OBJECTIVES: While there have been some attempts to investigate potential factors influencing the registration status of orphan drugs, clinical data for these drugs (such as evidence on effectiveness, safety and cost-effectiveness) are limited. We aimed to assess the association between available clinical data for orphan drugs and the registration status assigned by the European Medicines Agency (EMA).

METHODS: The analysis included medicines with an orphan designation for June 1, 2020, in the EMA registry. Clinical data were collected from the EPAR reports for each drug, containing such information as clinical trial characteristics or drug safety and efficacy. Data were categorized, and statistical analysis was performed.

RESULTS: We identified 968 studies reporting the results of 1342 clinical evaluations of 105 orphan drugs in a total number of almost 130 000 patients. There were 447 open-label studies (46%), 151 randomized controlled trials (16%), 37 retrospective studies (4%), and 178 dose-response studies (18%). Single or double blinding was used in 209 studies (22%), while placebo in 180 trials (19%). At least one control group was included in 294 studies (30%). In multiple logistic regression, each additional dose-response trial was associated with a 33-fold increase in the odds for authorisation with additional monitoring (OR=33.1, 95%CI: 1.90-833.99; p=0.02). Each additional study with a safety endpoint assessed within 2 months was associated with a 63% reduction in the odds for exceptional circumstances status (OR=0.37, 95%CI: 0.10-0.93; p=0.03). Each additional percent point for a study with a study duration longer than 2 years was associated with a 98% reduction in the odds for accelerated assessment (OR=0.02, 95%CI: 0.00-0.50; p=0.01).

CONCLUSIONS: Our innovative quantitative analysis of the EMA authorization decision-making process revealed that the characteristics of a clinical trial and the quality of collected evidence can be significantly associated with the odds for a specific authorization status.