gms | German Medical Science

Adaptive designs are well known and often recommended for use in clinical trials to better cope with uncertainties at the planning stage. Particularly in the field of rare diseases, adaptive designs are often proposed as an alternative to the classical randomized parallel group design eventually including an interim analysis [1], [2]. The authors claim that adaptive designs are suitable in the context of small populations because they will in general reduce sample size, but only little is said about the details or the price to be paid when using adaptive designs.

As already stated in the draft FDA Guidance for adaptive design clinical trials for drugs and biologics it should be noted that adaption of sample size“[…] should be used only for increases in the sample size, not for decreases” [3]. In addition the time point of interim analysis should be carefully chosen as the estimates after only a few patients can be misleading largely or small.

On this poster we will focus on the usefulness of adaptive two stage designs in the context of rare diseases and do eventually compare to group sequential designs. Considering the standard Bauer & Köhne two-stage design [4] we discuss implications of design modifications on trial size and interpretation.