gms | German Medical Science

More than 10 years ago the European Medicines Agency (EMA) published a reflection paper on confirmatory adaptive clinical trials [1], which outlines basic principles of planning and analyzing adaptive designs.

Adaptive designs are nowadays common practice in confirmatory trials. Especially group sequential designs with early stopping for efficacy or futility are used in many confirmatory trials. Newer developments allow much broader design modifications (e.g. sample size re-estimation, chance of the randomization ratio, or modifications to the number of treatment arms). Changes of the primary endpoint(s) or the primary analysis population (e.g. enrichment designs) are presented as well but are often not well understood. The main focus of regulatory assessment are the control of the type 1 error, bias and the conduct and integrity of the ongoing trial. With the advent of complex clinical trials such as basket, umbrella and platform trials many of the discussed issues become a new relevance and an added layer of complexity. Specific adaptations might furthermore render the confirmatory nature of a trial questionable and thus limit the applicability of adaptive designs in confirmatory studies.

This talk will give an overview of the European regulatory perspective and provide a brief comparison to the recent FDA guidance on adaptive designs [2].

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.