FDA Direct: Catching Up on Agency Reforms

We're rolling.

So Aerial is
like a professional videographer editor,

but her iPhone only has one lens camera
lens. So.

You gotta upgrade.

You need 
Big, heavy cameras.

Okay.

i-phones for birds for you, I guess.

I feel like the iPhone camera's gotten
so good, it often rivals

even the best K cameras.

Yeah, I don't use my professional
camera anymore.

What do you use, Bigfoot?

IPhone?
Oh.

Android iPhone debate.  
Yeah.

All right.

Good to see you guys. It's good. Awesome.

Lots going on.

It's an exciting time right now.

So, we've got some exciting news
about Rick Pazdur.

Yeah. Very exciting. Well-received.

People come up to me all the time
and talk to me about how much they love

the guy.  He's been here a while.
That's thrilling. As well.

Only a quarter century.

He's a true innovator, an academic.

He's excited about the role.

I saw you guys having breakfast, was trying
to get him to come join us, but,

he had to run to a meeting.
He's got a lot of meetings.

Yeah, we just had
we just had breakfast with him

and I think we're excited about Rick
is stepping up to take over CDER and,

you know, people may not know, but
Rick and I have been working hand in glove

the last few months, maybe about five,
six months, because for a long time,

the Oncology Center of Excellence,
which Rick has been

running, was supposed to be a go
between between CDER and CBER.

But across all the different indications,
all the different cancers.

There wasn't always alignment.

You know, sometimes they demanded
one thing and we demanded another thing.

Sometimes our standards
are a little bit different.

Sometimes communication
wasn't free flowing.

That's all changed now.

It is.

Organ system by organ system.

People are talking to each other.

We're getting clarity and consistency
across endpoints.

And, CDER and CBER.

And it's been a lot of fun.

You know, you're in a room
with a bunch of the best oncologists

talking about the best science.

And so I've enjoyed working with Rick
the last few months.

Yeah, he's really terrific. I have, too. He,

is really a team player.

But, when you said there
hasn't always been great alignment,

I think that's putting it mildly.  

And there's been sort of infighting here,
you know, territorial tribal lines,

gerrymandering of what goes in
what center and what goes in oncology

and what.  
Like medieval Europe, you know, a lot of warring clans.

Yes, a lot of clans. Yes.

Now the Roman Empire is coming.

No it's not.

We’re one team, right?

You know, one organization, one FDA. 
Well, that's the cool thing.

And that has been

the prerequisite for serving in leadership
here is you have to be able

to serve the broader mission of the agency
and engage in impeccable teamwork

like we've never seen before
here at the agency.

So it's going terrific.

And, I'm really excited.

You know, what makes Rick unique
is that he's a career regulator.

He's been here for a quarter century,
but he's also an innovative thinker.

He's not stuck in doing things.

The way they were.

And for years he's
been innovating in the oncology space.

You know,
we don't have to go through the list,

but there's been dozens of things
from, achieving harmony across the U.S.

in Europe, dosing, moving
randomized trials to the front line,

using a single seamless trial design, a
lot of innovations in the oncology space,

and a lot of things that he has planned
for how to make reviews more efficient.

We've been impressed
by talking to him about all his ideas,

for making reviewers

go faster and be able to provide
more timely feedback to sponsors.

Now, I can tell you
one thing that he pitched to me

just the other day was just like,

we've been working together in oncology,
creating alignment between CBER and CDER.

He proposes that we have a similar team
of people in cardiology nephrology

to create a line, and rare diseases, to
create alignment between the two centers.

And I’m an enthusiastic supporter of that.

You know, whether you're a biologic gene
therapy or small molecule

inhibitor,
if it's the same disease population,

sponsors should expect some consistency
in how CBER and CDER will treat you.

And I think that's good for the public.

It's good for patients. It's
good for sponsors.

And Rick and I will work together 
to get that through.

It's something we heard a lot
in the CEO listening tour as well.

Right. That inconsistency. So that's good
that you guys are thinking about that.

Yeah. We talk about it a lot.

And when you say have the reviewers work

faster, we're not talking about
increasing the workload.

We're just talking
about cutting the idle time.

And that is the key.

And so right now, if you get your reviews
done in, let's say eight weeks,

because so many other

people involved in that review
have until, say, a year,

then you're not accelerating the decision
to go out.

We're not. You know,
we're not moving the ball forward.

And so we can create more alignment here.

And that that just reduces
the stacks of paperwork, so to speak.

These are obviously in the computer
system, but that, you know, conceptually,

the idea of the stacks of papers
on your desk are lower.

There's more decisions going out.

And so there's less of a backlog.

Is it fair to call it
like parallel tracking?

A lot of the
the reviews and steps of the review?

Yeah, I think alignment is a good word.

And, you and I, Vinay, have been big fans

of Rick's
concept of using surrogate markers.

And we've talked many, many times
before you came in, when you came in,

when we met with Rick and and after that,
we believe in both in surrogate.

Surrogates and clinical end points. 
And clinical endpoints.

And that's what Rick has done.

Rick, is you run a single trial
based on an early

look at the study, and a surrogate end
point is better.

You get an accelerated approval,
then you just follow that trial out a year

or two later, confirm

what we've already, what we expect
and hope just to make sure it's true.

Or you think of another way
you can get at that question,

which we're going to talk
about credibility in a minute.

But you think of other ways
you can address is this doing what I think

it's doing?

Yeah.

And and even outside of accelerated
approvals,

we have now reliable surrogate

endpoints that we think are

validated markers of clinical benefit.

And so if.

So, this is something
that maybe people don't fully appreciate,

which is that
you can receive an accelerated approval

if the surrogate is reasonably likely
to predict a clinical benefit.

Okay.

But you can receive a regular
or traditional approval

for a surrogate endpoint that is,

that has been
validated to predict clinical benefit.

And we actually, you know, in CBER
you're going to see some of that.

You're going to see some, some things

where you're going
to see a surrogate endpoint.

The ball is hit so far out of the park

that it doesn't make sense
to have an accelerator approval.

It's going to get a traditional approval.
Yeah.

Yeah. It's it's really cool stuff.

I think, you know, we have to innovate
the regulatory process.

We can't just keep using the same process.

We have to keep that process
impeccably independent.

And at the same time, we have to think
about what to do differently.

And Rick has really innovated
the regulatory process

in my mind
more than anyone here at the agency.

I mean, Project Orbis,
the whole concept of surrogate endpoints

going from, baseline

default to clinical trial requirement
down to one with a confirmatory trial

or post-marketing commitment
of some kind afterwards.

He has really been thinking differently.

And I think, you know,
when we have proposed ideas

agency wide here in our broader
work on drug reform, oftentimes,

he'll say at the meeting, we've been doing
that in the OCE for years.

And people haven't followed our lead.

But now hopefully more people
That will change. Yeah.

Like you talked about independence.

And I think that's an important word

because I see sometimes,
people confuse two things.

When we talk about independence,
we want our decisions to be made

based on the science
and the public and patient interest.

You know, first and foremost, as science
and public and patient interest,

not special interests.

You know, but the public still has
an ultimate say in how the FDA works.

And I think that's important to emphasize
that this is not a place where

there's a fourth branch of government
setting the policies.

It's the public who
we are ultimately accountable to through

their elected representatives and the laws
they pass in terms of helping us balance

that speed, certainty, spectrums,
helping us balance,

how promising things are,
how quick to bring them to market.

The public makes that decision.

On the innovating the process.

I know
you both have been talking a lot about,

you know, different study requirements
and, you know,

what do you need to do here?

How do you both think about the credit,

maintain credibility and reliability
and all of that?

I think what we want to see

is evidence that something works, right?

That I mean, that's the ultimate question.

And so, you know, maybe the old Bayesian
statistical model

can be seen in a new light now,
or we can run continuous

statistical analysis with AI in real time
and have stopping rules

that are maybe not linear,
you know, maybe they're curvilinear.

Maybe they account for the fact that,

every drug is different
and every population is different.

And so the old idea
that everything has to hit .

you can actually mathematically
have more power in a study

with a single study
than two separate studies,

which has been the default requirement
the FDA has had.

You know people are obsessed with this,
with with with one thing here or there.

And but what Marty's
pointing out is credibility.

So, you know, what we care about FDA is
does this product

actually help you live longer or
live better?

And there's all sorts of ways
credibility is demonstrated.

One is effect size,

you know, is it a very small difference
or is it a huge difference.

And when you have a drug 
that makes a huge difference,

you can see the effect from space.

You know, the drug imatinib in chronic
myeloid leukemia turned a disease

with a median survival of 

to years to one, with the normal life
expectancy of like years.

This has been shown in Swedish data.

Population data.

When people say, oh, you can't use
observational real world data, 

yeah, you can.  For Gleevec,
look at the SEER data,

look at Sweden's reports like you can see
the effect of Gleevec from space.

You could stand on a mountaintop
and see that the survival curves

are different in the population of people
with the disease.

We also think about pre
specification of endpoints.

We want you to paint
the target on the wall

and then shoot for the target, not shoot
at the wall and paint later you know.

So pre specification matters.

The choice of controls matter.

In other words
what are you comparing against.

Is it the best available care or something
beneath it?

After somebody has disease progression
or the disease gets worse?

What are the kinds of treatments
they're getting?

Are those on par with the U.S standard?

What about the endpoint?

Is it a validated surrogate, a surrogate
we have confidence

in, or is it a completely novel surrogate,

even novel can be useful
if it has a lot of biologic rationale.

And then do you hit the target?

Are all the intermediate
clinical endpoints

consistent with the big treatment effect?

So I hear people obsessed
with how many studies.

It's not about quantity.

It's about the quality of the evidence generated from a totality of these factors.

And and then the last thing you said
was Bayesian.

So pretest probability matters.

So for instance,

and a new Alzheimer's drug,
although we want Alzheimer's breakthroughs

that's you got to be a little bit
more skeptical of that

than a new drug that helps somebody
with a blood clotting factor

deficiency, clotting factors
we've been making for decades.

And they have all, you know,
pretty much all work.  Alzheimer's drugs.

We've tried for decades.

And they've pretty much mostly failed.

And so your pretest probability changes
in those two classes.

And so Marty's
talking about being a Bayesian.

That's a statistician

who takes into account priors, your prior
confidence in a hypothesis.

And I think we have a Bayesian
framework coming, a clinical guidelines

coming from our centers
that will lend credence to that.

But like you said, like being so wedded
to one of these things.

Oh, the p value has to be .

Oh, it has to be two trials.

Oh, it has to be.  Being wedded to any
one thing without looking at the totality.

That's myopic.

That's that's not good regulatory science.

And then so,
you know, talking out loud here,

on this,

you know, on camera here,
these are the things we're talking about,

you know, should we have this default
basal requirement

of two clinical trials
for a, as a requirement?

Can we, use non Bayesian statistics
to answer the question?

Does something work?

Can we ask ourselves

what are what should
the requirements of real world data be?

And can we let the companies know
this is what we like

to see in real world data,
but then not have,

limitations on what they're allowed
to submit in terms of real world data.

And so these are all things
we're talking about right now.

We are, socializing these ideas.

We want there to be a consensus

within the agency,
and we want to do the right thing.

But these are things
we are actively talking about.

And, hopefully in the coming months,
we'll have some and good announcements.

We want to do things right.

We're on path with our animal testing,

roadmap to reduce animal testing
requirements.

We're on path with a lot of these ideas
that we've been getting from our, our,

listening sessions.

And, so anyway,
good stuff is happening across the board.

And the National Priority Review
Voucher Program, I think going very well.

The first review I thought went

beautifully, incredible discussion.

And it shows the feasibility
of the program.

You know,
this is kind of a minimal viable product.

Initial, run.

But I'm excited about some of these
potentially promising treatments.

And some of them are in
your field of oncology, Vinay.  

You got a lot of oncologists around here.
Now, you got me, got Rick.

You got, you know,
Too many. Too many. Yeah.

Well it's a little bit.

Oh you can never have
too many oncologists. Yeah.

You want to tell us more
about those oncology products.

Yeah. Let's talk about it.

So, the two we've announced
so far, Zongertinib and Dostarlimab.

Two really important products
in the oncology space.

So one is for,

a subset of

non-small cell lung cancer called Her
mutant non-small cell lung cancer.

So what do you need to know?

You know, for so many years, lung
cancer was divided into the small cell

variety, which often affected smokers
and the non-small cell variety,

which also often affects smokers.

But there was a subgroup of people
in that non-small cell category tend

to be younger Asian female nonsmokers
who developed lung cancer.

And over the years, we've learned that
a number of activating mutations

actually is responsible for cancer
in those people, including in EGFR.

ALK rearrangement,

BRAF and now we're learning about Her

which is yet another, it's the same Her
that's present in breast cancer.

It's the same Herthat Dennis Slamon
and others, developed trastuzumab for,

and one of the first targeted therapies
done by Genentech.

And now we have a small molecule inhibitor
that when given to the patients

with this type of lung cancer,
this unique lung cancer,

it results in dramatic tumor
shrinkage and dramatic response rate.

We're talking about % of people
have a have

their tumors shrink %
or more in clinical studies.

Does that change what additional care
you need as part of that,

like the amount of chemotherapy
or that you would need?

Well, it would be in lieu of chemotherapy,
I mean, in lieu of chemotherapy

or in lieu of a perhaps a less potent Her
directed strategy.

But you're talking about like,
I mean, if I could give an analogy

from when I was a, you know,
practicing oncologist for the last decade

and, you know, until I,
until the day before I came here,

I hope to get my clinic back going again
soon.

Someday.

But, you know, you would have a patient
come in, and we're talking about disease

that's everywhere.

Lung cancer, widespread,

metastatic disease in the belly,
in the lungs, even in the brain.

I've even seen a comatose patient
come in with brain metastases.

We powdered up one of these drugs
and put it down a dobhof tube.

And that woman woke up.
She had a Lazarus like effect from this.

So we're talking about extremely potent
targeted drugs.

We're working on durability,
you know, making them last.

This one has a median duration response
I think about a year.

But what we want
we don't want just one year.

We want these drugs
to work for three years and five years.

And and like Gleevec years.

That's that's a work in progress.

But we never let the perfect
be the enemy of the good.

And this is a great product.

Extremely promising.

I think everyone patients, doctors,
the company, us we're all excited.

And to Sanjula’s point,
you know, I remember

from being in the operating room
involved in lung resections

is these drugs dramatically change
the margin of resection.

And that directly correlates with
the amount of disability from the procedure.

I mean, preserving healthy lung tissue,
especially in an older individual

and an older individual where there's
a risk of lung tumor recurrence,

that is a very valuable,
end point in the surgery.

So, you know, these
these response rates are impressive

and reducing the margin of resection,
there's a real benefit there.

And that fits with the next one, Dostarlimab.
Dostarlimab.

Oh, we should also mention the KRAS
inhibitor for pancreatic

and maybe other cancers.

But pancreatic cancer.  We announced?
By Revolution Medicine.

Yeah, we've announced that one.

But we can talk about that one, too.

But, Dostarlimab. 
Yeah.

One of those incredible things again,
potentially promising.

We we now have some good clinical data.

We have to look at the totality of
data that is, submitted. But

individuals who have had

tumors in the rectum,
these are typically for GI cancers with a

microsatellite instability
resulting in some mismatch.

Yeah. Mutation.

So they have
and that might be or or %

depending on the population of people
with a GI tumor.

But they have had a complete
pathologic response.

And I mean, there's nothing
that gets an oncologist or Bigfoot

more exciting than a complete response,
a complete pathologic response,

not to be confused with CPR
and not confused with a CR letter.

Yeah, so we shouldn't confuse the two.
A complete response.

Unbelievable.

Without the need for chemo, surgery,
or radiation.

So they're following people now that have
had a CR and they're following them.

And, you know, it appears that there's
some potentially promising results here.

I like that product because,

you know, people forget that
like the rectum

anatomically is so close
to the end of the GI tract that,

treating those cancers has always been,
kind of tricky.

We use chemotherapy in combination
with radiotherapy because the rectum,

unlike the colon, is fixed in place.

It doesn't move around.
So you can hit it with radiation.

That's toxic. I mean,
people don't like going through that.

I mean, they can have rectal bleeding.
They can have pain.

They can have, you know, constipation.
Proctitis.

I mean, it really hurt.

After that, if they do well, after that,
they're rewarded

with the surgical resection,
which is again

often requires an ostomy placement

where the gut is rerouted to the skin
and only later connected.

And people don't.

And that's your reward for having done
well on chemo RT.

And that's been the standard of care for,
I don't know, years.

Instead of that for these people
with the mismatch repair deficiency

and MSI high tumors, as you say, like
a % of people instead of that. 

Was it as much as %?

Yeah, I think it's slightly different.

An early stage is a little bit

higher than in later stage,
but ten, % I think easily.

It's good.

That's good.

And they get this I.V. medication.

The toxicity profile
is like compared to chemotherapy.

This is like a breeze.  I mean.
It's like a haircut.

Yeah, it's like a hair.
That's huge for cancer patients, right?

I mean, these treatments are brutal.

I've had.
RT I think is brutal. 

So do I cut you off? No, no. Go ahead.

I was going to say
I've had cancer patients.

When you start explaining the regimen,
the chemo regimen,

that they start zoning out
like, no, no, thank you.

Just,
you know, I'm going to just live my life.

And you wonder if you could offer

an alternative that doesn't have
the toxicity, doesn't have the sessions

where you come in and sit in a, you know,
park in the lot and get your parking

validated and navigate a campus map
and sit in a chemo chair and.

Not always validated.  
Check in, not validated.

And, and, you know, surgery, I mean,

surgery has risks no matter,
you know, how good of a candidate you are.

And immunotherapy
I mean, it's not side effect free.

There are occasionally autoimmune
things that happen.

But but but it's just worth pointing that.

But dostarlimab 
is much better than chemo RT and surgery.

That there's no question about it
in terms of tolerability.

And these patients, not only,

the tumor shrank, but you can take,
you can do a colonoscopy.

You don't see a, any tumor.

You can biopsy the rectum at random.

You don't see any tumor.

I mean, we're

talking about near-total eradication
in the people who've had this done,

and then they're being followed.

They're not requiring chemo RT.
They're not requiring surgery.

You know, everyone knows
that I don't like the term game changer.

I think it's used too loosely,

but I think this is really at that level
where you spare me all this?

Before I even joined the FDA,
we hypothesized that doing

randomized studies here doesn't make sense
because I'm a patient with this.

I don't want to be randomized
to the old way.

And we actually devised, people can pull
our paper.

It's called the Parachute Study Design,
a different study design,

which is kind of innovative stuff
we talk with Rick about.

Yeah.

If you see a tumor melt away with complete
response, do you want to get randomized?

No. You know, right.

So it's like, don't you have to this is
this is where Rick is a genius, right?

Because he has thought a lot
about the guidance that we give companies

to do these studies early on.

And if a company does that guidance,
look it's a pretty simple pathway here.

Yeah.

If you follow the guidance and
the drug works it's going to get approved.

And so it's a pretty simple, path.

But it's it's cool, seeing that,
you know, to be able to be here at a time

when we may be able to usher
in some of these potentially promising

treatments, it is really cool.

And the piece of it
that I like as sort of a side,

as sort of a side benefit

is that in thinking about the health care
system,

the cost of all of these new medications
and advancements in medicine,

which we absolutely need
and we need to continue to,

advance
and promote and incentivize innovation.

It's making the health care system

and state of the art
care out of reach for many people.

And so this affordability
issue is a real issue.

And so we are actually seeing now
medications

that are reducing downstream
health care utilization massively.

Well dostarlimab might be one
because although you pay per

the price of the medication
you're not requiring chemo RT.

All the additional services. Yeah.

I mean you you both
I remember there's a lot of the research

I did prior to coming here was flagging
some of these macro trends, particularly

for the provider organizations,
where we would model out and say

these innovative future
pipeline of therapies are going

to fundamentally substitute or replace
high margin, high volume procedures.

And so this is kind of an example of that.

And that does have cost savings long term.

And we've been hearing about medicines
being cost effective.

Often, you know, a storyline to justify
their widespread use, for a long time.

And the reality is
the ROI just has not panned out.

I think we're at an inflection point
now where we are actually seeing

interventions that are going to reduce
downstream health care costs

not by % or %,
but by a, you know, %.

I mean,
think about some of these interventions.

I mean, avoiding the need of a low
anterior rectal resection,

avoiding the need for chemotherapy,
avoiding the need for

radiation

sessions three times a week for weeks.

I mean, it is an exciting time and we.

Let alone your biosimilars.

So and so, I mean, one way you're lowering

cost is by introducing products to market
that, that reduce hospitalizations

and other health care spending.

The other way
you're lowering cost is by introducing

more options into the marketplace
with more biosimilars.

And each biosimilar probably roughly
cuts the price of a branded product

by maybe ten percentage points as well.

That's going to be even greater.

You know. Once you get or biosimilars.

Then market.

Especially three. Yeah.

And you really see those prices come down.
And that's what we want.

Lower drug prices for everyday, lower
health care costs.

We want to see this kind of stuff
translate into, hey, you know what

your health insurance next year,
premium is going to go down by %.

I mean, that's where you know what
we'd like to get to

in a health care system
to make it more affordable.

Yeah. Cool. Good.

Yeah. It's good.

Yeah. And, hopefully more stuff.

On the plausible mechanism
coming out soon.

Maybe in the next couple of weeks
we'll be talking more about that.

Yeah, we'll be talking more and the New England 
Journal paper came out.

We'll be talking more about it
in the next couple of weeks

with some more, press on it
and more coverage on it.

Right. It's been a busy week.

I mean, we've done a lot on the drug side.

You've done
some speaking on the food side as well.

So there's a big agenda.

Yeah. Big MAHA event. Yeah.

And met with the, distribution
companies, a critical part

of our health care system, part
that many people don't appreciate.

Packaging and distribution
of devices and medications.

You know, that group said

they historically have not really engaged
with the FDA Commissioner.

And they're so appreciative to be able
to be having these dialogs

and be thinking about new,
innovative approaches.

Well, it's a national security issue.

We've got to be talking about all this,
and we need to talk to everybody.

And at the same time,
while we're out there

talking to everybody, we need to be here
doing our job and getting our work done.

And if we are good,

good, employees

here, we get to do our little play session
and come out here and talk.

So, so that was fun.

So thanks for doing this.

Yeah, and I forgot.

I mean, it's been a short
but productive week.

We had the big HRT announcement
this week as well,

which has just been so well received
and is a huge boon for women.

Huge boon for women.

And maybe,

maybe we should get an information
page out there with some of the articles

people asking for some, references,
you know, the circulation paper and.

two years ago.

Yeah, that was a powerful review of 

randomized controlled trials
and showed a profound % reduction

in long term cardiovascular, events

and a % reduction in all cause mortality

in women who started HRT within ten years
of the onset of menopause.

And so these are some profound new ways
of thinking about public health.

You know, unfortunately, people don't,

think of women as dying of a heart attack.

It's just this old bias that lives in the,
you know,

the CPR, you know, mannequin is a man.

And, you know, they just,

you know, we tend to always
just think heart disease is a man’s disease.

Not true. It's the number one
cause of death in women.

Here is a powerful intervention
that can reduce it

at a magnitude
perhaps greater than statins.

And I didn't

I didn't realize,

but apparently the warning label
was also on, like, vaginal and topical.

estrogen..  Yeah, yeah, yeah. Local forms.
Yeah. That's right.

Yeah, exactly. And classic, overreach.

You know.

It just you think about the medical field,
how much time,

energy and money goes into teaching CPR,
which is important.

We have to do it,
and we should be doing it.

And, you know, getting an AED machine
in every bathroom,

in every mall in America
or wherever they live.

Yeah.

Again, we we should be doing it.

No, no, but you're saying the magnitude
of the reductions.  Right. 

What is what is that, risk reduction, %?

You mean for having an AED in a mall?

And teaching CPR in every high school
in America?

Again, we need to do it. Important.
Yeah, but. What?

I mean, just. I'm just saying
I think it's hard to quantify.

It's probably quite small, actually,
because, I mean, CPR is notoriously,

you know, it's still necessary, but.
We do it.

We do it.
But just and often let's.

Just do a quick a quick survey.

So how many times have you done CPR
and how many times has it saved someone's

life. 
To hospital discharge?

I would say
I mean, probably only I've done it.

Probably times, times, times
something like that.

And I've saved a life to a hospital
discharge five times, probably.

And the five times are probably pulmonary
embolism where I push to TPA.

Shockable 

rhythms in somebody who, you know,
you can correct the underlying defect.

They had ischemia or something like that.

We have a paper on in my research group
from a prior life on,

reverse medical reversals
in, in cardiopulmonary resuscitation,

I think it's a mayo clinic paper,
and it just shows that the field has

had so many people trying things,
and a lot of those efforts were in vain.

It's a difficult,
to bring somebody back from being dead.

Shockable rhythm is one thing
and reversible causes another.

But, you know, asystole PEA 
with electrolyte derangement.

A hospitalized patient who's otherwise
very sick, you know, low probability.

And that's that's a

that's a, success rate in the hospital
when you have all the equipment.

Out of hospital,

cardiac arrest unobserved, for instance,
like these are abysmally low success rate.

Yeah.

I had a brief stint as an EMT,
and we did, you know, a handful of


Yeah, I do.  That's cool.

Yeah.  I was an EMT also.

Yeah. TI didn't know that.

I would say my success rate
was a little better than five in 

And I don't know if that's because
I'm pushing harder or at a different pace.

A surgeon. Yeah. Your surgeon probably.

You're more likely to have people
who have less co-morbidities.

I'm an intern. I'm
an oncologist, internist.

I took a lot of bone
marrow transplant and leukemia service

over the years,
and those are tough populations.

But it's just amazing.

You talk about the risk

reduction of CPR again, which we should be
doing and continue to teach.

And the way we emphasize that
and not ever talk about an intervention

that may reduce
cardiovascular fatal events by to %.

Yeah. Population.
That logic.

Next you talk about diet and exercise
Marty I don't know what's going.

So how do, just to close up on that.

How do you all recommend.

Yeah in the medical curriculum,
medical education really start teaching.

You know the the power of HRT.

I know the black box
warning is a big key step in that.

But what else can can folks
do to educate the next.

And that's a
Medical education is so broken.

They're so busy trying to hammer
into everyone

the the names of the intermediary steps
of the Krebs cycle.

And so I don't have time
to talk about menopause.

You know.

They're very upset about this reduction

in how much student loans
you can take out for medical school.

You know, that that
that has recently come through.

Maybe med school shouldn't charge so much.

You know, the the. 
OK, open a can of worms.  

Yeah, don't get us started.

The number of.
Story for another day. Yeah.

Yeah. Okay.

Okay.

Well, yeah, it was a great event on HRT.

Thanks for bringing that up.

So, great to see you guys,
and we'll try to do something again soon

on plausible mechanism. 
Sounds good.