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time; but the formalization of, and broader emphasis on PROs has become increasingly important with the release of the draft guidance for industry on patient-reported outcomes.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.

Patient-reported outcomes (PRO's) in glaucoma: a systematic review

“…Hence, not using a framework can cause difficulties with (1) grouping and scoring of items into domains, (2) the analysis and (3) the interpretation of PRO-scores if one doesn't know what is assessed. 58 Second, many investigators only use expert opinion and/or a literature review to generate a preliminary list of items, yet the crucial factor to ensure a good breadth of relevance, which is the perspective of patients, was neglected in 11 instruments. According to the FDA 11 and the applied quality criteria, 12 PRO-instrument itemgeneration is incomplete without patient involvement (eg, patient interviews or focus groups) and should incorporate the input of a wide range of patients with the condition of interest to represent appropriate variations in severity and in population characteristics (eg, age, gender).…”

“…In a conceptual framework, the interrelationships between items within a domain and of domains within a PRO-concept are depicted in a way that the concept of interest can be operationalized and appropriate psychometric analysis can be performed. 11,58 It should provide the rationale for, and specification of, the PRO-outcomes of interest (eg, side effects) in the population of interest (eg, glaucoma patients undergoing eye drop treatment) for a particular decision (eg, choice of appropriate eye drop treatment). Hence, not using a framework can cause difficulties with (1) grouping and scoring of items into domains, (2) the analysis and (3) the interpretation of PRO-scores if one doesn't know what is assessed.…”

Current Treatments of Alzheimer Disease: Are Main Caregivers Satisfied with the Drug Treatments Received by Their Patients?

“…Patient-reported outcomes are important to understand the impact that the treatment has on the patient's functioning and wellbeing, providing valuable information for evaluating the adequacy of treatment outcomes [41] and for regulatory decisions [42,43] . While cognitive and functional tests may be good assessment instruments to rate the efficacy of different treatments, patient-reported outcomes on satisfaction with treatment more accurately evaluate the 'effectiveness' of treatment [44,45] , as patients' satisfaction is strongly associated with adherence [41,46] .…”

Health span or life span: The role of patient-reported outcomes in informing health policy

“…[15] It is vital to have sufficient evidence that PRO concept is adequately measured by a PRO instrument. [16] In recent decades there has been an exponential growth in the measures and it is important to consider not only the psychometric properties but also the utility in making treatment decisions and policy development.…”