Interpreting patient-reported outcome results: US FDA guidance and emerging methods

Abstract

In recent years, the US FDA has become more critical of instruments used to measure patient-reported outcomes (PROs) in clinical trials. To facilitate decisions related to the approval of drugs, labels and promotional claims based on PROs, the FDA created the Study Endpoints and Label Development (SEALD) group. SEALD has developed a PRO guidance related to the use of PRO measures used to support drug approvals and label claims, including recommendations for establishing thresholds for meaningful change at the individual level (i.e., defining a responder). This article examines in detail the FDA-recommended methodology for defining a responder and analyzing responder-based PRO measure results. We also present other responder analysis approaches for consideration in furthering the precision and interpretation of this methodology.

Figures

Figure 1. Sample cumulative distribution function

The data used to draw this figure were generated for illustration purposes.

Figure 2. Sample cumulative distribution function with confidence bands

The data used to draw this figure were generated for illustration purposes. CI: Confidence interval.

Figure 3. Sample receiver operating characteristic curve

Data from [14].