Abstract and Introduction
Randomized clinical trials are critical for evaluating the safety and efficacy of interventions in oncology and informing regulatory decisions, practice guidelines, and health policy. Patient-reported outcomes (PROs) are increasingly used in randomized trials to reflect the impact of receiving cancer therapies from the patient perspective and can inform evaluations of interventions by providing evidence that cannot be obtained or deduced from clinicians' reports or from other biomedical measures. This commentary focuses on how PROs add value to clinical trials by representing the patient voice. We employed 2 previously published descriptive frameworks (addressing how PROs are used in clinical trials and how PROs have an impact, respectively) and selected 9 clinical trial publications that illustrate the value of PROs according to the framework categories. These include 3 trials where PROs were a primary trial endpoint, 3 trials where PROs as secondary endpoints supported the primary endpoint, and 3 trials where PROs as secondary endpoints contrast the primary endpoint findings in clinically important ways. The 9 examples illustrate that PROs add valuable data to the care and treatment context by informing future patients about how they may feel and function on different treatments and by providing clinicians with evidence to support changes to clinical practice and shared decision making. Beyond the patient and clinician, PROs can enable administrators to consider the cost-effectiveness of implementing new interventions and contribute vital information to policy makers, health technology assessors, and regulators. These examples provide a strong case for the wider implementation of PROs in cancer trials.
Randomized clinical trials (RCTs) are critical for evaluating the safety and efficacy of interventions in oncology and thus for informing regulatory decisions, clinical practice guidelines, and health policy. Typically, RCTs evaluate a new intervention against a standard of care for a specific patient population, based on a hypothesis that the new intervention is either superior, equivalent, or not worse (noninferior) than the standard arm by a prespecified clinically relevant margin on the primary study outcome. Patient-reported outcomes (PROs) are commonly included in these RCTs to reflect the impact of receiving cancer therapies from the patient perspective. PROs vary in their content, including symptoms (eg, fatigue, appetite loss, anxiety), psychological well-being, and functional status (eg, physical functioning, sexual functioning, ability to work). PROs are scored based on questionnaires referred to as PRO measures (PROMs), completed directly by the patient, without modification or interpretation by another observer.[1,2] A PRO may be the primary outcome, or more frequently, secondary outcomes that, for example, assess physical function or tolerability. Importantly, PROs have the potential to inform evaluations of oncological interventions by providing evidence that cannot be obtained or deduced from clinicians' reports or from other biomedical measures (eg, to assess pain, nausea, neuropathy).[3,4]
PROs are increasingly being included in cancer clinical trials,[2,5] complementing other clinical assessments including clinician-reported outcomes, observer-reported outcomes, or performance-based outcomes. Over several decades, the field has benefited from the development of several established PROMs with strong evidence of reliability and validity in a broad range of cancer patient populations. Recent US Food and Drug Administration guidance provides recommendations for the collection and analysis of a core set of PROs for use in cancer clinical trials, including measures of disease-related symptoms, symptomatic adverse events, measures of physical function and role function, and an overall measure of the impact of side effects.[2,6] Further, the guidance recognizes the need to use specific measures in relevant clinical trials that are fit for purpose for patient populations with specific symptoms and functional domains of interest (for example, xerostomia and swallowing function in patients with head and neck cancers). A fit for purpose measure's properties include the following: it validly and reliably measures concepts important to patients and clinicians and can be communicated in a way that is accurate, interpretable, and not misleading. There now exist many PROMs of health status, health-related quality of life (HRQOL), and symptom burden that have been rigorously developed and tested to ensure that they address issues relevant to clinicians and patients and that also meet standards for reliability and validity,[5,7] some of which are available in multiple languages and cultural adaptations. PROs addressing adverse events [such as the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) system] are now available. Beyond measures of symptoms and HRQOL, health utility measures, such as the EQ-5D, may also be of value for cost-effectiveness analyses and health technology assessments.
But do these PROs add value to the interpretation of RCTs by providing information that can inform clinical and regulatory decision making? This commentary addresses this question with illustrative examples of how PROs have added value beyond that provided by conventional clinical outcome measures such as survival, disease response, and clinician-reported toxicity rates. We undertook this commentary as a key strategic initiative of the Patient-Reported Outcomes Tools: Engaging Users & Stakeholders (PROTEUS) Trials Consortium—a collaboration of 27 international stakeholder organizations that aims to optimize the use of PROs in research studies. This summary was designed to demonstrate ways in which PROs were key components (as either primary or secondary outcomes) of well-conducted cancer clinical trials.
J Natl Cancer Inst. 2022;114(10):1323-1332. © 2022 Oxford University Press