Maternal Immunization to Protect Mothers and their Babies

February 01, 2023

Information

YCSC Grand Rounds January 31, 2023
Saad Omer, MBBS, MPH, PhD, FIDSA
Director, Yale Institute for Global Health; Harvey and Kate Cushing Professor of Medicine (Infectious Diseases), Yale School of Medicine; Professor of Epidemiology of Microbial Diseases, Yale School of Public Health

ID9429

To CiteDCA Citation Guide

00:00Good afternoon, everyone.
00:02Good afternoon. So welcome.
00:05Welcome to the final grand rounds of January.
00:09We've made it.
00:09Spring is around the corner,
00:11although I didn't feel that way when I
00:14saw the snow coming down this morning.
00:16So it's a pleasure to welcome you all here,
00:18just to preview for next week.
00:20As Andres mentioned,
00:21we've got a very special compassionate
00:23care rounds next week where we'll hear
00:26from a family who experienced care
00:28here at Yale together with Jillian
00:31Celentano and Christy Alski and
00:33talking about a family in transition
00:35and the importance of embracing
00:38and supporting gender diversity.
00:40And now over to today's presentation,
00:43it is our distinct pleasure to welcome,
00:46Doctor.
00:46At Omar to the Child Study Center,
00:49we've actually tried to coordinate
00:51this talk for around two years.
00:53But as you'll probably have noticed,
00:54Doctor Omar has been pretty busy providing
00:57expert guidance and advice to various
00:59different international organizations
01:00in response to the COVID-19 pandemic.
01:03And that's in part due to his expertise
01:06on the epidemiology of respiratory
01:09viruses and studies on interventions
01:11regarding immunization of mothers
01:13and the effects on maternal and.
01:16Not help.
01:17His work has been disseminated
01:19widely and cited widely,
01:21so at least five of his publications
01:23have exceeded that Magic 1000 citations
01:25mark to enter into the Milli Pub club.
01:28And which is quite,
01:29quite tricky to say.
01:30And I think I that was data
01:31from a few weeks ago,
01:32so perhaps there's even more papers
01:34that have exceeded that threshold now.
01:36Last year Doctor Omar was elected
01:38into the National Academy of Medicine.
01:41And then sad news for Yale,
01:45as many of you will have read.
01:47Last week,
01:48but Dean Brown circulated an e-mail
01:50to congratulate as we extend our
01:52congratulations to Doctor Omar
01:54as well on becoming the incoming
01:56and inaugural Dean of the Peter
01:58O'Donnell Junior School of Public
02:00Health at the University of Texas
02:02Southwestern Medical Center.
02:04And the Irish person in me,
02:05when I heard the name of that center,
02:06the Peter O'Donnell school thought,
02:08am I related?
02:11So without any further ado,
02:12thank you for being with us
02:13in person today, Doctor Omar,
02:14and welcome to the Child City Center.
02:23So because of the Irish roots of
02:25our namesake of the new school,
02:26I'm going to the and the Texas existence.
02:31So we should have Irish whiskey as our
02:33official drink and biscuit as official food.
02:35That's the only logical, you know,
02:38thing to do there. Yeah,
02:40that would be my first order of business.
02:50So y'all focus mostly on kids.
02:56My focus has been pediatric
02:58vaccinations and pediatric outcomes,
03:00but also maternal immunization and
03:02its impact on early infancy and
03:05then increasingly long term impact.
03:07So what I'll do is I'll describe
03:09some of the work that I've been
03:10doing and we have been doing.
03:12It's a, it's a whole group of collaborators
03:15that have been working particularly
03:17in low resource settings to actualize
03:19the promise of maternal immunization
03:21and some of the outcomes are you
03:24know what you would expect prevention of.
03:26Infant out of of maternal
03:28outcomes and all of that,
03:29but also increasingly birth outcomes as
03:34well as you know briefly talk about some
03:36of the new work in longer term outcomes.
03:39So vaccines have been some of the
03:43most effective and cost effective
03:45public health interventions.
03:46In fact,
03:47CDC at the end of the last Millennium
03:52they came up with a list of 100 most.
03:56Useful,
03:57impactful public health interventions and
03:59vaccinations were at the top of that list,
04:02but they swear that it's not a ranked list.
04:05At the end of the day, you know,
04:07they're an organization with
04:08all sorts of stakeholders,
04:09so they don't want to annoy people who favor,
04:12you know,
04:13water and hygiene and all of that stuff.
04:14But it's no coincidence,
04:16coincidence that it's not
04:18alphabetically there.
04:19You know it doesn't.
04:21Vaccines don't start with the letter A,
04:23but they remain at the top of the
04:26list every time they revisit.
04:28But the most of the impact we have
04:30had is through childhood vaccination
04:33and the and the primary schedule
04:36although it's increasingly nuanced
04:38is mostly 610 fourteen weeks for
04:41most of the world in in the US
04:44and a lot of the developed world,
04:46we have two, four,
04:48six months primary studies.
04:50But what what happens is that the
04:52reason we give this primary series
04:54is because we need 2/3 doses for
04:57the vaccines to actually start
04:59having their full impact.
05:00And so therefore kids have this period
05:05of vulnerability through the 1st,
05:08essentially six months of life.
05:10And this even in a short period of 13
05:14years and that has increased substantially.
05:17Between 1990 and or 23 years and 2013
05:23there was a substantial reduction.
05:26So starting with 2.5 million underage
05:32children under age 5 had died of vaccine
05:35preventable diseases that reduced to 750,000.
05:37This is around the time a
05:40little bit before that.
05:41A lot of us started focusing
05:44on maternal vaccination.
05:46And so we said that look,
05:47and even the sustainable development
05:50goals are Millennium Development Goals.
05:53The the least progress we had seen.
05:56And same true with sustainable
05:58development goals was early infant
06:01mortality and unit of mortality was the
06:04most intractable part of the puzzle.
06:07And so even in the now approximately
06:093,000,000 deaths happen in the it's
06:11just the 1st 27 days of life and
06:13then it's not the full six months.
06:15So one way of dealing with this
06:18and one way of addressing it
06:20is vaccinating mothers.
06:22And that's one reason is that some
06:25infections are indeed more severe in
06:27pregnancy and influenza and hepatitis
06:29E is is one example and it seems that
06:33COVID-19 is is in that category as well.
06:36But the other reason is that you
06:39obviously vaccinate to protect the child.
06:42The first trial actually I did with my
06:46mentor who who was my MPH advisor and then
06:50sort of later when I was a faculty member,
06:53he was continued to be a collaborator.
06:56I worked the first trial I worked
06:58on of maternal immunization level
06:59talk about was called Mother's gift.
07:01You know, initially at that age,
07:03you know when you are at the
07:05faculty things look cheesy.
07:06You know, if it's too on the nose,
07:09but now in retrospect,
07:10I think it was a very appropriate name
07:13because you're vaccinating the mothers
07:15and they are enhancing their immunological
07:19or physiological gift to protect the baby.
07:23So a little bit about Physiology
07:26and immunology in pregnancy.
07:29Pregnancy is a dynamic stage and so you
07:32have an increase in in the sex hormones.
07:35I'm assuming this pointer shows
07:37up on the zoom side as well.
07:40And so, you know, the sex hormones increase,
07:43but it's not like a nice clean line.
07:45And obviously even this is a,
07:47you know, approximation,
07:48but it's it goes in steps, in stages,
07:51and there's some threshold effect.
07:53I'll come back to these two panels.
07:55But but if you look at it as a
07:57result of that and other changes,
07:59there are certain parts of the
08:02immune system that get upregulated
08:04as the pregnancy progresses.
08:06For example, monocytes and fibrocytes,
08:09dendritic cells.
08:10So a lot of the cells of the innate
08:13immune system and T regulatory
08:15cells which sort of keep the abuses
08:18of the immune system in check.
08:20So think of it as the internal
08:21affairs of the Police Department.
08:23And and so.
08:25On the other hand does she
08:28remodeling goes down because you
08:30don't want that level of remodeling.
08:32You know as the pregnancy
08:34progresses earlier on you,
08:35you want it and cell mediated immunity
08:38especially CD4 and CD8 cells,
08:41they go down and they're sort of
08:43functions decline if you will
08:45and natural killer cells go down.
08:47And as a result,
08:49perhaps you have things that are
08:51more severe like malaria that are
08:53more severe in early pregnancy.
08:55But there are other infections,
08:56especially viral infections that become,
09:00you know and they become malaria,
09:02becomes less severe at,
09:03becomes less severe as the
09:05pregnancy progresses.
09:06But there are other infections with
09:08severity goes up with pregnancy.
09:11And then sort of there is increasing
09:13evidence that with progression
09:16of pregnancy there are certain
09:18vaccine immunogenicity is no one.
09:21Sometimes it's the same and
09:22sometimes it's diminished with
09:24the similar clinical effects.
09:26But what we do know that in terms of
09:28vaccine immunogenicity in pregnancy,
09:30we can mount very good clinically meaningful
09:34effects of these vaccines and pregnancy.
09:38And and and therefore and
09:41the other thing is that
09:43through protection of moms to babies.
09:46Through antibodies, which we enhance,
09:48that's one major mechanism of giving
09:50moms the vaccine so that there's a
09:53transplacental transfer of these
09:55antibodies that goes up not in a linear,
09:59nice linear pressure.
10:01A fashion, they're kind of a
10:03sort of a substantial increase
10:04after 2032 weeks of vaccines,
10:0832 weeks of pregnancy.
10:10And so therefore you know how you time if
10:14your primary mechanism is just passive
10:16vaccination through antibody transfer.
10:18So you time it around you
10:21know late second trimester,
10:23early 3rd trimester so that you are
10:24at the peak of antibody response
10:25and that's where you when we design
10:27I do maternal immunization trials
10:28as well if you don't know anything
10:30about the physiological.
10:31Sponsor adequacy of response you
10:33that's where you vaccinate most
10:36women in the first trials and
10:38then you expand recommendations.
10:39And so we have you know embryo is also
10:43developing and so initially earlier
10:45on if you have an impact on systems,
10:48sometimes there is spontaneous abortion
10:50that you concerned about even you know
10:53after vaccination or as an adverse
10:55event that we look out for us as we
10:58are developing these vaccines later
10:59on it's more functional etcetera.
11:01So the fact is, the bottom line is
11:04that pregnancy is a dynamic state.
11:06It's a non linearly dynamic state,
11:08and if you will in terms of
11:11immunology of pregnancy,
11:12you can be slightly pregnant.
11:17When it comes to vaccines,
11:18the the there have been so tetanus
11:21has been with us for a while,
11:23technus vaccination etcetera
11:24in several countries.
11:25But that modern change started with
11:28influenza and and you know the story
11:30starts with I had the privilege of
11:32being part of this trial because
11:34in the US we had been recommending
11:37actually after the 1960s pandemic
11:41there was a flu pandemic in early 60s.
11:43That's when the so-called Advisory
11:45Committee on Immunization
11:46Practices was actually formed.
11:47The CDC, that is the main body that that
11:50develops recommendations for vaccinations,
11:53and one of the initial vaccination
11:55recommendations was vaccination
11:57against influenza in pregnant women.
11:59But that is that was one vaccination
12:00that was more aspirational for decades.
12:02It stuck around like 5 to 12% maximum.
12:05In a good year,
12:06it would be 15%.
12:08And that but,
12:09but there was a paradox you could
12:11because the primary indication was
12:12mothers and we could not do trials,
12:14randomized trials.
12:17Of these, because, you know,
12:19the so-called standard of care was
12:21that it was already recommended
12:23in the US and so we couldn't do
12:25randomized control trials of influenza
12:27vaccines in the US for this reason
12:29and for the reason of exploring
12:31the impact in low income countries,
12:33we did this trial in Bangladesh
12:36in early 2000s caused the mother's
12:39gift trial where we, you know,
12:42vaccinated moms and looked at the lab,
12:43confirmed influenza in infants and this
12:45was the first trial to demonstrate.
12:48But you can actually predict,
12:50prevent lab confirm in that case
12:51it was rapid test,
12:53it was a relatively small trial and
12:55showed 63% reduction in infant influenza
12:59after maternal vaccination in pregnancy.
13:01The first initial question was
13:04in terms of early childhood that
13:07was it happening due to some some
13:09sort of differential breastfeeding
13:11rates in the two groups.
13:14We know that breastfeeding is very
13:18protective against respiratory outcomes,
13:21you know the ammonia etcetera and
13:24all of that stuff in in babies even
13:27though it was a randomized trial,
13:28you know we went in and we looked at it
13:30and it turned out this was in Bangladesh.
13:32So exclusive breastfeeding.
13:37Everyone was bad for breastfeeding.
13:38So we could not say yes or no breastfeeding,
13:41but we could say exclusive and
13:43non exclusive breastfeeding.
13:44And we found that secession was happening
13:47if if if anything was happening in the
13:49influenza arm a little bit earlier.
13:51And so that wasn't the case.
13:52But that didn't mean that
13:53it wasn't being modified.
13:54And actually that rabbit hole has led
13:58me into actually looking at some very
14:01novel vaccine mechanisms of early
14:04vaccination. So stay tuned I got.
14:07Sidetracked during the pandemic
14:09uh have come back,
14:11have been coming back to my sort of
14:14passion of that so earlier on based on
14:16this work and the fact that in 2009,
14:202010.
14:23We had the H1N1 influenza
14:27pandemic and because that trial
14:30was out there, it was cited.
14:33And both domestically and internationally,
14:36pregnant women were for the first
14:38time prioritized to protect
14:40themselves and the babies during
14:42that pandemic for flu vaccination.
14:45And WHO also went and said that the
14:49countries that are going to prioritize,
14:51they're going to introduce.
14:52Influenza vaccines should prioritize
14:56maternal influenza vaccine.
14:58But then flu is a fickle friend in
15:00the sense that it changes every year.
15:03The vaccine effectiveness changes.
15:05And, you know,
15:07I'm more surprised by the consistency
15:09from place to place and year
15:11to year of influenza than I am
15:13by variation between the two.
15:15So, you know, a couple in Seattle.
15:19Called,
15:20Bill and Melinda Gates were increased.
15:24Increasingly intrigued by this
15:26prospect and with their team
15:29commissioned three additional
15:31trials to verify the findings from
15:33our little trial that could to see
15:37if these are consistent across
15:39geographies and and and the main
15:40interest was low income countries,
15:42low and middle income countries.
15:42So there are three.
15:46Groups of three vaccines were commissioned
15:50and that commissioning was three trial
15:54vaccine Trials Commission in Mali,
15:56Nepal and South Africa.
15:58And then they sort of contacted
16:01me to actually pull their data
16:04together and say, look,
16:05what is the overall synthesis from this?
16:08So it turns out.
16:10Uh, it worked.
16:11The vaccines worked across all sides
16:15to prevent infant influenza and and
16:19which is you know which was good
16:22and it wasn't surprising for us
16:25that that it raised the effect sizes
16:27ranged vary from place to place.
16:29That's true for every you know adult
16:31flu vaccine and and childhood flu
16:34vaccines you know so that wasn't
16:36surprising but but but we showed
16:38and they showed that you know.
16:40This vaccine works pretty consistently
16:42to prevent sizeable proportion
16:44of influenza and influenza is
16:46impactful is dangerous,
16:47particularly dangerous for
16:48young infants and older people,
16:51and these are the highest risk groups.
16:54But it also,
16:54we also show that overall in in,
16:57in the Paul,
16:58the confidence intervals were
16:59crossed and all but essentially
17:01it was protecting moms themselves
17:03as well and it was pretty safe.
17:05But we also found intriguingly the
17:07beauty of pooling data from 4 sites
17:09that were designed intentionally to
17:11compare outcomes that that happens
17:13when you know all their checks are
17:15coming from the same benefactors.
17:18They can nudge trial us to sit
17:20together and align their protocols
17:22rather than a company.
17:24Like Pfizer and and Mark doing
17:26trials you know that's they have to
17:28have more of a nudging from FDA to
17:31do that and that rarely happens.
17:33So this was pullable and what we
17:35found was that there was a reduction
17:38in all cause pneumonia in babies
17:41of 20% or 20 percentage points
17:45that's pretty substantial.
17:46So pneumonia is one of the biggest
17:50killers and the way it happens is we
17:52think it happens and we did other work.
17:54To show that as well that it's
17:57the one two punch of maternal of
18:01influenza virus predisposing babies
18:04for through to bacterial pneumonia.
18:08And this is what's happening.
18:09In fact,
18:11a gentleman called Tony Fauci and
18:14his colleagues went to Walter Reed
18:17and looked at specimens from 1918
18:20pandemic and actually showed that a
18:23lot of the deaths were happening from.
18:26Secondary influenza to secondary
18:28bacterial infection after the influence.
18:30It was the influenza pandemic,
18:31but it was the pneumococcus and
18:34perhaps HIV influenza diabetes
18:36that was actually killing people.
18:38So it was that one two punch I used
18:41to show a slide of Muhammad Ali
18:45delivering his famous 1/2 punch
18:47and then someone stole that slide
18:49and I have never been more annoyed.
18:52So so people, you know,
18:55steal someone's work fine.
18:57Don't steal someone's jokes.
18:59That's that's outright that's
19:00cruel plagiarism, but in any case.
19:02There's that one two punch that
19:04were that was that the virus was
19:06delivering and then you could leverage
19:09that through maternal vaccination.
19:11But here's the question.
19:12Look,
19:12this is a pretty substantial
19:14reducing 20% of all calls.
19:19Influenza pneumonia across three
19:22sites is pretty substantial.
19:25Is it true and if it were to be true,
19:28how could you show it and leverage
19:31this unique characteristics
19:32of influenza virus itself?
19:34Well, you leverage the seasonality of
19:36the virus and you see that if there was
19:39more virus circulating in the Community,
19:41you would have a higher effect size of
19:45this vaccine on infant influence and
19:47you would have literally or or sort
19:50of virtually no effect when there was
19:53no influenza in those communities.
19:55Where, where these trials were happening.
19:57So yes, when there was no influenza,
19:59there was no impact on infant pneumonia,
20:02all cosmia of maternal vaccination.
20:05The more virus there was in the community,
20:08the more impactful.
20:11Influenza vaccines were in protecting
20:14children against influenza,
20:16against all cause pneumonia.
20:19So it was pretty early on.
20:21So this is from 2012 actually.
20:23But to show that very earlier
20:26on these trials we,
20:27we published our trial in Bangladesh trial in
20:302008 and the other trials came subsequently.
20:34But very early on these were
20:35incorporated in global policy.
20:36But since then the lower income
20:41countries still have this barrier,
20:44they don't vaccinate against influenza.
20:49Yahoo does it.
20:50the US does it.
20:51A lot of other countries do it.
20:53So Latin America does it,
20:54but that's the nest next frontier.
20:58Then there is another virus,
21:01another bacterium or another
21:03just really pathogen for tassis
21:05which causes a lot of cases.
21:07And uh.
21:08But it disproportionately impacts
21:10children too young to be vaccinated.
21:14It has more disease,
21:15severe disease in young infants,
21:17and then the.
21:20This vaccine was after a few outbreaks,
21:23which we expect by the way,
21:25a few more outbreaks because
21:27routine vaccination has gone down
21:29in the US during the pandemic.
21:31And the two most unforgiving childhood
21:33pathogens are measles and pertussis,
21:35because they have,
21:37they have the higher so-called
21:39basic reproductive numbers,
21:40meaning they're most more infectious
21:42than a lot of other pathogens.
21:45And so you know, in the US after
21:47these outbreaks in California,
21:49et cetera, and folks in Texas.
21:50Saying that we can't do protect,
21:53do cocooning or you know,
21:56protect young infants through
21:58eliminating the transmission of the
22:00virus of the of the bacterium from
22:02their surrounding by vaccinating
22:04adults around them.
22:05It was return of the immunization was
22:08recommended but it was recommended without.
22:12The the evidence of from from
22:14a randomized controlled trial,
22:15so the first priority.
22:18Was to actually look at the safety of this,
22:21and the safety of this vaccine was.
22:28Was pretty good with the exception
22:30of two signals.
22:31So there was chorioamnionitis
22:33that was higher in the vaccinated
22:36group versus unvaccinated group.
22:38But interestingly for task says
22:40the preterm delivery rates were
22:43were not different.
22:44If anything it was lower
22:46in the vaccinated group.
22:47So that was reassuring.
22:48The other thing was this was done
22:51in large linked databases from Hmos
22:53and when we looked at this and
22:55this was led by one of my postdocs.
22:58Was not at CDC and and I was
23:00engaged with it as part of you know,
23:03this this network.
23:03And when we looked at this actually no,
23:06this was not led by my post doc.
23:07That was the next study.
23:08It was led by a colleague
23:09that was involved with this.
23:13And what we you know what was what we found
23:17was that if you looked at the evidence of.
23:23Supporting evidence of chorioamnionitis.
23:26Only 50% had any even sort of
23:29flimsy supporting evidence.
23:30So what was happening was OB's were
23:34essentially classifying all fever
23:35in 3rd trimester as core um unitus.
23:40Likely, and there is evidence of
23:42supporting that, likely due to
23:45concerns associated with litigation.
23:47And so, so that was a little bit
23:49going on but the most you know
23:51concerning outcome again thankfully
23:52which is preterm birth of course
23:54you have minus wasn't showing that.
23:56The other thing was the US recommended
23:58this vaccine in every pregnancy
24:00and with a tetanus and it's given
24:02as a combined tetanus diphtheria
24:04and acellular pertussis vaccine.
24:06And so therefore you know especially
24:08vaccine is very safe but it can
24:11be reacted genic,
24:12it can give you you know it's like mouthwash
24:14if it's hurting a little it's working.
24:16And and and it does hurt and is in
24:20terms of short-term reactogenicity,
24:22it does have that.
24:23And the concern was that if you
24:24are doing it too close together,
24:26a lot of women get pregnant
24:29pretty frequently.
24:29And so therefore we wanted to
24:31see if there was a difference.
24:32So compared to a greater than five years,
24:35if you women received this
24:37vaccine less than two years,
24:40there was less than two year
24:41gap and two to five year gap.
24:42There was no difference in terms of
24:45local reactions, the big ones small.
24:47Gestational age and freedom.
24:49That was good.
24:51So then we have another vaccine that
24:53is coming down the Pike, GBS vaccine.
24:55So Group B Strep is a problem.
24:58There are two types of groupies
25:01strep which is early onset,
25:03not so creatively named early and late onset,
25:06but but very appropriately described
25:08in the sense that early onset
25:10happens before it's seven days,
25:12late onset happens after between
25:157 to 90 days of age.
25:18The early onset presents without a focus.
25:21Access without a focus pneumonia
25:23meningitis in late onset.
25:25Meningitis is more focused,
25:27more frequent and the cases 30% are
25:32reasonable proportion have permanent
25:35sequelae you in the US what was
25:39recommended was universal screening and.
25:42You know antibiotic prophylaxis
25:44and that reduced the in pregnancy
25:49that reduced the rates of early
25:52onset Group B strep substantially,
25:54but the late onset disease remained the same.
25:58And so therefore there was this
26:00room for vaccination.
26:02But why do we worry about this?
26:03Well, it causes,
26:04if you look at invasive Group
26:06B strep disease,
26:08which is one form of disease,
26:09it causes a lot of stillbirths or
26:14spontaneous abortions and can have
26:16other adverse pregnancy outcomes.
26:18But but to to look into that in
26:20the fuller context, you have GBS,
26:23colonization,
26:24the supportive data that you know through.
26:28Intra amniotic you retract
26:30or systemic GBS infection,
26:32you have an association with preterm birth,
26:34which is the big thing that you're trying
26:36to prevent in terms of birth outcomes,
26:38adverse birth outcome.
26:40This preliminary data but
26:42increasing supporting data
26:43that due to systemic.
26:45Colonization and all due to
26:47systemic factors like cytokines etc.
26:50Even colonization may be
26:52associated with preterm birth.
26:53So there were like several vaccines
26:55initially it was this vaccine tribal.
26:57And there are new vaccines
26:58coming in coming down the Pike.
27:00And we hope to see a vaccine
27:02for GBS in the next few years.
27:04Then there is respiratory sensational virus.
27:07I couldn't have imagined
27:08like before the pandemic,
27:09the people would actually be talking about,
27:12you know, on PBS.
27:15Could be asked about RSV or like
27:17people would be talking about RSV
27:20which was frankly a niche virus
27:22for well physicians know about it,
27:25pediatricians know about it,
27:27but it's not a sort of virus
27:29well known but it has you know,
27:32you can ask me why we had those surge etc.
27:34But in any case those of us who do
27:36this for a living knew that RSV was
27:38a big problem and that's why they're
27:40there are vaccines in the pipeline and
27:42there's a lot of good news around this.
27:44And so it it is just RSV respiratory
27:48sensational virus disproportionately
27:50impacts infants younger than five months.
27:54And premature infants.
27:55So there are antibody products that are out
27:59there for especially premature infants,
28:00but it's not a viable strategy
28:03at the mass population level.
28:05And you know,
28:06early estimates showed that
28:07in the neonatal period,
28:09RSP was associated with a little
28:11over 2% of all cause mortality
28:14and 7% of all cause mortality in
28:17the post unit or infancy period.
28:20That's pretty that's a lot of debts but
28:23by a single pathogen and This is why
28:25it is an attractive target for prevention.
28:28We did some work in Australia that
28:29showed that some of this infection,
28:31early infection can,
28:32is pretty convincingly associated
28:34with later development of asthma.
28:35Uh,
28:36et cetera.
28:36And so a whole host of work points to
28:38this pathogen being actually a pretty bad
28:41pathogen that we should try to prevent.
28:43These numbers have sort of.
28:44I've been part of a lot of studies that
28:46have added nuance to these numbers.
28:48So the numbers are more variable.
28:50They vary from region to region.
28:52But the answer,
28:53the bottom line of all the burden assessment,
28:55especially from low income countries,
28:57including low income countries,
28:59is that this pathogen is worth preventing.
29:04And so there is this robust pipeline.
29:07This has been updated very recently.
29:09There was this vaccine by Novavax,
29:12which again to my surprise became a Moderna
29:16and Novavax used to be very niche companies.
29:19Without a lot of public recognition of them.
29:23Novavax had a product now Pfizer's
29:26product had moved forward.
29:27And then GSK, you know, Santa Fe.
29:31The product is also moving forward,
29:33but essentially after the initial work
29:36by Novavax Gates Foundation invested
29:39heavily in this vaccine and I'll tell
29:42you a nuanced story of this vaccine.
29:45That Novavax vaccine was done,
29:47it was a nanoparticle vaccine
29:50of a post fusion.
29:52I wouldn't get into the detail,
29:53but essentially there's a pre fusion
29:56molecule and a post fusion molecule
29:58post fusion is like in lab studies.
30:01Was shown to be likely more effective,
30:04but these guys had a pre fusion
30:06product and they recruited from all
30:08sorts of sites but essentially half of
30:11the subjects came from South Africa.
30:14For various reasons they overshot
30:17their optimism of the initial
30:19sample size was pretty decent,
30:22but then due to commercial reasons they
30:24had an early unplanned look and when you
30:27look at your data a little bit early.
30:30Regulatory entities add a penalty,
30:32you have a higher bar burden,
30:34statistical burden.
30:35So your P value,
30:37the target alpha changes,
30:39that's what happened.
30:40And then they became a little bit
30:44over optimistic based on the early
30:47data and they stopped the trial at
30:50based on the events in a pretty lower,
30:55almost half that initial target sample size.
30:57Here's what So what?
30:59What they did was they did safety
31:00assessment for six months,
31:02safety assessments for mom for six months,
31:04infants for one year,
31:05efficacy of three months,
31:07four months,
31:07five months and six years and then
31:09they were randomized to have two is
31:11to one more vaccine than placebo.
31:13You know when you have more confidence
31:15sometimes you give more vaccines et cetera.
31:18You know up up to one is 2/3,
31:20you get pretty good statistical efficiency
31:22very close to one is to 1 randomization.
31:26So that's done pretty
31:27frequently in vaccine trials.
31:30Efficacy is defined as in their case,
31:32prevention of infant lab confirmed.
31:36Outcomes of RSV and these are I'll show you
31:39go through the primary outcomes etcetera.
31:42This is medically significant RSV
31:45lower respiratory tract infection.
31:47So they had specifically criteria
31:48and this was the main outcome.
31:51This is the primary endpoint.
31:52Look what happened.
31:55It caused the null.
31:56And at the age of remember,
31:58these are not uniform distributions,
32:00so the tails are narrower,
32:01so it barely failed their primary endpoint,
32:06but on the other hand,
32:07for most of the other stuff.
32:11You know, on the overall analysis,
32:14primary endpoint with extended data set,
32:17which was pretty justifiable,
32:20the vaccine performed reasonably well.
32:22I don't work with any vaccine
32:24companies in the sense that I don't
32:26get paid with them for by them,
32:28including Novavax.
32:28I pay for my own meals if I show up
32:31at any of the scientific meetings.
32:34And the reason is not that there's
32:35nothing wrong with working with
32:36vaccines companies because I work
32:38on vaccine acceptance as well.
32:39That's I get to yell a little
32:41harder at some people.
32:42If, if I don't do that,
32:45but so with you know,
32:46disclosing that sort of kind of
32:47lack of conflict of interest,
32:49I have no personal interest in this.
32:50But this vaccine works.
32:52It doesn't work if you just stratify
32:54because most of the recruitment came
32:56from outside the US so obviously
32:58us only won't work and that wasn't
33:01the primary endpoint as well,
33:02but South Africa where most half of
33:05the subjects came. So it failed.
33:07And Dan Weinberger at the School of
33:09Public Health and I and a couple
33:11of others have been pushing.
33:134 actually.
33:16Doing what we call a Bayesian trial,
33:19take the the data from the previous trial.
33:23Add the next a few more subjects
33:26and then add a statistical penalty
33:28of doing it in two stages and
33:32then get gets the licensure.
33:35The company wasn't interested.
33:36Gates pulled their support because
33:39they were enamored by the next product.
33:41But are we so Nice is to think that you know,
33:45one magic product will be accessible to
33:48to the places where it's most required,
33:51despite all sorts of assurances and
33:53and press conferences and agreements?
33:55Now this,
33:57you know and and if you have any doubts
34:01about that you know Pfizer with with its.
34:04$100 billion,
34:05that's a, you know,
34:07billion with a B windfall and lack of.
34:12Access to M RNA vaccines throughout 2021.
34:15Now when the horse has left the barn,
34:18as in the neighboring barn,
34:21munching on some hay,
34:23now all the vaccine is available,
34:25et cetera.
34:26So.
34:26So the point I'm trying to make it
34:29is that it was a perfectly decent
34:31vaccine and they had much more stable
34:33agreements because they were a new company.
34:36Gates and other key players had
34:38much more say in global access
34:41and there was a lost opportunity.
34:43Even if the best case scenario is so
34:45there's a new vaccine that has shown.
34:46I'm not showing the data in the interest
34:48of time that has shown that maternal
34:50you know the new vaccine works but major
34:53pharmaceutical companies it's it's a
34:55risky bet for global access it will
34:57come our kids etcetera and the US will
35:00be protected for and and and moms and
35:02young kids will be protected starting
35:05ideally you know next year or so.
35:08So then COVID-19.
35:12So I had the privilege.
35:14I've done a few things around the pandemic,
35:15but including vaccines,
35:16and I had the privilege of being part
35:19of The Who COVID-19 vaccine group and
35:20also the National Academy of Medicine Group.
35:23That said, who gets it for a second?
35:25That's that that described that overall plan.
35:29Now, in retrospect,
35:30there's consensus that elderly,
35:32the elderly should, should get it.
35:34But when we were,
35:35when the sausage was being made, Oh my God,
35:38like, we got thousands of comments.
35:41We're impassioned pleas of prioritizing
35:44one group versus another, et cetera.
35:48And so, and pregnant women were
35:51included in those things.
35:53But remember,
35:54we didn't have data.
35:54And so, despite years of pushing
35:57that in public health emergencies,
35:59myself and my colleague Ruth Faden
36:02at Johns Hopkins,
36:04who who founded their bioethics institute.
36:07Have been and others have been
36:10pushing for early trials in
36:12pregnant women during public health
36:14emergencies because we know that,
36:15you know,
36:16that's where the questions will come within.
36:19Hours of the announcement,
36:22so I would get the announcement on the
36:24Sunday afternoon because of the the cadence,
36:26because of regulatory requirements,
36:29they would release their results
36:31on a Monday morning.
36:33So that because if it goes out early
36:35it can move the markets et cetera.
36:38So I would get an embargoed.
36:42Sort of results usually on a a
36:45call from a reporter on a on a on
36:49a Sunday afternoon for as these
36:51results were coming in saying I have
36:54something that I will share with you.
36:56I cannot tell you what it is but
36:58are you available between this
36:59hour and this hour?
37:00I'll send it to you 1520 minutes
37:03before I call you on a Sunday evening.
37:06We're was like it was like we get
37:08embargoed stuff all the time but this
37:10was strictly strictly embargoed.
37:12For for understandable reasons.
37:15And so.
37:17So, so as soon as I remember,
37:20the first vaccine comes out the 1st.
37:25Of, you know, an announcement comes out,
37:28it works.
37:29Within hours of that,
37:32I get a start getting emails on the
37:34first one from a pretty senior Yale
37:37colleague saying my daughter is
37:39also a physician and she's pregnant.
37:41What do you think about the safety
37:43of this vaccine in pregnant women?
37:45Remember,
37:46no pregnant women were included
37:47in these trials.
37:49And this was after years of
37:50advocacy saying that, look,
37:52and I'll talk about the ethics of it,
37:54that look,
37:55you can't do that because otherwise
37:57you're putting them by, you know,
38:00avoiding.
38:01Including them in in in primary trials,
38:03you're putting them at risk
38:05by giving they will get
38:07it, they'll have to get it
38:08especially the high risk months.
38:09And so therefore you know that was a concern.
38:12So very briefly I don't have
38:14the time to show all the data,
38:16but essentially very early on
38:19we knew that ICU admission. Was.
38:25Was more likely if you were
38:27pregnant versus non pregnant.
38:29It was behaving like a respiratory
38:32viral infection, like flu.
38:33Like other infections that do,
38:36RSV is not particularly
38:37dangerous in pregnant women.
38:38Not all of them do it, but it was
38:41not like it wasn't a huge surprise.
38:44The other thing is invasive ventilation
38:46and ECMO risk was higher if you're
38:49pregnant versus non pregnant
38:51and it was looking at you know,
38:54treatment bias, et cetera,
38:56healthcare seeking, no,
38:57even if you accounted for that,
38:59these were adjusted.
39:00That's why I'm just showing adjusted
39:02relative risk and odds ratios.
39:03This was very early on.
39:04So we knew this and since then
39:06impact on birth outcomes has
39:08come out and all of that stuff.
39:10But here's the thing I want to focus on.
39:13How do you not make this policy
39:16taking into account that 75% of
39:19your healthcare workforce is women?
39:21Uh, and at a given time,
39:23like the day you start your
39:27vaccination program.
39:28Approximately 330,000 are pregnant.
39:33You know,
39:34babies are not brought in by stocks.
39:36They're not surprises that come out of,
39:39you know, at the individual level,
39:40they some of them are surprises.
39:42I was a big one after 20 years of marriage,
39:44but having, you know,
39:46we can plan for this and we did.
39:50And these were the first set of
39:52questions that these were the most
39:54agonizing questions that we were,
39:56you know, the advisor.
39:57So we were meeting.
39:58Three times a week, et cetera.
39:59And that was the big data gap.
40:01And even now last night I
40:04actually sent an e-mail,
40:05again,
40:05I cannot disclose even now we
40:07are going back and forth about
40:09not just to vaccinate but where
40:11to prioritize pregnant women.
40:13So even now we're doing this kind
40:15of stuff like this last night
40:17in The Who process earlier on
40:20the ACIP had this long winded.
40:23Treatment with absence of
40:25evidence or we have this data in
40:27the absence of direct evidence,
40:29but essentially said give it to them,
40:33but said that in in paragraph or two which?
40:39Yeah, I love sound effects.
40:41I know someone is equally frustrated.
40:44As frustrated as I am.
40:47But, but yeah. And so.
40:51So they did that.
40:52But but the society for
40:54maternal fetal medicine.
40:56Was even more proactive.
40:57They came out and said that look,
41:01based on what we know about disease,
41:03based on what we know about
41:05vaccines generally in pregnancy,
41:07based on what we know about how
41:09the vaccine is behaving in terms
41:11of antecedents of the the effects
41:13that we are concerned about.
41:15So you know,
41:16if the vaccine was causing the
41:18crazy amount of faith fever and
41:20other aberrations in the non
41:21pregnant vaccination that healthcare
41:24workers especially were considered.
41:26Prioritize.
41:28Otherwise prioritized for vaccination
41:31should be offered the vaccine.
41:33If pregnant,
41:33it's offered the vaccine is where it started.
41:37And so you know I can tell you
41:39like so I used to make up for
41:41still wake up at 5:30 for calls
41:43because who calls are aligned with
41:45have to align from Seattle to.
41:49To to Australia and New Zealand
41:51and on all regions in between.
41:53So they happen at odd times you
41:55know you had to make that decision
41:58and and and I wish we did it better
42:01in terms of generating evidence.
42:02Now it's certain countries
42:04prioritize et cetera and that's
42:05the discussion we are having.
42:07What do we do as we go into
42:09the routine vaccination phase?
42:10A little bit about the ethics and
42:13and I want to again give it to
42:15you as a snapshot and especially
42:17for early stage colleagues etc.
42:19As you develop your careers,
42:20as you think about how to make
42:24develop evidence that impacts policy.
42:27Uh, so to conventionally,
42:30you think about vaccine ethics
42:33as risk versus benefit.
42:36In fact, this paradigm.
42:37And so as a detour,
42:38you introduce that that I'm going to Texas,
42:40you to Southwestern as the founding
42:42Dean for a new school of Public Health.
42:45Well,
42:45my office will overlook a Plaza
42:49called Seldom Plaza,
42:50and Don Selden was a Yale faculty
42:54member recruited in the 1950s.
42:57To help set up a new Medical
43:01Center in Dallas in Army barracks.
43:04And he ended up being the default
43:08chair of medicine because the other
43:11only other full-time faculty member
43:14in medicine who recruited him left.
43:16So he was the only full-time
43:18person and became a legendary
43:20chair and built that institution
43:23into a sort of reasonably effect,
43:26actually very effective research.
43:28Or have they?
43:28They have 6 Nobel prizes for a young,
43:30relatively young institution,
43:31and all of that stuff stayed the
43:34chair of medicine for 36 years.
43:36But here was the other thing he did.
43:38He was,
43:38he testified in the Nuremberg Trials as
43:40a US before coming to Yale as a U.S.
43:43Army doctor.
43:44And then his lifelong interest in
43:46ethics led him to chair what we
43:49call the Commission of Ethics.
43:52It had a slightly more official
43:54name that met in Belmont,
43:57MA and became the Belmont report
44:00that everyone has to study in our IRB
44:04exams, you know, tests.
44:05So he was a practicing physician.
44:08The reason I'm saying that is that, you know,
44:10it's a small world of people who have had
44:13who have developed these paradigms and.
44:15This risk benefit came out of these kinds
44:17of looks, looking at risks and benefits
44:21along different dimensions. So yes.
44:24As maternal vaccination came along,
44:27a lot of people applied the
44:29conventional risk benefit paradigm.
44:31But, but, but two sets of risk
44:34benefits mom and baby separately,
44:36risk and benefit.
44:37And in fact there was a paper in
44:41Lancet infectious diseases with three.
44:44WHO colleagues?
44:45Two of them really good friends of mine now,
44:48subsequently, and a prominent bioethicist.
44:52From Europe, who worked closely with WHO,
44:55they went through this reasoning
44:57and then said that based on this,
45:01maternal vaccine should only be recommended.
45:05Number one, because of this framework,
45:08if it's beneficial against a severe
45:12outcomes be both for the mom and the baby,
45:17so for this.
45:19Flu vaccine would be iffy because it's not
45:22preventing severe outcomes according to them.
45:24Then we subsequently show that
45:26it's preventing pneumonia.
45:27But even before that, although we had
45:31also shown birth outcome prevention.
45:32But Pratas says RSV no,
45:35that didn't say that.
45:36So while I was sitting in my
45:39office in Atlanta and a faculty
45:41member who was a former mentee,
45:43former PhD student who happened to be
45:46pregnant, came into my room and said like,
45:49look, you know,
45:49if you look at the parts of this reasoning,
45:51it does make sense.
45:54But as a whole,
45:56it really doesn't make sense because,
45:58you know, moms want to protect their babies.
46:02And I said, like, wasn't there a woman
46:04in the room who raised their hand?
46:07And said.
46:09That look, it doesn't make sense.
46:11I want to protect my baby,
46:12and I should have the right to
46:14actually do that without someone
46:16being patronizing about it, et cetera.
46:19And of course,
46:20well,
46:20guess what we found in the authors list?
46:24There was no weapon,
46:25and that this is important.
46:27It's not just sort of gratuitous snark,
46:29because that tells you that in
46:31these kinds of representation is
46:33not just about sort of tokenism.
46:36It's about sane, rational decision.
46:38And I'll show you why.
46:39That's it's a more sane decision
46:41and rational decision.
46:42So here's what we did we said look
46:44you know well meaning colleagues came
46:46up with this framework and prevented
46:49presented it in Lancet infection
46:51disease which is a prominent journal.
46:53So first of all we have to make our
46:57paradigm more salient more prominent
46:59so that you know we are heard it's
47:02not it can't be you know a me too kind
47:06of a write up so we collected first of all.
47:09A diverse, intellectually and
47:11otherwise diverse group of people,
47:13bioethicists or OBGYN people
47:15like myself and said,
47:17look,
47:18we need a new paradigm for
47:21maternal immunization.
47:22That has certain features and at
47:25the core of this is the legitimacy.
47:29Of a mother's interest in the
47:32welfare of her fetus
47:35and infant. Because it's not a side
47:38thing for for someone who's pregnant
47:40to say that I want to protect my baby,
47:43etcetera, and I should have what there
47:46was a keyword that they have agency,
47:49so I just autonomy. It's agency.
47:52Don't be the knight in shining
47:54armor who says no, you can't have
47:56that agency to protect your baby.
47:58The second thing is when
48:00you make these decisions,
48:01whether at the clinical level
48:03or a public health level,
48:04at the village level or
48:06in an advisory committee,
48:08or in the authorship of an ethics paradigm,
48:12you have to have those who are
48:14going to be pregnant or are
48:16pregnant in your decision making.
48:19And then we say the part
48:20this is different you limit.
48:22So I've I've done a lot of work on mandates,
48:24I'm pro soft mandate.
48:25I was involved with discussions
48:27with our mandate policy and
48:29continue to be engaged with this
48:31and and Kyle has taken a few notice
48:34especially the university side.
48:35The healthcare does slightly
48:37different approach.
48:38We have taken a pretty consistent
48:40but middle of the road.
48:41We are not draconian,
48:42we are not sort of throwing
48:44people out on the street,
48:45but on the other hand we
48:47have a pretty clear mandate.
48:48So that was like the that there
48:50was no accident but here I said
48:52because there are two entities
48:54involved there's a limit to mandating
48:56especially new vaccines in this
48:57context and so there was empirical
49:00evidence it wasn't just anecdotal.
49:02So we went to we we did several
49:05studies so this is in Kenya we ask
49:08we put women in a bind intentionally
49:10as pregnant women in a nationally
49:13representative study in conducted an
49:16antenatal clinics in Kenya and we asked them.
49:19For example,
49:20when deciding to get a vaccine,
49:22whose benefit do you prioritize?
49:25And this is like a direct prioritization.
49:28Whose benefit do you prioritize first,
49:30mother or the baby?
49:322/3 of them said right.
49:34All of them said it's it's.
49:35The rest of them said it's a Co
49:38prioritization now,
49:39but even if you frame it as a tough choice.
49:42Women choose pregnant women choose
49:45babies to prioritize first.
49:47So how do you take that agency away?
49:49How do you not do trials?
49:55That include pregnant women or
49:56at least have a second trial
49:57ready for pregnant women.
49:59And so a lot of us are pushing for
50:01actual legislation around this that
50:03your licensure requirement should
50:04have early studies in pregnant
50:06women and so on and so forth.
50:08So.
50:09So you know this was before the vaccine,
50:11so this was led by Ruth Faden who
50:14actually she and I actually did a
50:16lot of the ethics side of and policy
50:18side of work on The Who working group.
50:20Et cetera,
50:21but but focusing on public health
50:23emergency and this is the slide and
50:25this framework is before the pandemic.
50:27So yes we were successful but we were
50:30also not successful in certain things.
50:33And so therefore you know
50:35that keeps us charged and
50:37employed to do for the next thing to
50:40make sure that pregnant women have
50:42this you know we we vaccinate pregnant
50:44women for themselves and their babies
50:46in public health emergencies and
50:47otherwise some of the interesting
50:49work we are doing is so remember the.
50:51Two trials, these babies are now teens
50:54and some of them are approaching to be
50:57not young adults but late teens early
51:00like their ages are 1415 to 1819.
51:03So we have gone back to them.
51:06It's a randomized trial.
51:07So we have a study to look at
51:09their cognitive outcomes.
51:10We have educational attainment.
51:12We have all sorts of other stuff
51:15and that's the beauty of randomized
51:18controlled trials in in South Africa and.
51:21Bangladesh,
51:21I don't know what the outcome will be but.
51:25If we are able to show that
51:27these cumulative effects,
51:28prevention of early pneumonia,
51:30prevention of reduction in adverse birth
51:33outcomes etcetera has long term impact,
51:35that's a pretty convincing case
51:37for doing something about it.
51:38At least we hope so.
51:40You know a lot of the policy
51:41is wisdom based policy,
51:42not evidence based policy,
51:43but that's a different thing.
51:45So you know there's a lot of this work
51:47is all of this work is actually teamwork,
51:49our colleagues in Kenya, Guatemala,
51:51Pakistan and sort of various
51:53folks who have worked with me.
51:55On on this kind of work.
51:56Thanks.
51:57And this is not a complete list of people.
51:59Thank you.
52:08Thank you so much.
52:13Someone is raising their hand or
52:15they're waving at me. I don't know.
52:20I think that was Amanda.
52:21I think that might have been a clap,
52:23but Amanda, please.
52:25Sorry. Thank you so much.
52:28So that was incredibly compelling.
52:29I think if there's any pregnant
52:32individuals in the audience,
52:33they may be equally terrified and
52:35reassured about what can be done.
52:36But what can also go wrong in pregnancy?
52:38And do we have any questions for Doctor Omer?
52:46So we've heard a lot about anti
52:48vaxine and there are this those.
52:53Cross political lines a little bit
52:54and I'm wondering if what you're
52:56doing or what you're aware of others
52:58are doing to try to influence and
52:59frame and and different tax people
53:01maybe taking including yourself.
53:03So 1/3 of My Portfolio is vaccine
53:05acceptance for the last 20 years.
53:07Actually that's what my PhD was on.
53:12And. Even though I wanted to do my PhD
53:16on field trials in low income countries,
53:18I I got annoyed by the fact that
53:19people who are not taking vaccines.
53:21So I ended up doing the PhD thesis on this.
53:24So I Co chaired with Peter Hotez,
53:26who you may have seen on CNN,
53:27The Lancet Commission on Vaccine
53:30Acceptance and hesitancy in the US
53:32and we have come out with all sorts
53:35of recommendations that range from the
53:38fact that the government hasn't funded.
53:40Upstream research to actually do this
53:44so we expect evidence based vaccine
53:47development pathway is not but but you
53:49know fluff based vaccine acceptance
53:52interventions if you're not going to
53:54fund this kind of stuff especially
53:56for early stage investigators you
53:57know I'm going to get good science.
53:59So that's you know one thing.
54:01The other thing is I've been working
54:04with Meta actually and WHO and UNICEF
54:07to do randomized trials online
54:09like 10s of millions of people.
54:10What kind of messages work?
54:12So that's a whole different conversation.
54:14Well, we have evidence there.
54:16The third thing is to depoliticize
54:19vaccine conversations.
54:20So perhaps.
54:23You know, we have evidence worked
54:25with folks in political science,
54:27et cetera, that showed that we had a.
54:34If focus on. If we focus,
54:39we politicized vaccines.
54:40It was gonna backfire.
54:41For example, if you.
54:44Approved it close to the election
54:46would have had a backfire effect.
54:48We didn't do that.
54:49So even in 2021 it would have been
54:51better to make vaccines a little
54:53boring and have the vaccine briefings
54:55and public health briefings from
54:57Atlanta by uniform varying public
54:59health service people rather than
55:01well meaning well qualified political
55:03appointees in DC but you know,
55:05I say that with a lot of respect for
55:08people who were in charge, et cetera,
55:10but, but this is what happens.
55:12So we did.
55:13A study that came out in PNAS
55:15where we look followed the two
55:18snapshot of white evangelicals etc,
55:20which was a group that was had lower uptake.
55:23And we found that between fall
55:252020 and spring 2021 all the
55:28Persuadables were persuaded and
55:30nothing was working on them and
55:32likely was political polarization.
55:34So that.
55:35But the other thing is we did this study
55:37with Mushfiq Mubarak and Economics
55:3912 country study right before the
55:42the the vaccines were rolled out.
55:44And we found was,
55:46among other things.
55:47That consistently,
55:48and that was the least surprising part,
55:52was that the most trusted source of
55:55vaccine information was healthcare
55:57providers across cultures.
55:58This is what I have seen in 20 years.
56:01Every single time.
56:03And we're not leveraging that lots.
56:06Some of us,
56:07some of us have been jumping up and
56:09down since spring 2020 that we need
56:11to have a national CME program to
56:14incorporate evidence based approaches.
56:16So we physicians are primary
56:19care providers and all of these
56:22folks are really good at most of
56:25them are good at communications,
56:27but vaccines have are different
56:30and so there are approaches that
56:32work and so we developed our own.
56:34Hmm.
56:34So this was in,
56:36this is the most popular Yale
56:39CME program because it's open
56:41to everyone and the second most
56:43popular in first eleven months,
56:454000 people had taken it 4 certification,
56:49et cetera, without a lot of advertising,
56:51et cetera.
56:52And now it is I think more than you know,
56:54pretty much larger than that.
56:56And the second most popular was the
56:59state of Connecticut Mandatory CME
57:01that folks had today and there was one.
57:043rd popular than this,
57:05so there's a need for this.
57:06That's the other thing we do
57:08at the policy level.
57:09We have been pushing,
57:10and I've been pushing before, pandemic.
57:12There's a step that has taken now that
57:14a create a code for vaccine refusal,
57:17it has been now created and
57:20then reimburse it for it.
57:22Make it, you know, give primary care.
57:26Pediatricians barely break even,
57:28for example, on vaccine delivery,
57:32et cetera, in this country,
57:35even after Obamacare.
57:36And if you,
57:37if you throw in all sorts of other,
57:39you know, vaccine counseling,
57:41it's it's a losing proposition.
57:44So, so these are some of the
57:45individual and policy level
57:47recommendations that we can do.
57:51Sure. Thank you very much.
57:52Quickly what's the advantages and
57:55disadvantages of combining the vaccines
57:58like same visit and same while
58:01COVID and COVID and flew together.
58:04So wonderful question.
58:07So by default you start with the
58:10position that you know you test
58:12them separately and then you usually
58:14then you do smaller studies to
58:16see if they work and so you you
58:18don't take it for granted that.
58:20Every vaccine will be OK giving together
58:22both in terms of the accumulative
58:25or multiplicative immunogenicity,
58:27reactogenicity, short term side
58:28effects and all of that stuff.
58:30So for the vaccines, we routinely use flu,
58:33pretty good fluent protasis
58:35flu and COVID works well,
58:38but it wasn't sort of a given position.
58:41We know based on evidence et cetera.
58:44So, so, so yeah, do it because
58:46there is a programmatic incentive,
58:49it decreases in equities.
58:50The poorer you are,
58:51the fewer visits you do for vaccinations.
58:56Our political question,
58:57given the fact that we're about to
59:00have a GOP congressional oversight of
59:03the COVID response and executing Dr.
59:07Fauci and the like,
59:09is there in within the health community.
59:12Has there been a discussion about how
59:15to counter what is likely to be a kind
59:18of hysterical onslaught about this?
59:21I think we need to have.
59:24It is unfortunate.
59:26And I like, uh, Tony.
59:29I like doctor Fauci's response to this.
59:31His response to this is, look,
59:34Congress has a role in oversight.
59:38If he's called, he'll show up.
59:40First of all, show up, etcetera.
59:42And then you know he is no shrinking Violet,
59:46but. Look at the big picture.
59:50So I'll give you an example.
59:51In 2019, there was a Senate hearing that
59:54where I appeared on measles vaccination,
59:58there were measles outbreaks happening there,
59:59childhood vaccination in the Senate
01:00:02Health Committee, Health, Education,
01:00:04Labor and Pensions Committee.
01:00:06It was organized by Lamar Alexander,
01:00:08who was the committee chair,
01:00:09and Patty Murray,
01:00:10who is the ranking member.
01:00:12He was a Kumbaya from Republican
01:00:15and Democratic sites, etcetera,
01:00:17with one exception, Senator Ron.
01:00:20And Paul who misquoted Ben Franklin so
01:00:23and and as in you know immigrant who
01:00:26has the zeal of the convert about U.S.
01:00:29history and civics.
01:00:30I I read up on it before
01:00:32deciding to become a U.S.
01:00:34citizen next day.
01:00:35I actually wrote a Washington Post
01:00:38op-ed going after him for among
01:00:41other things misquoting Ben Franklin
01:00:43in a in a in a Senate hearing.
01:00:45But the reason I'm saying
01:00:47is he was an exception.
01:00:48Senator Cassidy from Louisiana
01:00:50actually came back to him.
01:00:53So he didn't ask any questions so that
01:00:55none of us could sort of clarify.
01:00:57And there were a lot of things he
01:00:59said about positively about vaccines,
01:01:00too, you know, to set aside the start.
01:01:03But the bottom line was there was
01:01:07enough bipartisan support for vaccines,
01:01:10especially in seven.
01:01:12Having said that,
01:01:13there there's always been that there
01:01:15was a senator from Indiana who would
01:01:17you who fanned the flames of the the
01:01:19vaccine autism controversy for for a long,
01:01:22long time.
01:01:23And so we need to make sure
01:01:26that we don't get swept up.
01:01:29They realized that political
01:01:30doesn't have to be partisan.
01:01:33And there are serious people who were
01:01:36vaccine allies and are ostensibly
01:01:39are vaccine allies from in on all
01:01:42sides of of this political spectrum.
01:01:45In fact, on the other hand,
01:01:47Marin County in,
01:01:48you know,
01:01:49as crunchy granola as it gets
01:01:52in the Bay Area used to be.
01:01:56An epicenter of vaccine refusal until
01:01:58recently in California and May very well
01:02:01end up going back to its old position.
01:02:03So we first of all,
01:02:06irrespective of your political leanings
01:02:08or our political leanings we need,
01:02:11we cannot afford to get on
01:02:12a high horse around this.
01:02:14Vaccine opposition can come from all sides.
01:02:17Right now it's more right leaning.
01:02:20But that wasn't always the case.
01:02:21There may not be always the
01:02:23case going forward.
01:02:24Second, their allies,
01:02:26Senator McConnell,
01:02:27who had polio when he was young,
01:02:29is a big vaccine ally on that side.
01:02:34Senator Romney is a big basin
01:02:35alive in in the house.
01:02:37There are a lot of folks who are pro
01:02:39vaccine and both sides of the aisle,
01:02:41et cetera.
01:02:41So this is how you handle it as
01:02:43a public health community.
01:02:44You just can't kid around
01:02:46with this kind of stuff,
01:02:47not get inflamed and then play the long game.
01:02:51The long game is vaccines
01:02:53are effective and safe.
01:02:54They benefit everyone in blue
01:02:56States and red States and blue
01:02:58counties and red counties.