Podcast Episode
84: Mailbag: Learning Healthcare, Multiplicities, and the Pace of Innovation
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Scott Berry, Ph.D.
President & Senior Statistical Scientist
In this mailbag episode of "In the Interim…", Dr. Scott Berry answers two listener questions and weighs in on the pace of innovation in clinical trial science.
In this mailbag episode of "In the Interim…", Dr. Scott Berry answers two listener questions and weighs in on the pace of innovation in clinical trial science. Asked what infrastructure a learning healthcare system would require, Scott defines one through the REMAP structure (randomized, embedded, multifactorial, adaptive platform) that Derek Angus named for REMAP-CAP, and uses REMAP Periop at UPMC to argue that embedding randomization and data collection in routine care keeps the cost low while letting a health system learn from tens of thousands of patients a year. On multiplicities, Scott explains why he interprets subgroups, endpoints, and related trials within a Bayesian hierarchical model rather than by adjusting alpha, with the assumed variability across units (tau) setting how far each estimate shrinks toward the overall effect, and he critiques hierarchical testing as non-Bayesian. The episode closes on the contrast between fast-moving innovation, including the AI-accelerated redesign of FACTS, Berry's clinical trial simulation platform, and ARPA-H's SURPASS call for adaptive platform trials, and the conservatism of the EMA's draft reflection paper on platform trials and ICH E20.
Key Highlights
REMAP (randomized, embedded, multifactorial, adaptive platform) as a working definition of a learning healthcare system.
Embedding randomization and data collection in routine care to remove a large share of trial costs.
REMAP Periop and learning from tens of thousands of elective surgeries a year.
A Bayesian view of multiplicities: hierarchical models in place of alpha adjustment.
Tau, shrinkage, and reading a subgroup result against the overall effect.
AI, digital twins, and ARPA-H's SURPASS call for continuous adaptive platform trials.
The contrast with the EMA's draft platform trial reflection paper and ICH E20.
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84: Mailbag: Learning Healthcare, Multiplicities, and the Pace of Innovation
In this mailbag episode of "In the Interim…", Dr. Scott Berry answers two listener questions and weighs in on the pace of innovation in clinical trial science.
83: Reflecting on EMA Reflections on Platform Trials
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Kert Viele, Director of Research at Berry Consultants, review the European Medicines Agency's draft reflection paper on methodological aspects in confirmatory platform trials.
82: Statistical Methodology Groups in the Pharmaceutical Industry
In this episode of "In the Interim…", Scott Berry is joined by Jenny Devenport and Kaspar Rufibach of Merck Group, co-authors of the EFSPI Statistical Methodology Leaders paper "Statistical Methodology Groups in the Pharmaceutical Industry," and May Mo of Amgen, a co-author of the commentary on the paper from the Statistical Innovation Community, an ASA Biopharmaceutical working group.
81: A Discussion on Virtual Controls
In this episode of "In the Interim…", Dr. Scott Berry shares the framework he presented at a CSRC regulatory science hackathon on digital twins and synthetic controls in cardiovascular clinical trials.
80: Clinical Trial Arenas: Direct Communication to Patients
In this episode of "In the Interim…", Dr. Scott Berry recounts a presentation he gave to the Speak Foundation, a patient organization focused on limb-girdle muscular dystrophy and makes the case for master protocols directly to the stakeholder trials exist to serve.
79: Science Coaching With Alun Bedding
In this episode of "In the Interim…", Dr. Scott Berry talks with Dr. Alun Bedding, a professional certified coach and statistician who spent decades in pharmaceutical statistics, including as global head of statistical methods, collaboration, and outreach at Roche, before founding his own coaching and consulting practice.
78: The CHIPS Trial: Bayesian Adaptive Trial in JAMA
In this episode of “In the Interim…,” Dr. Scott Berry talks with Dr. Roger Lewis, Dr. Anna McGlothlin, and Dr. Nick Berry — all co-authors on the CHIPS trial results recently published in JAMA (Spinella et al., August 2026) — about the design, implementation, and results.
77: NFL Study of CTE: The Issues
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76: Talkin' 'bout Sweet Time
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75: Mammograms: Death Threats, Hillary Clinton and Lead-Time Bias
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74: REMAP-CAP Results: Oseltamivir in Critically-Ill Influenza Patients
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73: ICECAP: The Results
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72: Failure of the Proportional Odds is the Result
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71: Adaptive Design Actions Matrix
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70: A Visit with Tim Berry
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69: Fairness in Soccer and Clinical Trials
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68: Bias in Stopping Trials Early
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67: A Statistician Reads JAMA: A Futile Issue
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66: Response-Adaptive Randomization in Clinical Trials
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65: REMAP-CAP: The Origin
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64: Fighting Time in Adaptive Trials
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63: ICECAP: The Adaptive Design
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62: Multi-Platform RCT
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61: Sports and Clinical Trials: The 1927 Yankees, 15 Tarzans, and Modern Athletes
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60: AI @ Berry
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59: Drug Development and Sports: The 10-Run Rule and Futility
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58: ICH-E20, Regulators, and False Choices
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57: PANTHER: A Phase 2 International Platform Trial in ARDS
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56: A Visit with Byron Gajewski: KUMC, Innovative Trial Designs, the HOBIT Trial
In this episode of "In the Interim…", Dr. Scott Berry connects with Dr. Byron Gajewski, professor of biostatistics and data science at the University of Kansas Medical Center (KUMC), for a detailed discussion on the design, simulation, and operational realities of Bayesian adaptive clinical trials in academic environments.
55: A Visit with Stephen Senn: Time, Concurrent Controls, and the Bayesian Guidance
In this episode of "In the Interim...", Dr. Scott Berry hosts Dr. Stephen Senn, award-winning statistician and author, for a discussion on advanced challenges in adaptive and platform trial methodology.
54: Making Sense of Hierarchical Composites
In this episode of "In the Interim…", Dr. Scott Berry is joined by statisticians Dr. Amy Crawford, Dr. Cora Allen-Savietta, and Dr. Jessica Overbey for a technical deep dive into hierarchical composite endpoints and the win ratio in clinical trial design.
53: The SNAP Trial with Professors Tong and Davis
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52: Bayesian Borrowing in Phase 3 Trials
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51: The Art of Storytelling with Shaun Cassidy
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50: The Fallacy of Ordinal Endpoints
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49: Mr. Berry Goes to Washington
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48: Platform Trial in Orthopaedic Surgery
Dr. Nathan O’Hara (University of Maryland), Dr. Gerard Slobogean (UC Irvine), and Dr. Sheila Sprague (McMaster University) describe the launch and design of the Musculoskeletal Adaptive Platform Trial (MAPT)—the first major adaptive platform trial in orthopaedic surgery.
47: A Visit with Michael Harhay
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46: The FDA Bayesian Guidance
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45: Path 2 Parkinson's Prevention with Drs. Simuni and Wendelberger
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44: Statistical Communication
In this episode of “In the Interim…,” host Dr. Scott Berry examines the challenge of communicating complex statistical concepts to non-statistical audiences.
43: The Rumor of One Trial for Substantial Evidence
In this episode of "In the Interim…", host Dr. Scott Berry and frequent co-host Dr. Kert Viele, Senior Statistical Scientist at Berry Consultants, analyze the potential shift in FDA regulatory policy from requiring two independent trials to accepting a single trial as sufficient for “substantial evidence” in drug approvals.
42: Communication for Scientists: A Discussion with Jenny Devenport
In this episode of "In the Interim…", Dr. Jenny Devenport, Global Head of Methods, Collaboration, and Outreach at Roche, joins Dr. Scott Berry for a detailed discussion on career evolution, statistical culture, and communication in the pharmaceutical industry.
41: Navigating the Arena: Platform Trials
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40: Jumping Hurdles: Interim Analyses for Funding Decisions
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39: Discussion with Kaspar Rufibach
In this episode of "In the Interim...", Dr. Scott Berry interviews Dr. Kaspar Rufibach, Co-Head of Advanced Biostatistical Sciences at Merck.
38: Bayesian Statistics in Clinical trials: The Past, Present, and Future
In this episode of "In the Interim…" guest host Cooper Berry moderates a detailed discussion on the evolution and practice of Bayesian methodology in clinical trials with fellow family members Dr. Don Berry, Dr. Scott Berry, Dr. Lindsay Berry, and Dr. Nick Berry.
37: A Visit with Stroke Neurologist Dr. Jeff Saver
In episode 37 of "In the Interim…", Dr. Jeff Saver, Director of the UCLA Comprehensive Stroke and Vascular Neurology Program, details his shift from behavioral neurology to clinical stroke research after early engagement with multicenter trials like TOAST.
36: The Saga of the Lecanemab Adaptive Phase II Trial
In Episode 36 of "In the Interim…", Dr. Scott Berry and Dr. Don Berry analyze the Phase II trial of Lecanemab (BAN2401) in Alzheimer’s disease, focusing on the application of adaptive Bayesian methods following persistent failures in Alzheimer’s drug development.
35: Teaching Statistics and Data Science through Sports
On this episode of “In the Interim…”, which is co-sponsored by the Journal of Statistics and Data Science Education, Dr. Scott Berry talks with Dr. Jim Albert, Professor Emeritus at Bowling Green State University, whose extensive work encompasses Bayesian statistics and computation, sports analytics, and decades of exemplary teaching.
34: Digital Googols
In this episode of "In the Interim…", Dr. Scott Berry examines the concept of “digital twins” in clinical trials. He details how simulation of clinical trials is a direct analog of digital twin methodology, allowing for the in-silico modeling of the physical trial conduct, enrollment, dropouts, and patient outcomes under varied assumptions.
33: A Visit with Andrew Thomson
In this episode of "In the Interim…", Dr. Scott Berry interviews Dr. Andrew Thomson, owner and lead consultant of Regnitio.
32: Moving Clinical Trial Goalposts
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Kert Viele analyze how regulatory, editorial, and science community standards often impose additional, inconsistent requirements for novel methods in clinical trial design, rarely applied to standard approaches.
31: The Not So Promising Zone Design
In this episode of "In the Interim…", Dr. Scott Berry examines the mathematical foundations and efficiency claims of the promising zone design for adaptive sample size in clinical trials.
30: A Visit with Dr. Janet Wittes
Episode 30 of “In the Interim…” features Dr. Janet Wittes, Fellow of the American Statistical Association, past president of the Society of Clinical Trials, and founder of Statistics Collaborative, in discussion with Dr. Scott Berry.
29: Bayesian Clinical Trials with Frank Harrell
In this episode of "In the Interim…", Dr. Scott Berry chats with Frank Harrell, a professor of Biostatistics at Vanderbilt University and W.J. Dixon Award winner. Harrell describes his transition from frequentist to Bayesian clinical trial design, prompted by a decisive meeting with Dr. Don Berry, informed by David Spiegelhalter’s published work.
28: A Visit with Dr. Derek Angus
In this episode of "In the Interim…", Dr. Scott Berry interviews Dr. Derek Angus, Distinguished Professor and Chair of Critical Care Medicine at the University of Pittsburgh and senior editor at JAMA.
27: The Mystery of Clinical Trial Simulation
Dr. Scott Berry hosts this episode of "In the Interim…", opening with statistical analysis of elite athletes before focusing on the misunderstood role of clinical trial simulation.
26: Discussions on the ICH E20 Draft Guidance
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Kert Viele review the ICH E20 draft guidance on adaptive clinical trial designs, offering a technical yet accessible breakdown for trial sponsors, practitioners, and those interested in clinical development.
25: A Discussion with Michael Proschan on Response-Adaptive Randomization
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24: STEP Statistical Modeling
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23: Bayesian Approach in Clinical Trials
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22: The Time Machine
Dr. Scott Berry and Dr. Kert Viele discuss the origins and implementation of the “time machine” modeling approach, beginning with sports analytics and progressing to adaptive platform clinical trials.
21: The Legend of I-SPY 2 - Part B
In this episode, Dr. Don Berry and Dr. Scott Berry provide an in-depth account of I-SPY 2, focusing on the trial’s use of the “time machine” methodology—an Bayesian solution allowing bridging across arms to inform ongoing analyses.
20: The Legend of I-SPY 2 - Part A
In Episode 20 of Berry’s "In the Interim..." Podcast, The Legend of I-SPY 2 - Part A, Dr. Don Berry and Dr. Scott Berry discuss the origins and design of the I-SPY trials.
19: The STEP Platform with Dr. Eva Mistry and Dr. Jordan Elm
This episode of "In the Interim..." features an in-depth discussion of the StrokeNet Thrombectomy Endovascular Platform (STEP), a multi-domain, adaptive platform trial for acute stroke, anchored in the NIH StrokeNet network.
18: A Statistician Reads JAMA
Dr. Scott Berry applies a statistician’s review of a random trial result published in JAMA – the FAIR-HF2 clinical trial. Interrogating the frequentist paradigm and the focus on the binary outcome of the primary hypothesis test.
17: Seamless 2/3 Trial Designs
Scott Berry convenes co-authors Kert Viele, Joe Marion, and Lindsay Berry to discuss the statistical and developmental nuances of inferentially seamless phase 2/3 clinical trial designs.
16: Spending Alpha
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15: Prof Craig Ritchie: Looking Back at EPAD, Moving Forward in Alzheimer's Disease
Scott Berry, Founder of Berry Consultants, interviews Professor Craig Ritchie—specialist in brain health and neurodegenerative diseases, Chief Investigator of EPAD (European Prevention of Alzheimer Dementia), and CEO of Scottish Brain Sciences—for a precise analysis of platform trial methodology in Alzheimer’s research.
14: Drug Developers' Lessons from Sports: Regression-to-the-Mean
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13: DSMBs in Adaptive Trials with Roger Lewis
In this episode of "In the Interim…", host Dr. Scott Berry is true to the name of the podcast, as he discusses the unblinded world of adaptive clinical trials alongside Dr. Roger Lewis, a renowned expert in both statistical science and clinical medicine.
12: Platform Trial in Psychiatry with Dr. Husseini Manji
In the latest episode of "In the Interim...", Dr. Scott Berry and Dr. Mike Krams sit down with Dr. Husseini Manji, to explore the potential of platform trials in advancing precision medicine within psychiatry, particularly in tackling complex mental illnesses.
11: Implementing Adaptive Trials
In Episode 11 of "In the Interim...", host Scott Berry discusses the nuances of implementing adaptive clinical trials with Dr. Anna McGlothlin and Dr. Michelle Detry from Berry Consultants.
10: Revisiting Seamless 2/3 Trial for GLP-1 Agonist
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9: I-SPY 2 to GBM AGILE and Beyond
In this episode of "In the Interim...," we sit down with Dr. Meredith Buxton to explore the evolution of platform trials from I-SPY 2 to GBM AGILE and Beyond.
8: External Data in Clinical Trials
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7: Remembering Jimmie Savage
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6: The Art and Slog of Innovating
In this compelling episode of "In the Interim," Dr. Mike Krams, a seasoned expert in clinical trials and drug development, joins us to discuss the art and slog of innovation in pharmaceutical companies.
5: Religion, Politics, and Ordinal Outcomes
In this episode of "In the Interim," Scott Berry discusses the vital topic of ordinal outcomes in clinical trials—a subject as controversial as politics and religion at the dinner table.
4: HEALEY ALS Platform Trial with Dr. Merit Cudkowicz and Dr. Melanie Quintana
In this episode of the podcast, we sit down with Dr. Merit Cudkowicz and Dr. Melanie Quintana to discuss the inception and execution of the Healy ALS Platform Trial, a revolutionary approach designed for efficiency and impactful data collection.
3: FACTS 7.1 Release with Tom Parke
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2: When should you use adaptive design clinical trials?
In this episode of "In the Interim," we consider the nuances of adaptive design clinical trials with distinguished guests Dr. Scott Berry and Dr. Kert Viele from Berry Consultants. The conversation centers around the vital question: when should these adaptive designs be implemented?
1: The story of Berry Consultants
Discover the transformative journey of Berry Consultants, pioneers in adaptive clinical trials, and their impact on the future of medical research.