Master Protocols for Drug and Biological Product Development; Guidance for Industry; Draft Guidance

The commenter provides technical feedback on the draft guidance for Master Protocols for Drug and Biological Product Development.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.

Mark Obermeyer, an independent researcher, argues that the FDA failed to follow its own "Master Protocols" by not identifying and quantifying long-term adverse events associated with nasopharyngeal swabs during the COVID-19 pandemic. He contends that these swabs caused accelerated infections and increased mortality, and he advocates for the immediate discontinuation of the procedure in favor of safer alternatives.

Daiichi Sankyo, a global pharmaceutical company, submitted comments providing specific technical feedback and requests for clarification on the draft guidance for master protocols. They advocate for more detailed guidance on oncology trials, randomization practicalities, and the inclusion of combination regimens.

Pharmaceutical Research Manufacturers of America (PhRMA) supports the FDA's draft guidance on master protocols for drug and biological product development, noting it aligns with previous recommendations and mandates.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policy, supports the development of master protocols for clinical trials but recommends specific enhancements to the draft guidance.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Boehringer Ingelheim Pharmaceuticals, Inc. provides comments on the draft guidance for Master Protocols for Drug and Biological Product Development.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.

AstraZeneca supports the draft guidance on Master Protocols for Drug and Biological Product Development, noting it is timely and supportive of innovation. The company suggests expanding the guidance to include more detail on basket trials, precision medicine, rare diseases, and practical considerations like patient centricity and sample size estimation.

The commenter, likely a pharmaceutical or clinical research company, provides specific technical feedback on the draft guidance for master protocols. They suggest clarifying language regarding randomization ratios, informed consent procedures for platform trials, and the distinction between sub-study and overarching protocol amendments to improve practical feasibility and patient experience.