Multi-Platform RCT

In this episode of "In the Interim…", Dr. Scott Berry details the design, execution, and results of the multi-platform randomized clinical trial (mpRCT) pioneered during the COVID-19 pandemic. He describes how REMAP-CAP, ATTACC, and ACTIV-4a—each developed independently—pooled data prospectively for joint analysis to address therapeutic anticoagulation in hospitalized COVID-19 patients. Scott outlines the operational rigor required to harmonize endpoints, establish monthly adaptive analyses, and stratify patients by disease severity and D-dimer level. He examines the unified Bayesian hierarchical modeling approach, dynamic borrowing across strata, and the process for simultaneous DSMB reviews coordinated across all platforms. The mpRCT framework enabled real-time, evidence-based adaptations and rigorous distinction of treatment effect by patient subgroup. Results were incorporated into clinical guidelines because prospectively specified analysis revealed benefit for moderate patients and futility or harm for severe patients—findings that would have been missed by standard post hoc pooling.

Key Highlights

• Integration of REMAP-CAP, ATTACC, and ACTIV-4a under a prospectively unified analysis plan.
• Primary endpoint and stratified patient subgroups defined in advance.
• Monthly adaptive analyses using a shared Bayesian hierarchical model.
• Simultaneous oversight by joint statistical and DSMB committees.
• Superiority of therapeutic anticoagulation in moderate, non-critically ill groups; futility and possible harm in severe patients.
• mpRCT model established a framework for future global multi-platform trials.

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