The clinical assessment of studies on orphan drugs in relation to the EMA's authorization marketing decisions in Europe

Szczepan Jakubowski Krzysztof Malinowski Paweł Kawalec ^*

• Jagiellonian University Medical College, Kraków, Poland

The main objective of this study was to assess the correlation between the methodological characteristics of clinical trials on orphan drugs and the special statuses granted by the European Medicines Agency (EMA).Material and Methods: Data was collected for all medicines with orphan designation assigned by 2020. From August 2019 to June 2020 special statuses (authorization statuses and registration requirements) and general information on orphan drugs was obtained from the EMA's web-based registry. The following clinical data were collected: the number of patients; clinical phase; randomization; masking; control group; treatment duration; safety and efficacy follow-up. Descriptive, comparative, multivariate and univariate analyses of data were conducted.Results: Results were provided for 105 medicines with orphan designation. The odds of an orphan drug receiving conditional approval were lower for studies with randomization (p=0.002) and active controlled trials (p=0.010), but they increased with a treatment duration of 3 to 12 months (p=0.002) and a safety and efficacy follow-up of 2 to 6 months (p=0.008 and p=0.035, respectively). Approval under exceptional circumstances was less likely for each additional 1000 patients included in reference trials (p=0.002), randomization (p=0.024), double blinding (p=0.033), and active controlled trials (p=0.006). However, it was more likely for phase II/III trials (p=0.039), a treatment duration of 3 to 12 months (p=0.03), and safety and efficacy followup longer than 6 months (p=0.022 and p=0.047, respectively).The type of clinical trial and its methodological characteristics are correlated with EMA decisions. Randomization, double blinding, and active controlled trials reduce the odds of ODs receiving EMA special status. In contrast, phase II/III trials, specific duration of treatment and specific safety and efficacy follow-up increased these odds.