The distribution characteristics and regulations of adaptive designs
from 2008 to 2020: an overview of EMA approvals
Objective: To identify and characterize all European Medicines Agency
(EMA) approvals that made use of adaptive designs in clinical trials and
to evaluate the conditions where adaptive designs were required.
Methods: We gathered relevant files derived from the EMA database based
on a list of the keywords related to adaptive designs between 2008 and
2020. We collected the trial characteristics from approvals and Fisher
exact test was used to compare the characteristics. Results: We found 41
approvals derived from 91 original EMA files contained adaptive designs.
Group sequential was the most popular adaptive design (17/41). Most of
the approvals (32/41) were pivotal trials and were not under accelerated
assessment (38/41). Among 32 confirmatory trials planned with adaptive
designs, the proportion of AM status showed a statistically significant
increase (P < 0.0001) from 0% in 2008–2012 to 90.48% in
2017–2020. The percentage of antitumor drugs in approved drugs with
ongoing clinical trials was 82.35%, compared to 20.83% with completed
trials (P=0.0001). The proportion of companies that required
post-authorization safety or efficacy studies or that were
granted CMA for drugs that were approved but still had ongoing clinical
trials significantly differed from the other group (P = 0.0230).
Conclusion: An increasing trend was observed in the number of EMA
approvals related to adaptive designs from 2008 to 2020. Extra
regulations will be necessary for ongoing trials due to unknown,
uncertain circumstances raised from adaptive design, such as addtitonal
monitoring, conditional marketing authorization.