PFDD: BIO Comments on FDA Draft Guidance Patient-Focused Drug Development: Collecting Comprehensive and Representative Input

September 11, 2018

Re: Docket No. FDA 2018-D-1893: FDA Draft Guidance Patient-Focused Drug Development: Collecting Comprehensive and Representative Input

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments regarding the Draft Guidance on Patient-Focused Drug Development: Collecting Comprehensive and Representative Input.

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.

BIO applauds the FDA’s initiative to continue to advance the use of patient experience data (PED) to inform drug development and regulatory review. BIO appreciates the FDA’s organization of a public dialogue on the topic through the public workshop “Patient-Focused Drug Development: Guidance 1 – Collecting Comprehensive and Representative Input,” on December 18, 2017 as well as the associated discussion document (and accompanying appendices and glossary). Furthermore, BIO appreciates the FDA’s efforts to develop the first Draft Guidance addressing comprehensive and representative input as required by section 3002 of the 21st Century Cures Act, and commitments made by FDA under the sixth authorization of the Prescription Drug User Fee Act (PDUFA VI).

BIO sees this first Draft Guidance, addressing comprehensive and representative input, as an important tool for strengthening our collective understanding of the relevant evidence needed to support the FDA regulatory process with PED. The Draft Guidance is well-written and provides discussion of standard research methods and study designs used to collect PED as well as utilizable suggestions as to whom to obtain PED from as well as why and how the information could be collected.

The Draft Guidance presents approaches that adhere to established standards for good research practice and provides enough information to gain insight into what is needed to compose an appropriate research study. However, BIO strongly believes that in order for a broad adoption of PED, the upcoming guidance documents should emphasize the FDA’s willingness to exercise regulatory flexibility and acceptance of innovative designs and approaches for collecting PED. For example, the Draft Guidance is highly focused on statistical requirements for collection of subjective measures and although representation of the population is paramount, there is also a need to balance such representativeness with statistical validity, as the requirement of many strata for representation could have a negative impact on statistical power. The Draft Guidance also lists several sampling methods along with their inherent limitations, however, such sampling methods may not be feasible under all circumstances and thus flexibility on the part of the FDA will be needed. The FDA also recommends that if the sample size is limited due to practical considerations (e.g., rare diseases), the research objectives should be adjusted accordingly and noted as a limitation in the study report. To not discourage the collection of PED in the context of rare diseases, we also ask the FDA to exercise flexibility and acceptance of innovative designs and approaches for collecting such data, especially in cases where there are limited patient populations.

We also note FDA’s use of the term “ultra-rare disease populations” in the Draft Guidance (Line 708); to our knowledge, the term has not been defined in statute, regulations, or existing FDA guidance.[1] As such, we encourage the Agency to continue to employ the established terminology and definition of a rare disease (e.g., affecting fewer than 200,000 persons in the United States) until there have been sufficient opportunities to discuss with all stakeholders; including industry Sponsors and patient organizations; and establish definition or terminology based on scientific evidence.

We have included additional comments below as well as proposed specific line edits for the FDA’s consideration as they work to finalize the Draft Guidance.


[1] While “ultra-rare disease population” is not included in statute, regulation, or guidance BIO is aware of Commissioner Gottlieb’s use of the term during FDA remarks at the 11th Rare Disease Day on February 26th 2018 and the FDA’s reference to “rare diseases of low prevalence” defined as ”a condition affecting approximately 5,000 persons or less in the United States” in the FDA’s Draft Guidance on “Slowly Progressive, Low-prevalence Rare Diseases with Substrate Deposition that Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies.