OBJECTIVES: To review and compare policies released by the FDA and EMA regarding PRO studies in drug development.

METHODS: Review articles summarizing and commenting on FDA and/or EMA PRO policies were identified through searching on PubMed and Web of Science from 2009 to 2019. We reviewed and screened the reference lists of the review articles in order to further identify official PRO policy documents. Google, FDA and EMA official websites were also used to search and retrieve those policy documents.

We extracted policy names, disease scope, year of publication, definitions of PRO, PRO instruments and criteria for study design, further comparing the two agencies’ criteria on PRO studies. Descriptive analyses were used to summarize the results.

RESULTS: A total of five documents were identified: in which three were released by the FDA in 2009, 2016 and 2018, and two by the EMA in 2005 and 2016. While health-related quality of life (HRQL) is viewed as a type of PRO by the EMA, the FDA does not include HRQL in the definition of PRO. Two documents focus on oncology, and three documents have no specific disease scope. Three documents mention the evaluation on the PRO instruments, and four documents state the consideration for study design. Comparison between the FDA and EMA shows: 1) The EMA accepts clinical studies with PRO measures as secondary or exploratory outcomes for regulatory submissions, while the FDA prefers symptom-based endpoints. 2) The EMA lends more endorsement to established measurements validated and supported by existing publications; The FDA evaluates the PRO instruments with the conceptual framework. 3) Double-blinding design is not strictly required by the EMA, but the FDA specifies single-arm studies are barely accepted.

CONCLUSIONS: FDA and EMA policies have different criteria on PRO studies in terms of HRQL as endpoints, PRO instruments and study designs.