Talkin' 'bout Sweet Time

In this episode of "In the Interim...", Dr. Scott Berry dissects prevailing concepts of “clinically meaningful difference” in clinical trials focusing on progressive diseases. Through detailed examples from pancreatic cancer (Ben Sasse, Revolution Medicines), emphysema (Elevair), Alzheimer’s disease (lecanemab), and IVF, Scott challenges the adequacy of the population-mean of a continuous outcome in reflecting true patient benefit. The episode discusses inconsistent usage and interpretation of acronyms such as MCID, CSD, and Target Product Profile (TPP). Dr. Berry advises trialists to resist interpreting the mean difference using patient-level minimal effects, and adopt responder analyses and cumulative probability approaches to enhance patient-level relevance. Guidance is offered for analyzing the effect of time-saved instead of a mean differences in a clinical endpoint at a single time for progressive diseases – measuring “sweet time.”Key HighlightsFocus on added time not the change from baseline as the most meaningful outcome for a progressive disease.In-depth evaluation of MCID, CSD, TPP, and risk of misinterpretation.Critique of trying to interpret mean-based endpoints for clinical meaningfulness such as six-minute walk distance and CDR sum of boxes.FDA advisory panel guidance on MCID for IVF live birth endpoints and dichotomous versus continuous endpoints.Advocacy for responder analyses and cumulative probability of achieving thresholds in reporting the clinical effect of a treatment.For more, visit us at https://www.berryconsultants.com/