title: Patient-reported outcomes: conceptual issues.
abstract: There is a broad agreement that patient-reported outcome (PRO) assessment in health care should proceed from a strong conceptual basis, with rationales clearly articulated in advance concerning what is to be measured and how this is to be accomplished. The representation of the patient's perspective has been part of clinical trials for some time; but the formalization of, and broader emphasis on PROs has become increasingly important with the release of the draft guidance for industry on patient-reported outcomes. In response, we address the challenges in constructing the conceptual foundations for PRO assessment to support drug product labeling claims submitted to regulatory agencies worldwide. After discussing what constitutes a PRO concept and an adequate basis for framing a PRO assessment, we examine the consequences of choosing PRO instruments without reference to a well-established conceptual framework for measurement. Then we illustrate through a hypothetical example the important interplay between the sponsor's proposed product claim, the corresponding conceptual model that depicts hypotheses involving the PRO concept(s) in the claim, and the resulting conceptual framework(s) for measurement to guide instrument selection and psychometric analyses. We discuss how these conceptual issues may vary or evolve over time depending on the phase of product development. As the science of PRO measurement continues to develop and experience accumulates, a consensus may emerge on how best to articulate the conceptual basis of PRO measurement for purposes of product labeling and regulation. In the meantime, one point is imminently clear: in regulatory decisions expected to affect not only the quantity but the quality of life, it is imperative to incorporate the patient's own perspective on the illness experience and the effects of therapy.
authors.affiliation: Johnson & Johnson Pharmaceutical Services LLC, Raritan, NJ, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Rothman
authors.forename: Philippe
authors.initials: P
authors.lastname: Beltran
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.forename: Joseph
authors.initials: J
authors.lastname: Lipscomb
authors.forename: Bonnie
authors.initials: B
authors.lastname: Teschendorf
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003625:Data Collection / Q000379:methods* / Q000706:statistics & numerical data; D004335:Drug and Narcotic Control; D006801:Humans; D008962:Models, Theoretical; D017060:Patient Satisfaction / Q000706:statistics & numerical data*; D011356:Product Labeling / Q000592:standards / Q000706:statistics & numerical data*; D012107:Research Design; D016896:Treatment Outcome; D014481:United States