DO PATIENT-REPORTED OUTCOMES CONTRIBUTE TO REGULATORY DECISIONS IN THE USA AND EUROPE? A SYSTEMATIC REVIEW OF GUIDANCE DOCUMENTS AND AUTHORIZATIONS OF MEDICINAL PRODUCTS FROM 2006 TO 2010

Purpose: To review the extent to which HRQL and other PROs have played a role in drug approval and labeling since the FDA issued its draft guidance on the use of PRO measures and the EMA, its reflection paper on HRQL in 2006.

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

Result: 15 FDA and 34 EMA guidance documents were released containing recommendations for the inclusion of PRO endpoints in clinical trials. The FDA referred to HRQL specifically (as a secondary endpoint) in three of 15 (20%) guidance documents mentioning PRO endpoints – for chronic obstructive pulmonary disease, oncology and weight management. The EMA recommended use of HRQL endpoints in 22 of the 34 (65%) guidances. Interestingly guidelines issued by the EMA during our period of analysis have gained in precision and clarity compared to previous periods. The FDA approved 93 products with label claims that included PRO endpoints (21.5% of 432 total approvals). Of those, 8 products (8.6% of all products with a PRO claim) documented treatment benefits characterized as HRQL. The EMA approved 54 products that included PRO endpoints (21.8% of 248 total approvals), of which 16 products (29.62% of all products with a PRO claim) reflected HRQL data.

Conclusion: Our review showed that patients‘ perspective in clinical research is important for the EMA and FDA, with HRQL endpoints still playing a minor role in product claims. Our analysis suggests that EMA’s receptivity to HRQL endpoints is greater than FDA’s, and that both agencies value patient-reported symptom data. The discrepancy in the prevalence of PRO and HRQL between guidance documents and product labels suggests that for successful submissions additional work is required to comply with current regulatory standards for evaluating PRO in clinical trials. The role of PRO and HRQL should be considered beyond clinical research and labeling claim, into patients’ real life and their influence on payers’ decisions and prescribers’ attitudes should be further studied.