Perspectives on patient-reported outcomes : content validity and qualitative research in a changing clinical trial environment.

Patient-reported outcomes (PROs) represent the voice of the patient in drug and device evaluation. As such, the outcomes selected for evaluation must be relevant to the patient, and the instruments used to capture them must have sound measurement properties. This paper discusses the role of qualitative research methods in assuring PRO clarity and content validity in a clinical trial environment characterized by evolving regulatory policy, new advances in technology and increasingly diverse samples within global clinical trials. Three important PRO measurement issues influenced by these changes are addressed: (i) endpoint selection and instrument development; (ii) the adaptation of instruments for electronic administration; and (iii) conceptual equivalence of measures across diverse samples. These are viewed as interrelated issues of content validity that can be addressed through the appropriate and rigorous application of qualitative research methods. Focus groups, cognitive debriefing, user acceptance testing and translation methodologies are discussed as ways to address and document the content validity of PRO instruments and ensure the empirical data representing the voice of the patient is sound.