Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess the efficacy of a drug. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts: symptomatic adverse events, physical function, and disease-related symptoms, which are key contributors to the effect of a therapy on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials.

A clinician-reported outcome (ClinRO) assessment is a type of clinical outcome assessment (COA). ClinRO assessments, like all COAs (patient-reported, observer-reported, or performance outcome assessments), are used to 1) measure patients’ health status and 2) define end points that can be interpreted as treatment benefits of medical interventions on how patients feel, function, or survive in clinical trials. Like other COAs, ClinRO assessments can be influenced by human choices, judgment, or motivation. A ClinRO assessment is conducted and reported by a trained health care professional and requires specialized professional training to evaluate the patient’s health status. This is the second of two reports by the ISPOR Clinical Outcomes Assessment—Emerging Good Practices for Outcomes Research Task Force. The first report provided an overview of COAs including definitions important for an understanding of COA measurement practices. This report focuses specifically on issues related to ClinRO assessments. In this report, we define three types of ClinRO assessments (readings, ratings, and clinician global assessments) and describe emerging good measurement practices in their development and evaluation. The good measurement practices include 1) defining the context of use; 2) identifying the concept of interest measured; 3) defining the intended treatment benefit on how patients feel, function, or survive reflected by the ClinRO assessment and evaluating the relationship between that intended treatment benefit and the concept of interest; 4) documenting content validity; 5) evaluating other measurement properties once content validity is established (including intra- and inter-rater reliability); 6) defining study objectives and end point(s) objectives, and defining study end points and placing study end points within the hierarchy of end points; 7) establishing interpretability in trial results; and 8) evaluating operational considerations for the implementation of ClinRO assessments used as end points in clinical trials. Applying good measurement practices to ClinRO assessment development and evaluation will lead to more efficient and accurate measurement of treatment effects. This is important beyond regulatory approval in that it provides evidence for the uptake of new interventions into clinical practice and provides justification to payers for reimbursement on the basis of the clearly demonstrated added value of the new intervention.

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Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and Drug Administration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations.