Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms

Abstract

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.

Patient-reported outcome measurement in drug discovery: a tool to improve accuracy and completeness of efficacy and safety data

“…For this reason, the FDA and EMA assert that for assessment of symptoms or other domains that patients know best, PROs are the gold standard for data collection [1,8]. Collection of PROs with thoughtful implementation in clinical trials has been found to be feasible, with over 80% patient compliance in cooperative group trials and over 90% in many industry trials either with paper forms or electronic data collection via web, automated telephone system, or handheld device [9].…”

“…PRO questionnaires can also be used to support economic analyses such as costeffectiveness and may be requested or required by some authorities. PRO questionnaires are commonly used for this purpose and can also reflect overall impact on the health status or functioning of study participants, but may not have sufficient precision to reflect specific symptoms or aspects of physical functioning [8]. Treatment satisfaction can also be assessed as a supportive metric not for labeling purposes, for example as done in the evaluation of rivaroxaban for longterm anticoagulation in deep venous thrombosis [14].…”

“…For a labeling claim, adjustment for multiplicity across all clinical and PRO endpoints is typically warranted, and this can be discussed with regulatory authority representatives. For PRO-based adverse event reporting, descriptive statistics without adjustment for multiplicity is appropriate [8]. Continuous distribution of response displays are useful to show the full spectrum of patient responses at a given time point and to show that study conclusions were not dependent on the single selected clinically meaningful score change [23,24].…”

Toward a National Initiative in Cancer Rehabilitation: Recommendations From a Subject Matter Expert Group

“…17,18 A focus on assessment and management of physical health and function is needed to promote improved health-related quality of life. 19,20 Recommendations and standards from the Institute of Medicine and the American College of Surgeons' Commission on Cancer, among others, provide a framework for alleviating deficits in cancer care and the resulting failures to recognize and manage functional loss and disability. [21][22][23] Rehabilitation professionals are an optimal addition to the cancer care team and offer expertise in functional assessment, morbidity management, and disability prevention.…”

Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials—Letter

“…Kluetz et al from the FDA [1] provide a welcome overview of the challenges related to patient-reported outcomes assessment in cancer clinical trials seen from a regulatory perspective.…”