The FDA Final Guidance: Key Considerations for Sponsors Collecting PRO and ePRO Data
Clinical researchers who gather data directly from patients have anticipated the FDA Final PRO Guidance for more than 3 years. The document released in December 2009 provides constructive support for collecting PRO and ePRO (electronic PRO) data with scientific rigor. It establishes that FDA reviewers will evaluate protocols with respect to the targeted labeling claims, an endpoint model, conceptual framework of PRO instruments and the content validity of PRO items. Each of these key elements is defined and explained in the final guidance itself. The collaborative effort extended in developing the Final PRO Guidance should help clinical researchers to rely on patient self-reported information in support of market authorizations and advertising claims.
The purpose of this article is to provide Sponsors and CROs with a point by point review of the differences between the Final FDA PRO Guidance and the Draft, highlighting the choices made by FDA during the 3 years following the Draft PRO Guidance. These choices reveal the FDA deliberations and resulting emphasis, and we also suggest in our review what some of the differences might imply. Note that where terms appear highlighted or emphasized in quotes from the final guidance, the emphasis has been done in the original FDA document.
The focus of the Final Guidance has been altered from a review of best practices for PRO instrument development, to FDA review considerations for PRO instruments, establishing guidelines for evaluating existing, modified or newly created [e] PRO instruments. The Final Guidance also provides more precise directives on how to leverage PRO for labeling claims, and greater direction to Sponsors and CROs. The Final Guidance recommends that Sponsors should begin [PRO or ePRO] instrument development and evaluation early in medical product development, and should also engage the FDA in a discussion about a new or unique PRO [or ePRO] instrument before confirmatory clinical trial protocols are finalized.
3 Key Takeaways:
- The Final Guidance emphasizes three aspects of PRO instruments used to support claims in approved medical product labeling: the conceptual framework, endpoint model, and content validity.
- The Guidance includes an Appendix to help Sponsors prepare a dossier to be submitted to FDA that explains and justifies the PRO instruments planned for an investigation.
- PRO instrument development and use should be completed before commencing confirmatory trials. PHT suggests that Sponsors discuss planned PRO measures with us during the development phase so that we can help them optimize item and instrument selection to suit the trial objectives and to obtain scientifically compelling data directly from patients as they experience a new medical therapy.
It is critical that the clinical trial protocol define the endpoint measures and the criteria for the statistical analysis and interpretation of results, including a specification of the conditions for a positive clinical trial conclusion, because determination of these criteria and conditions after data are unblinded will not be credible.
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