Responder Analyses-A PhRMA Position Paper

Ideally, a clinical trial should be able to demonstrate not only a statistically significant improvement in the primary efficacy endpoint, but also that the magnitude of the effect is clinically relevant. One approach to address this question, often proposed by clinical societies and regulatory guidance, is a responder analysis, in which a continuous primary efficacy measure is dichotomized into responders and nonresponders. This article represents a Pharmaceutical Research and Manufacturers of America (PhRMA) position on responder analyses. With respect to demonstration of the existence of a treatment effect, we find that the well-known loss of statistical power associated with a responder analysis outweighs any real or perceived benefits of this approach. However, between-group comparisons of the percentages of responders can play a role in the assessment and reporting of the clinical meaningfulness of the treatment effect.