Mind the Methods

In this episode of Mind the Methods (the ICTM podcast), Dr. Kemi Olugemo, ISCTM Scientific Committee member and consulting Chief Medical Officer at Junevity, and Dr. Siân Ratcliffe Smethurst, ISCTM President-Elect and Chief Operating Officer of Premier Research, discuss how biomarkers can accelerate CNS drug development without creating false confidence and what practical methods sponsors can use to create regulatory flexibility while preserving scientific rigor. 

A biomarker is only useful within a clearly defined context of use. The same measure can support enrichment, target engagement, dose selection, monitoring, or approval in different settings. Kemi and Siân emphasize that regulatory flexibility is earned through rigorous evidence, early engagement, and a credible confirmatory strategy, not by lowering evidentiary standards.

Tune in to ISCTM’s Mind the Methods podcast with Dr. Kemi Olugemo, ISCTM Scientific Committee member and consulting Chief Medical Officer at Junevity, and Dr. Mo Heidaran, NIH-trained scientist and former FDA Division of Cell and Gene Therapy leader. Together, they explore precision and safety in genetic medicines for CNS disorders—from gene-editing platforms and manufacturing quality to patient selection, off-target effects, and long-term safety monitoring. They also discuss how AI can support development while keeping human expertise and accountability central.

In this episode of Mind the Methods (the ISCTM podcast), Dr. Mark Opler speaks with Dr. Elizabeth Ballard, Associate Scientist at the NIMH Intramural Research Program and the 2025 recipient of the ISCTM Lewis Alan Opler Prize, about the evolving science of suicidal ideation and behavior. Dr. Elizabeth Ballard explains why many commonly used tools were built for risk documentation and legal protection, not for detecting treatment-related changes in clinical trials, and how repurposing them can obscure true signals, particularly for rapidly acting interventions. Drawing on trial examples, Dr. Elizabeth Ballard highlights how different measures (full scales vs. single items/subscales) can yield different conclusions about treatment effects, underscoring that measurement choice can be the difference between “it didn’t work” and “we didn’t measure it correctly.” The conversation also addresses the field’s “catch-22”: trials often exclude participants with suicidal ideation/behavior, limiting what we can learn about how treatments affect people with lived experience. Dr. Ballard discusses practical steps to safely include higher-risk participants, IRB and DSMB education, clear monitoring and response pathways, adverse event planning, and shared resources across research networks. Looking forward, Dr. Elizabeth Ballard describes a “both/and” future that blends clinician interviews with self-report, ecological momentary assessment, and emerging objective/implicit measures, arguing that suicide risk is dynamic and variable, and our tools must evolve to capture that reality.

In Part 2, Amir Kalali, MD, Independent Consultant, continues the discussion with Luca Pani, MD, focusing on how AI could fundamentally transform CNS drug development by enabling deeper biological insight, patient enrichment, and real-world outcome assessment, while emphasizing the cultural resistance, regulatory transparency, ethical trust, and leadership readiness required for responsible adoption.

In Part 1, Gary Sachs, MD, Clinical Vice President at Signant Health, moderates a discussion with Luca Pani, MD, President of ISCTM and Chief Regulatory and Innovation Officer at NetraMark. The conversation examines how AI can be used to support drug development, clinical trial design, and data interpretation, alongside key regulatory, ethical, and scientific considerations.

In this introductory episode of Mind the Methods, host Elizabeth Pappadopulos, PhD, introduces the mission, scope, and audience of the ISCTM podcast. She outlines how the series will explore innovations in CNS clinical trial design and methodology ranging from digital endpoints, adaptive protocols, and generative AI to patient-centric approaches and real-world challenges across psychiatric, neurologic, and neurodegenerative research. Episode 00 sets the stage for thoughtful, expert-led conversations with researchers, clinicians, industry leaders, and regulators, all focused on advancing rigorous methodology and improving outcomes for patients in CNS drug development.