論文の公開元へInvestigation of appropriate implementation of the pathway to deliver drugs faster to patients : analysis based on the Accelerated Approval in the United States
概要
Background: Accelerated approval (AA) is a program that grants approval to drugs based on clinical trial data for a surrogate endpoint or an intermediate clinical endpoint in the United States. Pharmaceutical companies are required to conduct a confirmatory trial to demonstrate true clinical benefit of the drug to obtain full approval (FA) for the AA. In this thesis, Research 1 aimed at clarifying the points that should be considered by examining the characteristics of AA indications in all disease areas and the factors related to the status of conversio n fro m AA to FA. Research 2 aimed at clarifying how the efficacy and safety were verified after AA by analyzing the design, etc. of the confirmatory trial conducted at the time of FA acquisition in all disease areas.
Methods: In Research 1, AA indications granted from January 1, 2000, to June 30, 2016, were investigated from the aspects of the characteristics of AAs and the status of conversion from AA to FA. In Research 2, AA indications that were successfully converted to FA from January 1, 2000 to June 30, 2020 were investigated from confir matory trials performed to obtain FA.
Results: In Research 1, 89 AAs were examined, of which 65 were converted to FA and 24 were not. A significant association was found between the FA status and period in which AA was granted, disease area, availability of interim analysis data of a confirmatory trial for FA at the time of AA, and sales ranking of the company. In Research 2, 83 AAs were initially identified, of which 67 in total were reviewed. It was found that post-marketing confir matory trials for obtaining FA were designed with high level of evidence; most trials were randomized (n=66, 85%) and comparative (active controlled) (48, 62%), though open-label (53, 68%). They were relatively large scaled.
Conclusions: To successfully convert from AA to FA, a development plan that focuses not only on AA but also on future FA needs to be considered and implemented from the early stage of development in line with the FDA guidance. In particular, for companies with insufficient experience in the development of AA indications and for products/indications without an established endpoint, more active discussion with the regulatory authorities from an early stage of development should be encouraged. In Japan, Conditional Early Approval System for pharmaceuticals has been implemented since October 2017, and more pharmaceutical products would be granted early approval under this system in the near future. We need to appropriately implement the system to deliver innovative drugs faster to patients by drawing on the experience in the United States.
