On August 31, 2020, the FDA released its draft guidance titled “Principles for Selecting, Developing, Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Evaluation.”
While its title suggests that the draft guidance applies only to medical devices, the best practices outlined by the agency should be considered when evaluating PROs intended to support drug submissions as well as medical devices. The draft offers several recommendations related to the development, evaluation, and regulatory review of clinical outcome assessments and states that its purpose is to supplement existing resources.
Some of the major highlights from the draft guidance include:
- The agency encourages modifying and adapting existing PRO instruments, where feasible, rather than creating new measures.
- Concepts and changes in concepts measured by the PRO instrument should be meaningful to patients. Consideration should also be given to aspects of a given concept that may be important to patients (e.g., frequency, severity, interference with activities of daily living).
- The agency recognizes that patients may prioritize some concepts over others (for example, itching may be more important than dry skin).
- Content validity evidence may be generated by multiple sources outside of clinical research (e.g., electronic health records, claims and billing activities, product and disease registries, or health-monitoring devices) – this expands the usual practice of evidence derived from literature review, KOL input, and qualitative research with patients, caregivers, and other stakeholders.
- To improve generalizability of findings, it is encouraged that cognitive interviews (to evaluate the item wording and response options) include patients with limited English-language proficiency and health literacy.
- The FDA may assess an instrument’s “fit-for-purpose” classification by considering the similarities and differences between the population in the pivotal clinical study (e.g., stage of disease) and the population that informed instrument development.
- The role of the PRO instrument should be clearly specified in a study protocol and statistical analysis plan and should include information about the amount of change that is clinically meaningful.
- Assessment of a PRO instrument as “fit for purpose” is flexible rather than absolute. For example, the evidence required to support the validity of a measure will vary based on whether the instrument supports a study’s primary endpoint, inclusion criteria, or a safety outcome.
- When developing new instruments, collaboration with other sponsors and stakeholders is encouraged.
- The draft guidance provides a subset of the BEST glossary to clarify PRO-related terminology.
The FDA will be accepting comments on this draft guidance for 60 days. Read and comment on the draft guidance here: