The Role of Health-Related Quality of Life Data in the Drug Approval Processes in the US and Europe

Objective: The objective of this research was to review the extent to which health-related quality of life (HR-QOL) and other patient-reported outcomes (PROs) have played a role in drug approval and labelling since 2006, when the US FDA issued its draft guidance on the use of PRO measures and the European Medicines Agency (EMA), its reflection paper on HR-QOL.

Methods: This research was conducted through a systematic manual review of therapy area-specific regulatory guidelines (US and EU) and product labels issued during the period 1 January 2006 to 16 November 2010.

Results: Fifteen (39.5% of all guidance documents) and 34 (35.8%) guidance documents containing recommendations for the inclusion of PRO endpoints in clinical trials were released by the FDA and the EMA, respectively. The FDAreferred to HR-QOL (as a secondary endpoint) in 3 of the 15 (20%) guidances. The EMA recommended use of HR-QOL endpoints in 22 of the 34 (65%) guidance documents. The FDA approved 93 products with PRO endpoints in labelling (out of 432 total approvals). Of those, eight products (8.6% of all products with a PRO claim) documented treatment benefits characterized as HR-QOL. The EMA approved 54 products that included PRO endpoints in labelling (out of 248 total approvals), of which 16 products (29.6% of all products with a PRO claim) reflected HR-QOL data.

Conclusion: Our review shows that the patients’ perspective in clinical research is important for the EMA and FDA, with HR-QOL endpoints still playing a minor role in product claims. Our analysis suggests that the EMA’s receptivity to HR-QOL endpoints is greater than the FDA’s, and that both agencies value patient-reported symptom data. Differences between the agencies’ acceptance of PRO endpoints, especially HRQOL, might reflect differences in their structure and organization. As the world’s largest medical regulatory agency, the FDA employs an ‘army’ of experts to review submissions and develop guidance. This internal expertise enables the FDA to take an active role in defining endpoints, developing guidance and regulations that clarify their expectations, and enforcing regulatory policy. By contrast, the EMA, working with a network of over 4500 European experts, relies on clinicians and the scientific community for the definition of validity and the acceptance of an endpoint. Historically, the EMA has been more likely to accept existing measures, including global assessment and diaries, provided the assessments are supported by peer-reviewed publications of the development and validity of the instruments. Thus, the peer-review process and acceptance by the scientific and medical communities greatly influence the acceptance of PRO claims in EMA product approvals. Finally, the FDA’s stance may be driven, in part, by the potential use of PRO information in direct-to-consumer advertising and whether such measures are meaningful and interpretable by patients. For the future, we believe that the empowerment of patients in healthcare decision making will foster the use of specific PROs for evaluating the benefits of treatments on criteria that are meaningful to patients, in addition to traditional clinical endpoints.