OBJECTIVES. In 2016, the IRDiRC concluded that the use of patient-reported outcome (PRO) measures is a necessity in clinical research on rare diseases because they measure the real benefits of the treatment from the patient's point of view. The objective of our study was to evaluate the extent to which PROs were used in the evaluation of orphan drugs authorized by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the last 15 years.

METHODS. The FDA and EMA websites were reviewed to retrieve all products approved with an orphan designation from 01/2002 to 06/2017 included. The label (FDA) and the summary of product characteristics (EMA) of all products were analyzed to find any mention of PROs used and found relevant by the agencies.

RESULTS. The review of both data sets (FDA/EMA), excluding duplicate records, led to a single data set of 452 distinct designations. Designations for products indicated for oncology purpose were excluded, leaving 258 designations to review. Among those, only 45 designations included PRO claims in their labeling, i.e., 17.4% of the total designations of non-oncology products. These 45 designations represented 42 different products of which 10 were common to both agencies. The PRO measures mentioned in the label were primarily focused on symptoms (e.g., dyspnea, fatigue, pain), rarely on functioning or health-related quality of life. In few cases (e.g., CAPS, cystic fibrosis, acromegaly), measures were specific and developed for the rare condition.

CONCLUSIONS. This review shows that the patient’s perspective in the evaluation of orphan drugs is not fully implemented. The high number of rare diseases, the small number of patients for each pathology, the lack of information on the natural history of certain diseases, or the association with significant disability and cognitive impairments, make the development of specific PROs an arduous task.