Considerations on the Use of Patient-Reported Outcomes in Comparative Effectiveness Research

Comparative effectiveness research (CER) involves studies that generate evidence through an evaluation of the spectrum of health care interventions and services that reflect patient choices for a given clinical situation, with the intent of improving patient and physician decision-making. In this paradigm, CER can be defined as a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients.1 Such studies may compare similar treatments, such as competing drugs, or they may analyze very different approaches, like surgery and drug therapy.1 To date, the areas of emphasis in CER have primarily been on clinical endpoints, with extensive work in mixed and indirect treatment comparisons,2-3 use of Bayesian approaches,4 simulated treatment comparisons,5 realworld data use,6-8 and therapeutic index determination.9 Despite the potential role of patient-reported outcomes (PRO) data in CER, a central role for PRO data has not yet been fully established in CER because of the challenges associated with the collection and interpretation of such data within and across studies. A PRO is any report on the status of a patient’s health condition that comes directly from the patient.10 PRO is an umbrella term that includes a whole host of subjective outcomes, such as pain, fatigue, depression, aspects of well-being (e.g., physical, functional, psychological), treatment satisfaction, health-related quality of life, and physical symptoms, such as nausea and vomiting.11 In the traditional clinical research domain, there have been great advances with regard to the recognition of the role of PROs,12 as evidenced also by the recent publications of guidance documents by regulatory agencies.13-14 In different parts of the world, agencies or government bodies like the Institute for Quality and Efficiency in Healthcare (IQWiG) in Germany, the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, the National Institute of Health and Clinical Excellence (NICE) in the United Kingdom, and the Canadian Agency for Drugs and Technologies in Health (CADTH) in Canada have long histories of using PROs. While there are ongoing initiatives aimed at selecting preferred PRO instruments that would support validity and comparability of PRO measures and results, the use of PROs for CER is less defined than it is for regulatory approval. In this paper we discuss the role of PROs in CER, review the challenges associated with the inclusion of PROs in CER initiatives, provide a framework for their effective utilization, and propose several areas for future research.