Close

Endpoints: BIO Comments on FDA Multiple Endpoints in Clinical Trials

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the Draft Guidance “Multiple Endpoints in Clinical Trials” (Draft Guidance).

Re: Docket No. FDA-2016-D-4460: Multiple Endpoints in Clinical Trials
 
Dear Sir/Madam:
 
The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the Draft Guidance “Multiple Endpoints in Clinical Trials” (Draft Guidance).
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This important Draft Guidance was well written and provides instrumental guidance and recommendations to handle major multiplicity problems in clinical trials. BIO believes that the Draft Guidance is a very helpful document to Sponsors. However, we note that the Draft Guidance fails to address a few points that are worthy of attention:
 
  • multiplicity adjustments at the interim analysis (either directly in this Draft Guidance or via reference to ICH E9 or the Guidance for Industry Adaptive Design Clinical Trials for Drugs and Biologics);
  • multiplicity adjustment on safety endpoints when assessing important safety signals as part of the objectives of the trial (e.g., with p-values reported) to control the overall false discovery rate of safety signals;
  • elucidation of the calculation methods to be used with the truncated Holm and truncated Hochberg procedures (e.g., for the truncated Hochberg example, the α passed to the next level); and
  • basic principles, such as closed test or partition principles, which many of the multiple comparison methods in the guidance are based upon.
BIO further believes that it would be helpful if the Draft Guidance stated at the beginning, perhaps more clearly and emphatically than it does now, the areas that are mentioned in other sections as being out of scope. It would also be helpful to explain why these areas are outside of the scope. For example, the Draft Guidance states that multiplicity in interim analysis is not within the scope of the document (lines 180-184). This is something that should also be stated in the introduction. Simulation based multiplicity adjustment is another area that is not included in the guidance. If related topics are outside the scope but they have been the subject of previous FDA guidance, such guidance should be referenced.

Click the link below for full comments