Use of pain instruments as endpoints in regulatory submissions: implications of the US FDA's new Patient Reported Outcomes (PRO) Guidance

Abstract

The goal of this poster is to review aspects of the FDA's PRO Guidance which have implications for measuring pain as an endpoint in clinical trials. This information will be of immediate interest to researchers developing or using pain instruments to evaluate pain treatments for eventual regulatory submission and subsequent approval. Pain management across therapeutic categories remains a key area for the use of PRO instruments and the interpretation of PRO endpoints to inform drug and device labeling decisions. While academic and medical recommendations exist to inform the development and use of pain instruments (e.g., IMMPACT, OARSI), it remains unclear as to how these recommendations harmonize with emerging regulatory guidelines. In 2009 the US FDA finalized a guidance for the use of PROs for regulatory submissions/approval (FDA, 2009). This guidance outlines criteria for the development, implementation, and interpretation of PROs when used to support primary and secondary endpoints in clinical trials. Moreover, the FDA has indicated that PRO instruments will not be “grandfathered” (i.e., accepted for present or future use based on previous regulatory approvals) and, therefore, will require the same level of validation and documentation to defend and support their use to regulators. To meet regulatory expectations, researchers will have to substantiate their measurement strategy decisions within the context of the PRO Guidance. We will cite the salient aspects of the PRO Guidance, summarize methods and provide citations that can be used to help researchers successfully achieve these new standards set by the FDA. Specific areas of focus will include, but not be limited to: - Recall period and retrospective recall issues - Frequency and timing of assessments - Validation or psychometric evaluation of existing pain scales for use in other pain therapeutic areas - Translation and linguistic validation requirements - Paper to electronic platform migration.