Master Protocols for Drug and Biological Product Development; Guidance for Industry; Draft Guidance

The commenter provides technical feedback on the draft guidance for Master Protocols for Drug and Biological Product Development. They suggest specific improvements regarding Diversity Action Plans, endpoint harmonization in basket trials, operational mechanics for database locks, and biomarker/diagnostic assay validation.

Pharmaceutical Research Manufacturers of America (PhRMA) supports the FDA's draft guidance on master protocols for drug and biological product development, noting it aligns with previous recommendations and mandates. They suggest specific improvements, such as expanding the discussion on basket trials, clarifying combination therapy scope, and refining definitions for substudies and informed consent.

Arnold Ventures, a philanthropy focused on evidence-based policy, supports the development of master protocols for clinical trials but recommends specific enhancements to the draft guidance. They argue for stronger requirements for randomization to internal control groups, more emphasis on double-blinded trials over partially blinded ones, and clearer expectations for statistical analysis plans regarding interim results and concurrent enrollment.

Boehringer Ingelheim Pharmaceuticals, Inc. provides comments on the draft guidance for Master Protocols for Drug and Biological Product Development. The company supports the general direction of the guidance but suggests specific clarifications regarding sponsor responsibilities, randomization methods for irrational ratios, operational burdens of changing ratios, and the inclusion of control patients in primary analyses.

The Methodology Working Party of the European Medicines Agency submitted comments providing technical feedback and suggestions for the finalization of the draft guidance. They offer specific recommendations on clarifying adaptive design features, multiplicity, and the scope of basket trials within the master protocols.

The Multi-Regional Clinical Trials Center (MRCT Center) of Brigham and Women's Hospital and Harvard supports the FDA's effort to extend master protocol guidance beyond the COVID-19 pandemic. They provide specific feedback on definitions, scope, informed consent, and data sharing, while requesting further clarification on rare disease trials and multi-national considerations.

The Biotechnology Innovation Organization (BIO) supports the draft guidance on Master Protocols for Drug and Biological Product Development, noting that it comprehensively summarizes common practices. However, the organization provides numerous specific recommendations to improve the guidance, including clarifying definitions, expanding the scope to include basket trials and pediatrics, and providing more detail on adaptive designs and sample size considerations.

The Oncology / Immuno-Oncology subteam of the Innovative Design Scientific Working Group (IDSWG), representing several pharmaceutical companies and independent consultants, provides detailed technical feedback on the draft guidance. They request specific clarifications on trial definitions, statistical methodologies (such as adaptive randomization and multiplicity), and operational considerations like IRB structures and informed consent.

The Coalition for Epidemic Preparedness Innovations (CEPI) supports the use of master protocols as a tool for responding to public health emergencies and developing vaccines. They suggest expanding the guidance to include more details on diverse technologies and diseases, as well as clarifying ownership of INDs for multiple products.

The commenter, likely an academic or researcher given the citation of a peer-reviewed medical journal, supports the guidance but suggests refining the definition of "concurrent control" to be broader for platform trials. They also advocate for including specific requirements regarding "Participant Randomization Schemes" to ensure valid data interpretation in data-sharing arrangements.