Judith: Welcome to Berry's In the Interim podcast, where we explore the
cutting edge of innovative clinical trial design for the pharmaceutical and
medical industries, and so much more.
Let's dive in.
Brandon Giella: Hello and welcome to Barry's in the interim podcast.
This is episode number one, the very first inaugural episode of the podcast.
I'm so excited to talk to you guys.
I have with me Dr.
Don Barry and Dr.
Scott Barry, statisticians, experts, thought leaders, and founders of Barry
consultants, and I want to get into all of that, but we are kicking off this
show because This is the 25th anniversary coming up for Berry Consultants and it
is such a momentous occasion And I'm so glad to have the founders and uh and
experts in this arena because you guys really are the trendsetters in Statistical
trials, clinical trials, adaptive trials.
I want to get into all that We're celebrating this year with so many
new projects and just a lot of excitement, um, coming up in 2025.
So this podcast is a part of that.
Um, and so as such, I would love to hear the story of Barry consultants and I
have, uh, the best people to do that.
Um, and so I would love to hear and share with our audience and our network.
What.
How did Barry begin?
What was the motivations behind the firm?
Um, who impacted you in those early beginning stages?
What kind of conversations do you have?
What are the stories, what challenges did you encounter?
And then toward the end of the show, I would love to hear what's next.
You know, where are we going from here?
And so Don, you, you are the founder, you are the, the man of the hour.
I would love to hear.
What was it like when you started Barry?
How did that come about?
And why, why are we here today?
Don Berry: So I was a graduate student at Yale University,
Scott Berry: Heh, heh,
Don Berry: Frank Anscombe, a very famous statistician, and my wife
was pregnant at the time, and, um,
Frank asked me, he said, so how are you going to pay for this?
And I said, I have no idea.
Uh, and he said, well, When your wife is in the hospital and you
get the bill, bring it to me.
I brought it to him, and he had a grant that paid for the, uh,
the hospital and everything.
I don't know how he did it, but he did it.
Um, and I count that as Scott's very first grant, because
Scott was the, The, uh, baby.
And of course, you see him now, he's no longer a baby.
Um, but he still, is, uh, thinking in very naive thoughts and very creative thoughts.
And that's really the beginning of Berry Consultants.
Just a word about, uh, the interim.
In the interim between that and when we founded Berry, Berry.
wasn't a particular time that Barry came into being.
It was, uh, I was known as a radical reactionary, crazy guy, loosey goosey,
some people called me, trying to change the way we looked at medical research.
And so it was my touring around, Brandon, I use the term, Johnny Appleseed, around
the country and pharmaceutical companies and wherever, whoever would listen, I
would, give them a talk and, spur them on.
Uh, just an anecdote about that, along the way, I was in Washington, D.
C.,
on the metro, and, uh, coming back from one of my talks, And a guy came
up to me, it turned out to be he was a statistician at the FDA, and he said, Dr.
Berry, uh, I'm a fan of yours, every time I hear you talk, I
become a Bayesian for five minutes.
Can you work on a sustained release version?
So, uh, I did.
But, uh, when did Barry start?
It started like 2001.
Scott and I happened to be in Texas.
and I had been doing consulting and, Scott, take it from here.
Scott Berry: So, 33 years after Frank Anscombe's grant, uh, with that,
so, I was on faculty at Texas A&M Statistics, and, doing research, very
much enjoying it, teaching, and a number of projects came through Don, who is
at MD Anderson Cancer Center, building clinical trial designs, and so I was
helping with those, and I loved them.
Everyone turned out to be a puzzle.
I love board games.
chess, bridge, settlers of Catan, and they all have, what's the problem to solve?
And all of these had a problem to solve.
We were using all of The techniques, the statistics, the science to solve
these and everyone I worked on, I loved.
And so after five years, I wanted to do more of that.
so we talked about what would this look like?
Suppose we started a business to, to, design better, smarter trials.
And so in 2000, June of 2000, we decided I would leave academia and
we would start Berry Consultants.
I was the full time person.
Don was at MD Anderson Cancer Center.
And so June 1st, 2000, we started Berry Consultants with, really No
idea what was going to happen, but we had shared interest, desires
to design smarter, better clinical trials and really enjoyed it.
And so we started it, the two of us.
Brandon Giella: And how's that been for you
Scott Berry: Uh, fabulous.
Still, still, still going on 25 years and still very much enjoying every day of it.
Brandon Giella: I love that.
I love that.
Well, I'm curious, what was, I mean, starting your, your first, uh,
starting your, your company like this.
And, and I know you, you had, you know, clients that were needing
your expertise, very complicated, sophisticated trials, you know, big,
big money involved in some of the, um, you know, pharmaceutical companies
or medical devices, things like that.
Um, what were some of the challenges that you encountered early on?
Thanks, Tom.
And how did that shape Barry now into to who it's become?
Scott Berry: Yeah, it's, uh, we've been.
Part of what we're trying to do is, is through change, it's always changing
the status quo when you're trying to do something different and just to set
this up, the standard of a clinical trial is, um, the standard thing is
let's enroll 200 patients, enroll the trial for four years, gather the data
and look at the data after four years and see if we've answered the question.
Invariably, you look at the data and you say, Oh, Shoot.
I wish I wish we'd have done something different.
I wish we to change the patients, change the treatment gone longer gone shorter.
Uh, we could have done a better trial, but the sort of not looking
at the data for four years.
So Let's design smarter trials.
We were, we were doing something different.
Uh, and early on, what was great is early on Don's going around as Johnny Appleseed
was saying, we need to do this different, uh, and saying we need to do it different
and publishing about doing it different.
And now we were going to do it different.
We were creating a company that was going to overcome all of the challenges.
The regulatory challenges, the operational challenges, the people
that say you can't do that, the people who don't do this as normal things.
So, any time you're saying you're going to do it different, you have to sort
of tear down all of those barriers.
And we had a number of people who believed in this.
Believed we are doing good things, believe this was better.
So we had those, um, you know, the, the, the people who saw differently,
that were a huge part of, uh, thinking that what we were going to
do was, was the right way to do it.
Don Berry: So the believers, yes, um, there were, uh,
people that were on our side.
People that were on our side didn't know they were on our
side until we talked with them.
And Brandon, you said, um, that companies needed our expertise.
They didn't know that.
Brandon Giella: hmm.
Don Berry: Uh, they had to be persuaded that there was something better.
Um, and some of them took, uh, uh, uh, you know, first steps.
Um, I mentioned to you a stroke trial that I designed for Pfizer.
Uh, and there was one very key person, uh, in the audience for a,
uh, short course that I was giving, it was Mike Krams, who was an MD.
Um, this was in, in the United States, but he was, he was based
in Europe and England, in fact.
It's still part of Europe, uh, and, um, he asked me if I could design a trial for
him, um, and I did, uh, and just to talk about the, uh, the various companies.
After, this was, he was for, working for Pfizer, uh, after Pfizer, Uh,
ran the trial, they decided that it was a terrific thing and the, the
upper management decided it was a, a terrific, uh, trial that answered the
question as efficiently as possible.
Turned out to be a very negative question, which was good because it
got rid of the drug and it's, you know, no longer using, uh, resources
that there are many, many drugs in the world that deserve them better.
Um, and the company, Pfizer, wanted to patent the algorithm that ran the trial.
And, um, the reason they wanted to do that is not necessarily they wanted
to do additional trials like it, but they didn't want anybody else to be.
They wanted to own it.
Luckily for me Uh, our contract said that I own it,
Brandon Giella: Hmm,
Don Berry: them.
So they weren't able to patent it.
Um, and it's, it's that kind of thing that we were really providing the service
that they didn't know they needed, but we knew the world needed, needed it
because we were going to change the world.
And it was that kind of.
dedication, and almost a religion, um, that we have the answer.
And the point was to convince other people.
And slowly, but surely, we've done it.
So we now, I don't think Scott mentioned, but now we have like 35, uh,
people, uh, mostly PhD statisticians.
who are carrying the ball for us.
And we're really, uh, you know, fast forward, changing the world
because of the, some of the trials that we, uh, have designed and
that have been very successful.
Scott Berry: So that was the Aston stroke trial and that was actually pre Barry.
That was probably one of the things that helped get us started.
Um, and another interesting person involved in that was Tom Park.
So Don had designed this amazing adaptive trial with many, many looks in the trial.
Uh, uh, 16 doses and to implement that was brand new.
Don Berry: Daily, daily randomization changes in the algorithm
that was picking the doses.
There were 15 positive doses.
Scott Berry: So even today that would be considered a very innovative trial
design and Tom Park was at Tasella at the time and helped us implement that.
He's now at Berry and he runs our software division and
helps us overcome the barrier.
So we've run into a number of people like this that have a huge, a
huge, uh, uh, impact, uh, in Berry.
Brandon Giella: Well, I want to pick up on a thread that you were talking about,
Scott, that you you're, you know, it's always about change and kind of disrupting
the status quo, if I could call it that.
And so you guys have touched on the different ways that you do trials
and, and, and how that's come about.
But I'm curious, both of you, how would you describe succinctly or briefly or how,
yeah, just in a, in a, in a short way, how would you think, how would you describe
the difference That Barry is compared to the traditional way to do Either clinical
trial designs or the way that you run your firm or their culture Like if i'm let's
say i'm at pfizer And i'm looking across the the sea of you know statisticians
that I could interact with across a different Um, you know range of firms and
different people that are doing that and what is it that makes barry so different?
Scott Berry: Oh, it's a great question.
I think Traditionally, there's not a ton of statisticians who have a huge impact
on the trial design, really focusing on what's the question being asked.
And so we dive in and thoroughly investigate that and show through
clinical trial simulation, which is one of the things we've sort
of helped developed over 25 years.
What the trial is going to do.
It's almost like, um, uh, you use simulation to design an airplane,
to design the most efficient cars.
We now do it with clinical trials.
We're able to show them what it looks like.
Here's alternatives.
You could shape this this way.
You could do it that way.
And the wonderful thing about it is if you're trying to get somebody to do
something different, you can't tell them.
Do it differently.
We, we, we're named consultants, but if you go in and say, I think
you should do this, it doesn't work.
What they want to see is they want to see and compare and you show them,
if you do it this way, you get this.
If you do it this way, you get this or this way.
And then, Oh, I want to do that.
And, and I want to do that.
And I would do that and they get to this place and it was them.
They're making the decisions, they're driving it.
They're the, they're the agent of change.
We help show them that, you know, we don't tell them what to do.
We show them the possible ways and the scenarios, and it allows
them to be the biggest advocate for the direction they're going.
Brandon Giella: So
Don Berry: So, Brandon, um,
Somewhere in this conversation, we want to talk about the FDA because it has been
essential for our existence, essential for what we do, back in 2010, the FDA issued
a guidance for adaptive design that, uh, that said, simulation for controlling
type 1 error rate is little understood.
And, um, the Bayesian approach, which we take in statistics, Uh,
is heavily dependent on that very thing, about simulating a trial.
Simulating a trial, what we mean is, we make an assumption
about what the truth is.
Is the drug good or not?
Uh, and if it's good, how good is it?
And we simulate a trial to show that regardless of what the truth
is, we're going to find the truth.
But We have complicated trials.
The ASTIN trial is updating daily.
The results coming in by fax in those days.
Um, and, um, the, the simulations, when we do 100, 000 of them, sort of
guarantee that we've got the answer.
That it's, it's doing, you know, it has a 5 percent error rate, but we
demonstrate that from the simulations.
And that was a big block for us, the fact that the FDA said
they didn't understand it.
And they weren't convinced that it was, uh, the right thing to do.
Or that it was giving you the correct answer.
Um, and so we were lucky.
Another person to mention in this is at the FDA was Lissa LaVange,
who took over, uh, shortly after that guidance was issued.
Um, and was head of the statistics group at the CDER, the Center
for Devices, Center for Drugs.
And, um, she arranged for bringing in the statistical community over the
next 10 years to help them understand.
And in 2019 they issued another guidance for adaptive clinical trial
design That said, simulation is okay.
And that was a really big thing for us, because we have this software that you,
that Scott mentioned that Tom Parks is in charge of, um, it's FACTS, it's called,
uh, uh, Fixed and Adaptive Clinical Trial Simulator, and it can be used to simulate
any trial, not just the ones we design.
But, it's out in the world and people are using it to design
these trials and now, I've said too much, uh, Scott, back to you,
Scott Berry: No, it's, it's, it's one of the list has been a huge,
a huge benefit to the scientific community, medical community, for sure.
Brandon Giella: Well, I'm really glad for people like you because when I
was getting my MBA in finance, I had a statistics class in my curriculum.
Never taken statistics before, and I'm proud to announce that I got a C.
So I'm really glad.
So I'm glad people like you exist.
I can't do it.
Don Berry: no, no, you, if you, we hate it when somebody says, uh, you
know, I talk about clinical trial design, I'm helping advise a company.
And there's this old geezer, maybe even older than me, um, who says, I've
designed clinical trials for 30 years.
I know how to design a trial.
Immediately, you know that his head is blocked off.
He's not going to listen to anything you say.
We don't like people who think they know the answer because they don't.
Uh, and they don't know what the best way is to do a clinical trial.
That's what we deliver to them.
is you're going to take this trial, the one Scott mentioned,
you know, 200 patients, four years.
We're going to give you the answer in six months, maybe.
We don't know.
Maybe we have to go longer, but we can give you, in this Aston trial,
as I said, it stopped the trial, um, as soon as it was allowed to do so.
And it was because it was looking, it was like artificial intelligence,
it was looking across the spectrum of the doses, and it started out looking
at the low doses and comparing to placebo, decided that wasn't good
enough, and it moved up the chain.
It finally started to focus on the highest doses compared to placebo,
uh, decided nothing was there.
And the good news is for patients that it started to go to placebo.
Um, namely it wasn't any good.
And that thing saved Pfizer millions in terms of the patients, in terms
of the patient resources, but also an uncountable, you know, a priceless.
benefit, that it got them off that thing.
This was a, a particular, uh, uh, mechanism, mechanism of action, um, that,
uh, the Pfizer and the rest of the stroke community decided was not the way to go.
Uh, and so it saved, we, we really don't know how to quantify it, but
it saved, uh, I mean it's almost priceless what the benefit was.
Scott Berry: Yeah, it's always hard to quantify time in it.
So the, the, the story of brain, and so we started off.
So it was Don and me, and we, we didn't know whether this was going to work.
Um, and we, we were doing a lot of medical device trials.
There's been a long history of, of innovative Bayesian things at the center
for devices, Greg Campbell was a huge, uh, uh, a huge innovator at the FDA for that.
And all of a sudden we had people that were interested.
in looking at adaptive trials, looking at flexible trials.
full time employee other than myself.
Jason Connor joined several years after that.
Um, and we kept getting more and more interest.
And as Don described, 2010, it was a little bit where was drugs going to go?
Center for Drugs were doing a lot of devices.
And the Center for Drugs became more and more interested.
Pharma became more interested.
And we have now been steadily growing since 2010.
Uh, within that setting up to now, as Don described, our 35 scientists
here at Berry Consultants, uh, still, still growing and still innovating.
Brandon Giella: Yeah, it's, it's such an amazing story and it's to Don point the
way that you guys do your, your trials and the way you run your business, it is
so incredibly helpful, not just for the firms that hire you, your clients and how,
you know, you can save them money and time and all of that, but also for the patients
themselves and to be, to have the, the, the specificity, um, that you have for
these trials is, is really amazing.
So how I guess following that point scott, um, and we'll take maybe the last 10
minutes or so of the show Uh, how would you describe the current state of barry?
You know, what what is what do you got?
What are maybe projects you're you're working on?
Um, you know different things that you guys are thinking through and innovating
And then where do you see barry going over the next year five years ten years?
Where where are you pointing your ship if I can ask that?
Don Berry: So, uh, let me try to address that.
Uh, there's, back around this 2010, um, I was designing clinical trials for the
cancer leukemia group B in breast cancer.
And, um, uh, a friend of mine that I, uh, uh, uh, developed a relationship
with was Laura Esserman, who's the surgeon at, um, at UCSF, University
of California, San Francisco.
Um, and she was, you know, I was radical, but she was off the deep end.
Um, and, uh, wanted to do things.
That, similar to what I wanted to do, and we built a trial together.
We couldn't do it through the National Cancer Institute, which
sponsored these CLGB, uh, trials.
So we went to the Foundation for the NIH, and we worked with them to fund the trial.
This is a, a public private partnership with, uh, NIH leaders and industry.
And so we built a trial called iSpy2, um, that was, had lots of innovations,
had Scott's, um, uh, innovation for using historical controls that he had designed
when he wrote, uh, uh, an article that won the, uh, Journal of the American
Statistical Association award for best.
article that year in Applied Statistics, uh, that used the, in baseball,
Babe Ruth versus, um, uh, who,
Scott Berry: Mark McGuire.
Don Berry: Mark McGuire, um, uh, and who was better, adjusting for the time.
And so he built this thing that used things in the past, Well,
we wanted to use controls.
We were randomizing, but we wanted to keep those controls, uh, randomization,
uh, patients in the trial that we could continue to use as a, as a basis.
That was just one of the many innovations.
Another innovation, and speaking to your point about patients,
was we wanted to treat these women as effectively as possible.
So we built in adaptive randomization.
So, if a drug was doing poorly in a subset of women, it got lower
probability of being assigned and soon was zeroed out because there were
other drugs that we were looking at.
So, we ended up over the course of the next 10 years, um, evaluating 23 drugs, 9
of them went on to bigger things, um, and, um, the, the, the, the, the, the, the,
Scott Berry: So like, so, so Don, let me jump into that part since,
since you stole my question.
Let me, let me steal this from you and take the ball.
So, uh, so the, the, imagine how different this is.
The, the historical way this is done is you have a drug a
And you build a whole trial.
It's like it would be like the NFL deciding every time they're going to do
a game, they build a whole new stadium, they play a game and they take it down
and then they build a whole nother one.
This is what we do.
So this I-SPY 2 trial was building a single stadium, a single protocol and
move 25 drugs through the protocol.
Using the same stadium, comparing them, using common controls.
If you have four trials, all enrolling 50 percent controls and you move
them all together and have one arm of control, you've now saved patients.
You've saved time.
So this was a landmark trial in 2010 in breast cancer, and it's
called a platform trial and it was, it was as it was off the deep end.
Fast forward to COVID.
The pandemic hits and we're trying to figure out how to treat COVID and
you can't wait two years to build a clinical trial to investigate
a single drug, tear it down.
So platform trials globally that copied I-SPY 2 were used to treat COVID.
Everything we learned how to treat therapeutically COVID came from platform
trials that really the grandfather of that was this crazy idea of I-SPY 2.
So what is that?
Now we're doing, we're doing trials of that in ALS, in glioblastoma, uh,
in, in a number of rare diseases.
And it was all born out of these crazy ideas of Laura, Laura and Don in 2010.
So that's where we're going.
But we don't know what that innovation is.
We have all kinds of ideas of how to make this more efficient.
And we have to, it's too expensive.
We've got it.
We there's so many amazing medical therapies out there to be using 50 year
old trial designs doesn't really work.
So we want to be on that cutting edge.
We want the next eye spy, the next thing to, to do better science in this for
patients for, for better treatments.
We don't know what it's going to be, but we want to be on that sort of cutting
edge and, and, and, and doing this better.
Don Berry: So, one important, important note to that, um, in the glioblastoma
study, uh, it's a phase three trial.
That means that if a drug does well in, in, in, uh, GBM Agile,
we call it, um, we take it to the FDA and the FDA will approve it.
We worked with the FDA.
Uh, really intimately, uh, interacting with them and building
the trial that they would okay.
So, and they sent us a letter saying, if you build the, if you have an arm
that comes through, a treatment arm that comes through the trial, uh, that
graduates and is confirmed within GBM Agile, within this, uh, uh, adaptive
platform trial, we'll approve it.
So, and that was a sea change.
iSpy 2 trial was great.
It's known throughout the world as being an innovative trial that
people want to, uh, uh, uh, imitate.
But it's a phase 2 trial.
It evaluates these drugs and then moves them, decides which drugs
can go into a phase 3 trial.
GBM Agile does the phase 3 trial within itself.
Moving seamlessly from one part of the drug development spectrum, namely,
uh, is it, is the drug working, to the, uh, confirmatory phase.
And this we owe to the FDA, who has just been enormously helpful to us
and to, you know, uh, medical research and drug development generally.
Brandon Giella: I love these stories.
I love hearing that something that you designed and brought into the
world, You know 15 years ago is still impacting the world in huge ways
like covid and some of these other major Major diseases and issues.
It's such an amazing Legacy if you want to call it that
Don Berry: Just to mention Alzheimer's and
Scott Berry: heh
Don Berry: Uh, and just to mention diabetes type 2, and just to mention
the new craze, the weight loss craze with the GLP1 agonists, um,
we designed the first trial for, uh, uh, Eli Lilly's, uh, dulagletide,
trulicity, uh, that became their best selling drug and, uh, type 2 diabetes.
But in that trial We also saw, um, you know, it's a 5 billion drug, has been, uh,
and, and was the original approved, uh, GLP 1 agonist, and it showed in the trial
we designed a benefit on weight loss that was essentially the same benefit that they
eventually saw when they got Trulicity approved for weight loss, and now the,
Well, you know the rest of the story.
The world is getting skinnier all the time, in part because
of these, uh, Glyphon agonists.
Brandon Giella: quickly on its axis uh, no, I So if if I could summarize
all of this or if I guess if you could summarize all of this what is one thing?
in one minute That you two are very excited about in this coming year
the 25th anniversary 2025 Barry is going through a lot of change,
very exciting things happening.
What is one thing that you want listeners to take away from, or one
thing that you wish that they knew about Barry in this upcoming year?
Scott Berry: Oh boy.
Uh, that's a great question.
I'm most excited about all of the new statisticians and
scientists we have at Berry.
they're brilliant.
They've, they're coming into this with all new ideas.
They're also their communication is, fantastic.
so I'm excited to see what they do.
it was incredible, over these 25 years, but, it's, they're much smarter than I am.
and so I'm really excited to see what they're going to do with clinical trials.
Brandon Giella: There are at least B students for sure.
Scott Berry: Yeah.
Yep.
Don Berry: Jason Connor, who, Scott mentioned was our first employee,
went off on his own, partway along.
I told Jason That my loyalties are with people.
My loyalty is with you.
and Jason Kept, has his own, company and he consults.
He's part of what I call the Berry Diaspora, who is spreading the word.
we can't change the word, the world, in Austin, Texas.
we want to change the world in,
Peoria, in Australia, in China, in Europe, and we're partway along with that.
GBM Agile, for example, is accruing patients in Australia and in, Europe,
in addition to the United States.
that's, that's the exciting thing, is to change the world, one person at a time.
Brandon Giella: I love that.
Doctors Barry.
Don and Scott, thank you so much for the work that you're doing.
And I'm very excited about the 25th anniversary this year, about next year and
all the things that you guys are doing.
And I'm excited for the show.
I think it's gonna be a lot of fun and I can't wait to have other guests.
I know we've got 30 something episodes that we're kind of
planning out and working on.
So I'm really excited to keep this going and we'll see you again on episode two.
Scott Berry: Appreciate it.
Thanks, Brandon.
Don Berry: thanks, Brendan.
Thanks, Scott.