Podcast Episode
72: Failure of the Proportional Odds is the Result
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Scott Berry, Ph.D.
President & Senior Statistical Scientist
Elizabeth Lorenzi, Ph.D.
Senior Statistical Scientist
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Elizabeth Lorenzi systematically examine the analytic pitfalls in recent acute ischemic stroke trials, especially the implications of violating the proportional odds assumption on the modified Rankin Scale.
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Elizabeth Lorenzi systematically examine the analytic pitfalls in recent acute ischemic stroke trials, especially the implications of violating the proportional odds assumption on the modified Rankin Scale. The discussion draws on the DISCOUNT, INSTANT, ESCAPE-MeVo, and ORIENTAL-MeVo trials, spotlighting frequent reactive shifts to dichotomous analysis after proportional odds violations. Scott and Elizabeth detail how such post-hoc approaches obscure clinically relevant heterogeneity and often rely on arbitrary, inconsistent endpoint definitions. They advocate for adaptive Bayesian methodologies, like those implemented in the STEP platform, to illuminate which patients actually benefit or are harmed by endovascular therapy, moving beyond population-average summaries. The episode underscores the necessity for trial designs that explicitly address heterogeneity of treatment effect and consider weighted utility approaches over simplistic dichotomies. Listeners gain an unvarnished critique of prevailing reporting practices and an actionable vision for rigorous, individualized trial analytics.
Key Highlights
DISCOUNT trial’s interim analysis and futility stopping.
Issues with endpoint dichotomization after proportional odds violations.
Comparison across multiple recent stroke trials with inconsistent endpoint definitions.
The case for individualized effect estimation and weighted utility analysis.
Adaptive Bayesian trial design strategies in STEP platform.
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72: Failure of the Proportional Odds is the Result
In this episode of "In the Interim…", Dr. Scott Berry and Dr. Elizabeth Lorenzi systematically examine the analytic pitfalls in recent acute ischemic stroke trials, especially the implications of violating the proportional odds assumption on the modified Rankin Scale.
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