Clinical Trials: BIO Comments on FDA Draft Guidance : Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments to the Draft Guidance on Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.

BIO is the world's largest trade association representing biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial, and environmental biotechnology products.

This Draft Guidance provides important information to allow companies to use master protocols and is welcomed by our members. The clinical sections are well-covered, however, the statistical sections lack completeness and clarity. For example, information critical for controlling for type I error in Master Protocols appears to be missing from this draft guidance. The full potential of a confirmatory master protocol trial can only be realized with consensus on type I error control. We have provided comments below to address this issue that we hope the Agency will consider.  

As a general comment, we find that FDA’s thinking and expectations for master protocols used in early stage trials versus late stage trials is not fully clear. It would be helpful if FDA would provide further explanation for what should be considered for an early stage trial and, similarly, for a late stage trial, and what would apply to both.

Secondly, BIO believes the Draft Guidance could define the three types of Master Protocol trials that are introduced in Section 1: Basket, Umbrella, and Platform. In addition, it would be beneficial to add a description of platform trials under Section IV, as it was done for basket and umbrella trials. For reference, we would suggest the definitions included in Janet Woodcock’s 2017 publication, “Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both”[1].

Furthermore, the Draft Guidance should provide additional clarification over certain master protocol design specifications such as in the disease areas where multiple acceptable standards of care (SOC) are available for the studied population, would the agency agree that one investigational arm may be compared to two different control arms? In addition, the Draft Guidance should provide additional information around how to handle a master protocol with sub-studies which will form a basis of a marketing application (i.e., phase 3 trial).

BIO appreciates this opportunity to submit comments on the Draft Guidance on Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics. We provide additional specific, detailed comments to improve the clarity of the Draft Guidance in the following chart. We would be pleased to provide further input or clarification of our comments, as needed.