Reporting of master protocols towards a standardized approach: A systematic review

Area of Science:

• Clinical Trial Design
• Regulatory Science

Background:

• Industry interest in master protocols (basket, umbrella, platform trials) is increasing, evidenced by FDA draft guidance.
• Master protocols evaluate multiple hypotheses under a single overarching design.
• Inconsistent reporting of master protocols in scientific literature necessitates standardization.

Purpose of the Study:

• To systematically review and describe the reporting of master protocols.
• To identify inconsistencies in the definitions and reporting of master protocols.
• To facilitate the development and adoption of standardized master protocol reporting.

Main Methods:

• Systematic literature search of MEDLINE, EMBASE, and CENTRAL databases.
• Supplemented searches with trial registries and bibliographies of reviews.
• Compared self-reported master protocols against FDA definitions.

Main Results:

• Identified 278 master protocol publications (228 protocols, 50 reviews).
• Observed significant heterogeneity in definitions, with 54% using oncology-specific language.
• 57% of self-classified master protocols aligned with FDA definitions.

Conclusions:

• Terms like 'master protocol,' 'basket trial,' 'umbrella trial,' and 'platform trial' are inconsistently defined.
• Adherence to FDA definitions will enhance understanding and utilization of master protocols.
• Encouraging consistent terminology is crucial for advancing clinical research methodology.