WEBVTT NOTE This file was generated by Descript 00:00:00.996 --> 00:00:04.756 Judith: Welcome to Berry's In the Interim podcast, where we explore the 00:00:04.756 --> 00:00:08.796 cutting edge of innovative clinical trial design for the pharmaceutical and 00:00:08.796 --> 00:00:11.086 medical industries, and so much more. 00:00:11.836 --> 00:00:12.446 Let's dive in. 00:00:14.113 --> 00:00:18.303 Brandon Giella: Hello and welcome to Barry's in the interim podcast. 00:00:18.353 --> 00:00:23.753 This is episode number one, the very first inaugural episode of the podcast. 00:00:23.763 --> 00:00:25.883 I'm so excited to talk to you guys. 00:00:25.913 --> 00:00:27.973 I have with me Dr. 00:00:27.973 --> 00:00:29.603 Don Barry and Dr. 00:00:29.603 --> 00:00:36.383 Scott Barry, statisticians, experts, thought leaders, and founders of Barry 00:00:36.383 --> 00:00:41.203 consultants, and I want to get into all of that, but we are kicking off this 00:00:41.203 --> 00:00:47.053 show because This is the 25th anniversary coming up for Berry Consultants and it 00:00:47.053 --> 00:00:52.573 is such a momentous occasion And I'm so glad to have the founders and uh and 00:00:52.583 --> 00:00:58.273 experts in this arena because you guys really are the trendsetters in Statistical 00:00:58.273 --> 00:01:00.663 trials, clinical trials, adaptive trials. 00:01:00.713 --> 00:01:04.728 I want to get into all that We're celebrating this year with so many 00:01:04.728 --> 00:01:08.768 new projects and just a lot of excitement, um, coming up in 2025. 00:01:09.118 --> 00:01:10.928 So this podcast is a part of that. 00:01:11.418 --> 00:01:18.258 Um, and so as such, I would love to hear the story of Barry consultants and I 00:01:18.258 --> 00:01:20.818 have, uh, the best people to do that. 00:01:21.298 --> 00:01:26.298 Um, and so I would love to hear and share with our audience and our network. 00:01:26.618 --> 00:01:27.128 What. 00:01:27.633 --> 00:01:29.883 How did Barry begin? 00:01:29.993 --> 00:01:33.143 What was the motivations behind the firm? 00:01:33.513 --> 00:01:37.193 Um, who impacted you in those early beginning stages? 00:01:37.193 --> 00:01:38.933 What kind of conversations do you have? 00:01:38.933 --> 00:01:42.523 What are the stories, what challenges did you encounter? 00:01:42.863 --> 00:01:46.748 And then toward the end of the show, I would love to hear what's next. 00:01:46.748 --> 00:01:48.183 You know, where are we going from here? 00:01:48.633 --> 00:01:54.433 And so Don, you, you are the founder, you are the, the man of the hour. 00:01:54.453 --> 00:01:55.563 I would love to hear. 00:01:55.803 --> 00:01:57.873 What was it like when you started Barry? 00:01:57.883 --> 00:01:59.473 How did that come about? 00:01:59.513 --> 00:02:01.493 And why, why are we here today? 00:02:03.633 --> 00:02:07.063 Don Berry: So I was a graduate student at Yale University, 00:02:07.653 --> 00:02:12.233 Scott Berry: Heh, heh, 00:02:12.553 --> 00:02:18.313 Don Berry: Frank Anscombe, a very famous statistician, and my wife 00:02:18.313 --> 00:02:22.663 was pregnant at the time, and, um, 00:02:25.123 --> 00:02:30.183 Frank asked me, he said, so how are you going to pay for this? 00:02:31.613 --> 00:02:33.243 And I said, I have no idea. 00:02:33.243 --> 00:02:41.593 Uh, and he said, well, When your wife is in the hospital and you 00:02:41.593 --> 00:02:43.373 get the bill, bring it to me. 00:02:44.993 --> 00:02:52.233 I brought it to him, and he had a grant that paid for the, uh, 00:02:52.363 --> 00:02:54.483 the hospital and everything. 00:02:54.643 --> 00:02:56.353 I don't know how he did it, but he did it. 00:02:57.283 --> 00:03:04.303 Um, and I count that as Scott's very first grant, because 00:03:04.313 --> 00:03:08.243 Scott was the, The, uh, baby. 00:03:09.213 --> 00:03:12.163 And of course, you see him now, he's no longer a baby. 00:03:12.933 --> 00:03:23.033 Um, but he still, is, uh, thinking in very naive thoughts and very creative thoughts. 00:03:23.523 --> 00:03:26.783 And that's really the beginning of Berry Consultants. 00:03:27.603 --> 00:03:30.823 Just a word about, uh, the interim. 00:03:31.503 --> 00:03:35.178 In the interim between that and when we founded Berry, Berry. 00:03:36.678 --> 00:03:40.278 wasn't a particular time that Barry came into being. 00:03:40.278 --> 00:03:50.528 It was, uh, I was known as a radical reactionary, crazy guy, loosey goosey, 00:03:50.528 --> 00:03:56.828 some people called me, trying to change the way we looked at medical research. 00:03:57.568 --> 00:04:06.258 And so it was my touring around, Brandon, I use the term, Johnny Appleseed, around 00:04:06.268 --> 00:04:12.868 the country and pharmaceutical companies and wherever, whoever would listen, I 00:04:12.868 --> 00:04:18.228 would, give them a talk and, spur them on. 00:04:19.088 --> 00:04:23.828 Uh, just an anecdote about that, along the way, I was in Washington, D. 00:04:23.828 --> 00:04:24.458 C., 00:04:25.408 --> 00:04:31.618 on the metro, and, uh, coming back from one of my talks, And a guy came 00:04:31.618 --> 00:04:38.558 up to me, it turned out to be he was a statistician at the FDA, and he said, Dr. 00:04:38.558 --> 00:04:47.003 Berry, uh, I'm a fan of yours, every time I hear you talk, I 00:04:47.183 --> 00:04:51.313 become a Bayesian for five minutes. 00:04:52.743 --> 00:04:55.753 Can you work on a sustained release version? 00:04:56.863 --> 00:04:59.173 So, uh, I did. 00:04:59.733 --> 00:05:03.773 But, uh, when did Barry start? 00:05:03.773 --> 00:05:05.843 It started like 2001. 00:05:06.843 --> 00:05:09.313 Scott and I happened to be in Texas. 00:05:10.733 --> 00:05:16.293 and I had been doing consulting and, Scott, take it from here. 00:05:17.163 --> 00:05:23.373 Scott Berry: So, 33 years after Frank Anscombe's grant, uh, with that, 00:05:23.383 --> 00:05:31.713 so, I was on faculty at Texas A&M Statistics, and, doing research, very 00:05:31.713 --> 00:05:36.533 much enjoying it, teaching, and a number of projects came through Don, who is 00:05:36.533 --> 00:05:41.083 at MD Anderson Cancer Center, building clinical trial designs, and so I was 00:05:41.093 --> 00:05:44.393 helping with those, and I loved them. 00:05:45.023 --> 00:05:47.433 Everyone turned out to be a puzzle. 00:05:47.773 --> 00:05:49.293 I love board games. 00:05:50.203 --> 00:05:55.373 chess, bridge, settlers of Catan, and they all have, what's the problem to solve? 00:05:55.373 --> 00:05:57.643 And all of these had a problem to solve. 00:05:57.943 --> 00:06:02.693 We were using all of The techniques, the statistics, the science to solve 00:06:02.703 --> 00:06:05.163 these and everyone I worked on, I loved. 00:06:05.163 --> 00:06:08.943 And so after five years, I wanted to do more of that. 00:06:09.863 --> 00:06:12.343 so we talked about what would this look like? 00:06:12.343 --> 00:06:18.673 Suppose we started a business to, to, design better, smarter trials. 00:06:19.053 --> 00:06:25.893 And so in 2000, June of 2000, we decided I would leave academia and 00:06:25.893 --> 00:06:27.643 we would start Berry Consultants. 00:06:27.683 --> 00:06:29.373 I was the full time person. 00:06:29.383 --> 00:06:31.763 Don was at MD Anderson Cancer Center. 00:06:32.153 --> 00:06:38.408 And so June 1st, 2000, we started Berry Consultants with, really No 00:06:38.408 --> 00:06:43.758 idea what was going to happen, but we had shared interest, desires 00:06:43.798 --> 00:06:47.468 to design smarter, better clinical trials and really enjoyed it. 00:06:47.618 --> 00:06:49.608 And so we started it, the two of us. 00:06:50.623 --> 00:06:51.593 Brandon Giella: And how's that been for you 00:06:52.538 --> 00:06:53.718 Scott Berry: Uh, fabulous. 00:06:53.918 --> 00:06:59.648 Still, still, still going on 25 years and still very much enjoying every day of it. 00:07:00.233 --> 00:07:00.773 Brandon Giella: I love that. 00:07:00.903 --> 00:07:01.463 I love that. 00:07:01.853 --> 00:07:05.363 Well, I'm curious, what was, I mean, starting your, your first, uh, 00:07:05.373 --> 00:07:07.103 starting your, your company like this. 00:07:07.103 --> 00:07:11.203 And, and I know you, you had, you know, clients that were needing 00:07:11.203 --> 00:07:15.853 your expertise, very complicated, sophisticated trials, you know, big, 00:07:15.933 --> 00:07:20.183 big money involved in some of the, um, you know, pharmaceutical companies 00:07:20.183 --> 00:07:21.513 or medical devices, things like that. 00:07:21.923 --> 00:07:25.523 Um, what were some of the challenges that you encountered early on? 00:07:25.523 --> 00:07:25.583 Thanks, Tom. 00:07:25.943 --> 00:07:30.143 And how did that shape Barry now into to who it's become? 00:07:31.808 --> 00:07:33.718 Scott Berry: Yeah, it's, uh, we've been. 00:07:34.453 --> 00:07:39.523 Part of what we're trying to do is, is through change, it's always changing 00:07:39.523 --> 00:07:43.773 the status quo when you're trying to do something different and just to set 00:07:43.773 --> 00:07:49.323 this up, the standard of a clinical trial is, um, the standard thing is 00:07:49.353 --> 00:07:56.013 let's enroll 200 patients, enroll the trial for four years, gather the data 00:07:56.013 --> 00:07:59.213 and look at the data after four years and see if we've answered the question. 00:07:59.723 --> 00:08:03.198 Invariably, you look at the data and you say, Oh, Shoot. 00:08:03.348 --> 00:08:05.768 I wish I wish we'd have done something different. 00:08:06.058 --> 00:08:11.008 I wish we to change the patients, change the treatment gone longer gone shorter. 00:08:11.358 --> 00:08:17.638 Uh, we could have done a better trial, but the sort of not looking 00:08:17.638 --> 00:08:18.948 at the data for four years. 00:08:18.948 --> 00:08:21.373 So Let's design smarter trials. 00:08:21.833 --> 00:08:24.543 We were, we were doing something different. 00:08:24.723 --> 00:08:30.313 Uh, and early on, what was great is early on Don's going around as Johnny Appleseed 00:08:30.313 --> 00:08:34.693 was saying, we need to do this different, uh, and saying we need to do it different 00:08:34.863 --> 00:08:36.663 and publishing about doing it different. 00:08:36.663 --> 00:08:38.453 And now we were going to do it different. 00:08:38.473 --> 00:08:42.433 We were creating a company that was going to overcome all of the challenges. 00:08:42.973 --> 00:08:46.953 The regulatory challenges, the operational challenges, the people 00:08:46.953 --> 00:08:50.523 that say you can't do that, the people who don't do this as normal things. 00:08:50.523 --> 00:08:55.373 So, any time you're saying you're going to do it different, you have to sort 00:08:55.373 --> 00:08:57.233 of tear down all of those barriers. 00:08:57.233 --> 00:09:00.423 And we had a number of people who believed in this. 00:09:00.668 --> 00:09:04.548 Believed we are doing good things, believe this was better. 00:09:04.728 --> 00:09:09.118 So we had those, um, you know, the, the, the people who saw differently, 00:09:09.118 --> 00:09:13.348 that were a huge part of, uh, thinking that what we were going to 00:09:13.348 --> 00:09:14.878 do was, was the right way to do it. 00:09:16.683 --> 00:09:21.143 Don Berry: So the believers, yes, um, there were, uh, 00:09:21.193 --> 00:09:23.813 people that were on our side. 00:09:24.573 --> 00:09:26.823 People that were on our side didn't know they were on our 00:09:26.823 --> 00:09:29.203 side until we talked with them. 00:09:29.563 --> 00:09:33.573 And Brandon, you said, um, that companies needed our expertise. 00:09:33.573 --> 00:09:36.763 They didn't know that. 00:09:37.253 --> 00:09:37.583 Brandon Giella: hmm. 00:09:37.973 --> 00:09:43.533 Don Berry: Uh, they had to be persuaded that there was something better. 00:09:44.283 --> 00:09:50.058 Um, and some of them took, uh, uh, uh, you know, first steps. 00:09:50.708 --> 00:09:56.178 Um, I mentioned to you a stroke trial that I designed for Pfizer. 00:09:56.788 --> 00:10:02.508 Uh, and there was one very key person, uh, in the audience for a, 00:10:02.928 --> 00:10:06.718 uh, short course that I was giving, it was Mike Krams, who was an MD. 00:10:07.318 --> 00:10:13.378 Um, this was in, in the United States, but he was, he was based 00:10:13.378 --> 00:10:15.988 in Europe and England, in fact. 00:10:16.608 --> 00:10:26.828 It's still part of Europe, uh, and, um, he asked me if I could design a trial for 00:10:26.838 --> 00:10:37.198 him, um, and I did, uh, and just to talk about the, uh, the various companies. 00:10:37.868 --> 00:10:44.978 After, this was, he was for, working for Pfizer, uh, after Pfizer, Uh, 00:10:44.978 --> 00:10:53.058 ran the trial, they decided that it was a terrific thing and the, the 00:10:53.078 --> 00:10:58.208 upper management decided it was a, a terrific, uh, trial that answered the 00:10:58.208 --> 00:11:01.358 question as efficiently as possible. 00:11:01.388 --> 00:11:05.178 Turned out to be a very negative question, which was good because it 00:11:05.178 --> 00:11:09.818 got rid of the drug and it's, you know, no longer using, uh, resources 00:11:09.818 --> 00:11:13.558 that there are many, many drugs in the world that deserve them better. 00:11:14.308 --> 00:11:24.968 Um, and the company, Pfizer, wanted to patent the algorithm that ran the trial. 00:11:26.288 --> 00:11:33.528 And, um, the reason they wanted to do that is not necessarily they wanted 00:11:33.898 --> 00:11:37.568 to do additional trials like it, but they didn't want anybody else to be. 00:11:38.268 --> 00:11:39.518 They wanted to own it. 00:11:40.278 --> 00:11:45.588 Luckily for me Uh, our contract said that I own it, 00:11:46.443 --> 00:11:46.683 Brandon Giella: Hmm, 00:11:46.978 --> 00:11:47.328 Don Berry: them. 00:11:47.808 --> 00:11:49.528 So they weren't able to patent it. 00:11:50.408 --> 00:11:57.608 Um, and it's, it's that kind of thing that we were really providing the service 00:11:57.648 --> 00:12:03.508 that they didn't know they needed, but we knew the world needed, needed it 00:12:03.538 --> 00:12:06.058 because we were going to change the world. 00:12:06.638 --> 00:12:08.188 And it was that kind of. 00:12:09.603 --> 00:12:15.513 dedication, and almost a religion, um, that we have the answer. 00:12:16.393 --> 00:12:20.323 And the point was to convince other people. 00:12:20.893 --> 00:12:23.503 And slowly, but surely, we've done it. 00:12:23.893 --> 00:12:29.223 So we now, I don't think Scott mentioned, but now we have like 35, uh, 00:12:29.283 --> 00:12:32.403 people, uh, mostly PhD statisticians. 00:12:32.833 --> 00:12:35.703 who are carrying the ball for us. 00:12:36.263 --> 00:12:40.093 And we're really, uh, you know, fast forward, changing the world 00:12:40.773 --> 00:12:44.693 because of the, some of the trials that we, uh, have designed and 00:12:44.693 --> 00:12:46.273 that have been very successful. 00:12:47.198 --> 00:12:50.968 Scott Berry: So that was the Aston stroke trial and that was actually pre Barry. 00:12:51.368 --> 00:12:54.868 That was probably one of the things that helped get us started. 00:12:55.188 --> 00:12:59.328 Um, and another interesting person involved in that was Tom Park. 00:12:59.908 --> 00:13:06.468 So Don had designed this amazing adaptive trial with many, many looks in the trial. 00:13:06.848 --> 00:13:12.828 Uh, uh, 16 doses and to implement that was brand new. 00:13:13.443 --> 00:13:17.873 Don Berry: Daily, daily randomization changes in the algorithm 00:13:17.873 --> 00:13:20.013 that was picking the doses. 00:13:20.023 --> 00:13:21.903 There were 15 positive doses. 00:13:22.833 --> 00:13:27.633 Scott Berry: So even today that would be considered a very innovative trial 00:13:27.633 --> 00:13:32.263 design and Tom Park was at Tasella at the time and helped us implement that. 00:13:32.523 --> 00:13:36.613 He's now at Berry and he runs our software division and 00:13:36.623 --> 00:13:38.703 helps us overcome the barrier. 00:13:38.703 --> 00:13:42.273 So we've run into a number of people like this that have a huge, a 00:13:42.273 --> 00:13:45.113 huge, uh, uh, impact, uh, in Berry. 00:13:46.553 --> 00:13:48.593 Brandon Giella: Well, I want to pick up on a thread that you were talking about, 00:13:48.593 --> 00:13:52.943 Scott, that you you're, you know, it's always about change and kind of disrupting 00:13:52.943 --> 00:13:55.113 the status quo, if I could call it that. 00:13:55.113 --> 00:13:58.403 And so you guys have touched on the different ways that you do trials 00:13:58.403 --> 00:13:59.943 and, and, and how that's come about. 00:13:59.943 --> 00:14:05.073 But I'm curious, both of you, how would you describe succinctly or briefly or how, 00:14:05.273 --> 00:14:09.593 yeah, just in a, in a, in a short way, how would you think, how would you describe 00:14:09.603 --> 00:14:16.463 the difference That Barry is compared to the traditional way to do Either clinical 00:14:16.463 --> 00:14:21.803 trial designs or the way that you run your firm or their culture Like if i'm let's 00:14:21.803 --> 00:14:26.353 say i'm at pfizer And i'm looking across the the sea of you know statisticians 00:14:26.353 --> 00:14:30.973 that I could interact with across a different Um, you know range of firms and 00:14:30.983 --> 00:14:34.323 different people that are doing that and what is it that makes barry so different? 00:14:36.433 --> 00:14:38.343 Scott Berry: Oh, it's a great question. 00:14:38.353 --> 00:14:46.803 I think Traditionally, there's not a ton of statisticians who have a huge impact 00:14:46.803 --> 00:14:51.683 on the trial design, really focusing on what's the question being asked. 00:14:52.133 --> 00:14:57.383 And so we dive in and thoroughly investigate that and show through 00:14:57.383 --> 00:15:00.363 clinical trial simulation, which is one of the things we've sort 00:15:00.363 --> 00:15:02.843 of helped developed over 25 years. 00:15:03.568 --> 00:15:05.068 What the trial is going to do. 00:15:05.068 --> 00:15:10.538 It's almost like, um, uh, you use simulation to design an airplane, 00:15:10.798 --> 00:15:12.868 to design the most efficient cars. 00:15:12.868 --> 00:15:14.788 We now do it with clinical trials. 00:15:14.788 --> 00:15:16.818 We're able to show them what it looks like. 00:15:17.068 --> 00:15:18.438 Here's alternatives. 00:15:18.438 --> 00:15:19.858 You could shape this this way. 00:15:19.858 --> 00:15:20.858 You could do it that way. 00:15:21.348 --> 00:15:25.648 And the wonderful thing about it is if you're trying to get somebody to do 00:15:25.648 --> 00:15:28.368 something different, you can't tell them. 00:15:28.918 --> 00:15:29.998 Do it differently. 00:15:30.358 --> 00:15:33.898 We, we, we're named consultants, but if you go in and say, I think 00:15:33.908 --> 00:15:35.298 you should do this, it doesn't work. 00:15:35.908 --> 00:15:41.768 What they want to see is they want to see and compare and you show them, 00:15:41.788 --> 00:15:43.458 if you do it this way, you get this. 00:15:43.458 --> 00:15:45.818 If you do it this way, you get this or this way. 00:15:46.248 --> 00:15:47.558 And then, Oh, I want to do that. 00:15:47.958 --> 00:15:49.448 And, and I want to do that. 00:15:49.448 --> 00:15:52.698 And I would do that and they get to this place and it was them. 00:15:52.718 --> 00:15:55.118 They're making the decisions, they're driving it. 00:15:55.118 --> 00:15:57.298 They're the, they're the agent of change. 00:15:57.298 --> 00:16:02.088 We help show them that, you know, we don't tell them what to do. 00:16:02.098 --> 00:16:06.398 We show them the possible ways and the scenarios, and it allows 00:16:06.398 --> 00:16:09.628 them to be the biggest advocate for the direction they're going. 00:16:10.543 --> 00:16:10.563 Brandon Giella: So 00:16:11.533 --> 00:16:13.033 Don Berry: So, Brandon, um, 00:16:15.413 --> 00:16:19.943 Somewhere in this conversation, we want to talk about the FDA because it has been 00:16:19.943 --> 00:16:26.328 essential for our existence, essential for what we do, back in 2010, the FDA issued 00:16:26.328 --> 00:16:35.198 a guidance for adaptive design that, uh, that said, simulation for controlling 00:16:35.208 --> 00:16:40.438 type 1 error rate is little understood. 00:16:41.898 --> 00:16:48.258 And, um, the Bayesian approach, which we take in statistics, Uh, 00:16:48.258 --> 00:16:52.908 is heavily dependent on that very thing, about simulating a trial. 00:16:53.218 --> 00:16:57.308 Simulating a trial, what we mean is, we make an assumption 00:16:57.338 --> 00:16:59.728 about what the truth is. 00:16:59.848 --> 00:17:01.448 Is the drug good or not? 00:17:02.398 --> 00:17:04.978 Uh, and if it's good, how good is it? 00:17:05.558 --> 00:17:11.738 And we simulate a trial to show that regardless of what the truth 00:17:11.768 --> 00:17:13.528 is, we're going to find the truth. 00:17:14.978 --> 00:17:17.683 But We have complicated trials. 00:17:17.683 --> 00:17:20.413 The ASTIN trial is updating daily. 00:17:21.123 --> 00:17:24.103 The results coming in by fax in those days. 00:17:24.843 --> 00:17:35.973 Um, and, um, the, the simulations, when we do 100, 000 of them, sort of 00:17:36.023 --> 00:17:37.933 guarantee that we've got the answer. 00:17:37.933 --> 00:17:42.493 That it's, it's doing, you know, it has a 5 percent error rate, but we 00:17:42.493 --> 00:17:44.613 demonstrate that from the simulations. 00:17:45.413 --> 00:17:50.563 And that was a big block for us, the fact that the FDA said 00:17:50.573 --> 00:17:51.873 they didn't understand it. 00:17:52.703 --> 00:17:56.993 And they weren't convinced that it was, uh, the right thing to do. 00:17:57.013 --> 00:18:00.053 Or that it was giving you the correct answer. 00:18:00.863 --> 00:18:03.563 Um, and so we were lucky. 00:18:03.563 --> 00:18:08.763 Another person to mention in this is at the FDA was Lissa LaVange, 00:18:08.763 --> 00:18:12.973 who took over, uh, shortly after that guidance was issued. 00:18:12.993 --> 00:18:20.063 Um, and was head of the statistics group at the CDER, the Center 00:18:20.063 --> 00:18:22.363 for Devices, Center for Drugs. 00:18:23.163 --> 00:18:30.003 And, um, she arranged for bringing in the statistical community over the 00:18:30.003 --> 00:18:33.943 next 10 years to help them understand. 00:18:34.753 --> 00:18:40.873 And in 2019 they issued another guidance for adaptive clinical trial 00:18:40.873 --> 00:18:46.613 design That said, simulation is okay. 00:18:47.403 --> 00:18:53.563 And that was a really big thing for us, because we have this software that you, 00:18:53.603 --> 00:18:59.803 that Scott mentioned that Tom Parks is in charge of, um, it's FACTS, it's called, 00:18:59.893 --> 00:19:06.406 uh, uh, Fixed and Adaptive Clinical Trial Simulator, and it can be used to simulate 00:19:06.406 --> 00:19:09.528 any trial, not just the ones we design. 00:19:10.338 --> 00:19:13.828 But, it's out in the world and people are using it to design 00:19:13.828 --> 00:19:18.918 these trials and now, I've said too much, uh, Scott, back to you, 00:19:19.088 --> 00:19:21.898 Scott Berry: No, it's, it's, it's one of the list has been a huge, 00:19:22.118 --> 00:19:25.738 a huge benefit to the scientific community, medical community, for sure. 00:19:27.218 --> 00:19:30.618 Brandon Giella: Well, I'm really glad for people like you because when I 00:19:30.618 --> 00:19:34.718 was getting my MBA in finance, I had a statistics class in my curriculum. 00:19:34.798 --> 00:19:38.748 Never taken statistics before, and I'm proud to announce that I got a C. 00:19:39.218 --> 00:19:41.138 So I'm really glad. 00:19:42.358 --> 00:19:44.358 So I'm glad people like you exist. 00:19:44.468 --> 00:19:45.218 I can't do it. 00:19:46.068 --> 00:19:53.448 Don Berry: no, no, you, if you, we hate it when somebody says, uh, you 00:19:53.448 --> 00:19:56.928 know, I talk about clinical trial design, I'm helping advise a company. 00:19:57.383 --> 00:20:04.393 And there's this old geezer, maybe even older than me, um, who says, I've 00:20:04.393 --> 00:20:07.323 designed clinical trials for 30 years. 00:20:07.423 --> 00:20:09.323 I know how to design a trial. 00:20:09.493 --> 00:20:12.903 Immediately, you know that his head is blocked off. 00:20:12.903 --> 00:20:14.773 He's not going to listen to anything you say. 00:20:15.653 --> 00:20:19.913 We don't like people who think they know the answer because they don't. 00:20:20.643 --> 00:20:24.833 Uh, and they don't know what the best way is to do a clinical trial. 00:20:25.073 --> 00:20:26.743 That's what we deliver to them. 00:20:27.148 --> 00:20:30.308 is you're going to take this trial, the one Scott mentioned, 00:20:30.308 --> 00:20:32.198 you know, 200 patients, four years. 00:20:32.888 --> 00:20:37.568 We're going to give you the answer in six months, maybe. 00:20:38.098 --> 00:20:38.808 We don't know. 00:20:39.578 --> 00:20:43.878 Maybe we have to go longer, but we can give you, in this Aston trial, 00:20:43.878 --> 00:20:51.878 as I said, it stopped the trial, um, as soon as it was allowed to do so. 00:20:52.778 --> 00:20:57.238 And it was because it was looking, it was like artificial intelligence, 00:20:57.468 --> 00:21:03.678 it was looking across the spectrum of the doses, and it started out looking 00:21:03.688 --> 00:21:08.668 at the low doses and comparing to placebo, decided that wasn't good 00:21:08.668 --> 00:21:11.108 enough, and it moved up the chain. 00:21:11.518 --> 00:21:17.838 It finally started to focus on the highest doses compared to placebo, 00:21:17.838 --> 00:21:20.738 uh, decided nothing was there. 00:21:21.068 --> 00:21:27.178 And the good news is for patients that it started to go to placebo. 00:21:27.978 --> 00:21:31.498 Um, namely it wasn't any good. 00:21:31.948 --> 00:21:42.348 And that thing saved Pfizer millions in terms of the patients, in terms 00:21:42.348 --> 00:21:48.068 of the patient resources, but also an uncountable, you know, a priceless. 00:21:48.523 --> 00:21:51.043 benefit, that it got them off that thing. 00:21:51.043 --> 00:21:59.193 This was a, a particular, uh, uh, mechanism, mechanism of action, um, that, 00:21:59.363 --> 00:22:04.183 uh, the Pfizer and the rest of the stroke community decided was not the way to go. 00:22:04.903 --> 00:22:11.733 Uh, and so it saved, we, we really don't know how to quantify it, but 00:22:11.733 --> 00:22:17.983 it saved, uh, I mean it's almost priceless what the benefit was. 00:22:18.588 --> 00:22:22.438 Scott Berry: Yeah, it's always hard to quantify time in it. 00:22:23.053 --> 00:22:25.893 So the, the, the story of brain, and so we started off. 00:22:25.893 --> 00:22:30.733 So it was Don and me, and we, we didn't know whether this was going to work. 00:22:30.893 --> 00:22:35.933 Um, and we, we were doing a lot of medical device trials. 00:22:35.933 --> 00:22:40.273 There's been a long history of, of innovative Bayesian things at the center 00:22:40.273 --> 00:22:46.713 for devices, Greg Campbell was a huge, uh, uh, a huge innovator at the FDA for that. 00:22:47.113 --> 00:22:50.013 And all of a sudden we had people that were interested. 00:22:50.253 --> 00:22:54.923 in looking at adaptive trials, looking at flexible trials. 00:22:57.183 --> 00:22:59.283 full time employee other than myself. 00:22:59.283 --> 00:23:01.913 Jason Connor joined several years after that. 00:23:02.333 --> 00:23:06.203 Um, and we kept getting more and more interest. 00:23:06.443 --> 00:23:10.653 And as Don described, 2010, it was a little bit where was drugs going to go? 00:23:10.653 --> 00:23:12.403 Center for Drugs were doing a lot of devices. 00:23:12.803 --> 00:23:15.363 And the Center for Drugs became more and more interested. 00:23:15.373 --> 00:23:17.213 Pharma became more interested. 00:23:17.573 --> 00:23:20.823 And we have now been steadily growing since 2010. 00:23:22.093 --> 00:23:26.673 Uh, within that setting up to now, as Don described, our 35 scientists 00:23:26.673 --> 00:23:30.763 here at Berry Consultants, uh, still, still growing and still innovating. 00:23:32.573 --> 00:23:36.503 Brandon Giella: Yeah, it's, it's such an amazing story and it's to Don point the 00:23:36.503 --> 00:23:40.643 way that you guys do your, your trials and the way you run your business, it is 00:23:40.643 --> 00:23:45.573 so incredibly helpful, not just for the firms that hire you, your clients and how, 00:23:45.673 --> 00:23:48.893 you know, you can save them money and time and all of that, but also for the patients 00:23:48.903 --> 00:23:54.783 themselves and to be, to have the, the, the specificity, um, that you have for 00:23:54.783 --> 00:23:56.333 these trials is, is really amazing. 00:23:56.813 --> 00:24:00.623 So how I guess following that point scott, um, and we'll take maybe the last 10 00:24:00.623 --> 00:24:05.973 minutes or so of the show Uh, how would you describe the current state of barry? 00:24:06.263 --> 00:24:07.963 You know, what what is what do you got? 00:24:07.973 --> 00:24:10.673 What are maybe projects you're you're working on? 00:24:10.703 --> 00:24:14.023 Um, you know different things that you guys are thinking through and innovating 00:24:14.353 --> 00:24:18.223 And then where do you see barry going over the next year five years ten years? 00:24:18.223 --> 00:24:20.353 Where where are you pointing your ship if I can ask that? 00:24:21.008 --> 00:24:24.328 Don Berry: So, uh, let me try to address that. 00:24:25.038 --> 00:24:35.248 Uh, there's, back around this 2010, um, I was designing clinical trials for the 00:24:35.248 --> 00:24:38.118 cancer leukemia group B in breast cancer. 00:24:39.648 --> 00:24:46.778 And, um, uh, a friend of mine that I, uh, uh, uh, developed a relationship 00:24:46.778 --> 00:24:54.188 with was Laura Esserman, who's the surgeon at, um, at UCSF, University 00:24:54.188 --> 00:24:55.698 of California, San Francisco. 00:24:56.418 --> 00:25:01.428 Um, and she was, you know, I was radical, but she was off the deep end. 00:25:02.158 --> 00:25:05.188 Um, and, uh, wanted to do things. 00:25:05.918 --> 00:25:09.608 That, similar to what I wanted to do, and we built a trial together. 00:25:10.178 --> 00:25:13.748 We couldn't do it through the National Cancer Institute, which 00:25:13.758 --> 00:25:17.348 sponsored these CLGB, uh, trials. 00:25:17.788 --> 00:25:25.978 So we went to the Foundation for the NIH, and we worked with them to fund the trial. 00:25:25.978 --> 00:25:33.738 This is a, a public private partnership with, uh, NIH leaders and industry. 00:25:35.043 --> 00:25:42.693 And so we built a trial called iSpy2, um, that was, had lots of innovations, 00:25:43.213 --> 00:25:52.613 had Scott's, um, uh, innovation for using historical controls that he had designed 00:25:53.203 --> 00:25:59.323 when he wrote, uh, uh, an article that won the, uh, Journal of the American 00:25:59.323 --> 00:26:01.823 Statistical Association award for best. 00:26:02.588 --> 00:26:11.238 article that year in Applied Statistics, uh, that used the, in baseball, 00:26:11.438 --> 00:26:16.158 Babe Ruth versus, um, uh, who, 00:26:16.468 --> 00:26:17.508 Scott Berry: Mark McGuire. 00:26:17.728 --> 00:26:24.698 Don Berry: Mark McGuire, um, uh, and who was better, adjusting for the time. 00:26:24.908 --> 00:26:28.903 And so he built this thing that used things in the past, Well, 00:26:28.903 --> 00:26:30.803 we wanted to use controls. 00:26:30.803 --> 00:26:36.183 We were randomizing, but we wanted to keep those controls, uh, randomization, 00:26:36.363 --> 00:26:42.613 uh, patients in the trial that we could continue to use as a, as a basis. 00:26:42.853 --> 00:26:45.273 That was just one of the many innovations. 00:26:45.313 --> 00:26:49.633 Another innovation, and speaking to your point about patients, 00:26:49.993 --> 00:26:54.283 was we wanted to treat these women as effectively as possible. 00:26:54.843 --> 00:26:57.763 So we built in adaptive randomization. 00:26:58.188 --> 00:27:03.198 So, if a drug was doing poorly in a subset of women, it got lower 00:27:03.198 --> 00:27:08.318 probability of being assigned and soon was zeroed out because there were 00:27:08.338 --> 00:27:10.128 other drugs that we were looking at. 00:27:10.648 --> 00:27:18.718 So, we ended up over the course of the next 10 years, um, evaluating 23 drugs, 9 00:27:18.718 --> 00:27:26.015 of them went on to bigger things, um, and, um, the, the, the, the, the, the, the, 00:27:26.098 --> 00:27:28.998 Scott Berry: So like, so, so Don, let me jump into that part since, 00:27:29.008 --> 00:27:30.638 since you stole my question. 00:27:30.638 --> 00:27:32.788 Let me, let me steal this from you and take the ball. 00:27:33.158 --> 00:27:38.418 So, uh, so the, the, imagine how different this is. 00:27:38.418 --> 00:27:41.358 The, the historical way this is done is you have a drug a 00:27:41.908 --> 00:27:43.818 And you build a whole trial. 00:27:43.828 --> 00:27:47.538 It's like it would be like the NFL deciding every time they're going to do 00:27:47.538 --> 00:27:52.258 a game, they build a whole new stadium, they play a game and they take it down 00:27:52.258 --> 00:27:53.538 and then they build a whole nother one. 00:27:53.548 --> 00:27:54.458 This is what we do. 00:27:54.838 --> 00:28:00.428 So this I-SPY 2 trial was building a single stadium, a single protocol and 00:28:00.428 --> 00:28:03.208 move 25 drugs through the protocol. 00:28:03.408 --> 00:28:08.368 Using the same stadium, comparing them, using common controls. 00:28:08.748 --> 00:28:13.088 If you have four trials, all enrolling 50 percent controls and you move 00:28:13.088 --> 00:28:16.638 them all together and have one arm of control, you've now saved patients. 00:28:16.638 --> 00:28:17.728 You've saved time. 00:28:18.028 --> 00:28:23.838 So this was a landmark trial in 2010 in breast cancer, and it's 00:28:23.838 --> 00:28:28.228 called a platform trial and it was, it was as it was off the deep end. 00:28:29.608 --> 00:28:31.328 Fast forward to COVID. 00:28:32.113 --> 00:28:38.043 The pandemic hits and we're trying to figure out how to treat COVID and 00:28:38.053 --> 00:28:42.223 you can't wait two years to build a clinical trial to investigate 00:28:42.223 --> 00:28:43.973 a single drug, tear it down. 00:28:44.333 --> 00:28:51.678 So platform trials globally that copied I-SPY 2 were used to treat COVID. 00:28:52.028 --> 00:28:56.848 Everything we learned how to treat therapeutically COVID came from platform 00:28:56.848 --> 00:29:02.618 trials that really the grandfather of that was this crazy idea of I-SPY 2. 00:29:03.878 --> 00:29:04.888 So what is that? 00:29:04.898 --> 00:29:10.218 Now we're doing, we're doing trials of that in ALS, in glioblastoma, uh, 00:29:10.288 --> 00:29:12.358 in, in a number of rare diseases. 00:29:12.358 --> 00:29:17.278 And it was all born out of these crazy ideas of Laura, Laura and Don in 2010. 00:29:18.488 --> 00:29:20.008 So that's where we're going. 00:29:20.608 --> 00:29:22.688 But we don't know what that innovation is. 00:29:22.688 --> 00:29:26.648 We have all kinds of ideas of how to make this more efficient. 00:29:26.678 --> 00:29:29.558 And we have to, it's too expensive. 00:29:29.558 --> 00:29:30.158 We've got it. 00:29:30.168 --> 00:29:36.118 We there's so many amazing medical therapies out there to be using 50 year 00:29:36.118 --> 00:29:38.008 old trial designs doesn't really work. 00:29:38.198 --> 00:29:40.998 So we want to be on that cutting edge. 00:29:41.228 --> 00:29:47.008 We want the next eye spy, the next thing to, to do better science in this for 00:29:47.008 --> 00:29:49.508 patients for, for better treatments. 00:29:49.588 --> 00:29:53.188 We don't know what it's going to be, but we want to be on that sort of cutting 00:29:53.188 --> 00:29:55.988 edge and, and, and, and doing this better. 00:29:56.893 --> 00:30:03.373 Don Berry: So, one important, important note to that, um, in the glioblastoma 00:30:03.383 --> 00:30:06.603 study, uh, it's a phase three trial. 00:30:07.373 --> 00:30:12.823 That means that if a drug does well in, in, in, uh, GBM Agile, 00:30:12.823 --> 00:30:17.883 we call it, um, we take it to the FDA and the FDA will approve it. 00:30:18.613 --> 00:30:20.443 We worked with the FDA. 00:30:21.338 --> 00:30:26.418 Uh, really intimately, uh, interacting with them and building 00:30:26.418 --> 00:30:29.278 the trial that they would okay. 00:30:29.578 --> 00:30:35.338 So, and they sent us a letter saying, if you build the, if you have an arm 00:30:35.438 --> 00:30:39.478 that comes through, a treatment arm that comes through the trial, uh, that 00:30:39.478 --> 00:30:44.918 graduates and is confirmed within GBM Agile, within this, uh, uh, adaptive 00:30:44.918 --> 00:30:47.448 platform trial, we'll approve it. 00:30:48.148 --> 00:30:51.228 So, and that was a sea change. 00:30:51.228 --> 00:30:53.778 iSpy 2 trial was great. 00:30:54.288 --> 00:30:58.798 It's known throughout the world as being an innovative trial that 00:30:58.798 --> 00:31:02.878 people want to, uh, uh, uh, imitate. 00:31:03.188 --> 00:31:04.618 But it's a phase 2 trial. 00:31:05.168 --> 00:31:09.528 It evaluates these drugs and then moves them, decides which drugs 00:31:09.528 --> 00:31:11.478 can go into a phase 3 trial. 00:31:12.238 --> 00:31:16.398 GBM Agile does the phase 3 trial within itself. 00:31:16.808 --> 00:31:22.648 Moving seamlessly from one part of the drug development spectrum, namely, 00:31:22.688 --> 00:31:28.928 uh, is it, is the drug working, to the, uh, confirmatory phase. 00:31:29.238 --> 00:31:35.068 And this we owe to the FDA, who has just been enormously helpful to us 00:31:35.328 --> 00:31:40.648 and to, you know, uh, medical research and drug development generally. 00:31:42.653 --> 00:31:43.743 Brandon Giella: I love these stories. 00:31:43.783 --> 00:31:47.193 I love hearing that something that you designed and brought into the 00:31:47.193 --> 00:31:52.793 world, You know 15 years ago is still impacting the world in huge ways 00:31:52.813 --> 00:31:56.313 like covid and some of these other major Major diseases and issues. 00:31:56.323 --> 00:31:59.053 It's such an amazing Legacy if you want to call it that 00:31:59.478 --> 00:32:02.118 Don Berry: Just to mention Alzheimer's and 00:32:02.548 --> 00:32:03.053 Scott Berry: heh 00:32:03.188 --> 00:32:08.328 Don Berry: Uh, and just to mention diabetes type 2, and just to mention 00:32:08.328 --> 00:32:15.588 the new craze, the weight loss craze with the GLP1 agonists, um, 00:32:15.998 --> 00:32:23.548 we designed the first trial for, uh, uh, Eli Lilly's, uh, dulagletide, 00:32:24.518 --> 00:32:30.258 trulicity, uh, that became their best selling drug and, uh, type 2 diabetes. 00:32:30.278 --> 00:32:39.353 But in that trial We also saw, um, you know, it's a 5 billion drug, has been, uh, 00:32:39.423 --> 00:32:45.983 and, and was the original approved, uh, GLP 1 agonist, and it showed in the trial 00:32:45.983 --> 00:32:53.643 we designed a benefit on weight loss that was essentially the same benefit that they 00:32:53.643 --> 00:32:58.573 eventually saw when they got Trulicity approved for weight loss, and now the, 00:32:59.948 --> 00:33:01.568 Well, you know the rest of the story. 00:33:01.568 --> 00:33:05.218 The world is getting skinnier all the time, in part because 00:33:05.218 --> 00:33:11.548 of these, uh, Glyphon agonists. 00:33:11.618 --> 00:33:16.468 Brandon Giella: quickly on its axis uh, no, I So if if I could summarize 00:33:16.468 --> 00:33:21.538 all of this or if I guess if you could summarize all of this what is one thing? 00:33:22.038 --> 00:33:27.558 in one minute That you two are very excited about in this coming year 00:33:27.568 --> 00:33:33.548 the 25th anniversary 2025 Barry is going through a lot of change, 00:33:33.548 --> 00:33:35.078 very exciting things happening. 00:33:35.388 --> 00:33:38.398 What is one thing that you want listeners to take away from, or one 00:33:38.398 --> 00:33:41.908 thing that you wish that they knew about Barry in this upcoming year? 00:33:43.468 --> 00:33:44.098 Scott Berry: Oh boy. 00:33:44.378 --> 00:33:45.868 Uh, that's a great question. 00:33:46.168 --> 00:33:51.448 I'm most excited about all of the new statisticians and 00:33:51.448 --> 00:33:52.768 scientists we have at Berry. 00:33:54.408 --> 00:33:54.878 they're brilliant. 00:33:54.878 --> 00:33:59.408 They've, they're coming into this with all new ideas. 00:34:00.698 --> 00:34:03.938 They're also their communication is, fantastic. 00:34:04.648 --> 00:34:06.918 so I'm excited to see what they do. 00:34:07.698 --> 00:34:15.488 it was incredible, over these 25 years, but, it's, they're much smarter than I am. 00:34:16.118 --> 00:34:21.868 and so I'm really excited to see what they're going to do with clinical trials. 00:34:22.258 --> 00:34:24.078 Brandon Giella: There are at least B students for sure. 00:34:24.478 --> 00:34:24.608 Scott Berry: Yeah. 00:34:25.218 --> 00:34:28.583 Yep. 00:34:31.458 --> 00:34:35.778 Don Berry: Jason Connor, who, Scott mentioned was our first employee, 00:34:37.618 --> 00:34:40.708 went off on his own, partway along. 00:34:40.738 --> 00:34:45.533 I told Jason That my loyalties are with people. 00:34:45.553 --> 00:34:47.153 My loyalty is with you. 00:34:48.963 --> 00:34:53.943 and Jason Kept, has his own, company and he consults. 00:34:54.283 --> 00:35:00.433 He's part of what I call the Berry Diaspora, who is spreading the word. 00:35:00.833 --> 00:35:06.413 we can't change the word, the world, in Austin, Texas. 00:35:07.993 --> 00:35:10.053 we want to change the world in, 00:35:12.068 --> 00:35:20.498 Peoria, in Australia, in China, in Europe, and we're partway along with that. 00:35:22.128 --> 00:35:28.348 GBM Agile, for example, is accruing patients in Australia and in, Europe, 00:35:28.348 --> 00:35:30.108 in addition to the United States. 00:35:32.188 --> 00:35:40.878 that's, that's the exciting thing, is to change the world, one person at a time. 00:35:41.888 --> 00:35:42.418 Brandon Giella: I love that. 00:35:43.628 --> 00:35:44.728 Doctors Barry. 00:35:45.188 --> 00:35:48.268 Don and Scott, thank you so much for the work that you're doing. 00:35:48.278 --> 00:35:52.868 And I'm very excited about the 25th anniversary this year, about next year and 00:35:52.868 --> 00:35:53.928 all the things that you guys are doing. 00:35:53.938 --> 00:35:54.948 And I'm excited for the show. 00:35:54.948 --> 00:35:57.658 I think it's gonna be a lot of fun and I can't wait to have other guests. 00:35:57.658 --> 00:36:00.128 I know we've got 30 something episodes that we're kind of 00:36:00.128 --> 00:36:01.858 planning out and working on. 00:36:01.858 --> 00:36:07.338 So I'm really excited to keep this going and we'll see you again on episode two. 00:36:08.253 --> 00:36:09.013 Scott Berry: Appreciate it. 00:36:09.383 --> 00:36:09.953 Thanks, Brandon. 00:36:10.608 --> 00:36:11.438 Don Berry: thanks, Brendan. 00:36:11.898 --> 00:36:12.578 Thanks, Scott.