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. The discussion addresses the decades-long controversy surrounding steroid use in community-acquired pneumonia (CAP) and sepsis. The episode delivers a chronological assessment of the evidence base—summarizing trial results from pivotal studies, including CAPE COD, REMAP-CAP, ADRENAL, and multiple French trials led by Dr. Djillali Annane. Dr. Angus analyzes why discrepancies persist in outcomes, clinical recommendations, and international guidelines, and underscores the challenge of heterogeneous treatment effects. The episode closes with an argument for adaptive trial designs, Bayesian inference, and embedded randomization within learning health systems as critical tools for clarifying complex response patterns and improving patient care.

Key Highlights

• Historical evolution of clinical trials studying steroid regimens for CAP/sepsis
• Review of CAPE COD, REMAP-CAP, ADRENAL, and Annane-led French trials showing conflicting signals.
• Discussion of persistent heterogeneity in trial populations, interventions, and endpoints.
• Identification of methodological limitations—control contamination, endpoint definitions, varying inclusion criteria.
• Exploration of Bayesian and adaptive trial design, and operationalization of learning health systems to resolve evidence gaps.

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