In this episode of "In the Interim…", Dr. Scott Berry and Dr. Lindsay Berry investigate the statistical foundations and clinical implications of analyzing ordinal endpoints, drawing on experience from major stroke and COVID-19 trials. Discussion centers on the Modified Rankin Scale, DAWN, MR CLEAN, and REMAP-CAP, demonstrating that methods such as proportional odds, dichotomization, and utility weighting all impose explicit or implicit clinical weights on the outcome categories. The episode presents direct mathematical derivations, exposes the equivalence between proportional odds models and value-weighted analysis, and uses real trial data to explore how statistical and clinical perspectives on endpoint weighting may diverge. Emphasis remains on transparency and the need for clinically relevant weight assignment in trial endpoints.

Key Highlights

• Structural overview and clinical significance of the Modified Rankin Scale scores.
• Illustration that proportional odds models and dichotomized analyses apply hidden, prevalence-driven or threshold-based weights.
• Utility weighting in DAWN, formulated from EQ-5D patient utilities and economic studies, with observed alignment.
• MR CLEAN investigators' critique of utility weighting; empirical data demonstrated relative consistency and challenged the claim that statistical approaches resolve variation across patients.
• REMAP-CAP platform trial: Organ Support Free Days endpoint analyzed with proportional odds imposed weights on the scale from death to free of organ support .
• Extension of these arguments to win ratio/rank-based approaches, with caution that all methods encode clinical assumptions.

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In this episode of "In the Interim…", Dr. Scott Berry marks the podcast’s one-year anniversary, sharing listener metrics, watch data, and regional engagement. He then delivers a step-by-step analysis of the FDA meeting process, detailing the progression from initial sponsor meeting requests and question submission to briefing book preparation, feedback cycles, and in-person logistics for a Type C meeting at the White Oak facility. Drawing from more than 25 years of trial design and regulatory experience, Scott offers precise guidance on technical preparation, sponsor responsibilities, and common errors in sponsor-FDA dialog, emphasizing what works and what wastes time inside the one-hour meeting constraint. His practical approach focuses on clarity, respect for process, and actionable advice.

Key Highlights

• Slightly over 30,000 people tuned in during the first year across 45 episodes; about 10,000 via audio, 20,000 via video with a global worldwide reach.
• FDA meeting workflow: request, submit four to eight questions, draft briefing book, receive written feedback, strict one-hour in-person discussion controlled by sponsor.
• Advice on briefing book content, avoiding new materials at the meeting, even what not to bring through the White Oak facility.
• Sponsor pitfalls: disingenuous patient advocacy, asking impossible questions, taking adversarial stance in statistical discussion.

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Dr. Nathan O’Hara (University of Maryland), Dr. Gerard Slobogean (UC Irvine), and Dr. Sheila Sprague (McMaster University) describe the launch and design of the Musculoskeletal Adaptive Platform Trial (MAPT)—the first major adaptive platform trial in orthopaedic surgery. The discussion covers MAPT’s master protocol structure, patient-centered endpoint framework, and operational strategies for multinational implementation. Focus areas include the FASTER-HIP domain’s use of Bayesian modeling with a hierarchical clinical endpoint and the standards established for adaptation, data coordination, and future scalability. Listeners gain insight into a trial infrastructure designed to lower barriers for evidence generation and facilitate ongoing evidence generation in musculoskeletal trauma care.

Key Highlights

• MAPT as a scalable, master protocol for orthopaedic intervention evaluation
• Hierarchical, patient-centered endpoint (survival, 4-level ambulation, days alive/out of hospital), analyzed with a Bayesian-modeled, non-parametric win ratio
• Domain-specific adaptation thresholds based on clinical differentiation
• Interim analyses after 100 patients, then every 50, informing early adaptation
• 40 sites across US, Canada, and Europe, centralized data management at McMaster
• A unified DSMB structure with capacity for domain-specific expertise as needed
• Tiered protocol access: open sharing, collaboration, direct integration
• Infrastructure enables rapid domain addition and multi-investigator participation

For more, visit us at https://www.berryconsultants.com/