By Celeste Elash, Director, eCOA Sciences at YPrime
When people with cancer participate in clinical trials, clinicians typically assess and record the treatment side effects that patients experience. Many key endpoints in oncology trials are not patient- reported outcomes (PROs), but rather pertain to survival, which is essentially a measure of ‘treatment activity’, and do not provide information about how patients feel or function. In 2016, former FDA Commissioner Dr. Scott Gottlieb argued for a more risk-based approach to regulation. He suggested the FDA should be more open to use of surrogate measures, including those meaningful to patients. The 2016 Century Cures Act, which includes sections devoted to streamlining patient input and using patient experience data in drug development, builds on the FDA's work to incorporate patients’ perspectives into the development of drugs, biological products, and devices and helped focus drug development on patient-focused outcomes. In 2017, Gottlieb stated “Our aim is to facilitate the development and use of patient-focused methods in more parts of our regulatory activities as well as develop and elevate common standards for how to integrate the patient voice, as a matter of science, into product development. Among some of the long-term goals of these new efforts is the creation of consistent approaches to how the FDA develops clinical outcomes assessment tools such as patient-reported outcomes to inform our regulatory decisions.” With the reissuance of the Prescription Drug User Fee Act (PDUFA), patient engagement was elevated to be a core part of the FDA’s regulatory approvals process. Subsequently, the FDA has been clear that PROs could be the basis of approval of an oncology drug if that drug demonstrates symptom improvement (i.e., the way a patient “feels”), despite having no overall survival benefit.
Despite this promotion of patient-focused outcomes, and although PRO data are currently collected in oncology trials, regulatory approval of new therapies based on PRO data has been rare. In order to accept PRO data for labelling, FDA requires 1) rigorous PRO development and 2) PRO data collected from well controlled, i.e., randomized, double-blind, trials. Further, the FDA recommends focusing on the 3 key areas of disease; symptoms, physical function (i.e., impact of toxicity) and symptomatic AEs (i.e., bothersomeness).
While taking into consideration these recommendations, trial sponsors must evaluate their approach to PRO data collection and proactively minimize risks to both data integrity and patient experience during trial design and execution. In 2012, Ethan Basch and colleagues published the Center for Medical Technology Policy effectiveness guidance document to provide recommendations for the appropriate inclusion of PRO measures in the design and implementation of clinical research in adult oncology. The review includes specific recommendations for measure selection and data analysis and reporting, but of interest here are some of the practical recommendations for PRO implementation.