FDA Direct: From Menopause to Food Safety: FDA's Latest Regulatory Priorities

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I'm feeling old because we got so many young people here at the FDA.

And so it's pretty wild.

We got ... Hey Vinay, great to see you again.

And good to see you, Sanjula. So,

there are so many amazing people here at the FDA,

including a lot of young people.

I walk down to your office and there's a new person at every desk these days.

I mean, what's going on?

And a couple of them walked out here with us from my office to say hello.

We got,

Ceila and Ben is here, and Alex.

Alex is helping operate this camera.

So thank you, Alex.

And these lights are blinding, but.

And toasty.

It's like hot.

We've come a long way from just sitting in the office saying, hey, let's just walk

around the corner in the lobby, sit in those chairs and turn a camera on.

Now it's like a mini production. It keeps getting built up.

You know, you're a big, natural light guy.

We still got the natural light, but it doesn't make it all the way in here.

It doesn't make it all the way. And so they got

a bunch of big lights in our face. Gotta work with what we have.

I haven't seen the two of you together in a while.

It's been really busy around here. Hey, you know, I'm over in CBER there.

I don't know if you notice, at the end of the road out there, it's

like a half a mile down on this campus, so it's like a half a mile.

I hope you get a ton of stuff for the day. And I have to walk to see him.

You don't walk to see me. Let's be clear about how it works.

You don't have to walk in heels.

We have had farmers market

twice a week this week, and we're going to keep doing that.  Beautiful campus.

Lots of people. It's been busy.

People love that farmer's market. Busy.

But I hear it's collapsing. Yeah. Right.

That's right. Collapsing.

Well, I'm surprised you could make it in here with all the collapsing FDA stuff.

Yeah, the tiles are falling in here.

This is amazing facility. Great place, great people.

Tons of people want to come in and work at the FDA.

And we're interviewing amazing scientists and other core staff to come here.

It's it's an exciting time at the FDA.

And we might hit, some record numbers.

And in

terms of performance indicators of the FDA this year, don't want to jinx it yet,

but things are looking really good for hitting all our targets.

And maybe a record number of drugs that we approve this year.

We'll see. We'll see.

Of course, you don't know what's coming in the door

and what's further down the pipe Is that the ultimate metric

of success for you?

No, I don't think so.

Look, I think we want a great workplace culture.

I think we want to keep all the trains running on time.

We want to make sure everybody has the resources

they need to do their job well.

And I think we want to

innovate and try new creative things like the National Priority Review.

Like, I know you're doing lots of stuff in the gene therapy space.

Remove the REMS and some other regulation.

I know you're drafting a lot of stuff. You're working on the,

plausible mechanism pathway

and so we want to get it right, but we're working on new pathways.

The animal testing workshop that was, recent.

So we can think about what can we do to reduce

some of the idle time in the process.

So, yeah, I mean, let's talk about metrics of success.

It's a really interesting question.

So we're the Food and Drug Administration, so what have we done in foods?

I mean we've already done so many things in foods, from removing

petroleum based dyes to approving alternative dyes,

a whole bunch of initiatives around infant formula

that you've already talked about and that are in progress.

Kyle has come here and explained the food side of things for a lot.

You know, titanium dioxide and Skittles.

They took it out voluntarily, too.

Yeah.

I mean, we've been talking. The bully pulpit.

You know, they felt the bully pulpit of the FDA. Yeah.

Now let's talk about drugs.

So one metric that I've heard and in the past I've criticized

is that the sole metric of drug success isn't just the number of new drugs

you've approved. That's right.

But having said that, we're on pace to be one of the highest years in record,

but it's also the quality with which we perform

reviews and say no when we do say no.

And just today, I was in CBER and I was giving a talk to the CBER

group, the Biologics Center, and I praise them for our recent,

supplemental biologics licensing agreement to Moderna.

But I also praise them

for a couple of CR letters, which are What's a CR letter?

Yeah, yeah, a complete response.

It's basically a very formal and polite way

to explain to a company why they're not going to get an approval now.

Not at that time, not at that time.

It doesn't mean that they won't get in the future.

In fact,

many people use that as a learning opportunity

to improve manufacturing or get some better data,

more credible data, and come back to us.

And they do get approval eventually. And in fact,

it's sort of a service to companies to have it so patiently explained.

And I compliment the teams for writing what I think was professional.

Clear, succinct, thoughtful

guidance and reading through hundreds of thousands of pages.

Probably Marty has a big application to read and giving that letter.

So the metric of success is, as Marty says, you keep the trains running on time.

You give approval where it's warranted.

You are flexible where it's needed, but you also politely tell people

why you're not going to approve everything.

There's a tremendous value in well-written letters

and other correspondence coming out of the FDA.

I have seen in the past documents coming out of the FDA that are illegible.

They're uninterpretable.

It's like getting the Rosetta Stone, like, what do I you know, what's this saying?

You know, what's the thing? It's like, I'm sorry I wrote you a long letter.

I didn't have time to write a short one. The TL;DR section.

Yeah, well, sometimes a short sweet letter is like what people want.

These are the takeaway points is what we need to do

to turn this around, get back in there and get a resubmission.

That's right.

It shouldn't be.

It's sort of thought diarrhea on a CR letter.

And only the CR letter, we want them to be clear and good.

We want to improve communication.

We want to have more correspondence with sponsors.

But those CR letters are going to be public information.

They are public.

We announced that well we're it it takes time honestly to redact them really well.

Like we want a human redaction. We want lawyers to look at it.

We want to make sure we redact things well.

Marty, maybe just explain why we have to do redactions.

Well, we don't want to expose, commercial proprietary information in the letter.

We want to respect the sponsors

and the inventors and developers that are submitting these applications.

But the thinking of the FDA has been in a bit of a black box.

And so now anyone can see exactly

how the FDA thinks in those responses. And

how that study section.

that group that is in charge of reviewing that review group,

there are themes.

And so people can see summary statistics.

These were rejected for manufacturing.

This is the number of times it was rejected because the reviewer

or that team asked for a certain trial design that was not done.

It's amazing how many times.

Yeah. The trial design is specified by the FDA,

and the companies might say, well, you know what?

We're just going to do it differently and do a crossover and, you know,

they'll just have to live with what we're going to send them.

Oh, so that's interesting.

So first of all, I think this is this is a topic that he even undersells

how important this is.

Okay.

So this is this is something I've been interested in for a decade, which is that

people, the general public

and patients deserve data transparency.

I've been a proponent for, you know, NIH papers

to be freely available to all the taxpayers who paid for that.

I've been a proponent for the New England Journal and other prestigious journals

to make the primary,

individual, patient level data available for the primary figures,

which was once an international Committee

for Medical Journal Editors initiative that they walked away from.

And I've been a proponent,

along with many other people, that the FDA should release these CR letters.

But before this Commissioner,

there has been no FDA commissioner that took it all the way to release.

And by the way, you're not the only one who has expressed value in that.

Right.

Many people have been talking about this for years.

Many people who even disagree on other FDA philosophy all agree

that the CR letters,

insofar as legally possible, should be entered into the public

domain because of the advances in artificial intelligence.

We have a first pass redaction because of our excellent staff

here, we're getting the lawyers to look through these.

We've already released hundreds of them,

including many more than a dozen that had never been released before.

I noticed that some news outlets say

you only release things have been released before.

I think that's because you haven't read them all. You're right.

When you read them all, you'll see there's a bunch you haven't read before,

so maybe you want to get an expert that reads it before he gives a quote.

There's a lot of value in having it as a centralized data set.

We can study it. So you don't have to go looking all over the internet for it.

And now we're releasing even more and even more to come.

And the vision is that someday you'll release them in real time.

Now, the legal thing is, of course, that the closer it is to the actual moment,

the the CR letter is that there's a there's a risk of identifying the company

and these sorts of things.

And although the company owns the proprietary information,

the trade secrets which we acknowledge they do according to current law,

they don't own the thinking of the FDA reviewers.

That's right. That's the public domain.

And the public deserves to see that thinking.

And I think if the more sunshine you bring on these letters,

the more people will really appreciate that the FDA

is an extremely thoughtful place with mission driven people who work above

and beyond what's required to really guide companies to approval.

We're not even wrong to say yes or no.

We're trying to guide you to the path of bringing a successful product through.

Just follow the advice you know when you're getting it

To play that out longer term, right.

So that's good for the public.

You can learn a lot from that information.

How does that help drug developers?

Like is it gonna help them, reduce them making the same mistakes?

I guess, like if you're a big company, a huge company with 20,000 employees,

you have a wealth of knowledge.

You got a lot of people in your company who's brought drugs to market,

and you bought their biotech and all these things.

If you're a small company

and you care about a rare disease, and we have met so many CEOs,

they are running a team of five, ten, 15, 20 people.

They don't have 20,000 people to draw from.

These companies benefit so greatly.

You're really helping the mom

and pop American biotech company, the small entrepreneurial biotech company.

They can learn from the lessons of all the ones that came before.

They can have a competitive bid, not an advantage, but they can at least

try to get a level playing field with the big boat, big players.

It's a tide that raises all boats.

That's right.

Because if you if you really get the individual drug developers in a room,

they want predictability.

And markets like predictability, capital markets like predictability.

But drug developers like to be able to go into our process

and know that it's a level playing field.

And here are generally the hazards and the quicksand that

other previous drug developers have fallen into.

And that can help guide them because,

when it's not clear, it

lengthens that the process and they're just stumbling on the same.

You know,

I remember there was a chord in the ICU once that everybody was tripping it.

Right. They want you walk in, everyone's tripping.

And they said, oh, are we going to put this orange,

you know, mastic to push it down, push it down.

But cut that cord.

Yeah. I'm like, how about plug it in somewhere else?

Everybody is like, you can blame everybody for

stumbling on it, but these drug developers can stumble on the same thing.

And look, if the reviewer's review team is particular about something,

it becomes more clear.

And, you know,

he raises an interesting point, which is that

one of the things we heard on our listening tour

is that sometimes there's a regulatory schism, a difference of

opinion between CDER, the drug branch, and CBER, the biologics.

You make all the CR letters public.

There's a potential that someone out there will say like, look,

this is a space where you all need to reconcile your point of view, get in

the same position on this point of view. Help our internal reviewers.

Exactly. It can.

It can help us be better, too, because,

you know, as great as this place is and as thousands of tens

of thousands of people we have working here,

you can always benefit from someone else looking at the data

in a way you haven't thought.

Either way, thank you for not only being you've got two hats and two titles here.

Our CMO for FDA. I read I have three hats.

Marty, three, 4 or 5.

I don't know that no one told me that three hats or three, I have like three.

There's three

Got to get two hats.  Just two hats.

And he's also running CBER. And,

I have been And four jackets.

Four jackets, two hats. Yeah. Of course.

Yeah. Is one of them green?

And I don't have a green jacket and play it like.

Oh, no.

Yeah.

So, the morale at CBER has been amazing

and increasing, like, I'm hearing such great things.

So congrats and good work at CBER.

And we're going to hopefully have, new CDER leadership.

Soon.

The current acting head of CDER is announced.

She's going to move on, and we're trying.

We've been begging her to stay as long as she can.

I love her personally, I love her, she's terrific.

She's terrific. And she's been. And she's brilliant.

Brilliant and a perfect partner to help us think creatively about new ideas.

She's been here a while. She's got a lot of wisdom.

And so, she generously offered to stay here.

But we are.

We have a lot of amazing, incredibly credentialed individuals

with impeccable, backgrounds who want to come and run CDER.

So we've been talking to some incredible.

It's inspiring to see the number of people

that want to come in with impeccable credentials.

As soon as we decide, we will let folks know.

But it is. It's getting close.

We're seeing some pretty good talent. Yeah. Be good.

Can you talk about just what what workplace for a second?

You alluded to this,

but you know,

we've done some number of things in CBER that I think people have really enjoyed.

And here are a couple of those things.

We've got what we call the CBER directors round robin.

So just before I got here, the reason I was running late

was we had for like an hour and a half, two hours.

We get the individual review teams, they present an application

they're working on that has some conundrum,

something they're they're talking through, working through.

Then I invited everybody at CBER who's a medical reviewer,

a PhD or statistician who's interested to drop in.

And so we get people from different divisions who focus on different things.

And the only ground rule is we're going to have civil discourse,

say, your opinion, defend your opinion, and we're going to get the opinion

of people in the room. And it's been a lot of fun.

I mean, I'm learning things I never knew before.

I'm hearing different perspectives.

I'm seeing people debate in real time.

I think it's it's why people want to work here.

The scientific, intellectual stimulation. If you sort of democratize

the process and you get more input from more, you know, expertise.

So that's really. It's related to input and decisions.

I know there has been a kind of a recent decision

that came out of your, your shop and you're up a JAMA paper on that show.

Oh, the safety label.

Yeah. Oh, I thought yeah. Okay.

Yeah. The safety label change.

So yeah, the commission I put out a paper on Monday of this week

announcing an important class safety label change for the mRNA Covid 19 vaccines.

And what it basically says

is that all the mRNA vaccines into the future are going to get a warning.

If you're between the ages of, a man, between the ages of 12 and 25,

you're at elevated risk of myocarditis.

And that's important. And here's why.

One, myocarditis is an inflammation of the heart,

that causes people to have chest pain and feel unwell

and even go to the hospital when you have it.

And what we've learned through time and an FDA sponsored

study is the bad sequela of it don't go away immediately.

So we follow these kids out. Thinking about scarring that could alter

the conduction of the heart.

Absolutely.

We follow these kids about 160 and 170 days.

We perform magnetic resonance imaging on the heart and we see late

enhancement, late gadolinium, the the radio, the radiologic tracer.

We put in the IV enhancement in the heart.

And as the Commissioner points out, that historically is a marker of scarring

or necrosis or damage to the heart tissue

and in a number of studies is a harbinger for poor cardiac outcomes in the future.

Now, just to be clear, we're not fear mongering here,

we're not saying that bad things are definitely going to happen

because we don't have that data for vaccine induced myocarditis.

But what we are saying is that every additional dose carries a non-zero risk.

The risk

is something on the odds of 1 in 37,000 for men in this target demographic.

And it's not, as has so often incorrectly

been portrayed, as always mild and always resolving.

It's not always mild.

It can be severe.

Some of these kids are on pressors and chemo,

There was a death in the New England Journal initial series from.

Absolutely.

There's been a documented death

from at least one death multiple deaths in the in the Asian nations.

So it can lead to horrible outcomes.

It can have scarring people who are on long term antiarrhythmic therapy.

And what's under discussed

is a lot of these boys who've had it are told they can't play sports.

And when you're a 16 year old boy, I mean, that really is

a huge quality of life decrement not be able to play sports.

So what the current FDA, we've looked at the data, the best available data.

We see that there's there's there's not a safe number of doses.

You don't get out of this risk after one, two, three, four it persists.

We've added this as a safety label warning.

So which effectively means you're giving public the information to

then make a determination.

You're saying the risk benefit ratio supporting favoring vaccines flips

when you're talking about young healthy boys.

Well now you're asking that very important question

because thus far what we've said is this is a serious safety concern

that you need to be aware of.

But you're asking the question that the moment I truly believe the risk

benefit flips in that age

group, I'm going to have to do something more than just put a warning label on it.

I'm going to have to change the indication because we by law,

and this is something we have to convey to the public.

We by law, we cannot approve products if we are not substantively certain

the benefits outweigh the risks.

And as we speak, we are modeling this with the best available data

to answer the question for 2025, not 2020.

You know, that's a different world back then.

We're going to answer the question and we are going to take safety

extremely serious and extremely scientific.

We're not going to fear monger.

We're not going to do things beyond the science,

but we're not going to ignore safety signals.

That's a big part of, you know, your focus on post-market monitoring

and constantly evaluating the data and and doing what needs to be done there.

We talk about big data. Yeah. This is the use of big data.

I mean, there are other uses too.

This is the most important use of big data that has historically been done.

And there's no substitute for big data for these kinds of questions.

You're not going to find a 1 in 37,000 risk in a 40,000 person

randomized trial, because it might happen once, you know. Right.

So it's been a busy week.

So that that happened earlier this week.

I know, Commissioner, you were.

Eating ice cream is that.

Yeah I know yeah that's where I was. You know you guys a big topic change.

But you were eating ice cream literally. I don't know if you know this.

I was literally having ice cream at USDA, United States

Like, I saw the photos.

I think I didn't get the invite for that, Marty.

I got the I could eat some ice.

It was a very limited scientific group.

I got an expert tasting. A little tasting.

Yeah, but they've taken out the, the the dyes. Right.

The petroleum based some of the, the ice cream makers,

that is 90% of the ice cream industry had pledged to get rid of

petroleum based food dyes, all of them from their products, and to do it quickly.

So we celebrated with them with some ice cream

on National Ice Cream Day, which was Monday.

I saw some public health experts say, oh, it's not a big deal

to have petroleum based dyes in there.

And I was like, why do you want to eat it?

And also, don't we have randomized data that extremely

colorful foods actually increases hyperactivity in kids?

Like there's a Lancet study.

And in what I talk about observationally, it's it is a randomized controlled study

that shows that it increases hyperactivity.

You're not only have a randomized controlled trial.

And look, it wasn't perfect, but of course, it's found in association.

And at the same time, you have

parents who

are saying when they removed petroleum based food dyes, the attention

deficit disorder subsided or went away or improved,

and then subsequently it could be a year later when petroleum based

ice are reintroduced, because, let's be honest, it's hard to avoid them.

When the kids get back, you know, that behavior regresses

and then they stop it again and the behavior goes away.

So when you have parents describing that in their kids

over and over again, numerous parents, numerous families, those are data points.

It's not a randomized controlled trial, but you cannot ignore that.

Those data points. And why are we taking a risk?

We're not approving,

I guess I don't say who wants it, who wants to eat these petroleum based it?

I never wanted it in my food.

I suspect that

this part I don't know for sure,

but I suspect that brightly colored food is often used as an enticement

to get people to eat, perhaps even more than they ought to.

We were celebrating the long list of, you know, when we announced

we want to remove all nine petroleum based food dyes from the US food supply.

The naysayers out there, of course, were saying,

well, you're not really doing this.

You're just talk that now.

First they said you couldn't do it. First they said we couldn't do it.

Now they say, why did you do it?

I don't like why I say I love the blue, but also just saying it was all talk,

no show. Right. Yeah. You doing a firm action?

That's right. It's voluntary. That's right.

I don't want to sound, you know, sensitive.

The small, the vast majority of most people love it.

This is the way that they love it.

I mean, I think polling numbers show that 90 plus percent of parents

want to get these petroleum byproducts out of the food supply.

But there was this small group of naysayers,

usually, you know, it's the same group.

And so there's a list of companies that Ben, do you have that list?

Yeah. Nice strong work, Ben.

Check this out

a couple several weeks after the announcement that we want

to get rid of this Nestlé, ConAgra,

McCormick, Tyson Foods, Sam's Club.

I don't you know, I don't know how much they're putting in J.M.

Smucker like the, you know, jelly Hershey Kraft Heinz In 'n Out Burger.

And then we had the ice cream makers on Monday.

So we're making progress.

And I hear there are a couple more probably in the pipeline. There are more.

And we we're working with them because we don't want soft commitments.

We don't want like we're, you know,

we're the real deal where the real McCoy and the don't smoke us over with.

Oh yeah.

We're going to generally move towards this

general principle in the next, you know, 11 years.

We want to see these petroleum based food dyes

out of the food supply by the beginning of next school year.

That is next calendar year or soon after.

And so many have actually said they're going to accelerate the timeline

for their own.

They see the writing on the wall.

Yeah, that's something they're smart. They see.

I mean, many people have talked about this for many years.

You're getting it done.

Many people talked about the C.R. letters for many years.

We're getting it done. See our letters getting it.

And you're also making it possible.

Back to the dyes, right.

It's one thing to say we need to get rid of it,

but you're also introducing natural alternatives

and providing these companies with more options to work with.

Yeah.

What else are we doing?

We got the hormone therapy panel coming tomorrow. Tomorrow.

Yeah. Okay.

So this is an interesting topic because I happened to read your most recent book

and you talk about it in there,

and I guess. This is hormone replacement therapy for perimenopausal women.

And I think it's such an interesting topic because one, people feel passionately

about it.

So I suspect we can hear a lot of passionate speeches too.

It has a really interesting history in America.

So we're talking about when women go through menopause,

they often stop making or make much less of estrogen.

And these, you know, the hormones that are present in women pre menopause

and going through that process causes a bunch of symptoms

including hot flashes, vaginal dryness and going through that process also has

been thought to contribute to osteoporosis and a number of harmful things.

And we have a really interesting history in America

where based on observational data for about a decade and a half,

we widely promoted the use of hormone therapy based on a randomized study.

And just sorry, just to clarify, the hormone therapy is basically providing

that supplemental And exogenous and outside of the body hormone

estrogen to women who have got

who are going through, have gone through menopause.

Estrogen or estrogen plus progesterone. If a woman still has a uterus,

they recommend progesterone to add to the estrogen.

Yeah, absolutely.

And so that was what HRT that's a hormone replacement therapy.

And I think sometimes people call it hormone therapy.

Yeah.

And and and that's what people were doing for about a decade.

Then they,

they did a randomized control trial, which is considered the gold standard.

But this randomized trial is not a perfect randomized trials.

They often aren't.

It took women who were postmenopausal.

They had gone through menopause, but not just like last week like years prior.

There were many years postmenopausal.

And they randomized those women to these hormones and no hormones.

And they saw some concerning features.

Something like cardiovascular disease increased.

They saw a signal for breast cancer.

Death that Marty always points out was not statistically significant and never was.

And they probably oversold that as a risk.

And then they saw increase. In breast cancer mortality

and no increase in breast cancer mortality.

They also saw, favorable effects on bones.

But again this is women many years post menopause. Average age of 62

or something like that.

So it's not really relevant well educated population.

And so what it led to is we have a pendulum

swinging from lots of hormone therapy to like no hormone therapy.

It's the devil.

And a lot of people started to use it as an adjunct

for the perimenopausal women, for shorter courses, for shorter periods of time,

for women earlier in the menopause, they had a lot of subjective benefit.

And so it is a place where I think there are two camps.

You either love it or you hate it.

Maybe the truth is something in between and nuanced.

And that's what we try to get at the panel,

because you've invited people who are proponents, you've invited skeptics.

You yourself make no secret.

You know, you thought the skepticism went too hard.

That's what you write about in your book, I think really nicely.

And we're going to try to try to make head roads on this

really an issue that so many people care about.

Look, let's see this civil discourse play out.

There's been a tremendous amount of interest in this FDA expert roundtable.

But I, you know, I'm going to give you my

opinion ahead of this expert roundtable.

It counts for two votes, huh

I mean, we're not voting on anything, right?

We're just voting looking at the science behind

the issues. The scientific process, controversy is good.

That's that's hashed out. Let's hear that.

Well, we get to talk about it.

But not everyone likes to have debates anymore. We can talk about. Yeah.

Not everyone wants to hear alternative opinions okay.

What's your opinion? Talk about our meeting with the National Academy?

National academies.

So, yeah.

Look for for decades, hormone replacement

therapy was a miracle.

Not only did it alleviate the symptoms of perimenopause, that is the dryness,

the mood swings, the weight gain, the,

pain with, sexual activity.

I mean, there's 60 plus different symptoms of menopause,

and it helped alleviate or even sometimes eliminate some of those symptoms.

So people think of HRT

as a way to help with hot flashes and night sweats.

It's not just. It's not just that.

It's not just there are long term health benefits, but it has to be started within

ten years of the onset of perimenopause or before age 60 to get those benefits.

So in the famous Women's Health Initiative,

they were outside of that window with the average age.

And so what happens is you start having narrowing and hardening of the arteries.

Once you, your body does not have the estrogen

for an extended period of time and then it's too late to start it.

And so you will see an increase in these heart and cardiovascular complications

if you start it too late.

So that's why they say you've got to start

within ten years of the onset of menopause or before age 60.

And when you do a massive reduction in cognitive decline.

One study found a 35% reduced risk of Alzheimer's.

I mean, we have billion dollar drugs for Alzheimer's.

Who's talking about prevention of Alzheimer's?

There is some hormonal association.

Two thirds of Alzheimer's is in women.

But none of our Alzheimer's drugs are controversial at all.

Yeah.

Not no no no controversies.

Right. Yeah. Comment. No comment.

So so it literally reduces cognitive decline.

It reduces fatal heart attacks and reduces osteoporosis, which does kill women.

I mean, hip fractures can be deadly.

And the finding that there are these cardiac benefits has actually been around

for a long time.

Back in the early 1900s, Mayo Clinic actually had an observation

that when a woman had to have their ovaries removed at a young age,

say, in their 20s, for, you know, could have been a cancer or whatever.

The reason is, when both the ovaries were removed, what we now referred

to in sort of the hormonal literature as ovarian failure,

they had this markedly high rate

of fatal heart attacks in their 30s and 40s,

and they lost that cardioprotective effect.

Estrogen

Naturally occurring estrogen has always been associated

with cardio favorable effects.

But I think I mean, your fundamental point that perhaps

the effect of the product depends on when you take it

absolutely is a key point that I think is too often glossed over.

And this is classic effect modification.

The effect is modified by the state of the person taking it,

and we don't expect any pill to work for anyone at all ages.

Some pills work in different moments in time,

and I do think the commissioner has a very fair point

that when that women's health study came out because it had the word

randomized in the title, it led to a broad skepticism.

Yeah.

And, you know, and well, people will say that I am personally

a big proponent of randomized studies.

And I am you know, I love randomized studies.

But again, you can't be a slave to randomized studies.

I mean, you have to use them when they make sense.

You can't just be a complete devotee.

It doesn't make sense all the time.

And they can only answer the question they study.

They can't ask you to answer all the other.

Yeah, look, I look, I'm a randomized ologist,

but, it wasn't the randomization that was flawed.

It was the average age of.

Oh, sure, I think so for a study that was the type of scientific hypothesis.

It was the type of people, you know, they used,

I think horse estrogen or something like it was a type of equine equine.

So there were a lot of flaws to that study. But,

I'm just going to be very honest here.

My mom, went through

perimenopause around the time of that study

when women went from enjoying the benefits, the short term benefits,

not even talking about the long term.

Yet they were enjoying the benefits.

We didn't fully appreciate all the long term health benefits,

was denied hormone replacement therapy because, you know, the doctors immediately

warned everyone it causes breast cancer and flush your pills down the toilet.

And you know, there were lists, one doctor told me there were lists of panels

he had of people in his practice that were on it.

They went call off him because of breast cancer, come off of it.

And so the irony is that

it reduces

fatal heart attacks by up to 50% in some studies,

including there's randomized controlled trial data

showing these other benefits with osteoporosis and cognitive decline.

So there's randomization study these long term health benefits.

But tragically 50 million plus women have been denied

the health benefits of hormone replacement therapy because of the medical dogma

that it increases breast cancer mortality when no clinical trial

has ever found that it increases breast cancer mortality.

And even the advocates of those, even those original authors

will acknowledge to you that no clinical study has

no clinical trial, has ever found an increase in breast cancer mortality.

You know, I think I sometimes I think I learned something about you.

I'm starting to understand,

you know, what is it that motivates you in all these different issues?

I think one of the things you really don't like is you don't like dogmatism.

You don't like when people aren't even willing

to have a discussion on that topic. That's it.

And there's another one you're doing that I think is really brilliant.

And I'll tell you a little anecdote about it.

You're going to have a panel on SSRI use in pregnancy Monday, Monday.

Now, people feel strongly about this issue.

And sometimes I ask people when you feel strongly

about an issue in medicine, have you ever read about it?

And the answer is usually no.

You know, like a few issues

that there's just sacred issues and we just can't have the wrong opinion.

I know somebody who

was recently in a discussion in the pediatrics group

where they expressed concerns about pregnant women being on SSRI

and what it meant for the neonate.

Now, I think to even have such concerns is heretical in certain circles.

But we can't have this mentality that there are some questions

in science that we cannot even explore or talk about or ask.

And now that I think about the Commissioner,

I think that's what really animates him the most, is when he finds those places

where he wants to have a dialog, and he feels like

the people have not been willing to have that dialog.

Yeah. Is that right?

When doctors are guarding a sacred cow,

that you're not allowed to question, a topic that you're not allowed to,

But what also shows I mean, both of you have read all these studies, right?

I mean, you're saying all these statistics,

you know, off the top of your head, only you only skim milk.

You look so deep.

And I, you know, working in health care, right?

For so long, I rarely come across people who can really cite the specifics

and the weaknesses. You downplay yourself.

You used to put together this book that I would get in the mail every year, and,

you know, her book, and she would take all the studies of the year in like,

health policy and make the best figures I've ever seen.  What was the name of the book?

It was called Trends Shaping the Health Economy. Trends Shaping the Health Economy.

Amazing. Yeah. No, she I mean, you get into that, you get in there too.

She was a study ology. Yes. Study ologist.

I can't memorize the stats on top of my head as well as you too.

But the point being,

thank you for that, is that, you know, we don't, as an industry, go deep.

We don't unpack these layers and question

the studies, which is, you know, in all of our training,

the scientific method, you're taught to ask these questions.

And we don't we just can't take the headlines.

We've become so tribal.

You know, sometimes I think that like, you know,

that there's there's there's some people, a tiny fraction

that no matter what Marty does, they're not going to be happy.

FDA is collapsing. He stepped over rubble to get here.

I know they're never gonna be happy, but we can't.

We can't just think about the people.

Never gonna be happy. There are a lot of people who are happy.

And I think a lot of people are actually open minded.

They actually think, well, judge and based on what he does,

and instead of talking about collapse of FDA, whatever speculating

you can see in a year from now, has it collapsed or is it still running?

You know, that'll be the judge.

And I think open mindedness is a really important trait.

I think a lot of people who work here really have it.

Yeah, absolutely. Really have. I've been impressed by that.

So impressed. Because, you know, when you can

bust out of

the narrow lane that the medical establishment puts you in

because let's let's be honest, how many times in medical school

were you asked what specialty are you going to go into?

You're in the gym, okay.

You're between sets and you meet another doctor.

It's oh, where do you you know, I heard your student, 30 or so.

What are you going into? What are you going to do?

That's it's like, okay, I'm just trying to learn, you know, mean,

you know, like, we're not allowed to learn about two topics like, oh, you're ortho.

You don't need to know that.

Oh, you put into these define bucket for the bucket early.

Right.

But speaking at so I don't know if we can talk about this, but,

we had an interesting meeting. Was it yesterday?

National Academy of Medicine.

So let me just finish up when you can bust out of the mold that you're put

in, that you are only to be an expert in hematology, you really can't

you should not be questioning unnecessary C-sections and O.B.

or whatever the field might be when you can bust out of that,

when you have an academic environment, when you have a job like one of the jobs

at the FDA, when you can start being intellectually curious

and have the time to ask big questions and read studies

outside of your own area of specialty, it is liberating.

But to be fair, you know, before you got here,

you ran that research team at Hopkins.

Your research team

always tackled very different questions for, what, 15, 20 years?

You. Yeah, we published ophthalmology, orthopedic

surgery, cardiology, electrophysiology surgery.

Good for this job, I bet.

I mean, I think you're the same way.

Very intellectually curious.

You're the same way.

And there's a lot of people like that here. So a lot of people like that.

And that's why when we had the session on, I can't actually say

the exact disease, but it's a very rare blood based disease.

And then I ask people in the audience, like,

I knew many of the faces, but I haven't met everyone.

We got like thousands of employees,

and I wanted to introduce myself to all the people I hadn't met.

So where do you work? I work in vaccines.

I was like, oh, wow, you just coming in to sit on this?

I work on, you know, I work on nephrology.

Oh, you come on. Like so people are curious.

They want to know and they have great ideas.

Yeah.

Grand Rounds attracts people from every area of of, medical.

There really is that academic flair here.

I feel like every day there, you know, you're learning so much.

Well, this guy's also publishing an article every four days.

Oh, I can't do. I can't keep up with you.

I still have, like, one manuscript draft speaking to me.

So we have a New England Journal paper, and then I think we have

we have two JAMA papers together,

and I think I have another one on the the chikungunya vaccine.

But that's an interesting thing, which is that,

look, Marty and

I both believe that when you're the FDA publishing papers is not our goal.

No. NO

No, doing things is our goal.

It's an extracurricular. You're doing really well.

Yeah, it's an excuse, but believe me, I've published enough papers in my life

to be done with them.

But I do think it serves a purpose, which is we have to communicate

to everybody, which

why we're doing this on X and YouTube. We also have to communicate

to the academics in universities and they like to read.

I don't know why they like to read these journals.

They like to read these journals.

And and let's communicate in a different audience.

I think speaking audience. We were talking about this earlier.

You know, the both the, the fun and challenge of this,

you know, opportunity is that we have such a diverse audience, right?

So we have to communicate through all these channels

and talk about food and cat food today with stakeholders group.

I mean, it's pretty wild. Yeah.

I think Animal Health Institute. Yeah, yeah.

That's okay.

I'll admit that's the hat I'm not wearing. I'm not that.

Yeah, Veterinary medicine.

It was great.

I have some, some good friends who are in by the way.

So it was easy to buy dog food.

I'm referring to the food that is fed to the animal,

which is a dog, not the food they served in your cafeteria,

Oh, to process hospital food. Wow.

You know, what is it?

It tastes so bad and such small portions.

You know, it's like, this is a little joke.

Yeah, it's one way to, you know, keep your weight down.

There's always some jello to wash it down. So,

we were talking about the National Academy of Medicine.

We had a good meeting with them.

Good meeting with the leadership of the National Academy of Medicine.

That and you were tough on it, I'm sure.

I mean, I was surprised saying,

why are you talking about this or don't talk about this because we don't.

We talked about this today not to talk about it, but what right.

These are this is what the week was like.

A lot of me, we had a meeting, National Academies of Medicine,

and this is a very venerable 160 year old 60 year association.

And one of us here, the commissioner, is an inducted member,

which is considered like a career hallmark.

It is like one of the pinnacles of being a doctor.

And I, didn't know what to expect because I was

I saw the meeting on my calendar and I said,

Marty and Marty texted me saying, are you coming?

And so I got there quick.

I'm walking down from the half mile. Have a CMO with you at all times.

At all times.

I was summoned and, and he was tough on them.

And the topic was civil discourse and having important dialogs.

And the National Academies of Medicine is a prestigious association

that I think has a civic duty to have the dialogs on

controversial health and medicine issues that other people won't tackle.

And I kind of agree with the commissioner that they haven't done as good

a job of that as they ought to have done.

And you told him, and I acknowledge that there's opportunities to improve.

I was impressed at, the conversation we had with them.

You know, I specifically asked,

you know, what they do, just so you know, what they do is they often

convene experts and they put out a paper or a publication.

That's that's one of the things the National Academy of Medicine does.

They will convene, they will review the evidence,

and they will put out some document, and the government will hire them

to address certain topics or look at a certain question.

And so I asked, why did we not have

your convening power with a diverse group of scientific experts

around some of the biggest health controversies of the last five years,

masking toddlers, vaccine mandates, boosters in young,

healthy children, perpetuity in until forget goes year after year.

Yeah, yeah.

And school closure for more than 18 months of school closure in San Francisco.

Yeah.

No NAMs report on that masking a two year old in a cloth mask there.

No names report.

That's right. Recognizing natural immunity.

I mean, that was a big issue in the United States.

Mean you talk about the biggest health controversy of the last four years.

None of them were addressed by the National Academy of Medicine.

So I read a lot about reduction in federal workforce.

But that federal mandate for the vaccine had a big reduction federal workforce that

I don't think was covered by the media, and it certainly wasn't covered by NAMs.

And natural immunity was a crux of the debate, which was,

do you force someone who just had Covid to get a shot that, by the way,

it does not have a randomized controlled trial evidence in people

who've just had Covid that it reduces severe disease and hospitalization or not.

You know,

I do feel bad for these young, healthy, you know, cadets who joined the military.

They're 19 years old and thrown out.

And so, I mean, it is it's a, I think, a dark chapter, hopefully

a period of learning, but not to go down that road.

We had

a very productive meeting with them, and I think I saw some light bulbs go off.

And I think they're going to

I, you know, I think they're going to engage

in more civil discourse and create more of a diverse group of people

that can debate some of the biggest health

issues of our day, because it's not just these ones that have become polarizing.

It's also like the root causes of chronic diseases.

Why are sperm counts down 50% in the last half century.

Why are now 1 in 6 to 1 in 7 girls on the way

to getting an autoimmune disease at some point in their life?

I mean, what's causing this?

Why is cancer increasing in people under age 50, particularly GI cancers?

So we can talk about proton beam therapy and tech and AI and,

you know, gene editing and sophisticated operations.

But somebody needs to stop and look around and ask

why do 30% of kids have prediabetes?

Why do 40% of kids now have a chronic disease?

It's not their fault.

I don't think it's a willpower problem and it's not a genetic problem.

It's not it's not a genetic not a genetic problem.

Talk about your 100 days speech.

So this is another thing so many of you often say,

we got to go down right now because Marty's giving his 100 day

speech to the staff here, and I had a chance to go.

It was great.

Yes. Leadership across the organization.

Yeah. I wanted to convene.

I mean, you know,

we only have so much space here, but we convene the leader, the leaders here.

And, I was just very frank about the challenges

we had encountered early on, what we've done, about that assessment,

the reinstatement, getting jobs posted, which was,

you know, a task to get jobs posted again coming out of that,

the healing that we had to do here and, how to move on,

how to work with what we have and constantly reevaluate.

So I wanted their input.

I wanted to hear what was going well, what was not going well.

I mean, I need their ears on the ground to tell us what to fix,

and then we have to prioritize.

That's one thing you brought up, which was that

you raised a few issues that you heard from them and you've already solved,

you know, so, like if people tell us what is troubling them,

we can do what it takes. That's right.

Like the PMAP thing and some other internal stuff.

But it's also been exciting acronyms that nobody knows, but I, I walk around

here and I'm like, PMA,

PDP. I'm like, I don't know what I know I got I need a dictionary, I need it

makes the military look like Romper Room because it's so easy with the.

But, but we've also done a lot in the first 100 days and we did a little

Sanjula and I... You missed this, I watched it,

although I got some critiques that, you know, you, you avoided certain questions.

So the young crew that just started like,

we want to

really know what the commissioner eats, you know, MAHA lifestyle.

Oh, well, they do for fun. What did you eat for breakfast today?

Well, today I had a little acai juice.

I usually eat some acai juice or watermelon juice.

You do? Really? Good.

Although. Or what do you choose?

You just like it.

It's got some probiotics in it.

The brand I use, although it comes in a plastic container.

So I'm a little torn, a little torn microplastic there.

Yeah. Microplastic. It's everywhere. Right. And it's.

And it's all sounds fine. Like.

Oh, plastic.

It's, you know, it's like a friendly idea until you look at them under the electron

microscope and see the jagged edges and just picture you in your kitchen,

like, trying to, like, analyze your food, Kristof from the New York Times

had a thing where he drew his own serum

and looked at it under a microscope and just full of microplastics.

You know, Kristofe is doing that.

Is he bored

Or what? Isn't he an economist?

No, that's Krugman, Kristof, is this the long time foreign correspondent

And then he.

I think he tried to run for governor of Oregon.

And anyways, it's like, yeah, okay, wish him well.

Wish him well. So I don't think he went I don't think it went so well.

Okay. So so yeah.

The acai juice and the watermelon juice.

I got coffee cold.

I know why, you know, I've never seen you drink coffee.

I know we drink a lot of coffee, but at this...Willpower,

she has a great espresso machine in office.

She let me use it, though. Okay, good.

Yeah. So, so no coffee now and then. I,

I'll have, like, a little,

maybe a, a snack, like, there's some I don't want to say the

brand, right.

There's a lawyer still giving you a little.

Hey, Great job, but just, you know, one thing to point out

for next time, right?

You know, it's, anytime you go where the stock will go up or something,

and then the stock, anytime you have general positive,

feedback, you know, a specific negative is is on its way.

It's coming next.

But, for me, I said no.

Right.

That's okay. So what do you do?

So, then I, as Sanjula

knows, I'll eat in the cafeteria here.

And, if I don't make it to a farmers market or the farmers market,

which has been just awesome, or, but oftentimes I'll just have

I have these, cashew nuts with coconut sugar on them, or just a coconut cashews.

You know, you have, like, a little, like, like snack. Snack.

You guys are welcome to it.

And it is always a generously offering a snack.

But I'm not a snacker, so he's always a.

Oh, that's good discipline.

I knock away his cashews, but they look good now.

You kind of gave away some trade secrets here that I have this snack area.

Now, if it's gone, I think we can.

Somebody saw, you know, I was watching this, but.

Yeah.

No. So what?

Do you have a sensible dinner?

So. Yeah.

I mean, my wife buys from this place called

the Organic Butcher in McLean, which actually, it's called a butcher by day.

It's. Or it's seafood. It's pasta nuts blew up

their local.

I think it's a locally sourced.

Yeah. Local...I've been to his house for dinner before.

It's really good. Spectacular. The Italian Store.

They have, great passes imported from from Italy.

Speaking of that fun anecdote.

So you know how you know, I told you about my gluten sensitivity and how I run?

I travel abroad, so I discovered a restaurant locally here in the D.C.

area that imports their flour from Europe.

And so I took a gamble this past weekend, and I ate the regular pasta,

and I was totally fine.

So we got to figure out how they really think it's something to think about.

I 100% know that it is.

So that is like my ask this what I'm going to do.

I'm gonna do a blinded study on you.

I'm going to make pasta for you.

And I literally blind literally blind

taste.

Shelf. Yeah.

So, yeah, when you strip the fiber out of the flour and you chop it up

and it's got a high glycemic index, it's not the same as the flour that we get.

I wanted to test the hypothesis.

Some people have debated the enrichments.

You know, flowers are often enriched

with different things that are not as present in Europe.

And things of this Senator Roger Marshall had

I wanted to make it to go to this, but I, I wasn't able to.

He had a great gathering of farmers, farmers

and nutrition experts and policy people on at the Senate

to talk about soil like something we never talk about in health.

We never talk about it, you know, in the world.

I mean, have

you ever heard, in your medical education a discussion of the microbes and soil

and crop rotation and the importance of regenerative farming?

It's such an and like an it's something that we don't even think about.

But, potentially so important considering probably so much farmland in America

is just chemical soil.

They're not using raw manure,

and they're not thinking about this sort of regenerative farming.

That's right. They're raising crops on land.

I say so many, but this is this, this occurs.

I don't want to make a sweeping comment about American farmers,

but some of the food is micro nutrient poor.

And that's because it's being grown on caffeine for plants.

If you will.

This potassium, nitrogen, phosphorus I think it's like NPK type of,

solution that but so it's not rich.

And then the ingredients that come from healthy regenerative soil,

you know, one clear example of that is if you know

somebody who has a chicken coop and they give you eggs

and you crack the egg, the thickness of the shell,

the color of the yolk and the way the exits,

and then you go to a, an egg factory animal

that's been kept in a horrific prison like environment.

And they've been fed this, you know, nutrient poor grain,

and you crack the egg and it's a flimsy shell

and it's like a pale yolk and just completely different experience.

So clearly we need to do this more often because I think we have a bit of a break.

We're having fun.

I gotta go back to oh boy, a lot of stuff going.

Got meeting.

Sorry, but we're having fun on this good break.

And when are we going to do this again?

We don't know. No. When the lawyers let us when the

when the lawyers allow

you to, when they fully redact the video and put it out there.

Right.

So folks that ask if we don't do this for, you know, a week or two,

the sophisticated reason is we're busy, just don't have time to get out.

But this is fine.

Thanks so much Vinay. Great to see you, Sanjula, and good stuff to come.

Looking forward to our new roundtables coming up next couple days.

Yeah okay.

All right.

That folks, thanks a lot. We'll do it again.