, which is a mechanism used by viruses to express different open reading frames that can help viruses progress infections. The nucleoside-modified mRNA with pseudouridine increases frame-shifting significantly, up to tenfold. Next slide. And there's evidence that these unintended off-target proteins generate an immune response in humans, along with antibody production. The immunogenic or toxic properties of the non-spike proteins is unknown, and the health consequences of prolonged and persistent non-spike protein production have not been studied.

[2:19:12]
Next slide. Another issue I'd like to bring your attention to involves multiple reports of DNA impurities in Pfizer and Moderna mRNA vaccine vials. The most recent report came from Spiker et al., where they looked at 32 vials, including 16 unique vaccine lots, and found evidence of fragmented DNA, plasmid DNA, in both Pfizer and Moderna vials. And in all Pfizer vials, they found SV40 enhancer origin of replication that was not detected in any of the Moderna vials.

[2:20:01]
Next slide. So, there are some differences between the Pfizer and Moderna mRNA vaccines, principally around the SV40 promoter enhancer origin sequences, as well as the detectable amounts of DNA fragments. I would like to point out that the FDA limit of 10 nanograms was set for naked DNA, not DNA in the presence of lipid nanoparticles that can carry DNA into cells and their nuclei. Next slide. So, to summarize the DNA impurities, both the Pfizer and Moderna vaccines have been found to contain DNA that exceeds the FDA limits.

[2:21:12]
Importantly, the DNA impurity limits do not take into account lipid nanoparticles, which carry DNA into cells and nuclei. There are concerns due to known DNA integration and gene activation disruption by SV40 promoter enhancer sequences. Next slide. There has not been a reliable or really any population study in the United States with cancer outcomes after COVID vaccination. But cancers have been reported in mRNA vaccinated individuals in temporal association to immunization.

[2:22:04]
Actually, the number should be 48 case reports that are listed below. Primary cutaneous lymphomas is actually 24. And there is a study of 96 cases of pancreatic ductal adenocarcinoma with worse outcomes among those with higher IgG4 levels, which occurs, as Dr. Kuperwasser mentioned, with repeated vaccination. There's also a study not listed here with 76 colorectal cancers. It's a case control study where the vaccinated seem to have more mismatch repair deficient cancer. Next slide. There are gaps in our knowledge, including the extent of DNA contamination in current lots, the by distribution of any contaminating plasmid DNA that can persistently produce spike protein.

[2:23:16]
Genomic DNA and integration in tissues or tumors in vaccinated patients is an area we don't know much about at this point, along with the involved mechanisms. The prevalence of adverse outcomes from impurities versus the extent of contamination is an area that needs more information. We have a gap in our knowledge of the relationship between multiple vaccinations and spike persistence. We do not know enough about the cancer mechanisms, certainly questions about causality.

[2:24:01]
However, there are numerous plausible mechanisms. There are variations and host susceptibilities to adverse outcomes that are emerging for certain other adverse events that are likely relevant to the areas of uncertainty that we are speaking about. So, next slide. In summary, there are COVID vaccine safety concerns that stem from unexpected biological activities of mRNA gene therapy platforms raising questions about potential pathogenic mechanisms and human subjects research protections. We would like to put forth some recommendations, including proactive and modernized safety surveillance programs that involve blood and tissue-based monitoring, epidemiologic studies, AI-driven analysis using reliable standardized datasets, expanded autopsy programs to clarify causality in serious outcomes,

[2:25:11]
programs that systemically evaluate COVID-19 vaccine safety, FDA approval policies calibrated to gene therapy-like risks, importantly, DNA limits that take into account lipid nanoparticles, stronger pharmaceutical accountability, and CDC guidelines ensuring transparent risk disclosure, mitigation strategies, and robust informed consent. Thank you. Thank you for that.
[Martin Kulldorff]
And there is one more presentation from a COVID-19 workgroup member. That is Dr. Bruce Charlton.

Genomic and Vaccine-Induced Myocarditis by Dr. Bruce Charlton

[2:26:00]
Thank you. Hello.
[Dr. Bruce Carlton]
Just waiting for my slides.
[Martin Kulldorff]
Please go ahead.
[Dr. Bruce Carlton]
Sure, just waiting for my slides. I don't see them.
[Mina]
We're working on them.
[Dr. Bruce Carlton]
Okay.
[Mina]
Just a second. Thank you.
[Dr. Bruce Carlton]
No, not a problem. There we go. Hello, everyone, and thanks for the opportunity to share some of the research that I'm doing on vaccine-induced myocarditis from the COVID-19 vaccine. I'm Bruce Carlton, a professor of pediatrics in the Faculty of Medicine at the University of British Columbia. Next slide.

[2:27:03]
These are my disclosures. This particular work was funded by a grant to the Global Vaccine Data Network that was provided by the U.S. Centers for Disease Control. I have a number of government funding sources in Canada, and I am listed some past consultancies and also some work I'm doing on COVID-19 vaccination related to sodomia funded by REACT-19. Next slide. I've already mentioned the Global Vaccine Data Network. Next slide. As a funder. And this is a collaborative network of 32 countries and getting larger. Beyond the genomics work I'm going to present today, they also will be publishing the largest myocarditis and pericarditis COVID-19 vaccine study to date. As well as I think important to note that in that particular study, they also include booster doses.

[2:28:07]
Next slide. So this grant was canceled with 48 hours notice in March, but I had a chance to do some initial work. This is all very preliminary, and I'll talk about next steps at the end. But essentially, these are 50 patients that range in age from 11 to 83 years. You can see their self-reported ancestries. We will do some genetic ancestry on these particular patients as well to understand the generalizability of findings. We're looking at patients who receive both Pfizer and Moderna vaccines. And the data over when the myocarditis first occurred is listed by dose. So most of the cases occurred after the second dose.

[2:29:02]
There are some after the third and first doses. I only have, at the time, I only had data on the onset of myocarditis symptoms after vaccination for 30 of these 50 patients. And that was a median of four days with an interquartile range of 3 to 26 days. Next slide. So 50 cases were sequenced. We used an exome-captured library preparation for the NovaSeq 6000 system, reaching an average depth of 100x. The reads were aligned with the GRCh38 human reference genome, and 49 out of 50 samples passed the quality control process. One sample did not have sufficient quality DNA to proceed. And I specifically looked at variant frequencies that occurred in at least 50% of cases, of these 49 cases.

[2:30:02]
When the global allele frequency, as noted by ClinVar, a database that provides gene allele frequency information, when the global allele frequency was less than or no greater than 15%. So you're going to be seeing genes that actually occur in a very large number of cases compared to what should be occurring. Next slide. So these are the results. There are 18 different genes. And because we're looking at the exome, we're looking at the protein coding region only of the DNA. This allows us to look at some rarer variants, but certainly variants of no insignificance. And I've highlighted in yellow the seven variants across four different genes that have been previously identified to the development of myocarditis or cardiac inflammation in general. There are four titan variants, which I suppose isn't too surprising given that's a very large gene, but there are three others as well.

[2:31:07]
Next slide. And what this slide shows is that of the 30 patients that I had time to onset of myocarditis data at the time of this analysis, it shows the number of patients that are homozygous for these variants. So they have both copies of the variant. And you can see that since this is days after COVID-19 vaccination on the vertical axis, that as you increase the number of homozygous variants, you decrease the number of days after COVID vaccination in which symptoms begin. Now, again, these are very small numbers. I recognize that, but this is an interesting trend. Next slide. So what are these particular genes, these four genes and seven variants? Well, we have LDL receptor-related protein eight, which is a particular variant linked to cardiovascular inflammation and immune response, particularly in coronary artery disease and myocardial infarction.

[2:32:13]
And we had 10 patients homozygous for the risk allele and 19 heterozygous. Next slide. Angiotensin 2 type 1 receptor is something that's been discussed a lot with COVID-19 in the past. And these particular genotypes in this small population of patients were associated with previously with greater than 90% left anterior descending artery stenosis. Also associated with MI susceptibility and essential hypertension in other studies. And among these 49 cases, four were homozygous and 24 were heterozygous. Next slide. This is just a graphic showing the relationship between these variants and their function in the renin-angiotensin system.

[2:33:06]
And you can see that in the case of AGTR1, that has a enhancing effect to angiotensin 2, thereby developing hypertension, vasoconstriction and cardiac hypertrophy. The case of LRP8, it reduces the activity of APOE, which then results in higher p38 mark pathway activation and resulting cardiac inflammation. Next slide. EKRC1 is highly expressed in the heart. It's well known to be associated with warfarin dosage and vitamin K signaling. Also associated with arterial vascular diseases and vessel calcification. Three homozygous patients, 24 heterozygous. Next slide. Briefly in this picture, when you block the vitamin K cycle pathway here with these risk haplotypes, you end up with vascular calcification and atherosclerosis.

[2:34:16]
Next slide. Titan, most frequent causes of dilated cardiomyopathy, about 25% of familial and 18% of idiopathic cardiomyopathy are caused by these particular variants. Again, associated with acute myocarditis with a higher variant prevalence in cases than controls. This is in other work, not in this particular study. We had three homozygous for all four variants. Two homozygous for three and 21 heterozygous. Next slide. Essentially, Titan variants lead to sarcomere insufficiency, and you can follow the pathway there to dilated cardiomyopathy. Next slide.

[2:35:01]
So before this particular grant was canceled in March, the goal was to collect 275 cases of each of the following adverse events in the table on the left side, and then enroll also controls. These would be vaccinated patients without these adverse events, and then do case control genetic analysis, starting with genome-wide studies, and then following up with exomes. The next step after that, of course, is whole genome sequencing, where we can cover even more genes and get better coverage of the genome. Next slide. I'll just say this as a final slide, that genomic studies of drugs have really revolutionized drug therapy. More than 500 FDA-approved drugs have genetic information annotated in the drug labels. And doing the same type of work for vaccine adverse events would serve two purposes. First of all, it helps us understand the biological mechanisms underlying the pathophysiology of adverse events.

[2:36:07]
And second, in patients who have risk variants, we can allow for more personalized vaccine schedules. In the case of mRNA vaccines and myocarditis, switching patients to either protein or non-adenoviral vector vaccines, for example, would be one option. Thank you for your attention. I'm happy to answer questions at the appropriate time.
[Martin Kulldorff]
Thank you very much. We will have questions and answers, but we're going to move forward with the next presentations before that. And that will be Dr. Srinivasan.
[Dr. Arjun Srinivasan]
Thank you, John.

Economic Analysis of COVID-19 Vaccine by Dr. Srinivasan

I'll move now to an economic analysis of the COVID vaccine.

[2:37:01]
I'd like to acknowledge the research team, which includes collaborators from CDC, Wake Forest, and the University of Michigan, who have worked together to contribute to this analysis. There are no conflicts to report. The objectives of this study were to estimate annual population disease burden and healthcare utilization associated with COVID-19 illness and COVID-19 vaccination, including resource utilization, such as outpatient visits and hospitalization, total cases, total costs, death, and quality-adjusted life years, or QALYs, lost, as well as to estimate events averted by COVID-19 vaccination and incremental cost-effectiveness for subgroups by age and risk status. The intervention strategies included in the analysis were vaccination against COVID-19 illness with an updated generic mRNA booster and no updated mRNA booster, that is, vaccination against COVID-19 illness with primary series only or primary series plus current booster.

[2:38:01]
The target population included all U.S. adults stratified by age into 18 to 49 years, 50 to 64, and 65 plus, and risk status, either at high risk for COVID-19 complications or not. Pediatric and adolescent age groups were excluded from the current analysis as there were insufficient data to incorporate these age groups into this phase of the analysis. The time horizon for the analysis is one year, with costs and qualities lost due to long-term sequelae and deaths beyond one year accounted for. The analysis uses a societal perspective with a costing year of 2024 and a discount rate of 3%. We used simulation modeling to project costs and health outcomes for each age group. This slide shows a simplified schematic of the simulation model. In the model, an individual has some probability of remaining disease-free or experiencing COVID-19 illness.

[2:39:01]
If they experience COVID-19 illness, they can have an episode of non-hospitalized COVID-19 illness or become hospitalized due to COVID-19. Symptomatic individuals can also incur an outpatient or ED visit. If hospitalized, the severity of illness can require ICU care or ventilation. All individuals who had COVID-19 illness are at risk for long COVID. Hospitalized patients also have probabilities of long-term permanent sequelae or death. As simulated individuals travel through the model, they accumulate costs and loss in quality of life associated with each health state. Also included in the model are adverse events associated with vaccination, including systemic reactions, anaphylaxis, and severe events such as myocarditis. These events are associated with costs and loss in quality of life depending on the severity of the adverse event. Each probability, cost, and quality adjustment is represented by a most likely value and a range of plausible parameter values.

[2:40:05]
Identical cohorts are run through the two submodels, one in which all individuals in the cohort receive a dose of the COVID-19 vaccine and one in which they do not. The next few slides will briefly present the key inputs into the model. Many epidemiological inputs rely on unpublished data, which best reflect the current evidence based for COVID-19 illness and effectiveness of COVID-19 vaccination. This slide lists the categories of epidemiological inputs and associated data sources. Please note that long COVID is also included. This slide shows actual monthly rates of hospitalization from COVID net data and is included as an illustration of how hospitalization rates have been changing across seasons. The economic analysis uses data from the 23-24 season shown in blue.

[2:41:05]
This analysis uses seasonality adjusted vaccine impact or SAVI to implement vaccine effectiveness in the model. Seasonal adjusted vaccine impacts combine monthly rates of vaccine effectiveness and hospitalization to account for timing of vaccination with the seasonality of COVID-19 illness rates, that is, how illness rates vary by month. Costs include direct medical costs associated with COVID-19 illness or vaccination. Productivity losses associated with illness include lost productive time for paid and unpaid work due to illness. Time costs for the individual being vaccinated are also included. Quality of life adjustments are included for illness events and vaccination-related adverse events. These are included as a decrement to qualities in the model.

[2:42:05]
The analysis is designed to project disaggregated health and economic outcomes stratified by intervention strategy and by age and risk subgroups including cases, hospitalizations, deaths, costs, quality adjusted life years, adverse events, and number needed to vaccinate. Incremental cost effectiveness ratios in dollars per quality gained are calculated. Comparing updated COVID-19 dose to no updated COVID-19 dose. This metric measures the additional investment in vaccination or cost savings associated with the change in health benefits and accounts for offsets due to averted illness. Uncertainty analyses including probabilistic sensitivity analysis, univariate and multi-way sensitivity analyses, and scenario analyses were conducted to explore the robustness of the results to change in input parameters.

[2:43:10]
The next set of slides will review preliminary results from this phase of modeling. It is important to note that this presentation reports preliminary results from an ongoing analysis. This slide shows disaggregated results for projected cases, cases of long COVID, hospitalizations, ICU stays, and deaths stratified by age and risk group. Results are presented for cohorts of 100,000. The blue and orange dark shaded bars show the remaining events with vaccination in non-high risk and high risk groups by age. The light shaded bars show events averted with vaccination. The total height of the bar represents the number of events expected without vaccination. The figures in the top panel show that numbers of cases are relatively similar across age and risk groups.

[2:44:01]
The lower panels demonstrate the substantial variability across age and risk groups for hospitalizations, ICU stays, and deaths with much higher burden of disease and illness averted by vaccination in over 65. This slide reports incremental cost effectiveness ratios or ICERs for each age group using a societal perspective. For all age groups, vaccination requires an additional investment as shown in the incremental costs column and yields additional health benefits as measured in quality adjusted life years. The far right column displays incremental cost effectiveness ratios. These range from 498,000fornon−highriskadults18to49to149,000 per quality adjusted life year in non-high risk 65 and older. For high risk adults, the range is 375 to 44,000 per quality adjusted life year.

[2:45:05]
This slide shows the results of the probabilistic sensitivity analysis. In this analysis, key input parameters are coded into the model as distributions so that quasi confidence intervals can be generated for each outcome in the model. These results demonstrate substantial uncertainty associated with incremental cost effectiveness ratios except for the high risk over 65 age group. This uncertainty reflects the level of evidence available for COVID-19 as a new pathogen. This slide shows number needed to vaccinate to avoid one case, one hospitalization, or one death for each age risk group. Number needed to vaccinate is lower for high risk and older subgroups. This slide shows incremental cost effectiveness ratios using alternative measures of health benefit.

[2:46:00]
Again, here, cost per hospitalization or cost per death averted is lower for higher risk and older age groups. The next few slides present uncertainty analysis as input parameters are varied from their base case values. This tornado diagram displays one way sensitivity analyses for the most influential parameters in the analysis for the non-high risk 65 and older age group. The three most influential parameters were seasonality adjusted vaccine impact, probability of hospitalization, and cost of the vaccine dose. Incremental cost effectiveness ratios for this age group are highly sensitive to changes in input parameters. Not shown here are the one way sensitivity analyses for the other age and risk groups which show similar results. Results for high risk 65 and older are most robust to changes in input parameters. The next few slides will provide details of these sensitivity analyses.

[2:47:05]
This slide shows the change in cost effectiveness when varying the probability of hospitalization across lower and upper bounds for all age risk groups. These results show more favorable cost effectiveness ratios across all groups when the probability of hospitalization is set to the upper bound in the far right column and are cost saving in the high risk 65 and older group. The incremental cost effectiveness ratios are less favorable when using the lower bound. Results are highly sensitive to changes in the costs of vaccination. The largest component of the cost of vaccination is the cost of the vaccine dose. A lower cost per dose as shown on this slide is associated with substantially lower incremental cost effectiveness ratios. Varying the cost of vaccine dose to 60perdosewouldmovetheincrementalcosteffectivenessratiotolessthan198,000 per QALY for high risk and non high risk groups greater than or equal to 50 years and would be cost saving for the high risk 65 and older group.

[2:48:14]
Few cost effectiveness analyses include wastage as a separate cost in the analysis. When it is included, this is often in the case of a new vaccine where the price is unknown. Conventional assumption is that any costs associated with wastage are reflected in the price per dose if returns are allowed or the administration fee if provider bears the cost of unused doses. Scenario analysis on price per dose yields insights if wastage is not adequately captured by base case assumptions. This analysis includes limitations. Unpublished data has been used to derive key parameters in the model, vaccine effectiveness, symptomatic illness, probabilities of hospitalization and critical illness. Data sources vary in representativeness and generalizability.

[2:49:03]
VE estimates were derived from a single prior season's data. Few COVID-19 seasons are available to estimate seasonality. The evidence base for long COVID is especially scarce and the model does not include reduced transmission which is a conservative approach. In summary, vaccination averts substantial morbidity and mortality in all age and risk groups as demonstrated through estimated disaggregated outcomes. There is substantial variation in impact by age and risk status. Overall economic favorability has declined compared to estimates from earlier seasons due to declining burden of illness. Incremental cost effectiveness ratios for 65 plus age groups are robust to changes in perimeter inputs across plausible ranges. Incremental cost effectiveness ratios for 18 to 49 years and 50 to 64 year age groups are sensitive to changes in perimeter inputs and favorable only under certain conditions for high risk 50 to 64 year age groups.
[Martin Kulldorff]

[2:50:12]
Thank you very much and that also came in at less than the assigned time so I really appreciate that. Thank you so much. We have three short statements from the COVID-19 vaccine manufacturers.

COVID-19 Vaccine Manufacturer Statements: Sanofi

The first one is from Sanofi, Dr. Scharf please. Do we have Dr. Scharf on the line?
[Dr. Katie Scharf]

[2:51:00]
Hello, can you hear me?
[Martin Kulldorff]
Yes, thank you. Go ahead.
[Dr. Katie Scharf]
Hello, can you hear me?
[Martin Kulldorff]
Yes, we can hear you. So please go ahead.
[Dr. Katie Scharf]
Thank you for this opportunity to speak today on behalf of Sanofi and our partner Novavax. My name is Dr. Katie Scharf. I am a medical director for Sanofi and a practicing infectious disease physician. During the pandemic I was at the front lines as an infectious disease physician treating patients with COVID-19. Additionally, I provided clinical oversight for the state of Oregon's COVID-19 mass vaccination site, which administered over half a million doses of COVID-19 vaccines. Novavaxavid COVID-19 vaccine adjuvanted is a recombinant protein COVID-19 vaccine, which is based on a well-established technology platform.

[2:52:03]
It is the only non-mRNA protein-based vaccine available in the United States, providing Americans an important tool to protect themselves against COVID and ensure that they have choice in doing so. In May, the FDA fully licensed Novavaxavid based on pivotal phase three clinical trial data that showed Novavaxavid was safe and effective for the prevention of COVID-19. The product is indicated for adults 65 years and older and individuals ages 12 through 64 at higher risk for severe outcomes from COVID-19. The vaccine has also been fully approved by other regulatory authorities around the globe, including the European Medicines Agency. The ongoing safety and effectiveness of Novavaxavid is our utmost priority. We continue to generate and share clinical and real-world evidence to support the ongoing use of Novavaxavid.

[2:53:07]
This data is shared with the scientific community, regulatory authorities, and the public in a variety of forums. We have substantial post-marketing safety experience with Novavaxavid with a database that includes over 5 million doses administered globally. There were no new safety signals identified for the 2023-24 or 2024-25 formula of Novavaxavid. As with all our products, we continue to monitor and report to regulatory authorities any new or existing safety signals. Starting this fall, Sanofi is responsible for the commercialization of Novavaxavid. The product has a six-month shelf life and has already begun shipping to healthcare providers and local retailers in the United States. Sanofi looks forward to expanding awareness and access to Novavaxavid to allow eligible individuals the availability of the nation's only protein-based, non-mRNA COVID-19 vaccine this fall.

[2:54:12]
Thank you for the opportunity to speak today.
[Martin Kulldorff]
Thank you so much. And Dr. Sedyak, Moderna, please.
[Dr. Vishal Raskala]
Hello, checking that you can hear me.

COVID-19 Vaccine Manufacturer Statements: Moderna

[Martin Kulldorff]
We can hear you, thank you.
[Dr. Vishal Raskala]
Excellent, thank you. Well, thank you for the opportunity to speak. I'm Dr. Vishal Raskala, Moderna Medical Affairs. The COVID-19 pandemic was an unprecedented challenge. Moderna partnered with the U.S. government through Operation Warp Speed to deliver one of the first authorized vaccines.

[2:55:01]
Since then, we have worked with health authorities worldwide to ensure timely access to updated vaccines as variants emerge. Real-world evaluations in millions of U.S. recipients show that updated vaccination provides additional protection, especially for adults 65 years and older and those with risk factors at increased risk of serious outcomes. Those findings were confirmed this past winter by CDC and by governments, including Canada, the U.K., and across Europe. We monitor safety through clinical trials, post-authorization studies, and global pharmacovigilance. We review every safety signal that comes to our attention. Our product labels across 90 countries reflect all signals that have been verified. FDA and health authorities, including Canada, U.K., Europe, have recently approved the updated 2526 booster, including benefits exceed risks for those 65 and older and those younger with risk factors.

[2:56:06]
Individual benefit risk has been clearly established by the competent health authorities. We note that one of today's presentations includes assertions not aligned with the broader scientific evidence. Some conclusions extend beyond what reference studies support or are contradicted by careful reading. Others appear based on isolated case reports that are presented without relevant clinical context or omit a larger body of published evidence to the contrary. Claims of long-term persistence of vaccine-derived spike or mRNA are refuted by well-controlled biodistribution studies conducted to regulatory standards globally using licensed product and shared with FDA showing no evidence of long-term persistence. The side studies cannot distinguish spike from viral infection from that of vaccination.

[2:57:00]
One even reports higher spike levels in unvaccinated controls. Residual DNA is also mischaracterized. This is a tightly regulated quality attribute across vaccines and medicines using assays validated to FDA standards. Every lot is tested by Moderna and independently reviewed by FDA prior to release. FDA has stated that animal studies and extensive real-world monitoring after more than 1 billion doses show no sign of genotoxicity. The German Health Authority has noted that the non-validated methods described in reference studies overestimate DNA by counting RNA as DNA. Our commitment is straightforward transparency and rigorous assessment of the totality of evidence. We will continue publishing data using validated methods and we will work with regulators to examine any potential safety signal.

[2:58:01]
Your decision today is important to preserve choice and accessibility of FDA approved effective vaccines. Americans should have the right to choose protection if they wish.
[Martin Kulldorff]
The right of evidence supports maintaining that access. Thank you. Thank you very much. And I think I have to correct myself. I believe that was Dr. Rizkala and not Dr. Sedja, as I said. So apologies for that. The next one we have Dr. Paul Balmer, and I think the name will show differently, but I believe it's Dr. Balmer that will be speaking for Pfizer.

COVID-19 Vaccine Manufacturer Statements: Pfizer

[Dr. Paul Balmer]
Hi. Can I do a sound check? Can you hear me?
[Martin Kulldorff]
We can hear you very well. Thank you.
[Dr. Paul Balmer]
Thank you. Good morning. My name is Dr. Paul Balmer, and I'm the U.S. vaccines medical affairs lead at Pfizer. On behalf of our teams at Pfizer and BioNTech, thank you for the presentations today. I also thank the other manufacturers for the statements that were made, and I will not be repeating any of the comments from those statements.

[2:59:08]
I also want to thank the committee for the opportunity to make this statement. COVID-19 has transitioned from a pandemic to an endemic disease. Even so, COVID-19 disease still hospitalizes hundreds of thousands of Americans and is responsible for the death of thousands every year. Pfizer and BioNTech remain deeply committed to making safe and effective vaccines that help protect lives in the U.S. and around the world. The Pfizer-BioNTech COVID-19 vaccine has been reviewed by multiple regulatory authorities, including the FDA, and has met all safety and quality control guidelines. Pfizer's safety systems work in concert with U.S. government safety monitoring. We report information gathered to the appropriate governmental channels and carry out specific scientific studies under the approval of FDA.

[3:00:00]
In addition to routinely reviewing all published scientific literature for safety concerns, we are conducting many studies that use real-world data from millions of people to continue to assess the safety of our COVID-19 vaccines. At Pfizer, we carefully review every adverse event reported to us and ensure they are reported to VAERS. VAERS is an early warning system. However, it cannot assess causation. As such, FDA and CDC use multiple additional safety systems to understand causation. These were enhanced during the pandemic to include COVID-19 pregnancy registries and v-safe real-time user reporting. Each of these monitoring tools and surveillance systems have their own strengths and weaknesses, but together they build a safety monitoring net that enables identification and investigation of even rare safety signals. Since the COVID-19 vaccine was approved in 2020, assessments conducted along with regulatory bodies across the world show that the benefits of COVID-19 mRNA vaccines continue to outweigh the risks.

[3:01:08]
It's important to consider any potential risk in the context of the demonstrated benefits of vaccination. In the past year alone, COVID-19 vaccines prevented somewhere between 68,000 to 100,000 hospitalizations, averted 13,000 to 18,000 intensive care unit stays, and saved 5,000 to almost 7,000 lives in the U.S. In summary, Pfizer and BioNTech remain steadfast in our dedication to vaccine safety, quality, and effectiveness through constant safety monitoring and ongoing research. With 5 billion doses distributed to date globally and continued approval by regulatory agencies in 83 countries, our vaccines are among the most extensively monitored products licensed in the world, helping prevent hospitalizations and saving lives.

[3:02:02]
Thank you.
[Martin Kulldorff]
Thank you so much for that. And we will now move on to questions and answers.

Q&A Session with Presenters

As we say that you can ask questions to any of the presenters this morning. And also, for time perspectives, if I ask each one to ask all the questions you have, and then we'll go on for the next one without getting like the second time so we can go through and have everybody have a chance to ask questions and answers. Including the liaison members that we have on the phone, but as always, we obliged to first question and comments from the voting members and the ex officio members. And we do have a list here.

[3:03:01]
And the first one is Dr. Cody Meissner, please.

Dr. Meissner's Questions on COVID-19 Hospitalization Data and Maternal Vaccination

[Dr. Cody Meissner]
Thank you, Dr. First, let me say that this has been absolutely an amazing presentation by everyone this morning. It was a little bit like drink trying to drink from a fire hose. So much information. That's so important. And I think we could spend going over each presentation a lot of time. So let me as Dr. Kaldorf has requested, I will confine my comments. But first of all, I want to thank the CDC. I want to thank Dr. Levy and Dr. Kaldorf for putting this extraordinary presentation together.

[3:04:06]
I also thank the members of the work group and especially those members who are of the work group who are consultants. It was an absolutely fascinating morning. So I'm going to I have so many questions, but I'm going to confine my questions to the first presentation by Dr. Srinivasan and I apologize for mispronouncing and I'll call you Dr. S. The I think the question that I had is, as was pointed out by Dr. Malone, there's nothing unique about a COVID-19 respiratory viral infection. You can't differentiate COVID-19 from RSV from influenza.

[3:05:04]
And you addressed one of the critical problems that we've all had. That is, how many people were hospitalized with COVID and how many people were hospitalized because of who had disease? And I think you said it was there were two or three physicians who arbitrated that decision. So the first question I want to ask is, were those CDC docs or were those docs at the hospital? Who was it that that arbitrated that number one? And number two, you know, the state of Massachusetts, where I am, addressed this issue early on in the pandemic. And it was demonstrated that only about a third of patients who were hospitalized with what was called COVID were actually in the hospital because of COVID.

[3:06:04]
They were otherwise just essentially colonized. And what the state of Massachusetts did was to break that down as to who was getting dexamethasone. They used that as a kind of a surrogate marker, because if you were hospitalized with SARS-CoV-2 infection, just about everybody realizes if you're sick enough to get into the hospital with mild or moderate disease, then dexamethasone is one way to kind of a poor man's distinction between colonization and disease. So it's such it's it's such an important issue. And I wonder, just because there was a arbitration, someone had a positive PCR, which is very reliable assay.

[3:07:03]
I'd like to know a little bit about more about why, how they were classified as a COVID illness. And then the last question I'm going to ask, because I don't I don't want to be unreasonable, is about the data regarding vaccination of pregnant women and the difference in hospitalization with their infants. I guess I'm inherently skeptical of that. I think that a newborn who's born to a mother who's COVID positive is going to have a COVID test, whether the child is hospitalized or not. So can you tell us a little bit more about the reasons those children were hospitalized? And what what was it that led you to believe that the hospitalization of those newborns was because of of COVID-19?

[3:08:06]
What what symptoms did they have that differentiated them from others? Yeah. Yeah. RSV or from the children who were positive but not admitted. So thanks once again for everybody's presentation. And just it was fantastic. And I'll stop there.
[Dr. Reza Flevi]
Just a very quick comment, Dr. Meissner. Interestingly enough, you mentioned the fraction 30 percent. I think the data of the CDC when analyzed, if I'm not mistaken, in a paper that was shared with us, the fraction of people of patients that had a COVID diagnosis on their principal as a principal discharge diagnosis was 30 percent. Maybe it's a coincidence, but somehow coincides somewhat with the numbers that you state from Massachusetts.

[3:09:03]
And I think other other other places that did these studies showed similar numbers in a range between 50 to 30 percent. So I just find it interesting.
[Dr. Cody Meissner]
Thank you, Dr. Betts. And because this virus characteristically colonizes the the pharynx and will give a positive PCR assay even in the absence of symptoms. So it's a very important question. And I appreciate the CDC's willingness to discuss that a little further. Thank you.
[Martin Kulldorff]
Thank you. I agree with your assessment and praise for this presentation. That praise goes 100 percent to Dr. Levine and a member of his working group, as well as, of course, to the presenters. I would like now to hear a response from Dr. Vasson.
[Dr. Arjun Srinivasan]
Yeah. And let me open this up to the subject matter. There's a number of questions here to answer.

[3:10:00]
So let me open this up to the subject matter experts at CDC on the line to address the various questions that Dr. Meisner has raised. Go ahead.
[Chris Taylor]
Hi. Can you hear me? Yes, we can. Hi, this is Chris Taylor. And thank you for your questions, Dr. Meisner. I'll address your second one first regarding the infants. I don't know if we can probably isn't time to bring up the flow chart. But I want to make the point that for infants, for our reason for admission algorithm, we exclude infants who are hospitalized at the time of birth. So that subset of patients we do not include and we exclude them if it's a hospitalization at the time of birth. They're excluded as we would exclude a woman presenting for labor and delivery or someone who is presenting with an injury related to a car crash or a scheduled surgical procedure.
[Dr. Cody Meissner]
Understood. Thank you.
[Chris Taylor]
With regard to your second question, and I'll reiterate the point, I think what's really important to remember is that determining why someone is hospitalized is very difficult.

[3:11:06]
And our tool is the medical record. We are not the clinicians on the team. And so we make the best decisions we can with the data that are available to us and with our valued colleagues in the state and local health departments. And we know that ICD-10-CM codes are an imperfect data source and a peer reviewed publication from our program. We do cite the Massachusetts study looking at the systemic steroid use. You know, if you look at just steroid use or just other medications that are recommended for the treatment of severe COVID, if you look at reason for admission, if you look at discharge diagnosis, they're all going to tell a different story. What we've tried to do is identify the cases that we believe are most likely due to COVID hospitalization.

[3:12:02]
Hospitalizations where COVID-19 has a significant impact on the care, on the reason for admission, and also balances the needs of the data that are available to us with the timeliness in which it is required. So I do appreciate the question. I guess what I want to say is that we believe that what we are doing is not perfect. And I think ICD codes are not perfect. Using treatment guidelines is not always perfect because every patient is different. And we try to take that into account. And we hope you appreciate the effort that we put into this algorithm that has been in use for several years now.
[Dr. Cody Meissner]
Thank you, Dr. Taylor. I certainly do appreciate the enormity of the task that you have. And you've done an admirable job at trying to address it.

[3:13:02]
My only concern is that's the basis on which many people are advocating vaccination of pregnant women. And I don't think there's acknowledgment that this is a very uncertain parameter. And I think that should be more widely noted.
[Dr. Patton]
Hi, this is the S room. Thank you very much for that question. I think the important thing for COVID net is that we collect all hospitalizations among people living in certain catchment areas, which means we count every single hospitalization on a population level for those counties that are included in our surveillance system. And as you talked about, we do a very thorough process to determine which hospitalizations are for COVID and due to COVID.

[3:14:01]
And those are the data that we show when we show that one in five infants under six months who are hospitalized with COVID end up in the ICU. When we show that one in four children between the age of zero and 17 end up in the ICU. When we have published data that shows up to 40 percent of children hospitalized with COVID due to COVID-19 have a severe outcome, including death, ICU admission or receipt of mechanical ventilation. And in terms of the infants less than six months, as Dr. Taylor said, we exclude the infants who are hospitalized at birth. So the infants that are included in COVID net are only those infants who come in to the hospital and require hospitalization. The tests that we use to determine we actually don't do that. The hospitals determine which people are tested for COVID and we simply count them.

[3:15:01]
And it's really important to note that the infants under six months have hospitalization rates that are equivalent to the adults who are 65 to 74. That's what our national surveillance demonstrates. And that's demonstrated in many other systems in the United States. And so thank you very much.
[Dr. Cody Meissner]
Well, thank you. I'm not sure who that was. Who was that just talking?
[Dr. Patton]
Hi, this is Dr. Patton. I'm the team lead for this team that oversees the rest net surveillance system.
[Dr. Cody Meissner]
Thank you, Dr. Patton. And I don't want to prolong this conversation, but I'm looking at the chart that I printed out on Wednesday from the CDC. And it says weekly rates of COVID-19 associated hospitalizations by season. And since February, the hospitalization rate per hundred thousand has been less than zero point eight.
[Dr. Patton]
Hi, thank you. Those are weekly rates.

[3:16:00]
And so what we use to look at overall rates for the year are cumulative rates. So we look at the total number of infants who are hospitalized over a year divided by the population of people in those catchment areas. And those are the data that were shown on the slides today. If you look at the bar chart, I think it's challenging for us to pull up slides at this point. But if you look at the bar chart that shows the cumulative rates for this past year. You can see the cumulative ICU. Sorry, the cumulative hospitalization rates for infants less than six months. Infants six to 11 months and then by age group. And so weekly rates definitely vary based on, you know, circulation of the SARS-CoV-2 virus. And that's what we demonstrate on the website. Actually, if you if you go to the other section, there is also a section where you can see cumulative rates based on the selections that you'd like to look at.
[Dr. Cody Meissner]
Yes, but I'm but since October of last year, the hospitalization rate for children under 18 years of age has been less than one per thousand.

[3:17:08]
So I don't think we should make our decisions about future vaccines based on what's an accumulative data. The virus is changing. Immunity is changing because of vaccines and because of immunization. I think it should be based on more current data. And the current data is it's it's it's less than 0.4 per hundred thousand.
[Dr. Patton]
Yes. Thank you for that question. What's important to note is that when you group in the older children who are hospitalized at lower rates into the hospital, overall cumulative hospitalization rates. It does look like the overall rates for all children are low because we know those older children are not being hospitalized. What's really important when you're looking at epidemiology and how different diseases affect different populations to look at population specific rates of how that disease is affecting that specific population.

[3:18:07]
That's the really the great thing that about COVID net is that we can really drill down into which groups are being most impacted by COVID hospitalizations. So if you look, you can see that infants under six months have the highest rates among all groups of children infants age six to 11 months are the next highest and infants less than six months have a rate of 223 per 100,000 population. And so, you know, that's really what the purpose of these surveillance systems are is to be able to look at the impact of these diseases on different groups. Thank you.
[Dr. Cody Meissner]
Thank you for that and I am quite familiar with the point that you're making and it's a very true and valid point. But I, and I don't have the precise numbers for those under six months of age, but I still think that if you look at current times.

[3:19:08]
It's, it's not that high, and I think that there was an over emphasis on the amount of disease, relative to what's happening now the virus is becoming less invasive, it causes less severe disease. And everybody has immunity from an infection and or vaccination so I think that has to be taken into consideration. The question that I have for you. And if Dr. Kulldorff doesn't cut me off here. And it's the question I asked last time, at what point does the low uptake of a vaccine influence CDC recommendations. If less than 20%, for example, are accepting a vaccine. Shouldn't that be reflected in your guidance, if I mean it's, it's almost like prohibition, no one was supposed to drink alcohol but people did.

[3:20:03]
It's, why do you keep saying this when, because I'm worried it interrupts credibility for the CDC, if you make a recommendation that people are simply not going to follow. I don't think that's wise.
[Dr. Patton]
Thanks. I just one clarification on the cumulative rate, the cumulative rate is per season so when we talk about a cumulative rate. That's for this most recent year, not over the course of the entire five years. Thank you.
[Martin Kulldorff]
Thank you very much for your. Thank you for that. And next one is Dr. Levi. Okay, so there were Dr. Griffin.
[Evelyn Griffin]
Thank you.

Evelyn Griffin's Questions on Biodistribution and DNA Contamination

Actually I did have a comment. Thank you, Dr. Meisner for bringing up this issue because it does stem into my world of OBGYN. The comment on that presentation for the six month olds, or less than six month olds the comment was made that there is no approved vaccination for under six months of age, therefore, the mothers should get vaccinated.

[3:21:09]
So, this is a wonderful example of how confounding variables that are not unveiled can bias, the representation of the data. So, we, it wasn't just are described that there were confounders that were not discussed, but a statement was made that pregnant women So I'll present some scenarios for example that could be investigated, perhaps for a future study. For example, on slide 28. It was shown here in the presentation that more than three comorbidities have a statistically significant difference in COVID-19 hospitalizations. So, we can ask, you know, how many comorbidities did the, did the pregnant mothers have, did they have COVID, were they perhaps infected or were they vaccinated during, do we know if they were vaccinated during the, their pregnancy, and then their babies perhaps had been more susceptible because of altered immunogenicity to succumb to COVID diagnosis.

[3:22:22]
Were the babies preemies, back to the mother, you know, preeclampsia, hypertension, diabetes, obesity, those are the most common comorbidities in women and those rates are skyrocketing in our childbearing age population now in women. So just some thoughts. If I can move on to my questions now.
[Martin Kulldorff]
Please do.
[Evelyn Griffin]
Thank you. Regarding the biodistribution studies. There's a lot that was said here that I was not aware of. My first question is, which regulatory bodies have approved Pfizer and Moderna to not use their final end product to study if their product does not stay in the arm, as was stated, and actually travel to the brain and other organs.

[3:23:12]
And if I may, I'll ask a follow up question so perhaps all of them can be asked, answered is Pfizer and Moderna. Were they aware of the plasma DNA and SV 40 contamination. Did they try to replicate that study or initiate any population studies to test vaccine recipients, the recipients of their products. Dr Carlton, why was your study canceled in 48 hours. And last safety question was to the CDC presenter. Just discussion on the various reporting that came from CDC any comment on that. I'll be happy to repeat any of those.

[3:24:06]
Dr Carlton if you would like to go first.
[Raymond Pollack]
Sure.
[Dr. Bruce Carlton]
I don't know why the grant was canceled. I understand that that HHS has said the period of performance ended on March 25 the grant was several years long involves international surveillance, as I mentioned, network and that's the information I was given by the principal investigators.
[Evelyn Griffin]
Okay, thank you. And then to Pfizer and Moderna regarding the bio distribution studies.
[Dr. Reza Flevi]
So, I'm not sure if they're online the other two speakers. So, I think, so they are online so hopefully they can.
[Martin Kulldorff]
They should be online I think.
[Dr. Kupferwasser]

[3:25:03]
I can re ask later question address to is it to the working group folks are to the actual representatives from the companies, actual representative from the companies.
[Darren Edwards]
Yes, I can hear me.
[Evelyn Griffin]
Yes.
[Darren Edwards]
Yes. Hi, this is Darren Edwards corporate lead for code vaccines at Moderna. We have conducted by distribution studies to assess the not only the persistence of our drug product which is our mRNA and our LNP but also the spike protein. We have submitted those studies to the FDA. And what those studies demonstrate is that both the LNP, the mRNA, and the spike protein does primarily localized to the injection site, and the draining lymph node with some detection and other tissues and organs, but that does clear very rapidly post injection with no detection spike protein, or than 14 days after injection in those studies.
[Evelyn Griffin]

[3:26:03]
And was it the final end product that was used in those bio distribution study.
[Darren Edwards]
It was a, it was commercially representative material that was used in those studies. Correct.
[Evelyn Griffin]
What does that mean commercially representative I don't know what that means does that mean something different or know it's the same. Not the exact same thing.
[Darren Edwards]
A manufacturing process used.
[Evelyn Griffin]
Okay, I was just wondering, because this is novel to me the mRNA itself. Is it the exact same mRNA that was used in the vaccination product that I received, for example.
[Darren Edwards]
Yes, yes it is.
[Evelyn Griffin]
Okay, thank you.
[Carrie Sweeney]
So, this is a representative from Pfizer are by distribution studies were done in concert and consultation with the FDA. And we did use a Lucifer is based product that was manufactured the same way as our drug substance and our drug product or LNP itself.
[Dr. Robert Malone]

[3:27:09]
Can I follow up on that as a person who developed that essay and used it first in tissue, and also developed the various sub methods for analysis, you appear to have used the least sensitive method. Available, that being whole body imaging using a VIM camera, rather than the most sensitive method which is individual tissue dissection license and counting and Illuminator. Am I incorrect in that. And furthermore, the data that were submitted to the FDA were edited. They were edited relative to data that was submitted to other agencies, the actual images were edited. Can you comment on that, please.
[Carrie Sweeney]
So Pfizer does not have a further comment, other than we did work in close consultation with the FDA and all of our by distribution studies that were approved for our license product.
[Dr. Robert Malone]

[3:28:11]
Fascinating.
[Darren Edwards]
Moderna for detection of the in the study where we assessed the COVID vaccine about distribution of the COVID vaccine. We use detection methods specific to the spike, they were not for metric.
[Dr. Kupferwasser]
Dr. Griffin, did you have one question related to this that I didn't think I heard the answer to was whether or not the DNA impurities were measured by the companies.
[Evelyn Griffin]
And I was wondering the same.
[Darren Edwards]
Sorry, this is Darren Edwards with Moderna for every lot.

[3:29:00]
Part of our release testing is detection of DNA in each lot. We use industry standard methods to perform these assessments that is specific to DNA and does not detect RNA. Which is a flaw in a problem with some of the other methods cited Yes.
[Carrie Sweeney]
Hi, this is Carrie Sweeney head of analytical for vaccines. We follow on with what Moderna is saying that we did measure residual DNA within our product and our assay was validated to be specific for residual DNA and not RNA within the product.
[Dr. Robert Malone]
And I follow up on that question, please. Again, Dr. Malone, the thresholds that were used to establish that you were within allowed parameters are those that the FDA determined as acceptable for naked DNA. Is that true or false. I'm sorry, that was directed at the industry representatives were the thresholds used to determine lot release or DNA contamination.

[3:30:18]
Those that were developed for naked DNA or were they in some way reflective of the added delivery efficiency of your particular lipid nanoparticle formulation over.
[Martin Kulldorff]
We have a response from Dr. Palmer at Pfizer.
[Carrie Sweeney]
So the threshold used for our residual DNA test. We're following the approved to guidelines for residual DNA impurities within a vaccine product.
[Dr. Robert Malone]
In other words, those were the thresholds for a lot release that were established for naked DNA by the FDA true or false.
[Martin Kulldorff]
And can you state your name also.
[Carrie Sweeney]

[3:31:01]
This is Carrie Sweeney Efren from Pfizer analytical vaccines have been local. The who guidelines we followed were approved for residual DNA within vaccine products.
[Dr. Robert Malone]
Right. So you used to answer the question.
[Martin Kulldorff]
We have a response from Madonna. The same question.
[Darren Edwards]
Yes. Hi, this is Darren Edwards. The thresholds were developed for our product.
[Dr. Robert Malone]
I'm sorry. Did I just understand you to say that alternative thresholds for lot release were developed based on integration studies, which is the gold standard with naked DNA that the FDA applied. You did integration studies for DNA fragments using your delivery formulation. Is that true.

[3:32:03]
So all of the safety data is based on our control of these thresholds.
[Darren Edwards]
That's fundamental to our products are assessed. Therefore, the product thresholds are for our specific product.
[Dr. Robert Malone]
Yeah, I'm not understanding.
[Martin Kulldorff]
I'm sorry. Go ahead. Can you state the person that's responding. Can you state your name and company.
[Darren Edwards]
Yes, this was a response came from Darren Edwards. Thank you.
[Evelyn Griffin]
Can I.
[Martin Kulldorff]
So I think Dr. Griffin, if you had more questions or it'll it'll was everything was on this topic.
[Evelyn Griffin]
Just because I can't keep up with Dr. Malone's brain. This is where the rubber meets the road for OBGYNs because I was asked, you know, does this end up in breast milk.

[3:33:05]
So there is a study. And of course, we're all interested in conflicts of interest. The authors here did have grants from NIH I and they showed there was detection of messenger mRNA COVID-19 vaccines in human breast milk. This is Hannah at all. And I don't have the year exactly, but obviously it's recent. The other one is, is this going to my baby is the other question. This study has I cannot find the I cannot access the full article. It says, so I do not know the conflict of interest, but it is from an American. The American Journal of Obstetrics and Gynecology transplacental transmission of the COVID-19 vaccine messenger RNA evidence from placental maternal and cord blood analyses post vaccination. And then finally, there was a study no conflicts of interest here showing This one was intracellular that so this is showing reverse transcription that so for the media reverse transcription is basically what what happens normally in ourselves is we transcribe our DNA to RNA, which then makes protein.

[3:34:23]
If you go backwards, which we were told was not supposed to happen. You get reverse transcription so intracellular reverse transcription of Pfizer, Pfizer BioNTech COVID-19 mRNA vaccine BNT 162 B2 in vitro. So that means not studied on humans. Thank goodness, outside of humans, but it Reverse transcribed into human liver cell line. So this is concerning because then it's just that's reverse transcription into our DNA, but then we have not even started talking about epigenetic concerns epigenetic concerns come into play when other genes are turned on or off.

[3:35:06]
So one last paper I'll reference here. Erdogan at all no conflicts of interest. They showed prenatal exposure to COVID-19. Now this is a rat study COVID-19 mRNA vaccine induces autism like behaviors in male neonatal rats. So this. These are the questions that parents are asking. So I'm just bringing this to the table because there are studies that are being done to suggest this so just coming to the table to pose these questions and have hopefully industry and regulatory minds answer the questions for us. Thank you.
[Martin Kulldorff]
And who do you want you want the industry to response. But the Griffin. Do you want the industry to respond to somebody else.

Discussion on mRNA Vaccine in Breast Milk and Reverse Transcription

[Evelyn Griffin]
Sure. Any and all.
[Martin Kulldorff]
Who would you want to respond you to decide.
[Evelyn Griffin]

[3:36:02]
Pfizer, Moderna, whoever else we have some.
[Martin Kulldorff]
Okay, so can we have a response from Pfizer first. Hi, this is Kayvan Majerad from Pfizer. I'm the research and scientific lead for COVID-19 vaccine franchise. So, from the standpoint of biological plausibility RNA cannot reverse transcribe the DNA and transport from the cytoplasm, the nucleus to the nucleus and then integrate requires a set of molecules and enzymes that don't exist in humans, and are largely reserved for retroviruses and Madonna. If so, be sure from the donor.
[Dr. Vishal Raskala]
I'd like to add to Pfizer's statement we're great. But also like to raise the FDA's seekers later that was addressed in 2023 through evaluation of hundreds of millions of individuals, there was no indication of indicative indication of genomes.

[3:37:05]
Thank you.
[Martin Kulldorff]
And we do have more people on the list. I have tried to run a tight ship here but there's one thing I'm not going to deny you, and that is the lunch break. So, and on the schedule is only 20 minutes. I'm not going to shorten it. So we will now do lunch break, and we will resume here at 1220. Thank you very much.
[Dr. Robert Malone]

[3:59:46]
From this community.
[Martin Kulldorff]

[4:00:17]
So, we are continuing, continue, continuing the q amp a session. And the next person on the list here is Dr. Milan. So, please go ahead.
[Kirk Milhoan]
As a physician that takes care of children's children I often have, and people talk about the ethics of of whether this is appropriate but often families, parents will ask me, what would you do if it was your child.

Kirk Milhoan's Questions on Vaccine Hesitancy and Hospitalization Data

And so I thought, what's worthy to be brought up. And I think, I think Dr Meisner for sort of addressing this issue as well.

[4:01:05]
But when, when we're looking at hesitancy. And on what CDC might recommend what we might recommend as a committee. And you look at healthcare providers. Where the uptake is currently around 10%. I think that's very, excuse me, I think that's very telling. Excuse me. So that's one thing I wanted to bring up. The other thing I wanted to bring up as and thank Dr Carlton for bringing this up this issue up in terms of, of how do we get better at. Individualizing care, and I thought his specifically with even within vaccines, but he brought up a very important issue that I'm seeing dramatically increases in my care of children specifically they're coming to a pediatric cardiologist, and that is disautonomia or dysregulation between the autonomic nervous system and the body.

[4:02:13]
So I think that these are all very important things to consider that this disruption that has happened. In our community. The other thing I know a lot of people are gone, but I will bring up as a question. When we're talking about hospitalization of children. That is often a soft call. Dr Pagano and I were talking about this as an ER physician as a pediatrician we often find ourselves in situations where we will admit a kid who let's say has RSV, or, or COVID. And we really do it more for an observation then, as opposed to they needed be in, and there are many factors involved, even how tired the parent is have they been up all night.

[4:03:07]
This child needs to be observed closely. So I would ask, sir. When you looked at hospitalizations. Did you have length of stay in that or is it just positive hospitalization negative hospitalization. Thank you.
[Dr. Arjun Srinivasan]
Let me ask if someone in the subject of expert room has the details on whether or not we have length of stay with these admissions.
[Chris Taylor]
Go ahead, Dr. Taylor. We do collect. Thank you. This is Dr. Taylor. We do collect length of stay. I don't think I have the statistics at hand by age group. But it is it's including anyone who meets the case definition and then is hospitalized. But it excludes anything that would be classified as an observation.
[Kirk Milhoan]
Well, I mean, we call them observation, but in order to be an observation, it usually has to be less than 24 hours and we have to call it, but often what we'll do is we'll have a kid spend the night or a baby spend the night.

[4:04:10]
And they might spend more than 24 hours. But so I think that that that is something I appreciate all the work that has gone on to do this, but that is some subtleties that don't always give the clear picture. The other thing I wanted to bring up is, and I think this goes to the hesitancy issue, is there was sort of a new definition that you looked at the vaccine as of in terms of its effectiveness, but dismissed the issue of whether that it prevented infection. And I didn't see any data on that. And considering what the Cleveland Clinic study showed with over 50,000 health care workers, I would wonder if you could comment on that. And the other thing is when you talked about vaccine effectiveness.

[4:05:02]
Did you come up with those prospectively or was that retrospective that we're going to show these data where the vaccine is effective retrospectively as opposed to prospectively? So I'll let the SME room weigh in as well.
[Dr. Arjun Srinivasan]
The issue with the cases versus hospitalization is that cases, of course, with all the testing at home, it's impossible to capture the universe of testing, which was possible previously because, of course, all the testing had to be done in a health care facility. But to your other questions, let me let the SME room weigh in here as well.
[Ruth McGillis]
Hi, this is the SME room. This is Ruth McGillis. So we have previously shown data on vaccine effectiveness against SARS-CoV-2 infection through pharmacy testing. But the point just raised, there's so much home testing at this point and non-testing that people are not going to pharmacies to get tested.

[4:06:03]
And so those data are no longer adequate to answer a question about vaccine effectiveness specifically against infection. Likewise, in sort of an outpatient setting, people are not generally going to the doctor and getting a COVID test. And so those data aren't captured in a way that we can study VE specifically for infection. And so instead, what we do is we look at emergency department and urgent care VE as well as hospitalization vaccine effectiveness against severe disease, which are really the outcomes that respiratory virus vaccines are meant to protect against. And so what we've seen over time is that our VE against infection, when we could measure it, was very similar to what we would expect for other respiratory vaccines such as flu. And likewise, VE against hospitalization and more severe disease has also been very similar over time to what we would see for flu. Thank you.
[Kirk Milhoan]
One of the reasons I brought that out is because a few years ago, even coming from the CDC where if you get the vaccine, you won't get COVID.

[4:07:10]
And so early studies that were done is that you didn't even test people with COVID-like illnesses. If they were vaccinated, you only tested the unvaccinated because the assumption was in the medical community that it prevented infection. But I think all of us know that it's very hard to prevent a respiratory infection with an injectable vaccine because of the lack of IGA immunity. One last thing. Before medicine career, I had a PhD in pharmacology. And I guess I'm shocked at the lack of pharmacological rigor. In dosing, how that dose timing, dose accumulation, how long that dose lasts, and what are the pharmacokinetics of a biologic making a biologic?

[4:08:19]
And so when the question is asked, okay, so as a cardiologist, I see this by protein is cardiotoxic. I want to know how long that a biologic has made a biologic and how long it's going to last. Oh, it goes away quickly. Then we have the recent Yale study that showed femtomoles of spike protein, basically, until they stopped the assay. So my comment is, is I am really confused about the pharmacologic rigor for this product before it was released and now with evidence of contamination.

[4:09:10]
Why is this not pulled off like any other biologic or medicine that is found to have contamination?
[Martin Kulldorff]
Yes, response to that.
[Dr. Arjun Srinivasan]
That would be a question for the manufacturers or FDA.
[Martin Kulldorff]
Yeah, Dr. Yes. Hey, can you hear me?
[Tracy Beth Hoag]
Tracy Beth Hoag from the FDA. So I will say that so a lot of some of the information is proprietary information. And I will I will say the information that we have been provided by Pfizer and Moderna and what was shared with me, what they provided to the FDA was within the regulatory limits.

[4:10:06]
And I I will also acknowledge that, you know, this is something we take very seriously. And I want to I want to sincerely thank the independent researchers, many of whom I know who have brought this issue to the public's attention. And at the FDA, we take the public's safety and the safety of these products incredibly seriously. And I just want to give you all that message that this is not something that is being ignored. And I can only provide with you the information that I have been given about what the sponsors provided us regarding the DNA levels in their products. And and so that I think that I'm going to stop with that.
[Martin Kulldorff]
Dr. Do we have a comment from Pfizer or Moderna? Please state name and company.
[Kirk Milhoan]

[4:11:03]
Can I ask another quick question of Dr. Hoag? Please do Dr. Hoag. Are there any plans for a post production about independent evaluation by the FDA?
[Tracy Beth Hoag]
So I'll say that that is something that's being discussed and we we just we again, we we want to communicate that we take this issue very seriously. And and thank and thank everyone who has brought this to our attention.
[Martin Kulldorff]
Do you have a comment from Pfizer or Moderna? OK, so we're going to continue. We have a list here. So we're going to continue now with Dr. Pollack.
[Raymond Pollack]
Raymond Pollack.

Raymond Pollack's Questions on Neutralizing Antibodies and Immune Response

This would be a question for both the CDC and the drug manufacturers. I dare say in the room, the vast majority of people here who have had. Vaccination against COVID assume they're immune.

[4:12:04]
And that is not a common thought amongst the general population. Vaccination equals immunity. But actually, what we've learned from influenza virus vaccines is that may not be the case. And the elephant in the room today, from my perspective, is that we've heard nothing about the production of neutralizing antibody following the course of COVID vaccinations or following a booster of the COVID vaccine. Everybody in this room, I think, has heard of somebody who's quote had the vaccine and then I got COVID. Well, I had the flu injection and then I got flu. And they question the efficacy and the rationale in giving vaccines, if after all, they weren't protected in the first place. Maybe they weren't protected because they were in a high risk group, immunocompromised, over 65, inability to make antibody.

[4:13:03]
But I think we need to hear from the CDC and the manufacturers, what percentage of patients actually fail to make antibody in response to the vaccine, because there the risk benefit ratio may not be worth it. And it also contributes to vaccine hesitancy. Well, I heard my neighbor got the vaccine, they got COVID, I'm not going to go ahead and get the vaccine, regardless of what this committee and anybody else says. And that also begs the question of what to do about boosters. I get often asked in my consulting practice, I got the vaccine, and now I'm being told by my doctor I should get a booster. My next question is, well, did you make antibody to the first set of injections? And why would you need a booster if you already made antibody? And at what titer of antibody are you regarded as immune? Is it one in 200, one in 400, one in 1,000?

[4:14:00]
At what level of antibody, neutralizing antibody, is the individual regarded as immune? Because if you've made enough antibody, maybe you don't need a booster, even though the serotype and there's a lot of antigenic diversity amongst the new strains of the COVID virus. Maybe if the antibody is directed at a particular portion of the spike protein, maybe you don't need the booster. Then regarding the immune response that was described earlier by the working group, I had a number of questions there. Did the investigators look at things like cytokine gene polymorphisms? Everybody in this room, if I take a hammer and I bang you on the knee, the amount of swelling you'll develop in your knee will develop on your particular cytokine gene polymorphisms. And we all make cytokines at different rates. And depending on the alleles that you carry for your cytokine genes, my knee may not swell, but Dr. Heberlin's knee may get to the size of a basketball.

[4:15:01]
And yet we have the same knees, I think, maybe. Was that work repeated by any other independent labs to confirm what their findings were, particularly with regard to IgG4 antibodies, the production of anti-idiotype antibodies, and the long-term effect on the FC molecule of the IgG antibody, as well as the cytokine changes they observed? And then to echo what was said earlier, perhaps they were looking at patients who had been infected with wild COVID-19 or injected mRNA COVID. So those are the questions I had, and I'd be interested to hear their response.
[Martin Kulldorff]
And who would you like to respond? The CDC and the manufacturers?
[Raymond Pollack]
So the questions for the CDC was, are there studies out there looking at antibody levels?

[4:16:00]
At which level of antibody are you protected? If you have enough antibody, do you need the booster?
[Martin Kulldorff]
Can we have the response from CDC first?
[Raymond Pollack]
I don't believe we have specific. Okay, we're good. Perfect.
[Natalie Thornburg]
Yeah, sorry. This is Natalie Thornburg, Lab SME and NCIRD. So there are, we have done quite a lot of antibody studies. There's a lot of published antibody studies. The manufacturers have done a lot of antibody studies looking at antibody responses after vaccination and infection. And most people do produce very robust neutralizing antibodies, which do seem to correlate with protection. The issue with upper respiratory virus infections is immunity tends to not be sterilizing for any upper respiratory virus infection or after vaccination. Just because of the dynamic way the immune system works in infection happening at a mucosal surface and evolution of viruses.

[4:17:02]
So it's hard to come up with a very specific number to say this is the level of neutralizing antibodies that will protect a person against infection. And then it's additionally difficult to establish a number because the dynamic nature of a person's antibody response and that their antibody response today might not be protective tomorrow. Or against a lineage that emerges a week from now. So yes, neutralizing antibodies protect us. But it's such a dynamic environment with the viruses and waning immunity that a test today can't necessarily predict your susceptibility one week from now.
[Dr. Robert Malone]
This is Dr. Malone. You just made some statements about correlation between antibody or neutralizing antibody and protection.

[4:18:02]
But I'm trained in this area and I've worked on the development and performance of correlates protection analyses, for instance, for flu. Are there any well defined characterized correlates of protection for COVID? Yes or no? The answer is no. There are no clearly defined by standard methods correlates of protection for COVID. Not cellular, not humoral, not neutralizing. None of those have been subjected to formal analysis to define them as a correlative protection. So you really have no right to assert what your feelings or opinions are about whether or not there's a correlation between any of these outcomes, these adaptive immune responses and protection.

[4:19:03]
There is no established correlative protection for COVID.
[Dr. Cody Meissner]
Full stop and stop saying otherwise. Martin, can I make a comment here? This is Cody. Please, very short, Dr. Meister. Yeah. The issue of a correlate of protection is critical. There's no question. Everyone is interested in having a correlate of protection. However, there is a reasonable measurement of neutralizing or binding antibodies that correlate with protection against symptomatic infection in the first few months. Where is that study, Cody? Show me that study. I am happy to. It's in the New England Journal of Medicine. Because it's more likely that the protection is afforded by the cellular response, not the antibody response.
[Martin Kulldorff]

[4:20:01]
We'll let Dr. Meisner finish what he says and then Dr. Madelon can respond to that.
[Dr. Cody Meissner]
Robert, you're absolutely right. And that's what I was about to say. We know that as time goes by, the frequency of infection increases. It's primarily mild disease. Protection against severe disease defined such as hospitalization or death persists. So the question of what is a correlate of protection is enormously complex, as you pointed out. Because it involves multiple components of the immune system. So, but there is, I think there is a pretty well established correlate of protection. And I'm happy to forward that to everyone on the committee. But that only lasts for a short period of time, Robert.

[4:21:02]
Over. Dr. Madelon, you want to respond?
[Dr. Robert Malone]
Sorry, I live in the world of actual clinical testing and pathology and approved tests. And these soft endpoints that you're talking about are not the same as a defined correlate of protection. It's a very specific outcome that requires very rigorous testing. I completely concur. It's wicked hard to define. But this throwing around like, forgive me, our colleagues at the FDA repeatedly asserting that antibody titers in mice are somehow a predictor of effectiveness in SARS-CoV-2 vaccination is just, it is non-scientific. I'm choosing my words carefully. And this banding about of correlate of protection as a term, I personally find offensive as somebody who's had to deal with this and live in this world for years and years and years.

[4:22:07]
It is, as you say, Cody, I completely concur. It is a wicked hard thing to do. It's still problematic in influenza. In the case of flu, the correlate of protection that's established by the agency is probably only valid for that type of vaccine. And in the case of SARS-CoV-2, these surrogates that are being used to assert protection are not correlates of protection. They are indirect indicators of an immune response. An indicator of an immune response is not the same as a correlate of protection. I'm happy to direct this at you. I appreciate that you understand the issue. But for the more general audience, this is something that has been repeatedly misstated and misunderstood by our colleagues in the media and our colleagues in the pharmaceutical industry and, frankly, in public statements from former CDC directors.

[4:23:08]
Over.
[Dr. Cody Meissner]
I need to answer, if I may. I need to answer because there are several points that need to be made because this is really a very critical point. And you are correct. There are, as Stanley Plotkin and his co-workers have pointed out, there are mechanistic correlates of protection and non-mechanistic correlates of protection. It gets into a fairly complicated discussion. But it's the mechanistic correlates of protection that are most important. A statistical association with an immune response that is not involved in inactivation of the virus is not a correlate of protection. And I think that's what you're referring to. And I completely agree with you. The difficulty is it depends on the endpoint that's being addressed.

[4:24:03]
Remember, there are four different endpoints. It can be very severe disease due to COVID. It can be mild disease due to COVID. It can be asymptomatic infection with COVID, but still permits transmission. Or it can be an immune response that completely blocks infection. So there are four different endpoints that one can use. And defining a correlate of protection for each one of those is extremely difficult. It involves mucosal IgA, systemic IgG, a number of different subclasses of T cells. So that is a long discussion. But I think we do have a pretty well defined, and I will send you a paper that was in the New England Journal of Medicine a couple years ago, that derived a result based on all of the vaccine trials.

[4:25:06]
Over. Cody, are we aligned?
[Dr. Robert Malone]
Yes. That the titer, as reported, cannot be used as a surrogate for protection of an individual? It's such a complicated question. Okay, can we agree on this? That the mounting of an antibody response does not define protection?
[Dr. Cody Meissner]
There certainly can be an antibody response that does not confer protection. Yes. Thank you.
[Martin Kulldorff]
Well, I thank you for that discussion. I'm sure our friends in the media understood all of this with perfect clarity. I think Dr. Pollack was not quite done with this. I appreciate the discussion that the two of you just had.
[Raymond Pollack]
And I think any statement that comes out of this committee may want to include the fact that while this committee recognizes that COVID vaccine may not always guarantee 100% protection.

[4:26:11]
This is what this committee advises, because the lay public, and there are plenty of lay people in this room, believe that if you're vaccinated, you are immune. And if I'm not immune, I then have to weigh up the benefit and risk of getting the vaccine. And if I think the vaccine doesn't make me immune, why should I bother to expose myself to the risk of the vaccine?
[Martin Kulldorff]
So thank you for that discussion. And Dr. Blackmon?
[Hillary Blackburn]
Yeah, thank you.

Hillary Blackburn's Questions on Pharmacist Role and Package Insert Considerations

So first, I just wanted to highlight the role of pharmacists in vaccine access. And as evidenced in the slides, that pharmacies administered approximately 67% of COVID-19 vaccines to adults over 18.

[4:27:05]
And that we should consider that continued access to vaccines in pharmacy settings is essential to ensuring timely patient care. I also wanted to kind of tag on to the comment earlier about low uptake among healthcare professionals of the COVID vaccine coverage, which was notably low, reportedly around 10%. Were there any surveys conducted to better understand the reasons behind the low uptake? Additionally, was there consideration of whether high influenza vaccine rates may have been influenced by flu vaccine mandates in health systems and how that compares to COVID-19 uptake? And I do have one, I'll pause there. I do have another comment, but I'll let that be answered.
[Dr. Arjun Srinivasan]
Yeah, let me ask our SMEs if this, I know there is a survey that's done of healthcare personnel. I don't know if it gets into reasons for choosing to vaccinate or not vaccinate against COVID.

[4:28:03]
Let me ask our SMEs if we have any of that specific data.
[Dr. Laura Morris]
Yes, thank you. This is Carla Black from the Immunization Services Division. First, I'll respond to the second part of your question. Those data that were showed from the NHSN rely on facilities reporting their documented vaccination coverage to CMS. So they're obviously going to, they'll miss vaccinations where they don't have documentation. So a lot of the reason I think that you see higher flu coverage is because facilities are more likely to have requirements for flu vaccination and they're more likely to provide it on site. So they have, they're more likely to have that documentation. We do have also surveys of healthcare personnel and the coverage from surveys is much higher. It's around 40% that reported being vaccinated and that's overall, including non-clinical personnel. So if you look at just like physicians, it's closer to 50%. And when we ask reasons for non-vaccination, it's, you know, similar to the general population.

[4:29:05]
They feel like they're not at risk of getting COVID or they're not worried about getting COVID. So, you know, in times where there's more disease or new variants, you know, demand for vaccines is higher. And also if we look at whether vaccine is provided on site, coverage is much higher. So it's also a matter of access and convenience.
[Hillary Blackburn]
Okay. I also wanted to bring up some package insert considerations. Section 13.1 of the package inserts of Comirnaty and Spikevax. It states that the vaccine has not been evaluated for potential carcinogenicity, genotoxicity, or impairment of male fertility. So in lay terms, genotoxicity refers to the potential to damage genetic material or DNA. And while many drugs carry this type of language, some, for example, lisinopril, have actually been evaluated and specifically state no evidence of tumorogenic or immunogenic effects.

[4:30:09]
But given the rising cancer rates nationally and the case reports presented earlier, should additional studies be conducted to assess this concern more fully? And from personal experience, my mother experienced a dermatologic immune response following a COVID booster in early 2022 and subsequently developed EGFR positive lung cancer two years later. In my small hometown population of less than 13,000, four others in close proximity living within a two to three mile radius were also diagnosed with EGFR positive lung cancer. Could it represent a potential cluster? Would CDC epidemiologists be able to comment on whether such patterns are being tracked? Is it related to the vaccine virus environmental issues?

[4:31:02]
Definitely worth further study. But when I checked with the Mississippi Cancer Registry, I learned they still rely on fax forms and do not track biomarkers, which is surprising in 2025. And given that many people have questions, more robust studies could help confirm or rule out potential risks.
[Dr. Arjun Srinivasan]
Dr. Hogue, please.
[Tracy Beth Hoag]
Yes, I'm here. I apologize. I thought initially the question was for the CDC, but thank you for bringing that to our attention.

[4:32:01]
And I actually agree with your statement that the backbone of any initial analysis of this should be good epidemiological work to determine if there really is a rise in cancer rates associated with the COVID-19 vaccines and if there are specific types of cancer. And that would be a very good question also for the CDC to see if they've found any concerning trends. And then there are novel methodologies, of course, that are ways of looking into potential risks of carcinogenesis. But those are difficult studies to do in general. But again, I'm open to hearing people's thoughts here. And, you know, again, at the FDA, we are really here to protect the public's health and are appreciative of these questions and the information. So thank you.
[Martin Kulldorff]

[4:33:02]
So thank you for that. I think we'll continue with the next person on the list, which is actually I'm the next person. So I have questions for Pfizer and Dr. Paul Ballmer.

Martin Kulldorff's Questions on Pfizer's Pregnant Women Trial and Birth Defects

So before the meeting, Pfizer, you sent out some very important information, which I appreciate. And among that information, you described randomized controlled clinical trials, placebo controlled trial for Pfizer vaccine in pregnant women. And I would like to commend you and congratulate you for doing a placebo controlled randomized trials. That is what we need for these vaccines. I'm very happy that you did that study. It was a small study. I think you had a little over 150 in each arm vaccinated versus controls.

[4:34:00]
And when we look when we consider whether it's a drug or vaccine, when we consider that in pregnant women, one thing that we're always very concerned about are birth defects. And in the material you sent, there was a fourfold access risk or birth defect among the vaccinated mothers. The birth defect was in the child, but when the mother was vaccinated. And I calculated on my own and is the P value of point zero point zero five. So that is very concerning. I mean, the sample size is small, but it's very concerning to have a fourfold access risk of birth defects in these pregnant women. And I think it was I think I think the vaccinations here was weeks. The stationary is 22 to 32, but I must remember that's wrong.

[4:35:01]
So I would like to see if you would care to comment on that important finding.
[Alejandra Gertman]
Yeah, this is Alejandra Gertman. I'm the head of the vaccine clinical research and development group at Pfizer. Thank you for the question. So the study was done at a time where the study was initially designed at a time where we didn't have a recommendation for pregnancy. And so to your point of why the study was small, the study was interrupted. One, the recommendation became available for all pregnant women based on the risk benefit that was assessed at that moment for pregnant women. To your point, the vaccine in the study, which was about 350 women randomized one to one to vaccine and to placebo were given between 24 to 36 weeks of pregnancy. And the rates that you are referring to congenital abnormalities were about five percent in the vaccine group and three percent in the placebo group.

[4:36:07]
So there is not a full rise as you are referring. And the background rate for which these congenital abnormalities were seen was same or below what you will expect in pregnancy. So congenital anomalies, as everybody knows, happen in pregnancies and the rates that were seen in the study match what you will expect in the general population. Of note, most of these congenital abnormalities are part of the first trimester of pregnancy. So most of them were present prior to the vaccination. So it would be very hard to think that the vaccine actually had any causality on abnormalities based on the fact that the vaccine was given much later than during the first trimester of pregnancy.
[Martin Kulldorff]

[4:37:00]
So there were, I believe there were eight birth defects in the vaccinated group and there were two birth defects in the unvaccinated and eight divided by two. There was almost a one to one ratio. So eight divided by two is four. So would you agree that there was a fourfold excess risk or fourfold excess of birth defects in the vaccinated group?
[Alejandra Gertman]
No, as I mentioned before, the rates of the proportion of congenital anomalies in the two groups are about five percent versus three percent. And again, I'm going to repeat, those are very much what you will expect in normal and regular pregnancies.
[Martin Kulldorff]
So in the material that was sent, there was eight in the vaccinated group. Is that wrong? That number?

[4:38:03]
And there were two in the unvaccinated group. Is that number wrong?
[Alejandra Gertman]
There are two tables in the CSR that actually Pfizer public in the spirit of transparency. And the congenital anomalies can be seen in different ways, can be reported as serious adverse events, which is the table that I'm referring to. But they can be reported as adverse events of special interest. If you look at all of them as SAEs, that's the proportion that I'm talking between five percent and three percent.
[Martin Kulldorff]
And are you denying the eight birth defects in the vaccinated and the two in the unvaccinated? Are those numbers wrong?
[Alejandra Gertman]
I'm not denying the tables are published on the Pfizer website for everybody to go and take a look at what they just described.
[Martin Kulldorff]

[4:39:10]
So you agree that there were eight birth defects in the vaccinated group, there were two in the unvaccinated.
[Alejandra Gertman]
Now, we need to refer to the tables I am mentioning and to look at the differences between serious adverse events and adverse events of special interest.
[Dr. Robert Malone]
She's bundling them into total SAEs, as opposed to just looking at the at the specific AE of teratogenesis.
[Martin Kulldorff]
Well, in the material I read, there were eight birth defects in the vaccinated and two in the unvaccinated. And there were there were not the same type of birth defects, but it was eight and two. So I'm confused if there are those numbers wrong.

[4:40:02]
Eight and two, I would like to know if those numbers with eight birth defects in the vaccinated group and the two in the unvaccinated group, if those which I saw in the material that you said.
[Alejandra Gertman]
I'm referring you back to the way that those numbers are the correct. I am referring you back to the way that we describe the data where the data can be seen in two different ways. And we're happy to resend that to you if needed. I do want to acknowledge again that the birth defects that have been describing this reported on clinical trial.
[Martin Kulldorff]
This was from the randomized placebo controlled trials. And I think it's great that Pfizer conducted a randomized placebo controlled trials for vaccines in pregnant women. I think that was a great thing to do.

[4:41:01]
And I compliment you for doing that study. But I'm confused because the material that you said said there were eight birth defects in the vaccinated group and two in the unvaccinated. And it seems that I want to know if you think those numbers are correct that you presented or if those are wrong.
[Carol Hayes]
Excuse me. A point of order. All birth defects occur in the first trimester. And that was not when the vaccine was administered to the pregnant women. This is Carol Hayes with the American College of Nurses.
[Evelyn Griffin]
I would like to speak to that.
[Martin Kulldorff]
I would think that the birth defects is something that you find out after birth.
[Evelyn Griffin]
If I make it make a comment. So are we I'm not familiar with this particular study. Was it listed what what congenital anomalies were.
[Martin Kulldorff]
It was a variety. I don't remember them. But maybe if I can answer what type of birth defects were these versus two.
[Evelyn Griffin]

[4:42:00]
Yes, there are. There are congenital anomalies, although the majority the major structural development occurs earlier prior to 24 weeks. But there's others that can develop after. Can you tell us can you list each one of the anomalies.
[Alejandra Gertman]
Yeah, they are described on the table that we put, you know, that we posted online the request.
[Evelyn Griffin]
Thank you. Yes, we're not looking at that material. We don't have it on screen. Can you please read them? Dr. Koldorf said it was eight and one arm and then two in the other arm. If you can please read each arm for us.
[Alejandra Gertman]
We will pull the table here in the room where we are and we can come back with us.
[Evelyn Griffin]
Okay. Just to finish the thought, you know, after 24 weeks, we can develop, for example, microcephaly, ventriculomegaly, kidney anomalies, for example.

[4:43:07]
So there. So that's why I was asking the specific anomalies. Thank you.
[Martin Kulldorff]
And I think I know we have other representatives from Pfizer on the line. Is there a comment from Dr. Balmer on this issue? I see no additional comment from from Paul Balmer. Thank you. So we will now move forward and. We have Dr. Stein, please.
[Kathy Stein]
Thank you.

Kathy Stein's Questions on Hospitalization in Infants and Immunocompromised Adults

I will try to keep my questions. First, I'd like to go back to something that both Dr. Meissner and Dr. Millhorn were talking about in terms of the hot, relatively the high incidence of hospitalizations and babies less than six months. I noticed that the the other analysis later presented about vaccine effectiveness and stuff and hospitalizations were stratified by comorbidities.

[4:44:07]
Was that was there a way or was that a consideration looking at the babies?
[Dr. Arjun Srinivasan]
Let me ask. I believe the numbers were probably too small. Do you want to answer that question? Stratification for the infants.
[Dr. Patton]
Is Dr. Taylor on the phone? Yeah.
[Chris Taylor]
Hi. Could you could you please clarify your sentence? I'm wondering, are you asking about the hospitalization rates or prevalence of conditions?
[Kathy Stein]
Now, I'm asking is. Is there a way to explain that relatively high incidence of hospitalization in babies less than six months old? Is there any knowledge or data on any kind of comorbidities or anything like that?
[Chris Taylor]

[4:45:00]
We do have we do collect data on comorbidities for all of our age groups. I know, for example, for some age groups, I want to say six to 23 months, which I know is not the age group you're asking about. Prematurity is prevalent at about 20 percent. We have previously presented some data to this committee. It was not in the slides put forth for this meeting. But we do have data on underlying medical conditions among all age groups. I guess I would say in general, I don't think the patterns that we see in that particular age group differ other than. And I'm not a clinician, but I believe a lot. It takes some time for a child to develop the underlying medical conditions that we collect data on. So they might not be prevalent in that age group because it's just not a relative condition for children of that age.
[Dr. Arjun Srinivasan]
Let me ask Dr. Patton to comment as well. I believe she has a comment.
[Dr. Patton]
Hi, thanks for the question. Yes, we definitely look at medical conditions amongst all our patients, as Dr. Taylor said.

[4:46:03]
And among infants less than six months, the majority of them were healthy, previously healthy, had no underlying medical conditions. Seventy one percent of those infants that were hospitalized with COVID due to COVID had no underlying medical conditions. OK, 71 percent. Thank you.
[Kathy Stein]
Healthy. My second question also goes back to comorbidities, because I find it I think that's going to be an important topic. Right. In terms of identifying risk groups and in looking at you, see if I can find the right slide. I've been back and forth so much looking at the vaccine effectiveness analyses. And there was a really striking here. I don't know if this is slide 22. You don't have to pull it up. There's a graphic showing the vaccine effectiveness in immunocompromised adults age 65 and up.

[4:47:00]
I don't think there is another analysis looking at stratified by comorbidities. And that's probably a limitation of data you don't have. But I was wondering if you could comment about the implications of that. And this is not like a gotcha question, because that's one of our groups that we're most concerned about. Right. Are the groups that are immunocompromised and then some following from that individuals that have comorbidities. What are your thoughts about the decreased vaccine effectiveness in that group?
[Ruth McGillis]
Yes. Thank you. This is Ruth and Dallas in the room. We do collect data on underlying conditions, including both immunocompromising and non immunocompromising underlying conditions. As part of our standard analyses, we do sensitivity analyses, generally either stratifying or controlling for non immunocompromised underlying conditions. And we find very consistently that that non immunocompromising underlying conditions do not impact vaccine effectiveness.

[4:48:04]
So, in other words, folks with non immunocompromising underlying conditions have the same effectiveness of the vaccines as those with no underlying conditions. That's not true for immunocompromising conditions, where we do often see vaccine effectiveness different in those with and without immunocompromising conditions, which is why our primary analyses generally stratify by immunocompromised and then either control or not for underlying conditions that are not immunocompromising.
[Dr. Robert Malone]
Can I jump in on a question on that one? The issue of immunosenescence. Elderly condition is one of your risk factors. It's well known to be associated with immunosenescence, which is associated clearly with reduced vaccine immunogenicity and responsiveness. So, are you telling me that elderly cohorts that are prone to immunosenescence respond just the same as younger cohorts to these products?

[4:49:02]
Over.
[Ruth McGillis]
No, when we refer to underlying medical conditions, we're not talking about age. We're talking about things like cancer, diabetes. We do separately stratify by age by age group, because, as you say, we do know that older age groups may have immunosenescence. We generally recently have not had statistical power because of lower vaccine coverage rates to stratify above age. Sixty five what we saw earlier in the pandemic when quite a bit higher, and we were able to stratify by ten year age brackets above sixty five is that we do see a drop off in effectiveness happening around age. Seventy five and that has led to recent recommendations for a second dose annually for those sixty five and up who may have lower or may have more quicker waning.
[Martin Kulldorff]

[4:50:02]
Thank you for that.
[Kathy Stein]
Okay.
[Martin Kulldorff]
Dr. Stein.
[Kathy Stein]
I think. Well, more one question. One comment. I'll skip one of my questions in the vaccine safety signal and presentation. There was a table presented with a long list of adverse events of special interest, and I'm not sure this is a complete list. And so I guess it's a two part question. One is, why was the analysis other than time limitations, which is very reasonable? Why was the focus only on stroke? And were there other conditions considered that are not on this list, but potentially could be?
[Dr. Su]
Thanks for the question. So with regards. And if you could put up slide thirteen, please. So that's a list of the different adverse events of special interest that are being monitored via VSD.

[4:51:05]
And I'm sorry, your question was, were there other conditions being monitored? Yes. So I should emphasize that we have a number of complementing vaccine safety monitoring systems within CDC, and they are designed for different purposes. So in this case with VSD, the example that I went through, I was using that as an example. Okay. Okay. But that's a robust statistical analysis. But if we're talking about looking at. As our passive surveillance system comes in. Now, it's not designed to determine causality or statistical analysis, but it is designed to pick up on potential changes, reporting pattern, things we haven't seen before that can be pursued more robustly with a system like VSD. So each system has its design for certain purpose, and they have their strengths and they have their limitations, but they complement one another.

[4:52:05]
And together, they cover a lot of ground.
[Kathy Stein]
Thank you. And my last question. My last comment is just a really simple one. Actually, it refers back to something Dr. Milhoan said. I think Dr. Srinivasan did a really nice job presenting the vaccine effectiveness analysis because you didn't overplay it. Like the limitation of the test-negative design is that you're saying the sample is limited to who's coming to the hospital, right? And you were very clear that these are individuals who are presenting with respiratory symptoms and stuff. And so what I'm making the point is I'm not disagreeing with anybody at this point. I'm just explaining the outcome, and that's one that we really can understand.

[4:53:00]
I think you guys did a great job really honed down and get due to, as opposed to, I think that's a very important interpretation and people to not over-interpret. Kind of going back to Dr. Pollack's point about, you know, this doesn't mean that that's the vaccine effectiveness against infection. It's a completely different outcome. Thank you.
[Martin Kulldorff]
Thank you for that. It's also very important to hear from our liaison members. So the first, Dr. Hayes, please.

Liaison Comments: Carol Hayes

[Carol Hayes]
Yes, Carol Hayes with the American College of Nurse-Midwives. First of all, you did an excellent job of presenting data that we have been monitoring for the last five years. And I also wanted to give a shout-out to Tom Shimabukuro, who worked on v-safe, and that's where we first began collecting data on pregnant women being vaccinated. And he did a fabulous job. So thanks, everybody.
[Martin Kulldorff]
Thank you for that. Dr. Fryhofer.
[Carol Hayes]
Thank you.

Liaison Comments: Dr. Sandra Fryhofer

[Dr. Sandra Fryhofer]
I'm Sandra Fryhofer.

[4:54:00]
I'm a general and internal medicine physician in Atlanta. I'm in full-time practice. I'm also an adjunct associate professor of medicine at Emory. I've been an ACIP liaison for nearly 20 years, and I've served on multiple vaccine workgroups, including the COVID vaccine workgroup, since its inception, until the liaison was removed from the workgroup deliberations. And I want to say that the presentations today on the biodistribution and the T-cell studies were fascinating. They were technical. They were complicated. They were confusing. And I was surprised that this preliminary research was presented at this level and not at the workgroup level. But it does call for the need for more research. And as we all know, on August 5th, HHS delivered a death blow to mRNA vaccine development by canceling $500 million in contracts for mRNA vaccines.

[4:55:00]
HHS terminated 22 grants supporting refinement and development of mRNA vaccines. And canceling these research grants leaves us highly vulnerable to the next pandemic. It also puts development of mRNA-based cancer treatments at risk. And as we know, mRNA vaccines funded by Operation Warp Speed were essential to ending the COVID pandemic. They saved us during the pandemic. I also want to point out that the decisions this committee is making today really hit home for me. I have two grandbabies on the way. Both are due in November. And will these little babies be able to get COVID protection from maternal vaccination? Will they be able to get their COVID vaccines when they're six months old? We've heard the data. Rates of COVID hospitalization for children are highest under the age of two. Babies six months old are too young to be vaccinated. They're at highest risk.

[4:56:01]
And maternal vaccination can lower that risk. So please make these vaccines available to protect these little babies. I also want to make a...
[Martin Kulldorff]
Dr. Hopkins, please. Dr. Hopkins.
[Dr. Sandra Fryhofer]
Yeah, may I say one more thing, please, sir? I've waited very patiently. I also wanted to make a quick statement on behalf of the American Medical Association as AMA liaison. AMA has traditionally acted as a liaison to ACIP. And it's troubling to see the erosion of the committee's integrity. We're concerned about how vaccine recommendations are being developed by this new panel. Data is being selectively used to justify specific conclusions rather than considering all of the available evidence. And this lack of transparency diminishes trust, introduces bias, and raises doubts about the reliability of the committee's vaccine guidance. In June, the AMA and 79 medical societies confirmed their support for vaccines as the best protection during respiratory virus season.

[4:57:06]
And this includes COVID vaccines. It's crucial to keep vaccines accessible to protect everyone, especially those too young to be vaccinated and those who are immunocompromised. The administration has stated it will continue to make vaccines available to everyone who wants them. But we observe federal policies that contradict this goal.
[Martin Kulldorff]
You're taking time away from other liaison members. And I would like to ask that you limit your comments to things that are directly related to the COVID vaccine. So thank you, Dr. Fryhofer. Dr. Hopkins, please.
[Bob Hopkins]
Thank you for the acknowledgement.

Liaison Comments: Bob Hopkins

This is Bob Hopkins. I'm medical director for the National Foundation for Infectious Disease. Just some brief comments. I think it's important to note that we continue to see severe disease due to COVID-19 leading to hospitalization and deaths.

[4:58:01]
The impact is greatest in our population 75 and older, but is also significant in younger adults and in our youngest children. It's important to note that while the morbidity and mortality are greatest in adults who have comorbidities, that's not true for children. Children in the greater proportion do not have comorbidities that end up in the hospital with severe disease. Our vaccines remain effective for severe disease across all the age groups that have been tested. And any protection you get from the vaccine raises what little, none, or potential protection you have from previous exposure to the virus. Remembering that our children under six months have no protection that they get before mother being vaccinated at all. It's critically important that we maintain access of COVID-19 vaccine to all who want the vaccine. And low uptake, as Dr. Meissner had said, low uptake should not limit access to those who want to be vaccinated and reduce their risk for severe outcomes.

[4:59:03]
Thank you.
[Martin Kulldorff]
Thank you very much, Dr. Paulson. Do we have Dr. Paulson?

Liaison Comments: Grant Paulson

[Grant Paulson]
Apologize, sorry about that. Thank you. Thank you very much for the acknowledgement. This is Grant Paulson with the Pediatric Infectious Diseases Society. As was mentioned yesterday very clearly when we were talking about Hep B, there are populations in the public where trust in vaccines is low. I don't think anybody in the room or online is going to disagree with that. I think the hope from all of us is that the efforts of the ACIP committee continue to clinically review the science, raise concern where warranted, but also endorse the safety of vaccines when there are data supportive of that. As mentioned by the chair yesterday, open discussion is vital, as is an open mind when looking at the data, I think, on all fronts. So with that said, as part of today's discussion on COVID, I understand the work group values are not necessarily, they don't endorse using the statements of safe and effective as discussion points.

[5:00:07]
With respect to safety, I understand that point. As doctors, when we say something safe, as we've already talked about, that is partially accurate. There is no such thing as 100% safe vaccine or intervention in medicine. It is on balance with the risks and benefits. So that is probably a misnomer in some sense, but the writ large message for the public is on balance, the risks and benefits are acceptable when we talk about safety. Data on effectiveness, I think effectiveness should be discussed. I'm not talking about correlates or protection. I certainly agree with all the prior statements on that. But we've just had excellent presentations by the CDC on incidents and safety as well as efficacy, sorry, not efficacy, effectiveness of these vaccines. So what I guess my concern is relying on case reports, anecdotes, and sort of selected basic science data, is that enough to justify a change in policy or a recommendation that limits an effective vaccine based on concern rather than data on safety or adverse events.

[5:01:13]
The data presented by Dr. Carlton on myocarditis was actually fascinating. I could quite closely geek out on that and talk to him and ask lots of questions on the genetics of vaccine-induced myocarditis versus that induced by COVID itself or other causes. I think further research monitoring is certainly warranted. But with that said, the data are fairly clear. Young children in the less than 6-month-old, but then specifically in the 6- to 23-month-old that would be vaccine eligible, have similar risks to 50- to 64-year-olds. And of the children, over 50% of them do not have a comorbidity or underlying health problem. They're healthy children that get admitted to the hospital, and we know the vaccine is effective for them. So as a pediatric infectious disease provider, really my belief is that no one here online or in the room is out to harm children.

[5:02:02]
I think we all do want to protect them, minimize harms and risks. But I would encourage the committee to make decisions based on the data rather than theoretical concerns that are raised. Those are certainly valid concerns. I'm not here to dismiss them. Continued monitoring, continued research is vital but should really not be a barrier to families looking to access this tool to protect their children. My only question, and I will wrap up for the committee, is in the interest of transparency, can the language for the proposed vote be made available to the public prior to that presentation? Thank you very much.
[Martin Kulldorff]
Thank you for that. And Dr. Munoz?

Liaison Comments: Flor Munoz

[Flor Munoz]
Thank you. Flor Munoz with Infectious Diseases Society of America. Appreciate the acknowledgement. And I will be brief as I agree with the comments provided by many of our liaison colleagues as well. I just wanted to point out the fact that these discussions today are relevant and very important indeed with many scientific questions brought up, which really support the need for additional funding to be able to continue to address this.

[5:03:16]
In terms of the mRNA technology being a breakthrough technology that has allowed for the control of a pandemic in the U.S. and globally, and the fact that the mRNA vaccines in particular have been given to more people than probably any other vaccine in the short period of time, which allow us to have precisely a lot of information regarding their safety and clinical trials with efficacy and post-authorization trials with effectiveness that support their utilization. Apologize for the sound. I also wanted to briefly mention the fact that the mRNA vaccine is the one that has been, for the most part, utilized in pregnancy, and that we have sufficient evidence to indicate that this is a very important intervention to protect those infants who are not eligible for vaccination.

[5:04:08]
And my last request is to advocate for our most vulnerable populations, the older adults, the immunocompromised and those with high-risk conditions, and the very young children, especially those under two years of age, and more importantly, of course, less than six months, who depend on the maternal antibody, but under two who need their own vaccination as well, to be able to receive these vaccines in the future. With acknowledgement, again, that there may be several questions to address for which we do need the research money, we do need the follow-up, and we do need a long-term investigation so that this technology could also be applied to future vaccines.
[Martin Kulldorff]
Thank you. Thank you, Dr. Buchanan.
[Dr. Stacey Buchanan]
Good afternoon.

Liaison Comments: Dr. Stacey Buchanan

Thank everyone for the rich conversation that we've had surrounding the COVID-19 vaccine.

[5:05:03]
I, too, would like a little bit more clarity around the question that we're answering today as it pertains to COVID-19 vaccines. I have great concern here in Georgia with access. I know earlier this year it was stated that there shouldn't be issues with access, but unfortunately, with what we have as far as guidance, a lot of the providers here in the state of Georgia are limiting access for their patients, and I'll just give a very brief example of a colleague of mine whose grandchild is yet to be born and has two older siblings, and the mom reached out to their pediatrician to try to get the vaccine and was denied. And so that's what's going on. Like, we need clarity, please, about what the question is and also to make sure that the vaccine is accessible for those that want it, which is a barrier currently in real time here.
[Martin Kulldorff]

[5:06:04]
Thank you for that. And we are now going to continue with a presentation by Dr. Ratseff-Levi on the COVID-19 discussion framing.

COVID-19 Discussion Framing by Dr. Reza Flevi

So, please.
[Dr. Reza Flevi]
I'm going to try to be short as possible, but I do want to reflect the work that was done. Let me just wait for the slide. So, again, it was a pleasure to work with the colleagues on the workgroup. We had heated debates, but also very respectful debates that maybe show that you can have good conversations and disagree on things, but nevertheless respect each other. So, I want to start with the main takeaways of the workgroup. And when I say the workgroup, I mean most of the majority of the workgroup. Clearly, there was a consensus on everything. So, the first point is that many of us, or most of us, felt that the current assessments of protection levels provided by COVID-19 vaccines, and especially the seasonal boosters against severe outcomes, namely hospitalization, ICU, deaths, and long COVID, are based on very low quality data and analysis.

[5:07:19]
And that's kind of a major uncertainty that I think we all have to acknowledge. We also would like to flag that vaccine injuries are demonstrably not recognized by current pharmacovigilance systems. And in many cases, they leave vaccine-injured individuals abandoned and without appropriate care. And this is something that we intend to follow up on. We feel that that's something that is morally wrong and also from a public health perspective has to be addressed if we want to have trusted vaccine programs. Finally, we assess that there is ample published research.

[5:08:03]
This is not hypothetical. This is ample published research that suggests some serious safety uncertainties and concerns, including potential adaptation related to mRNA vaccines that are currently not appropriately addressed. As high-level kind of recommendation directions, I want to flag out that for this meeting, we feel that one of the recommendations is about the risk and uncertainties related to the COVID-19 vaccines should be appropriately communicated by CDC to patients and medical providers to enable the appropriate informed consent. And I'm going to be more specific about what we mean in that respect, because that's going to be a topic for a vote later on. A more longer-term goal that we put for ourselves to pursue in the next coming months is to work on recommendations related to development and enhancements of national efforts to appropriately diagnose the vaccine injured and care for them.

[5:09:09]
We are going to follow up with more specific recommendations, and we have a lot of people in the workgroup that are very experienced with both academic research and field experience in caring for vaccine injured and also long COVID patients. We also plan to follow up on recommendation with respect to the development and enhancements of a national safety surveillance systems to address safety uncertainties and assess the impact. So we already kind of had discussions about the reliability of the assessment of the protection that COVID vaccines provide, and I want to make it much more crystal. So the key metric when you want to assess protection of a vaccine is what is called the number needed to vaccinate.

[5:10:04]
This is basically the number of people you need to vaccinate in order to prevent one outcome. And despite many requests, including from the FDA about the number needed to vaccinate that were used to authorize the recent products, we were not able to get any numbers. This table is taken from something we've seen earlier today. This is a model. This is a simulated model that was presented previously by our colleagues at the CDC. Just to kind of make the point, what we see in the next slides is this is data that is taken from the health authorities in the UK that developed similar analysis. And it's kind of puzzling to see the difference in the numbers needed to vaccinate that basically are between six times or even more larger based on the UK analysis, which leaves you kind of concerned about what the right numbers are.

[5:11:00]
And also, what is the true efficacy and true benefits that these vaccines provide? And again, we are not in 2020 or 2021. We are in 2025 after multiple boosters, after drifting of the variants to be much less virulent. So these questions seem to be critical, but they don't seem to currently have reliable data. And we were very concerned by that. And by the way, we feel that that should be communicated to patients. We already talked about the concerns around the definition of what the COVID hospitalization is. I'm not going to repeat that. We talked about that. But there are other methodological limitations, and specifically, the current method used to assess the vaccine efficacy, the negative design control, is something that is clearly known in the literature. This is from the literature that is not appropriate to assess the vaccine efficacy for mortality and hospitalizations.

[5:12:03]
Without getting into too many technical details, I think that the major assumption here is that we are trying to assess the proportion of vaccinated people in the population by looking on the control cases, assuming that they are not associated or correlated with the vaccination status and take them as a proxy. But there are many, many biases to this. And just to, again, we're short on time, so I'm going to run fast here, but this method will show that the vaccine is efficacious, even when the vaccine has neutral impact on COVID and will make you more vulnerable for other cold viruses. Something that, by the way, the latter is something that there is some evidence to it. So this method cannot even distinguish between a situation when the vaccine maybe have adversarial negative impact, right, and a situation when the vaccine is efficacious.

[5:13:01]
So, again, I'm not trying to say what the answer is, and I'm not trying to judge the specific results or trying to infer here what the specific efficacy of the vaccine is. But I'm making a point here that the biases are all over the place, and this is really not a reliable methodology. And unfortunately, we are using it and ignoring a lot of other approaches that could be used. Some we are ignoring because maybe limited access to data that we need to address. But that, and again, I'm very happy that the FDA declared that they have intention to run randomized control trials. I think it's due, and we have to get reliable data on efficacy. Just as a side point, the RCTs that we know we have for the mRNA vaccines did not show benefits for all-cause mortality and all-cause hospitalization. In fact, there's some evidence to suggest that maybe they caused harm in that respect.

[5:14:03]
Okay. Other concerns. We are concerned about the short-term protection that these vaccines are providing. Even the most optimistic assessments talk about several months, and that's it. And given the fact that COVID, the SARS-CoV virus has two waves in a year, that's kind of a major reason for concerns. And finally, we are concerned by emerging literature that suggests that especially repeated vaccination, but that maybe any vaccination can increase the vulnerability to other respiratory virus. That is something that even analysis of the children, meta-analysis of all the children trials that were done suggests that they were more vulnerable to lower respiratory infection, tract infections, including RSV, which is a far more severe virus when it comes to children. So all of this makes us very, very concerned.

[5:15:02]
And maybe just end up by slide, again, the slide that we saw today. And I just want to point out that the curve, the red curve, is much, much lower than the previous year curves. The red curves represent the last season. So without change, without significant change in vaccination rates, we see a major decrease in the incidence of COVID, which suggests that other factors are really driving this virus, fortunately, to be less virulent and cause less harm. And this is good news. This is good news. And it's definitely something that we need to continue to monitor because the trend can change. But I think we need to also acknowledge the fact that we have consistent over the last couple of years, we have consistent trends that have lower virulence and not necessarily related to vaccination rates. I want to move and talk about some safety concerns. I think that was another thing that the workgroup members felt the CDC currently does not appropriately acknowledge several safety concerns and uncertainties.

[5:16:11]
I want to point out, in particular, outcomes and prognosis of myocarditis and cardiovascular adverse events, clinically documented prolonged vaccine injuries, specifically post-vaccine syndrome, and multiple documented unintended mechanism of actions of the mRNA vaccines and seemingly regulatory violations. I want to take a few minutes to talk about tests from myocarditis because that was something that was not discussed. What we see here, this is published literature from the U.S., two cases, three days and four days post-Pfizer dose two, analyzed by pathologists from Yale University and a team. It's basically saying the findings are utterly not typical to viral infection that causes myocarditis.

[5:17:01]
And they conclude that in all likelihood, these kids died in sleep because of fulminant myocarditis after vaccination. The CDC response to that is that they don't believe that necessarily this is happening from the vaccine because they found in one of them virus, some other virus and another one, a bacteria. And the response of the pathologists is that essentially this is not typical to viral infection, very different pattern and the other bacteria is something that is typical to post-mortem kind of autopsies. I have to stop here and I want all of us to ask, do we have a culture of safety? And what would it take for us to acknowledge that there is a problem when at the same time, someone that died two weeks after a positive COVID infection will be considered a COVID-associated death.

[5:18:01]
Whereas kids that died three days from a known mechanism of the vaccine in their sleep are not counted as vaccine deaths. I think that I hope that we all can agree that there is a problem here. And I think we need to think we need to adopt a more safety culture that really acknowledge that when there are problems. Again, this has nothing to do whether we need to take the vaccine or not. This has to do with acknowledging what the risks are and be truthful to parents and patients about what are the risks. And these kids die from subclinical myocarditis. And I want to point out that we have two studies that tested people before and after vaccination. And in both of them, between two to three percent of the people that took the vaccine had hallmark biomarker of a heart damage and heart attack. This is namely elevated troponin. This is published literature.

[5:19:02]
And moreover, published literature from other countries suggests that you can actually die from that. And that's actually consistent with long term literature about subclinical myocarditis. We currently completely ignore this aspect. And I want to emphasize two things here. First, look at the number of males and females because we kind of adopted the perception that this is only a problem for boys. This suggests to me that potentially we need to recalibrate our perception because it seems that females are also affected. And the other thing that I would like to emphasize here is that subclinical myocarditis can cause death. It's proven. It's not questionable. And nevertheless, we are not talking about this with patients and we are not stating that risk. And the last thing I want to say about this, that it's well known, well known in the literature, that the long term prognosis of myocarditis is problematic.

[5:20:05]
Now, we don't know what will be the specific prognosis of these individuals that were harmed by the vaccine. But I'm not sure we have any monitoring system in place to actually monitor that or even understand the scope of the problem. And that to me, again, that's to the work group was a big problem. The other thing I want to say that the injuries of PVS are prolonged, debilitating and involve diverse symptoms and conditions that may be overlapping with long COVID injuries. The symptoms include the range of conditions. I'm not going to get into this. The doctors that care for them that are part of the work group can classify this much better than me. But I do want to say something very important. We don't know what the frequency of PVS, but one thing is clear that our current system that really looks on diagnosis is not going to capture them.

[5:21:00]
And the reason is that there is no diagnosis to these conditions and the symptoms are so diverse. Some of them actually are common to transient symptoms that you have after vaccination, but just prolonged. And they continue for years. And this is just a recent paper, still unpublished, but very fascinating by Professor Christine Stable Ben that actually describes why we should be very concerned that our current approaches to safety are not going to capture those. So this is taken from the CDC website. It explains to people how the mRNA vaccines work. And it tells them that they clear the mRNA and the vaccine clears from the body shortly after vaccination. That's not true. And we heard the lecture, the fascinating talk presentation from the people in the work group. Again, I want to go back to a culture of safety. One of the things when you think about safety of complex systems or products, if they don't work as intended, that's by itself a safety concern.

[5:22:08]
And you have to actually be very concerned about that, even without knowing what the specific outcomes or consequences of that would be. And we have a range of things on the mRNA platforms that really suggest that it doesn't work as intended. And I think that we all have to consider that when we think about the safety of these products. Vaccination and pregnancy was a highly debated thing among the work group. I think that there were people that felt that we should recommend pregnant women to vaccinate for the reasons that people mentioned here. But most of the people felt that there is strong reason actually not to recommend them. I think that after all, we decided not to bring it to a vote today. But we do hope that the FDA and the CDC will look much more carefully into this, because most of us are extremely concerned about the safety and the lack of robust evidence, both on safety and efficacy for not only pregnant women, but their babies.

[5:23:10]
This is something that I think really deviates from any standards that we knew in the past. Vaccine specific recommendation, this is something very plausible. We didn't feel that we have time and enough data to make those kind of distinguished recommendations. But I do want to point out two things. There is one study that suggests that the adenovirus vaccines that were part of the initial launch of the vaccines in 2021 actually did reduce all cause mortality in clinical trials, whereas the mRNA vaccine didn't. And the other thing is that there are also multiple studies that show that Moderna provides higher protection against COVID and lower rate of adverse events. This is, again, published data from multiple studies from the VA and other places.

[5:24:00]
So I think that going forward, we want to encourage the FDA and the CDC to really think about more nuanced recommendations, including considering vaccines that potentially are not currently authorized in the U.S., because we want to find the best tradeoff of risk and benefits for patients. I do want to talk about public trust, because I think it's a critical thing. I don't think that the public currently believes to the narrative of safe and effective. This is kind of a recent poll, and this is just building up on prior polls. And the trust is not just a problem among the public. It's among the people. We saw this slide today. Ten percent, eight percent of health care workers believe the current recommendation. What does it tell us about our ability to come and continue to forcefully recommend these products when the very same people that are supposed to administer them and recommend them show by their legs, by their action, that they don't trust and don't take them?

[5:25:06]
I think that this is something that we all need to think about. Okay. So I want to quickly kind of talk about this more specific kind of things that we wanted to bring to the table today. And the first thing was the informed consent. We feel that most of us felt were very concerned that the existing administration processes of the COVID-19 vaccine products do not ensure a meaningful informed consent. We were very much relying on a recent paper that talks about this and really kind of states the ideal informed consent, but also really points out that the vaccine information statement that is basically the basis of most of the informed consents in most states currently for vaccination does not necessarily in its current form and the current way it's being administered play that role,

[5:26:02]
play an effective role to facilitate an appropriate informed consent. We feel very strongly that that should be addressed. And that kind of led to our recommendation that the CDC engages in effort to create more consistent and comprehensive informed consent processes. And as part of that considers adding language accessible to patients and medical providers to describe the following risks and uncertainties. The first one is current assessments regarding the protection provided by COVID-19 vaccines and especially seasonal COVID-19 boosters against severe outcomes. For example, death, hospitalizations and long COVID are of low quality. At best, the additional protection provided by seasonal booster is moderate and of short term. Second, there is evidence that repeated seasonal mRNA boosters cause acquired changes in the immune system and may be associated with increased vulnerability to future infections including SARS-CoV-2 and other respiratory viruses.

[5:27:04]
These risks as well as potential risk of autoimmunity, chronic inflammation, immune tolerance and impaired immune surveillance including immune fatigue or suppression are not currently well understood. Third, there are documented deaths from symptomatic and subclinical myocarditis, pericarditis and potentially other cardiovascular conditions post COVID-19 vaccination including of healthy children with probable causal relationship to the mRNA vaccines. This risk is likely relatively small but currently not well understood. Fourth, clinical reports demonstrate that in some cases COVID-19 vaccines can cause prolonged and debilitating post vaccine syndrome, PVS. The injuries associated with PVS involve diverse symptoms and conditions, many overlapping with long COVID injuries. Some of the observed symptoms and conditions may include insomnia, chronic pain and fatigue, dysautonomia like POTS, immune dysregulation and deficiency, autoimmune disorders, severe neuropathy and neurodegenerative conditions, cardiovascular and neurovascular injuries and severe clotting.

[5:28:17]
The frequency of PVS and related risk factors are currently not well understood. Five, there is evidence that in some individuals vaccinated with mRNA vaccines, the resulting spike protein, the mRNA and the nanolipid formulation components persist in different body organs including lymph nodes and the heart for a prolonged period of months and possibly years in some patients. Prolonged and persistent exposure to spike mRNA and nanolipid practicals is associated with post vaccine syndrome injuries as well as potentially other side effects that are currently only partially understood.

[5:29:00]
Six, the safety and the efficacy of COVID-19 vaccines during pregnancy have never been tested in appropriately powered randomized clinical trials. In one randomized clinical trial, there was observed numerical imbalance of higher number of babies with congenital malformations among those born to vaccinated women. Now, I just want to clarify the context here. We are not expecting the CDC to use this specific language but we really encourage the CDC both for the vaccine information statement as well as other communication channels to find the right language to communicate these risks and uncertainties to patients and medical providers so we can actually have the appropriate informed concerns and discussion of risk and benefits that are realistic to the current knowledge and the current gaps in knowledge that we currently face. The last thing I want to say is to talk a little bit about the guiding principles that we took in order to kind of recommend the specific policy recommendations about who should be vaccinated and what form.

[5:30:05]
Our first assumption was we want to access within the authorized FDA population, especially benefits and risk and uncertainty must be communicated as part of informed consent. We debated mostly between individual-based decisions and group recommendations and I think that the majority of the work group felt strongly, but in a second we'll hear the minority opinion as well, the majority of the group felt that individual-based decision is appropriate and specifically we feel that these vaccines should now be prescribed as a prescription and I want to say a few words about why. I think that there are two major reasons why. One is that when you try to quantify the risks and benefits, you very quickly and we also already saw that in our discussion today, you get to a lot of nuance where you had prior infections recently, what is your immune response currently, what exactly are your comorbidities, how your comorbidities increase your risk for COVID versus risk from vaccination.

[5:31:13]
We feel that this is too nuanced and since we are not talking about now an emergency situation, we think that it's appropriate to bring it to something that is being discussed between a physician or medical provider and a patient as part of a prescription. Now, the other thing that causes us to feel like that, that there is also nuances of what products to use and also what are the uncertainties and how they are being communicated and I think the flip side of that, there is kind of a lot of concern about access because you just heard that, for example, many people take it in the pharmacy. I don't want to respond to that. If you think about who is supposed to take those vaccines, these are people that are presumably high risk, have health conditions, and take other drugs, other prescribed drugs.

[5:32:09]
So they are by design or currently are engaged with their physicians with respect to different prescriptions, with different care, with different diagnostic and we don't feel that for those patients it would be something unreasonable to expect that there will be a discussion around whether or not they should be taking a seasonal booster or new vaccines. As I said, there was a minority sentiment in the workgroup and we're going to hear soon from three colleagues, Professor Bernstein, Professor Miklis, and Professor Perlman, that I truly appreciate their engagement in the workgroup and while we did not agree on all the things, they were instrumental in driving the discussions in the group.
[Martin Kulldorff]
Thank you for that. Dr. Bernstein, please.
[Dr. Bernstein]
Thank you.

Minority Opinion on COVID-19 Vaccine Recommendations by Dr. Bernstein

[5:33:09]
It's an honor to be presenting today and we appreciate this opportunity to present our thinking. Drs. Perlman, Miklis, and I are sharing our reflections on the recent workgroup considerations. None of us have any conflicts of interest. Next slide, please. This slide demonstrates the simple, stable recommendations can increase vaccine coverage. As you can see, as vaccine coverage increases, the red dotted line, disease incidence decreases over time, the blue line. It clearly highlights the delicate balance between perceived benefits and risks of vaccination. And now you note that this balance is linked closely to vaccine acceptance, as we've heard from others.

[5:34:04]
And you can see when vaccine coverage decreases because of loss of confidence, outbreaks happen and we heard earlier about the measles outbreak that we all experienced. Next slide, please. Vaccine development is a long and challenging process, often lasting many years and involving the combination of both public and private partnership. Operation Warp Speed was a huge success as COVID-19 vaccine continues to work incredibly well. Most importantly, safety is carefully evaluated at every step of vaccine development, even after the vaccines have been licensed and implemented. Next slide, please.

[5:35:04]
Next slide, please. Thank you. The safety monitoring that has been conducted by the CDC has been historic and it was needed because of the pandemic. We have talked about these different groups and I'll focus specifically on VAERS, the Vaccine Adverse Event Reporting System. This is the country's early warning system for vaccine safety. Everyone needs to appreciate that anyone, the public, providers, anyone can submit a vaccine experience to VAERS. But it is important to understand that VAERS does not identify causality. Rather, it is a signal detection tool and it's valuable in that way because then it can be explored in more depth.

[5:36:05]
Next slide, please. Did I lose my slides? Are my slides projecting?
[Mina]
We're working on it.
[Dr. Bernstein]
Thank you.

[5:37:34]
Dr. Levy, is this problem because we had the minority opinion?
[Dr. Reza Flevi]
No, I can tell you, I was cut by half of what I was supposed to say. So I guess we cut everywhere. But you remind me, I have six kids and all of them think that I'm unfair to them. So I tell them I'm unfairly to all of them together.
[Dr. Bernstein]
We have the slides, so please continue. Great, thank you.

[5:38:00]
COVID vaccine, as I mentioned to you, COVID-19 vaccine safety has been extensive, continuous, and is ongoing. And you can see the different elements here on this slide. I do want to point out that the pregnancy registry maintains longitudinal assessment of both maternal and infant outcomes. And rapid cycle analyses monitor a small set of pre-specified outcomes to detect potential concerns that warrant further investigation. Next slide, please. COVID-19 vaccine is effective providing additional protection against COVID-19 associated ER visits, urgent care visits, hospitalizations, and critical illnesses. As you can see on this slide, it's among children, similar with other age groups, hospitalization as well.

[5:39:03]
And remember that some of the comparisons are for those that have been vaccinated versus those that have not been vaccinated. Vaccine effectiveness should be interpreted then as an additional benefit of COVID-19 vaccination in a population that has high levels of infection-induced immunity, vaccine-induced immunity, or both. Next slide, please. There are three pillars of the ACIP. Science is front and center, but there is much more. These three guiding principles help inform the decision-making of the ACIP. Science supports the COVID-19 vaccine works. It is incredibly safe and effective. But the vaccine also must be easily accessible for everyone who wants it.

[5:40:01]
Next slide, please. Shared clinical decision-making and a need for provider prescription create barriers to COVID-19 vaccination. Healthcare providers always discuss vaccination pros and cons with their patients. And in principle, clear recommendations and shared clinical decision-making reach the same goal. However, with routine age or risk-based recommendations, the default decision is to vaccinate all patients that consent. Recommendations with shared clinical decision-making are perceived differently. Shared clinical decision-making has no default. Vaccination is often interpreted as optional. Plus, the need for a provider prescription creates an incredibly unnecessary step to receiving a vaccine and does not effectively target those at high risk.

[5:41:15]
Next slide, please. We also need to remember that there are 330 million people in the United States and there are more than 18 million children under the age of five who are more likely to be infection-naive and or unvaccinated. These are important considerations. Next slide, please. COVID-19 vaccine is safe in children six months to 11 years. And as noted on the red box, there are no confirmed myocarditis cases in children aged less than five years identified in VAERS or the VSD.

[5:42:05]
And rapid cycle analyses in the VSD demonstrate no increased risks for 22 other pre-specified outcomes following COVID-19 vaccination. Next slide, please. Our CDC colleagues eloquently updated this data. This was from the June meeting. And as you can see, this figure shows that the rates of COVID-19 associated hospitalizations are highest among infants and children less than two years of age. The purple curve are those that are less than six months and the blue curve are those that are six to 23 months. But you will notice that their rate per 100,000 population is still notable. And remember that a small percentage of a large number of children is a large number.

[5:43:07]
Next slide. COVID-19 causes severe disease in infants under six months of age. As shown on this slide, hospitalization rates for infants under six months of age are comparable to those 65 to 74 years of age. As we learned, and it was just updated earlier, this young group has the highest rate of COVID-19 associated hospitalization among the entire pediatric population of more than 18 million. Next slide, please. Pregnant women who receive COVID-19 vaccination pass their protective antibodies to their newborns and young infants. We know that's effective with RSV vaccine antipartum.

[5:44:03]
We know that works with influenza vaccine antipartum. We know that that works with Tdap antipartum. These are things that protect young infants who are not able to be vaccinated. This is very important because, as we said, infants under six months of age have the highest rate of COVID-19 associated hospitalization. Next slide. COVID-19 vaccine safety during pregnancy has shown no increased risk of these maternal outcomes, these pregnancy outcomes, or these infant outcomes. They are being closely monitored and should continue to be closely monitored. But we also recognize that the benefits far outweigh any risks. Next slide, please. This was mentioned earlier about immunosenescence.

[5:45:02]
Older people do not have as good an immune response as when they are younger. So those 65 years and older notably benefit by getting vaccinated, and I fit into that 65 and older category. Next slide, please. So these are the key messages for consideration that Dr. Perlman, Maglis, and myself discussed with our COVID-19 workgroup. The ACIP pillars are not driven by science alone. That is front and center. But implementation and ethics are additional important considerations for vaccine accessibility. Simple, stable recommendations can increase vaccine coverage. COVID-19 vaccines are highly safe and effective.

[5:46:01]
Or if we don't want to say safe and effective, they work. Shared clinical decision-making and the need for a provider prescription create unnecessary steps to receiving a vaccine and do not effectively target those that are at high risk. Next slide. COVID-19 vaccination rates in the younger pediatric population are very low. That's true. And many of them have not been vaccinated yet at all. And many of them are infection-naive. So the primary COVID-19 vaccination series needs to be available to those millions of children. Antepartum vaccination especially helps protect infection-naive newborns and young infants under six months of age. Older people do not make as good an immune response as when they were younger.

[5:47:04]
So in summary, COVID-19 vaccination matters for pregnant women, pediatric patients, especially those less than two years of age, people 65 years and older, those of any age with a weakened immune system or chronic medical conditions, and anyone who feels they want protection for themselves or their families. Thank you for your time.
[Martin Kulldorff]
Thank you very much. And I presume that presentation was from all three of you? Yes. Drs. Bernstein, Perelman, and Maglis. We will now hear the proposed recommendations from Dr. Levine.
[Dr. Reza Flevi]

[5:48:15]
We are going to propose multiple votes.

Proposed Recommendations for COVID-19 Vaccines

Maybe you can advance the slides. Okay. It is a sense of the committee that the CDC engages in an effort to promote more consistent and comprehensive informed consent processes, and as part of that considers adding language accessible to patients and medical providers to describe at least the six risks and uncertainties included in the workgroup chair presentation. That's what I was just talking about. So that's going to be the first vote. The second vote, it is the sense of the committee that the state and local jurisdictions should require prescription for the administration of COVID-19, of a COVID-19 vaccination.

[5:49:05]
That's kind of the second vote. The third vote, it is the sense of the committee that in conversations with patients before COVID-19 vaccinations, authorized healthcare providers discuss the risks and benefits of the vaccination for the individual patient. And the discussion should consider known risk factors for severe outcomes from COVID-19 such as age, prior infections, immunosuppression, and certain comorbidities identified by the CDC, and include the discussion of the potential benefits and risks of vaccination and related uncertainties, especially those outlined in the vaccine information statement as part of informed consent. And the next one. The pediatric and adult immunization schedule for administration of FDA approved COVID-19 vaccine should be updated as follows. Adults 65 and older, vaccination based on individual based decision making, also known as shared clinical decision making.

[5:50:07]
And then individual six months to 64 years, vaccination based on individual based decision making with an emphasis that risk benefits of vaccination is most favorable for individuals who are at an increased risk for severe COVID-19 disease, and lowest for individuals who are not at increased risk, according to the CDC list of COVID-19 risk factors. These are the four votes that are those four words.
[Martin Kulldorff]
Thank you very much for that. One important part of ACIP meetings is to receive public comments from the public. That is very important. And it's actually also a legal requirement. So we will now go to the public comments.

Public Comments: Robert Blancato

And I think we have 10 speakers.

[5:51:05]
And the first one is Robert Blancato.
[Robert Blancato]
Yes, my name is Robert Blancato and I am the executive director of the National Association of Nutrition and Aging Services Program. We are the leading organization advocating for community based nutrition programs for older adults. I have personally been advocating for broad affordable access to vaccines for this population for decades, because vaccination is the most effective and cost efficient way to protect the health of the aging and to reduce the need for more serious interventions like hospitalization. In just the past decade, the progress that has been made in the development of vaccines that specifically protect older adults has been astounding. Americans are older today than ever before. The number of Americans age 65 and older is expected to increase from 58 million to 82 million by 2050. Ensuring these Americans remain healthy and thriving in large part depends on access to vaccines.

[5:52:05]
To this point, we were very happy to see Secretary Kennedy confirmed the CDC guidance for the RSV vaccine earlier this year to include individuals age 50 and over who face a higher risk of serious illness. We know that many Americans and particularly people of color begin to suffer from chronic disease and illness before the age of 65. Guidance that allows for earlier access to vaccines will give these Americans a better chance at a healthier and longer life. Just as Secretary Kennedy recognized with the RSV vaccine, we urge this committee to do the same with the COVID-19 vaccine because black and Hispanic populations are disproportionately impacted by this virus at a younger age than white populations. The median age of black patients being hospitalized for COVID-19 is 60, and for Hispanic patients, the age is even lower at 57. This is compared to the median age of white patients at 71. So it stands to reason that lowering the age-based recommendation for the COVID-19 vaccine below age 65 would keep more Americans out of the hospital and reduce overall cost to the health system.

[5:53:10]
We also urge you to consider the priorities outlined in a letter led by the Alliance for Aging Research, which was sent to ACIP yesterday and signed by 75 organizations, including our organization. Our organizations are speaking with a united voice on behalf of a wide range of Americans who want to ensure the guidance on these lifesaving vaccines is clear, broad, and equitable. Not everyone across the country will decide to receive every vaccine available to them, but everyone in this country should have the choice to receive a vaccine that is safe and effective and can protect their health. This also requires ensuring adequate vaccine supply at pharmacies where a large portion of Americans receive their vaccines. Lastly, I want to encourage the CDC to consider including committee representation of experts who have a background and experience in treating older adults.

[5:54:02]
Vaccines support healthy living across the full lifespan, so recommendations for their use should also represent the expert opinions of those serving Americans in all stages of life. Thank you for the opportunity to present and provide these comments.
[Martin Kulldorff]
Thank you very much. Ms. Nisa Shafi?
[Nisa Shafi]
Good afternoon.

Public Comments: Nisa Shafi

My name is Nisa Shafi, Director of Advocacy at the Allergy and Asthma Network. I appreciate the opportunity to present before the Advisory Committee on Immunization Practices in staunch support of vaccine availability and access for consumers across all health insurance coverage types. Allergy and Asthma Network is a nationwide nonprofit patient advocacy organization that represents over 100 million Americans impacted by asthma, allergies, and related conditions like COPD. Individuals living with these chronic conditions are at a greater risk of developing complications from infectious diseases such as influenza, pertussis, measles, mumps, rubella, COVID-19, and respiratory syncytial virus, or RSV.

[5:55:09]
These conditions can exacerbate symptoms, leading to serious lung complications. Allergy and Asthma Network is deeply concerned about the recent changes to the national vaccine recommendations, which were originally shaped to emphasize the role of vaccines in attaining herd immunity, reduce complications in death, and mitigate public health disasters. Recent efforts in some states to hamper consumers' ability to receive COVID-19 vaccines without a prescription derails these immunization victories from Operation Warp Speed and will cause a ripple effect of access challenges, a spike in disease burden, and compromise herd immunity and increase health expenditures. Patients with asthma and other respiratory diseases rely on their vaccine administration to be covered by their insurance. ACIP's recommendations significantly influence insurance coverage for vaccines, as private insurers, Medicare Part D, and Medicaid are all typically required to cover vaccines with an ACIP recommendation at no cost.

[5:56:10]
We are concerned that any changes to the recommendations will result in vaccines not being covered by insurance and will reduce or prevent people from getting the vaccinations they need. In 2023, over 3,600 people died from asthma, with African Americans experiencing three times the rate of disease burden than non-Hispanic white Americans. Nearly 49% of adults under the age of 65 report cost barriers to asthma care, and asthma costs the nation nearly $82 billion in annual healthcare costs. We must not introduce undue barriers that prevent people from fulfilling this vital duty to protect themselves, their families, and their communities. Allergy and Asthma Network urges the Advisory Committee on Immunization Practices to maintain effective public health messaging and strong vaccine recommendations. Without intervention, these measures will jeopardize guidance on other critical vaccines that benefit people with chronic respiratory conditions, like asthma and COPD.

[5:57:08]
Thank you so much for the opportunity to present testimony today and for the work that you're doing.
[Martin Kulldorff]
Thank you very much. And the next speaker is Mr. Noah Luis Ferdinand.

Public Comments: Noah Luis Ferdinand

[Noah Luis Ferdinand]
Yeah, hi. My name is Noah Luis Ferdinand. I'm the Communications Coordinator at Voices for Vaccines. We're a national nonprofit that helps families find evidence-based information about immunizations. I wanted to comment on two of the issues being discussed at this current ACIP meeting. First, I appreciate ACIP's decision to more carefully review the evidence on the Hep B birth dose. The evidence collected and reviewed by previous ACIP convenings is clear. Hepatitis B is a safe vaccine, and that timely birth dose protects newborns from what is an incurable chronic infection that creates a one-in-four risk of liver cirrhosis and cancer.

[5:58:05]
Hepatitis B was the first cancer-preventing vaccine, and to maximize that cancer protection, the newborn must receive the vaccine quickly within the first day of life. That routine vaccine at birth is recommended as not all mothers are tested for Hep B, as has been discussed here, and of those tested, results are not always available at the time of birth. It is not proven to be a public health strategy that works to just do the testing. When you revisit this issue, I would ask that you draw from the predominant experts in hepatitis elimination who have made great progress worldwide. This includes John Ward, who is now the head of the Coalition for Global Hepatitis Elimination and the former director of the CDC's Viral Hepatitis Division. He submitted a written comment, which he asked me to mention here. The second issue I wanted to touch on is COVID-19 vaccine recommendations. At Voices for Vaccines, I frequently work with the parents of immunocompromised children who go to great lengths to keep them healthy, including getting seasonal COVID vaccines, which they're really getting for their children or other family members who might be vulnerable.

[5:59:11]
Any vote to not recommend or remove COVID-19 vaccines for adults from the DSC program, I understand that's not being discussed today, but now or in the future, would remove or limit that option for them in a country which, if we're being honest, does not really have a good plan to protect the immunocompromised from COVID. It's not something that I necessarily have to worry about as a healthy 26-year-old man, but I understand that there are people for whom this is really important. So I would really just encourage you not to limit access or to consider access in the future. I also think that much of the discussion of COVID vaccine safety today has been of questionable use to the public. I am grateful to the agency presenters who had very targeted and clear presentations, but some of the other discussion was based on speculation or questionable data. For example, the implication that COVID vaccines might change your DNA was based on a study of cancer cells, which by definition are cells not functioning normally, in a Petri dish, which I just think we should be using higher quality evidence when we're making decisions for the nation's health.

[6:00:09]
And so I would just urge a little bit more quality when making such claims or implications. It was also suggested that COVID vaccines may cause cancer. I'm obviously very sympathetic to anybody affected by cancer, but there really is no evidence to support this. Early onset cancers have been rising, as was noted here, but that's a decades-long trend going back before COVID even existed. My own beloved uncle unfortunately passed away just a few years ago from brain cancer, so I understand just how serious of a claim is being made when we say that the vaccines might cause cancer, and I think that's when you really have to bring solid evidence to make before kind of putting that out to the public. Thank you.
[Martin Kulldorff]
Thank you very much. The next speaker is Dr. Noor. Mrs. Candice DeMatteis.
[Candice DeMatteis]
Good afternoon.

Public Comments: Candice DeMatteis

I'm Candice DeMatteis, Vice President of Policy and Advocacy for the Partnership to Fight Infectious Disease.

[6:01:05]
We're very concerned about recent changes to ACIP membership and movement away from the evidence to recommendations processes, and most importantly, what those changes mean for access to vaccines and the public's health. Historically, ACIP's strength resulted from its rigorous deliberative processes, moving from evidence to recommendations by engaging a variety of experts to examine the research, and that's what delivered recommendations grounded in evidence that people could trust. Historically, becoming an ACIP member involved more than a year of careful vetting, reviewing independent expertise, committee needs, professional qualifications, and conflicts of interest. Often voting members started on working groups, gaining critical experience and insight into the detailed processes that informed ACIP deliberations. Those working groups allow experts from multiple fields to review scientific and clinical data, including fully investigating adverse events, before sharing options with the ACIP for consideration.

[6:02:02]
Traditionally, that's where data were examined instead of bringing up unvetted research and anecdotes during the course of discussion. Every current ACIP member was appointed outside of that process. Respectfully, that does not build trust or confidence. Yesterday's revelation that revisiting the hep B birth dose arose not because of new evidence of risk reduction or safety issues, but because of vaccine skepticism was shocking. That is not gold standard science and further erodes trust. Tabling that discussion today was the right decision. Your recommendations affect access and choice to vaccines across America. Physicians rely on ACIP recommendations and insurers and public health programs depend on sound recommendations to determine coverage. Recent changes at ACIP have so tarnished trust that several states are moving to divorce their vaccine policies from ACIP recommendations. That will mean disparate protection and access depending on the state of residence.

[6:03:03]
The former recommendations for MMRV and existing ones for hep B reflect the rigorous evidence-driven process that should guide ACIP decisions. Changes outside the evidence-to-recommendations process will lead to restrictions and access that will increase risk, limit coverage, and reduce access for families trying to keep themselves and their children healthy. On COVID, last year alone, polls estimate that more than 55 million American adults said they would definitely get a COVID booster. Their reasons vary and often include reducing risk to others. They should be able to make that choice. We urge you to recommit to and follow the processes foundational to ACIP's leadership.
[Martin Kulldorff]
Thank you. Thank you. And now Dr. Daniel Crawford.

Public Comments: Dr. Daniel Crawford

[Dr. Daniel Crawford]
Hello. Thank you for this opportunity to speak today. My name is Dr. Daniel Crawford. I've been a practicing neuroscience clinician specializing in childhood seizures for the past 14 years and a graduate nursing instructor for the majority of that time.

[6:04:06]
I'm the immediate past president of the National Association of Pediatric Nurse Practitioners. Nurses have been recognized as the most trusted profession in America for 23 consecutive years. I can't imagine the U.S. vaccine development delivery system without them. Nurses trust vaccines. On behalf of more than 70,000 trusted nurse practitioners caring for our nation's children who ensure their own families are vaccinated, I want to be clear. Vaccines save lives. Americans have trusted vaccines and the science experts at CDC and ACIP for decades because of the careful, evidence-based, and thorough manner of deliberating a vaccine science question. After observing the chaos of Secretary Kennedy's replacement committee yesterday, I fear that trust is gone. The HHS secretary has called for gold standard science and radical transparency and medical freedom. And instead we're seeing the opposite. The previous ACIP had a clear vaccine science question that had been posted and reviewed for months in work groups of specialists who used new data or clinical evidence to deliberate.

[6:05:09]
ACIP would populate its work groups with practicing clinicians and researchers with deep vaccine knowledge. The prior work groups respected clinical experts partnering with CDC subject matter experts, brought their hard work to the ACIP voting members, and used methodological analyses in the evidence and recommended framework to discuss the specific question in a structured manner. The current committee removed experts from working groups. What we're seeing these past two days from the replacement committee was predetermined ideology with individuals appointed just hours prior who ignored subject matter experts and comments from clinical liaisons who care for patients. The replacement committee struggled to give rationale for the very reason hepatitis B vaccine was even on the agenda to the point it was tabled. Hepatitis B has one of the best safety profiles of all vaccines and the birth dose has been used since 1991, preventing 99,000 deaths.

[6:06:04]
The recommendation needs no changes. For the MMRV discussion, the freedom for parents and clinicians to choose was lost yesterday by the vote to remove the combined MMRV to children under four who want to lower the number of pokes, understanding the low and mild risk of febrile seizures. Parents are now confused and today questioning the MMR vaccine. The replacement committee took parents' medical freedom away without new data and infused fear that is already causing parents to question this long proven safe and effective immunization. For COVID-19 vaccine, the trusted work group and ACIP committee would have reviewed COVID-19 vaccine data over the past year and presented at the June meeting, giving clinicians time to prepare for the busy back to school and fall vaccine season that we are now in. Because of the lack of trust in the replacement committee, our organization is now relying on outside experts in the vaccine integrity project, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.

[6:07:03]
And their review data has showed COVID-19 is safe and effective in pregnant women and all children and should especially.
[Martin Kulldorff]
That was over the three minutes, so the next speaker is Mrs. Patricia Armstrong.

Public Comments: Patricia Armstrong

[Patricia Armstrong]
Hello, good afternoon and thank you for the opportunity. I'm just a 73 year old woman with no medical or scientific background who wants her children and grandchildren and further generations to grow up safe and in a healthy world. I and many others are frightened. There is currently a war against vaccines, which save lives. But now they're called dangerous, poison, cause of autism, carry biomarkers or alter our genetics. And because of this war, vaccination rates have been dropping.

[6:08:00]
This makes our country and indeed our world less safe to live in. One result of this war is measles, once eradicated in our country, now making an unnecessary comeback. Even worse, our government clearly does not seem invested in vaccine science, developing new vaccines or even providing the existing vaccines to the public. How to combat this? Get the public educated and involved. Then once educated, encourage them to contact their representatives demanding access to all vaccines and a new investment in vaccine development. And what are these people afraid of? Points one and two formaldehyde and aluminum and vaccines. Why do I have to read on my own that a single pair contains more formaldehyde than any vaccine? And I wonder how many people don't know this. And is aluminum still used as an adjuvant since the creation of three or four new ones?

[6:09:01]
Altering our DNA is number three. I just learned a few days ago that after doing its job, the mRNA vaccine breaks down and leaves the body within five days to two weeks. And it's designed with no chance to alter our DNA. Why wasn't that explained when it started getting used for COVID? Four, causing autism. That was debunked years ago. And the doctor who spread that thought has been, I don't know what you call it, defrocked, if he's a priest, because he faked the data. And biomarkers, a 5G marker is too large to fit through a vaccine needle. So it's not physically possible. Our institutions of health and science need to get better at informing the public and making the information easy to understand and disseminate among their friends and families. Make newspaper or magazines article easy to understand with illustrations. Maybe ask a celebrity to interview you for free as a public service.

[6:10:02]
To get people's attention. Use all forms of social media with fun adult cartoons as illustrations and videos. Ask for discounts or freebies from videographers or illustrators to save money to accomplish these things. Get interviewed by honest podcasters, both conservative and liberal. The scientific communities need to move effectively, fight back against disinformation being spread, and it needs to happen before more people die from their own ignorance or from the ignorance of others.
[Martin Kulldorff]
Thank you for those comments. That was three minutes. Greatly appreciate it. And now it's Dr. Stephen Furr. Dr. Stephen Furr. We will go then to Dr. Richard Dang.
[Dr. Richard Dang]
Hi, my name is Dr. Richard Dang, and I'm a pharmacist and associate professor at the University of Southern California.

Public Comments: Dr. Richard Dang

[6:11:07]
Americans deserve clear, transparent, and evidence-based recommendations from ACIP, CDC, and HHS that preserve access and respect individual medical freedom so that people who want protection can get it and we can keep America healthy. Requiring a provider prescription for a COVID vaccine is unnecessary. We need practical access points across the healthcare system. Pharmacies are among the most accessible sites of care, with 90% of Americans living within five miles of one. And based on IQVIA claims data published by the CDC, pharmacies actually administer 90% of the total COVID vaccines in the 2024-25 season. People chose a convenient location and time, used their insurance, and were vaccinated without extra burden. Today, this season's delay of ACIP recommendations, the issuance of recommendations without credible evidence by HHS, and the state variability in tying pharmacists' authority to prescribe and administer vaccines to the public have led to confusion and barriers for Americans.

[6:12:12]
From the 2020 and 2021 rollout of COVID vaccines, we have learned that clarity, consistency, and timeliness in recommendations have real-world implications. I respectfully urge ACIP to 1. Approve schedules and issue recommendations that are based on the best available evidence and avoid actions that limit choice or access. 2. Uphold the gold standard process. Use the evidence-to-recommendations ETR framework and grade to keep recommendations anchored in evidence and transparency. And 3. Maintain and protect choice for Americans who want to protect themselves or their family members from illness, transmission, and long-term complications from infection. With over 13 billion doses administered worldwide, COVID vaccines have been the most closely monitored of any previous vaccines and have demonstrated safety and effectiveness across the lifespan.

[6:13:05]
Based on current evidence, anyone 6 months and older who desires protection should be able to receive the vaccine without added restrictions. For those who want to exercise their medical freedom and choose to get the vaccine, allow them the opportunities to do so. Pharmacists have the knowledge and training to work with patients who wish to receive a COVID vaccine and to evaluate the risks and benefits. Requiring a prescription because of ambiguous or non-evidence-based recommendations would strain an already stressed healthcare system, create barriers for patients, and risk deterring people who seek vaccination. Please help keep America healthy by preserving clear, evidence-based guidance and real-world access to these life-saving vaccines. Thank you for the opportunity to provide these comments today.
[Martin Kulldorff]
Thank you. Next is Dr. Stephen Furr.

[6:14:02]
Do we have Dr. Furr? You are on mute.
[Dr. Steve Furr]
Can you hear me now?
[Martin Kulldorff]
Yes.
[Dr. Steve Furr]
Okay.

Public Comments: Dr. Steve Furr

Thank you. My name is Dr. Steve Furr. I'm a board-certified family physician actively serving patients in a rural health clinic in Jackson, Alabama, while also serving as the board chair of the American Academy of Family Physicians, which represents 128,300 physicians. For more than 40 years, I've cared for patients, and every one of those years, I've provided vaccines for children and adults in my practice. Many of the vaccines we have today were not available when I started. Now, physicians rarely encounter once-common infectious diseases, but I'll never forget a shift during my residency when I stayed up all night monitoring multiple children suffering with Haemophilus influenzae type B epiglottitis, listening to them struggle to breathe and hoping they wouldn't need to be intubated.

[6:15:00]
Before the HIV vaccine, roughly 20,000 U.S. children contracted severe HIV every year, while 1,000 died from the infection. I haven't seen a case of HIV in decades due to the widespread use of HIV vaccines, vaccines recommended by ACIP for decades. I want to share concerns about changes to ACIP that undermine trust and put communities at risk for real-world consequences like hospitalizations and deaths. Surveys consistently show that Americans consider their personal physician to be the most trustworthy source of information on vaccines. Excluding fanning physicians from participating in ACIP decision-making only weakens public trust in this group. Dismissing workgroup liaisons from the AFP has reduced transparency in the evidence and process used to make recommendations. The AFP strongly believes that among the membership of this board, there should be members who routinely counsel and provide vaccines to patients. We are concerned that the committee abandoned the evidence-to-recommendation framework that assesses both the risk and benefits of any vaccine.

[6:16:06]
Because of these changes, the AFP believes ACIP's recommendations no longer addresses threats to public health, and therefore some AFP guidelines no longer align with ACIP's. The AFP will review this group's decisions on MMRV, hepatitis B, and COVID-19 vaccines. But without complete evidence and ETR frameworks, the AFP will have reservations adopting them. Narrowing MMRV and COVID recommendations reduces patient autonomy. Hepatitis B vaccines are critical at birth because hepatitis B infection is not limited to high-risk individuals. Children can be infected through any contact with blood from an asymptomatic infected person, including a small cut or any item with trace amounts of blood. The benefits of universal hep B vaccination at birth far outweigh the risk of vaccination. We urge ACIP to restore and prioritize scientific integrity, transparency, and continuity in deliberation to restore public trust in the broader healthcare system.

[6:17:04]
Thank you.
[Martin Kulldorff]
Thank you. Next speaker is Mr. Richard Su. Hi, my name is Richard Su.
[Richard Su]
I'm the executive director of Hep B Free.

Public Comments: Richard Su

We work on hepatitis B awareness and liver cancer prevention. For more than six years as the executive director, I've seen the real cost of hepatitis B and the liver cancer it causes in patients in the San Francisco Bay Area. And the stories are painfully consistent. I'm so glad I caught this, and I'm so glad I don't have to worry about this with my child now that immunization is regular at birth dose. You know, families who've lost someone say, if we only knew, had known before, before is too late. So universal birth dose, as mentioned by the previous doctor, has been critical for that so that no child falls through the cracks. There was mention that, you know, this is an STD or a sex-related or drug-related disease, but we know that the American healthcare system is fragmented and people can fall through the cracks.

[6:18:04]
And so this infant birth dose really shows that we can prevent those infections completely, and there's a long, long history of that success. Again, mentioned by other physicians, the Hep B vaccine has been one of the most safe and shown through data without any adverse side effects. So we really, though the issue was tabled, we really, really hope that that remains the case. In addition, we know that if you don't vaccinate infants, there is that higher risk of infection, like on the playground, like bites and scratches. We know that infants are biting each other and getting into tussles, or caregivers may be accidentally infecting folks, particularly because the Hep B virus is so infectious outside of the body. So this is a particular case in which many of those maybe perceived reduced risks are really, really serious.

[6:19:02]
Finally, I wanted to note that when the Hep B birth dose was suspended, historically, there was a lasting effect of folks not getting their infants vaccinated, even after that recommendation was reinstated. And so there are long-term effects of changes to proven scientific choices that may cast doubt into the future for generations to come. So thank you for your time, and I appreciate you listening to community members.
[Martin Kulldorff]
Thank you very much. And the last public speaker is Wendy Lu.

Public Comments: Wendy Lu

[Wendy Lu]
Good afternoon. My name is Wendy Lu. I speak as a patient living with chronic hepatitis B. I support the Hep B universal birth dose vaccination to ensure newborns can receive the safe, effective anti-cancer and lifesaving protection.

[6:20:06]
My story is a harbinger of the lifelong disease burden for infants if they are not vaccinated and get infected. I was infected mostly at birth, likely at birth. It was before the vaccine was available. If a child is infected at birth, 90% of them develop lifelong chronic infection, and up to 25% of those will die from complications such as cirrhosis, liver failure, and liver cancer. I am in the 90%, and I am fighting not to be in the 25%. I know firsthand what it's like to live with hepatitis B and its long-term consequences. It means ongoing and lifelong medical needs. It means indefinite antiviral medication with no cure. It means ongoing time, money, energy, attention spent on navigating the healthcare labyrinth, insurance, specialty pharmacy, and recurring medical expenses.

[6:21:05]
I live a life worrying about dying prematurely. Diagnosed with cirrhosis at one point, I didn't think I would see my children grow up. I went through a dark, dark period of mental health challenges. I worry about getting liver cancer. But you don't hear people talk about hepatitis B due to the misconceptions and stigma. I dealt with it in silence for decades. So hear me when I say this. I would not want anyone to have to experience this chronic, deadly disease, especially when it can be prevented. As a mother, I would do anything to keep my young ones safe. Thanks to the birth dose vaccine, my children are protected and prevented from hepatitis B. My mother experienced guilt for passing this to me. This is a burden that luckily I do not have to carry. In contrast, I feel relieved to know the vaccine worked.

[6:22:02]
In closing, I speak as a patient, a mother, and a fellow American. I am saying no to what is not right. Do not open the Pandora's box to allow this silent, deadly disease to return. Do not inflict harm to babies and children when it's preventable. Most of all, I am saying yes. Yes to the world that I want to create. Let's prevent and eliminate hepatitis B infection. The hep B vaccine saves lives and is our best tool. Thank you.
[Martin Kulldorff]
Thank you for that. And I would like to thank all of the public speakers. We will now go to the voting.

Vote on COVID-19 Vaccine Recommendations

We are. Yes, I'd like to make a brief statement.
[Joseph Hibblen]

[6:23:02]
Which is my own opinion. And that is that the evidence we have here is that we are not as a committee. Anti-vaxxers. The robust discussions of the science and the respect for each other's opinions and the inclusion of outside experts. Indicates to me. That we as a committee do not come with predetermined. Attitudes or predetermined. Opinions. And that we are respectful. To the public and respectful to other people. And I think the deliberations here are evidence of that. And should be communicated as such. I think that. Understanding the risks and benefits. Of vaccines are critical to our process.

[6:24:00]
And. Under that it's very difficult to quantify the risks and benefits. The FDA is working at it. The CDC is working at it and we're working at it.
[Martin Kulldorff]
And we're going to do our best to communicate those risks and benefits. Thank you. For those wise words. You have to go to the vote right now. And we will be able to have a debate for each of the votes. So I apologize for interrupting you there. We are going to change the order of the voting. So we're going to start with vote number four. So if you can get that on the screen. So for vote number four.

Vote on Recommendation Language for COVID-19 Vaccine Schedule

Do we have a motion to adopt the recommendation language? Presented.
[Dr. Robert Malone]
So moved.
[Martin Kulldorff]
We have a second. So it's moved and seconded to adopt the recommendation language presented to the committee. I open debate on this motion.

[6:25:01]
And we are restricting the debate now to members of the committee. So we can then vote. So I call for a vote. And please state your name and your conflict of interest and. And your vote. And we're going to start online this with Dr. Corey Meisner. I'm sorry, Martin.

Debate on Recommendation Language for COVID-19 Vaccine Schedule

[Dr. Cody Meissner]
I didn't get my hand up fast enough. Or did you have a, if you want to debate, please do. So if you have something to say, please do. Yes. I wanted actually a point of clarification. Does this mean that. Adults 65 and older couldn't go to a pharmacy. And and receive the COVID vaccine. That's a good question. So the.
[Martin Kulldorff]
The implications is that this will allow coverage with zero dollar cost sharing on the ship ACA plans. Medicare part B, et cetera. For all individuals, a six month and up.

[6:26:02]
Also it gives coverage from the vaccines for children's for age six months. Through age 18. So this means that there is no insurance restrictions. On getting this vaccine. So thank you for raising that. That is a very important thing. And also. Does that mean that a prescription is not necessary? That is not part of, of this vote. That is part of a different vote number two. But that is actually not something that our committee has any power over. We don't have power over the budget of CDC. We don't have power of. Of prescriptions. That is a state issue. So we can only make suggestions. So. That that is not something that this vote is at all about. Okay. Thank you. Forward with the vote. And so please state your name. If you have covered interest and your vote.

[6:27:03]
So.
[Dr. Cody Meissner]
Yeah, I'm sorry. Do you want me to speak?
[Martin Kulldorff]
So please go ahead. Yes.
[Dr. Cody Meissner]
Thank you. Dr. I think that. As long as an individual based. Decision-making does not need to involve a physician. I think a. Person that increased risk can decide for herself or himself. And so I would vote. Yes.
[Martin Kulldorff]
And these are conflict of interest.
[Dr. Cody Meissner]
No, no conflict of interest. Except I'm in that group. And your name. Cody Meissner. Thank you for that.
[Martin Kulldorff]
We have Dr. Pollack. To have you on the. On the phone.
[Raymond Pollack]
Hello. Can you hear me? Can you hear me?
[Martin Kulldorff]
Yes, we can.

[6:28:00]
Please state your name. Confident interest and your vote.
[Raymond Pollack]
Raymond Pollack. No conflict of interest vote. Yes.
[Martin Kulldorff]
And Dr. Malone.
[Dr. Robert Malone]
Malone. No conflict of interest. Yes. Yes.
[Martin Kulldorff]
Dr. Pagano. Yes. Dr. Malone. Kirk. No conflicts. Yes. Dr. Blackburn.
[Hillary Blackburn]
Hillary Blackburn. No conflicts. And I vote yes. And to clarify, pharmacists are included in that. Share clinical decision-making.
[Martin Kulldorff]
Thank you.
[Kathy Stein]
Dr. Kathy Stein, no conflicts and vote yes, but the Griffin Evelyn Griffin, no conflicts of interest.
[Evelyn Griffin]
I vote yes.
[Joseph Hibblen]
Dr. Joseph Hibble and no conflicts of interest. I concur with Dr. Blackburn and Dr. Meisner regarding pharmacists and I vote yes.
[Martin Kulldorff]

[6:29:06]
Dr. Pepsworth.
[Vicky Pebsworth]
Vicki Pepsworth, no conflicts of interest. Yes.
[Martin Kulldorff]
But Levi. Reza Flevi, no conflicts of interest. Yes. My name is Martin Kulldorff. No conflict of interest. I vote yes. We have a vote 12 yes, zero no and zero abstain. So it is passed. We will now move forward to vote number one. Thank you for having that on the screen. For vote number one, do I have a motion to adopt the recommendation language presented to our committee? So moved. Do you have a second?
[Hillary Blackburn]
Second.
[Martin Kulldorff]
Thank you. It was too fast for me. It is moved and seconded to adapt the recommendation language presented to the committee.

[6:30:03]
I open debate on this motion. Yep.
[Dr. Cody Meissner]
Cody Meisner. So I have a comment. Dr. Meisner. Yes. Thank you. And I just want to clarify again what this means. Does that mean an informed consent must be obtained?
[Dr. Reza Flevi]
So can I clarify what they mean, please? Yes. So I think that the idea here is to send a very strong message and recommendation that it has to change the way it communicates with patients and medical providers about the risks and uncertainties of the vaccine. And that includes the vaccine information statement as well as other communication channels. We don't intend to prescribe to the CDC exactly what language to use.

[6:31:01]
We express our strong desire that that should be done to ensure appropriate communications, including as part of informed consent.
[Joseph Hibblen]
And that's kind of how we should view this recommendation, I think.
[Dr. Robert Malone]
Can I comment?
[Joseph Hibblen]
Dr. Hibben. Briefly, with regards to your question of requirement, the way I read this proposition is that the CDC engages in an effort to provide more consistent and comprehensive language. I do not see the word required in this proposition.
[Dr. Robert Malone]
And it says considers as well. Dr. Malone. Yeah. It is not within the purview of the federal government or the CDC to regulate the practice of medicine that includes the practice of informed consent. That's a state's right issue. The intent here, as I understand it, as a member of the working group is to encourage the CDC to provide information which can be used by states to support informed consent processes should they so require.

[6:32:14]
Does that help, Cody?
[Dr. Reza Flevi]
And specifically, the vaccine information statement is a document that is being generated and updated by the CDC. So that's something that is also relevant.
[Dr. Robert Malone]
Yeah. In this in this paper that Redstaff listed in his presentation, there's a very clear was a capital senior author, very clear enumeration of of the long history of the interaction between states regulating practice of medicine and informed consent, the vaccine information sheet and the CDC. It's complex. And it's very clear that the federal government doesn't have the right to regulate the any requirements having to do with informed consent, but that the CDC has kind of stepped into the breach inadvertently in part due to needs to mitigate mitigate legal liability.

[6:33:12]
So it's really convoluted at this point, and we're just trying to make it incrementally better.
[Dr. Cody Meissner]
Yes.
[Martin Kulldorff]
And hold on. I also put myself on the list. So normally this type of votes are not done by the ACIP. It's usually done by CDC. I have full confidence in both the CDC staff and the CDC leadership, including the CDC director that they are able to take the discussions that we've had today and to do this on their own without us having to make a vote to recommend it. I think there was a lot of wisdom in the words said today.

[6:34:01]
And I think the CDC staff and leadership has the capacity to do that on their own. Can I respond to that? We have Dr. Meissner.
[Dr. Cody Meissner]
Okay, thank you. We've got a long line here. The thanks for that clarification to everyone. And so a vaccine information sheet is already required by law for for every vaccine. So what will change here is the content of the vaccine information sheet. Is that correct?
[Chris Braden]
Yes.
[Dr. Reza Flevi]
Yes. We suggest that the content will be changed, and again, the CDC will have to apply their judgment about how to do that exactly given this suggestion that we are making here.
[Dr. Cody Meissner]
Thank you. Thank you, Dr. Meissner.
[Amy Middleman]
Thank you for recognizing me. I'm sorry. I think it's been covered.

[6:35:00]
It sounds like usually vaccine recommendations are measurable and policy related. And this type of thing is usually a clinical part of the clinical recommendations that are in the text of a recommendation. So I just also want to make sure we clarify what is meant by it is the sense of the committee because we want to be obviously really clear that everything that we describe and discuss and recommend is evidence based. Thank you.
[Martin Kulldorff]
So I would like to address it.
[Dr. Reza Flevi]
So a few thoughts. First of all, I believe that it's appropriate and actually necessary that ACIP will think about vaccination policies related issues in a broader sense than just focus on a very specifically narrowly question of whether to and how to recommend one vaccine or another.

[6:36:01]
That's within the charter of the ACIP. I actually looked at this. Secondly, as much, you know, I understand the trust, we all trust the CDC, but the fact of the matter that the current V.I.S. of the COVID-19 vaccine does not reflect the current risk as we discussed today by no means. So I think it's important to make that statement. And I think that all the risks that are articulated there were formulated or the issues were formulated after deep literature review and deliberation about what the evidence suggests. And I also would like to make the last point is when we think about communicating to patients, we don't need to wait until there is absolutely 100% of evidence of harm. We need to be transparent about the risks and uncertainties that we have. And if we don't know something or we suspect something or we have missing information, that should be communicated to them.

[6:37:00]
And just an example is something that Dr. Meissner, you mentioned, like our understanding of what protection this vaccine is giving to different people is very lacking to say the least. And it's based on low quality evidence. We need to be honest and transparent about this. I think that the evidence suggests that we have not been that way. And I think that we, as ACIP, we should call it out and make a very explicit statement about that. I think it's not only appropriate. I think it's actually something that is in the core mission of what we are supposed to do.
[Martin Kulldorff]
Is the committee ready to vote on the motion?
[Dr. Robert Malone]
I move for a vote.
[Martin Kulldorff]
So the vote is listed here in the front of you. I will start. Please say your name, conflict of interest, and your vote. Dr. Meissner?

Vote on Recommendation Language for COVID-19 Vaccine Schedule (Continued)

You are on mute. I'm sorry.
[Dr. Cody Meissner]
Thank you. Cody Meissner, no conflict.

[6:38:02]
And I vote yes.
[Martin Kulldorff]
Dr. Pollack?
[Raymond Pollack]
Dr. Pollack here, no conflict. I vote yes.
[Martin Kulldorff]
Dr. Stein?
[Kathy Stein]
Kathy Stein, no conflicts. I vote yes.
[Martin Kulldorff]
Dr. Blackburn?
[Hillary Blackburn]
Hillary Blackburn, no conflicts, yes.
[Martin Kulldorff]
Dr. Milhom? Kirk Milhom, no conflicts, yes. Dr. Pagano?
[Dr. Jason Goldman]
Dr. Pagano, no conflicts, yes.
[Martin Kulldorff]
Dr. Malone?
[Dr. Robert Malone]
Malone, no conflicts, yes.
[Martin Kulldorff]
Dr. Griffin?
[Evelyn Griffin]
Evelyn Griffin, no conflicts. I vote yes.
[Joseph Hibblen]
Dr. Hibble? Joseph Hibble, no conflicts.
[Vicky Pebsworth]
I vote yes. Dr. Pepsworth? Vicky Pepsworth, no conflicts, yes.
[Dr. Reza Flevi]
Dr. Leva? Ratsaf Levi, no conflicts of interest.
[Martin Kulldorff]
I vote yes. Martin Kulldorff, no conflicts of interest. I vote no. We have 11 votes for yes and one vote for no.

[6:39:02]
So this motion passed. We will now move on to vote number two.
[Hillary Blackburn]
I move to make an amendment.

Motion to Amend Recommendation Language for COVID-19 Vaccine Prescription

[Martin Kulldorff]
First, we have a proposal for an amendment. Dr. Blackburn?
[Hillary Blackburn]
Yes, to strike the require a prescription. That is unless CMS is ready to authorize pharmacists as Part D providers. But I guess we're not able to make that decision right now. But to strike the require a prescription.
[Dr. Reza Flevi]
So again, could you explain more what you better what you mean? Sorry, I'm not sure I follow what your suggestion is.
[Hillary Blackburn]
We're not currently authorizes providers in Part B language. And so we can't currently write a prescription.
[Dr. Reza Flevi]
So in some in some states in some states.
[Hillary Blackburn]
We cannot write a prescription.

[6:40:00]
We can operate under a collaborative practice agreement in most states. But it would be a barrier for access if a prescription is required.
[Martin Kulldorff]
So is your suggested to make an amendment or you are arguing to vote a no?
[Hillary Blackburn]
No, just an amend the require a prescription.
[Joseph Hibblen]
Rather is the core of the of the vote.
[Vicky Pebsworth]
All right.
[Joseph Hibblen]
So let's see unless you have specific language to amend it. I think it was it comes down to a yes or no vote. She can.
[Martin Kulldorff]
I mean, it seems to suggest that you want to vote no on this on this. And is that okay to have it like that? Okay, good.
[Kathy Stein]
Great.

Debate on Requiring Prescription for COVID-19 Vaccination

[Martin Kulldorff]
We have the first two is the motion to adopt. I just want to say something about the this this before.

[6:41:01]
We will have the debate after we have done that. So is there a motion to adopt?
[Vicky Pebsworth]
Sure motion. Motion second.
[Martin Kulldorff]
So it's moved and seconded to adopt the recommended language presented to the committee. I open debate on this motion. Dr. Stein.
[Kathy Stein]
I'm all about informed consent. And I think given the earlier discussions about risks and benefits and unknown risks and unclear benefits, I think that that discussion is really important. But I'm really concerned about the requirement of a prescription because I believe the segment of the population that is underinsured has lack of access to health care. They're going to be unable to get a prescription. And those are the people that are at highest risk for a lot of these these comorbid conditions. And so I just that that's my only concern.
[Dr. Cody Meissner]
Thank you. We have Dr. Meissner. Yes, thank you. And I'm I'm strongly opposed to a requirement for the prescription.

[6:42:05]
I think the point that was just made is an accurate one. And remember the the vaccine information sheet will include most if not all of a discussion that would take place with a physician. But I think requiring a prescription is going to become a big barrier to administration of this vaccine. And if a person wants it for himself, herself, her children, they should be able to get it without a prescription. Over.
[Martin Kulldorff]
Dr. Hibon.
[Joseph Hibblen]
We're going for comments. It is a debate. That's very good. I am also concerned as it is my understanding that approximately 30 percent of Americans don't have access readily to primary health care provider.

[6:43:07]
It's my understanding that in Texas and and and more rural states, it can be an even higher barrier. And that inability to access a health care provider secondarily impairs the ability to have an intent and a risk benefit discussion with your provider. So I think that I concur with Dr. Blackburn, Stein, and Meissner that this would present a significant barrier to implementing all of the good things we've discussed.
[Martin Kulldorff]
Thank you, Dr. Luna.
[Joseph Hibblen]
Yeah, a few thoughts.
[Dr. Reza Flevi]
So first, just to put it in context. I think that this vote is about leaving this to every state to figure it out. And the state can decide not to do it if it's going to indeed limit access.

[6:44:01]
But I just want to talk a little bit about this access. So we are saying that people that don't see their medical don't have access to medical. So how would they get antibiotics? Based on that logic, right, we would need to also allow taking over-the-counter antibiotics and other prescription drugs. Now, why we don't do that? We don't do that because we believe that the prescription of these interventions requires some nuanced assessment of the medical condition of that person to actually decide whether it's appropriate for them or help them decide where it's appropriate for them to take it. I believe that given what we heard today, it's true about the COVID-19 vaccines. And if we believe that this is really a nuanced decision making, and that there should be a conversation with the patient that is deep, I think that it's very strange to me that then we say, oh, we don't require this for that particular product.

[6:45:04]
We are not talking about any vaccine. We're talking about this particular set of products. We just discussed how nuanced it is, and I don't see why this is different than any other prescribed drugs. Like, the same argument could be applied. Now, most of the people that are actually in risk for severe COVID are presumably under other drugs that are being prescribed to them, and they see the doctors either for care or for renewal of their prescription on a regular basis. So I have to say that I understand that this is maybe kind of an instinct that we are saying about access, but I'm not sure when you actually think through the rationale here that holds a lot of water. So I think we should actually go ahead with this. Thank you, yes.
[Evelyn Griffin]
I am very conscious of limiting access. Dr. Levy just took the words out of my mouth much more eloquently.

[6:46:06]
I have to agree with his comments, a very big proponent of informed consent, and I feel that getting a prescription would require that or necessitate that interaction with a provider that can discuss informed consent, much like getting a blood pressure medication refilled or started. And so I feel, I concur with Dr. Levy's comments, and I feel like the issue of access may be a separate one from that of informed consent, and I feel like we should work on that as a separate problem. Thank you.
[Dr. Cody Meissner]
Dr. Meissner? Yep, thanks. First of all, I'm a little uncomfortable, Reza, with the analogy between an antibiotic and a vaccine. An antibiotic means that somebody's sick, and they need to be seen by a physician to decide which antibiotic and whether or not an antibiotic is necessary.

[6:47:08]
That's a relatively urgent setting. A vaccine is generally administered to an otherwise healthy individual, and if we require a prescription, you know we're going to increase healthcare costs. And I don't, I mean, I don't think this is a reasonable basis to do that. I think if a person wants to get the vaccine, a physician is not going to talk her or him out of getting the vaccine. So I don't see what purpose it would serve. Over.
[Martin Kulldorff]
Dr. Malone?
[Dr. Robert Malone]
In fact, what we are talking about, because of the restrictions associated with the FDA authorization or licensure, is that they have largely restricted availability to those with one or more comorbidities.

[6:48:10]
So these are people that are not actually healthy. So the assertion is that we're talking about healthy, normal adults is not true, verifiably not true. We're talking about people who are at high risk with a variety of conditions. Presumably, hopefully, they are seeking medical care of one form or another. We're also speaking about, in the Contra case, we're talking about hypothetical situations and speculation about impact on accessibility that has no information behind it. It's based on feelings. What I am with, Dr. Griffin, that these products have the appearance of significant risk in a variety of forms, whether or not the risks outweigh the benefits is what's at on point here.

[6:49:09]
And that is clearly a very nuanced issue having to do with individual patients. So the requirement for informed consent is basically a requirement that some competent individual works through the risk-benefit ratio for that individual patient. And that individual patient is making an affirmative decision together with their health care provider as a consultant that this is the best path forward for them, as opposed to somebody who is subjected to propaganda, marketing, and other activities that are not based in an actual real-world assessment of their risks and benefits. So for me, I prefer to err on the side of an actual prescription after a discussion with a licensed health care provider that is well qualified to serve in a partnership role with the patient in making an assessment of risks and benefits based on the medical condition of that patient.
[Martin Kulldorff]

[6:50:26]
Over. Okay. Please, Dr. Blackburn.
[Hillary Blackburn]
To clarify, pharmacists are licensed health care professionals. And we do complete a full coursework that includes a full immunology course and are actually one of the only clinician types to complete a standalone national immunization delivery certificate, which reviews disease background, immunologic response, and how to conduct individual patient risk and benefit assessment for vaccines plus hands-on assessment.

[6:51:00]
And I was given some additional information. So in the slide deck from earlier, there was a slide showing the 67% reported pharmacy access. That was from a one-month time period. But according to claims data for total doses administered for the 2024-2025 season, 90% were given at pharmacies, 27,569,515 doses at pharmacies out of 30,775,189.
[Dr. Cody Meissner]
Can I go to Dr. Meissner? Yes. Thank you. Look, when I want to see my internist, I have to wait a year. I can't see them more than once a year. So that means it's going to be very difficult to get a prescription. And it's essentially going to be a barrier for people to have access to this vaccine.

[6:52:02]
And that is not the role of ACIP. And number one. Number two, maybe I misunderstood, but I thought we had already said that a person who's in a high-risk group or who's over 65 can get it without a prescription. Does this apply to everyone or is this just to otherwise healthy people?
[Martin Kulldorff]
Dr. Malone?
[Dr. Robert Malone]
I don't have any opinion about whether pharmacists are qualified or not qualified. And I certainly wasn't implying that. That's a matter of state law. And I'm just, if a well-qualified healthcare provider of any condition is authorized by their state or local jurisdiction to make a determination in the form of some sort of prescription authorization, that's up to the state.

[6:53:04]
This particular language is really pretty squishy. It's the sense of the committee that state and local jurisdictions should require prescription for the administration of this particular product. I yield to Dr. Levy.
[Martin Kulldorff]
Dr. Levy?
[Dr. Reza Flevi]
Yeah. So just to echo two points. First, I think that pharmacists definitely should be considered as a very good solution. I think that in my understanding, we checked that over 40 states currently, they will be able to do it even in the current state. And every state will have the ability to allow this to happen. That said, I also want to say that my experience of getting vaccines in the pharmacy, nobody ever talked to me about any risk and benefits. And they just handed me some, at the best, some form that I haven't read. And nobody even gave me time to read.

[6:54:00]
So I guess that part of this is saying and sending a message, there should be some conscious action here of someone has to explicitly document that they give you the intervention. And I think that the paper that we cited earlier today is talking exactly about that. So my point is, we are making an aspirational statement here that is guiding the states with finding a solution. And I think in all likelihood, every solution that the state will find will involve pharmacists for practical reasons, whether they decide not to adopt it because pharmacists cannot adopt it, cannot do it in their state or change the state rules to allow pharmacists to do it. Or in most states, the pharmacists already can do it. So practically, I don't think when you actually look on the practicality of this proposal, I don't think it's going to lead to any access problem because most states have a solution. The states that don't have a solution can either find a solution based on pharmacists or reject that. So in all honesty, I think the message here, the current informed consent process is broken.

[6:55:04]
And in pharmacy, and I suspect not in pharmacies, right? We just give these products essentially over the counter. And we're not talking about any vaccine. We're talking this particular vaccine that we heard about all the risks and uncertainties there with very low, you know, questionable benefits for a lot of people. So that's kind of, I think, how I view that, this vote.
[Hillary Blackburn]
Yeah. Well, historically, at least 19 states have required pharmacist authorization to be tied to ACIP recommendations. And so a lot of the states have been making their own recommendations to help clarify some of the confusion, which has been limiting some of the access, as we've seen with CVS and Walgreens pulling their COVID-19 vaccines for the season.
[Dr. Cody Meissner]
Retz, if you need to get a new pharmacy, if they don't ask you about allergies or reactions to vaccines.
[Dr. Reza Flevi]

[6:56:03]
I tried a few of them.
[Dr. Cody Meissner]
Please only speak when I ask you to do so.
[Martin Kulldorff]
Dr. Hogue, please.
[Joseph Hibblen]
If we're talking about personal experience.
[Martin Kulldorff]
Dr. Hogue has been requested to speak. If not, we're now going to go to Kelly Guder.
[Tracy Beth Hoag]
Yes, thank you for the opportunity. I'm sorry about that. Was there a question for me? I apologize. I couldn't get the unmute on.
[Martin Kulldorff]
I think it was requested for you. You have requested to speak, but if you're not, that is perfectly fine. Sorry.
[Tracy Beth Hoag]
Sorry to interrupt. No, I did not.
[Martin Kulldorff]
Okay. Does Kelly Guder have requested to speak?
[Tracy Beth Hoag]
Yes, thank you for the opportunity to speak.
[Kelly Guder]
Kelly Guder, representing the American Pharmacists Association.

[6:57:01]
I'd like to just clarify a couple of things. First, that in many states in the U.S., the authority for pharmacists to give vaccines is based on ACIP recommendation. So if an ACIP vote is that they have to have a prescription, then they may not be able to administer the vaccines because that may be determined that it would have to come from someone else that would write the prescription and not the pharmacist. Pharmacists are the most accessible healthcare provider who have relationships with patients and are well-equipped to determine risk based on medications and health histories. Furthermore, pharmacists are the healthcare providers who have the most experience with COVID-19 vaccines. Claims data show that 90% of COVID-19 vaccines have been given in pharmacies. Dr. Blackburn talked a little bit already about education. So requiring a prescription for COVID-19 vaccine will decrease access for patients, will highlight healthcare inequities, especially for patients who may not have access to any other healthcare provider in their communities, and decrease individual patient choice.

[6:58:04]
A prescription is not needed and will cause unnecessary steps to access. Pharmacists are qualified to regularly assess risk and balance it with benefits for their patients.
[Amy Middleman]
Thank you for the opportunity to speak.
[Martin Kulldorff]
Dr. Mittleman?
[Amy Middleman]
Thank you so much. I just want to clarify, I'm very concerned because after 21 years on the committee, it has always been clear that vaccines are a primary prevention public health strategy that is remarkably different from treatment with antibiotics or treatment for patients who are seeing providers on an individual basis. This is why a lot of the policy that currently exists around vaccines exists. If we start asking for prescriptions for vaccines, which are, again, a primary prevention public health strategy, we are going to overwhelm physicians' offices.

[6:59:06]
As a practicing physician, I'm sure others will agree with me. I'm not even sure what you mean by a prescription because when patients come to the doctor, there's an order, there can be standing orders. We don't send anybody with a prescription to the pharmacy. They can get it at the pharmacy. I'm not even clear on what this is about, but what I can tell you is that it's alarming to me that for a primary preventive strategy, we are actually adding access concerns and barriers rather than diminishing them. I think that this is a really important piece of improving public trust in vaccines. The job of the committee is to assess the risk and benefit as a public health strategy.

[7:00:01]
That's been done, so we should make it available and accessible. Thank you.
[Martin Kulldorff]
Thank you. We have already is way beyond the time. We should have finished quite some time ago. If we are able to vote on this depends on how many more people want to discuss it, how long they take. I'm talking, please. Dr. Malone, please.
[Dr. Robert Malone]
For clarification, do we have a modified amendment or not? And if the amendment as written stands, I move that we proceed to a vote. Over.
[Martin Kulldorff]
We don't have an amendment. We also have Dr. Melling.
[Kelly Guder]
Yes, thank you. The Association of Prevention, Teaching and Research. I just want to echo what my other liaison representatives and what Dr. Blackburn has so thoroughly stated is just and really urge the committee to really think about how this will impact access and that if pharmacists are the ones that the majority of patients

[7:01:05]
are going to obtain their COVID vaccine and if the committee, as they voted to pass the and vote number four are allowing for that choice and individual decision making again with vote one being that we have this more informed consent process, which I'm all in favor for. Maybe perhaps also our CMS representative can speak a little bit more to what this requirement of prescription would mean for limiting pharmacy ability to give this vaccine. Thank you for taking my comment.
[Dr. Steve Furr]
Thank you for that comment.
[Martin Kulldorff]
We have a motion to vote, right? Can you please? I'm talking now. I'm the chair of this meeting and that's the only way to finish is if you'd like to do that. Is the committee ready to vote on the motion? I move that we vote on this motion. I second that motion. That has already been passed.

[7:02:00]
I call for a vote.

Vote on Requiring Prescription for COVID-19 Vaccination

Can you please state your name, conflict of interest and your vote? We will start with Dr. Meissner.
[Dr. Cody Meissner]
Cody Meissner. No conflict of interest and a strong no here.
[Martin Kulldorff]
Dr. Pollack. Who is by phone?
[Raymond Pollack]
Dr. Pollack, Raymond Pollack here. No conflict of interest. Vote no.
[Martin Kulldorff]
Dr. Pagano also on the phone. Do we have Dr. Pagano on the phone? He will return to him. Dr. Stein.
[Kathy Stein]
Kathy Stein. No conflicts. Vote no.
[Martin Kulldorff]
Dr. Blackburn.
[Hillary Blackburn]
Hillary Blackburn. No conflicts. Strong no.
[Martin Kulldorff]
Dr. Milhoan. Kirk Milhoan. No conflicts. Yes. Dr. Malone.
[Dr. Robert Malone]
Malone. No conflict of interest. Yes.
[Martin Kulldorff]
Dr. Griffin.
[Evelyn Griffin]
Evelyn Griffin.

[7:03:00]
No conflicts of interest. I vote yes.
[Dr. Robert Malone]
Dr. Hibble.
[Joseph Hibblen]
Dr. Hibble. No conflicts of interest. I vote no. Dr. Pepsworth.
[Vicky Pebsworth]
Vicky Pepsworth. No conflict of interest. I vote yes. Dr. Levi.
[Dr. Reza Flevi]
Roza Flevi. No conflicts of interest. I vote yes.
[Martin Kulldorff]
Dr. Pagano.
[Dr. Jason Goldman]
It's Dr. Pagano here. No conflicts. I vote yes.
[Martin Kulldorff]
My name is Martin Kuldov. No conflicts of interest. I vote no. We have six votes for no. We have six votes for yes. Since it's a tie, the chair breaks it. I voted no. So the motion has failed.

Vote on Discussion of Risks and Benefits of COVID-19 Vaccination

[7:04:00]
We now have number three. We are half an hour over time. We have two options now because people are going to the airport. My view of this motion is that I agree with everything, just like I agree with apple pie, motherhood and fatherhood. If we can proceed to this vote without a discussion, I think we have time to do so. If a discussion is necessary, we might have to table the vote. So first of all, I would say is there a motion to adopt? So moved. Second. Thank you. It is moved and seconded to adopt the recommended language for this motion. Is there a debate? Motion does vote seconded. Is the committee ready to vote on the motion? There were no objections. So we proceed to vote. Please state your name and if you have conflicts of interest and your vote, we're going to start with Dr. Meissner.
[Dr. Cody Meissner]

[7:05:09]
Um, yes. I've hardly had a chance to read it. Cody Meissner, uh, no conflicts of interest. And, um, we can go back to you if you want. Yes. Dr. Pollock.
[Raymond Pollack]
Raymond Pollack. No conflicts. Vote. Yes.
[Martin Kulldorff]
Dr. Pagano. James Pagano. No conflicts. Yes. Dr. Stein.
[Kathy Stein]
Kathy Stein. No conflicts. Vote.
[Martin Kulldorff]
Yes. Dr. Blackburn.
[Hillary Blackburn]
Hillary Blackburn. No conflicts. Yes.
[Martin Kulldorff]
Dr. Melho. Kirk Melho. No conflicts. Yes. Dr. Malone.
[Dr. Cody Meissner]

[7:07:10]
Dr. Kohler. I don't know if you can hear me. I can't. Somehow I've lost a connection.
[Amy Middleman]
Hey, Cody, it's Amy Middleman. I think we've all have.
[Dr. Cody Meissner]
Thanks, Amy. Looks like they cut the feed.
[Nisa Shafi]
They probably lost the time. This is Phyllis Arthur with bio. I did email Dr. Zadeh to say that we lost sound right when Dr. Malone was voting.
[Dr. Bernstein]
How are you going to vote, Cody?
[Martin Kulldorff]

[7:08:20]
Dr. Meissner, can we have your vote, please?
[Dr. Cody Meissner]
Thank you. I've been waiting patiently. My understanding is the health care provider can be a pharmacist. And as long as the pharmacist, this isn't going to place undue weight, burden on the pharmacist, then I would vote yes.
[Martin Kulldorff]
Thank you. And since I have to vote last, I'm just going to repeat my vote. Martin Kulldorff, conflict of interest, no conflict of interest. I vote yes. So we have 12 votes yes and zero votes no. So the motion is carried.

Meeting Conclusion

[7:09:02]
So I would like just to thank everybody for spirited discussions, both within the working group, the public comments, the liaison members. I would like to thank the CDC staff. I would like to thank the representatives from the media who are coming here. I would like to thank all the viewers, listeners who did this online. I would also like to thank the staff here at the CDC, who sort of took care of all the logistics, the security details, and so on, who has done a great job, always smiling to us as we arrive. So I would like to thank all of you. And this concludes this meeting of the Advisory Committee on Minimization Practices. Thank you.
[Mina]

[7:10:14]
Do you need this for the airport?