In the 60th episode of “In the Interim…”, Dr. Scott Berry, Dr. Nick Berry, and Dr. Joe Marion discuss how Berry Consultants uses AI in clinical trial design and software development. The conversation addresses current applications, limitations, implications for productivity, and the ongoing need for human expertise in clinical trial design. The team examines both promising use cases and the risks associated with security, compliance, and AI-generated statistical work.

Key Highlights

• AI is used to develop user interfaces and code modules, notably expediting tasks like R Shiny app development and software prototyping.
• Statistical coding for complex modeling and simulation—such as numerical integration and predictive probability calculations—remains unreliable when delegated to AI and still requires direct oversight and manual review.
• Attention to security and confidentiality is central; Berry prohibits the use of client-sensitive or patient data within AI tools.
• Generative AI assists with drafting and editing documents, but the output tends to be non-specific, generic, and sometimes imprecise, requiring expert editorial input before use.
• While embracing AI to improve efficiency, the discussion is critical of current AI hype, especially around black-box modeling and pushes back against the perception that current AI can replace domain-specific statistical design or strategic judgment.

For more, visit us at https://www.berryconsultants.com/

In this episode of "In the Interim…", Dr. Scott Berry and Dr. Nick Berry investigate how futility in clinical trials and stopping rules in sports illuminate very similar decision problems, albeit with very different consequences. Drawing from baseball’s 10-run rule, tournament cuts in golf, the discussion confronts traditional and Bayesian strategies for interim decisions. The episode explains why simulation, not historical trial review, provides the empirical backbone for futility boundaries in clinical trials, and details the mechanics and consequences of aggressive stopping criteria. Using the Biogen aducanumab Alzheimer’s trials, the conversation exposes how a futility rule based on 20% predictive probability halted trials even when meaningful probability of success remained. Scott and Nick address the influence of ethical considerations, cost, regulatory priorities, and statistical rigor, and contrast Bayesian predictive probability’s strengths over conditional power.

Key Highlights

• Dissects sports futility rules (10-run rule, golf cuts, Bill James heuristic) and their application to clinical trial design
• Argues for prospective simulation to define adaptive futility thresholds
• Explains how Bayesian predictive probability provides a more robust framework than conditional probability for interim adaptive decisions
• Details how aggressive futility criteria may prematurely stop trials and risk missing beneficial treatments, as in the aducanumab case
• Explores the intersection of ethics, patient safety, operational efficiency, regulatory standards, and trial cost

In this episode of "In the Interim…", host Dr. Scott Berry undertakes a detailed, methodical critique of ICH-E20 draft guidance language as applied to adaptive clinical trial design. Focusing on an innocuous but corruptible paragraph in Section 3.1, Scott scrutinizes the logic behind regulatory reluctance to appreciate multiple or complex adaptations in confirmatory trials. Drawing on extensive experience, he highlights how such restrictive interpretations do not reflect practical development realities, instead setting up “false choices” where alternative designs desired by regulators are infeasible. Through operational scenarios—including the SEPSIS-ACT trial, an enrichment design, and sample size re-estimation examples—Scott illustrates the empirical benefits of seamless and multi-adaptive trials for sponsors, patients, and regulators. Technical discussion addresses misconceptions about complexity and bias and stresses the value of presenting realistic alternatives when engaging with regulatory authorities. The episode ultimately encourages a more nuanced dialogue to advance efficient and scientifically robust clinical trials.

Key Highlights

• Discussion of ICH-E20 section 3.1 guidance and its operational impact on adaptive designs.
• Dissection of “false choice” dilemmas in regulatory interactions, referencing real adaptive trial submissions.
• Case-based examples: SEPSIS-ACT, enrichment, and sample size adaptation trials.
• Highlighting myths regarding bias and operational burden from multiple interim analyses.
• Emphasis on practical strategies for more effective regulatory communication about adaptive trials and realistic alternatives.

For more, visit us at https://www.berryconsultants.com/