Identification of approval conditions for orphan drugs for neurological disorders by the Japanese regulatory agency

Abstract

ABSTRACTBackground: Orphan drugs are used to treat rare diseases. Since consistent criteria for regulating these drugs are not clarified, we sought to identify the regulatory requirements and trial design elements of clinical trials for orphan drugs approved by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.Research design and methods: We identified orphan drugs approved to treat neurological disorders during April 2006–March 2016, using PMDA data. We investigated characteristics of pivotal trials from drug labels and drug approval packages, and identified six elements of clinical trial design: use of controls, blinding, randomization, size, analysis type, and end point. The evidence for efficacy provided by the PMDA was also collected for each drug.Results: PMDA has approved orphan drugs for neurological diseases in a flexible manner. Randomized, double-blinded, placebo-controlled pivotal trials were not always included in the new drug application package. The PMDA tended to make a positive judgment decision when a controlled trial was performed in Japan, regardless of the existence of foreign data.Conclusions: We provide a review of the Japanese regulatory environment for orphan drug approval in the neurological field by assessing the characteristics of clinical trials for orphan drugs indicated for neurological diseases in Japan.