ABSTRACT
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.