gms | German Medical Science

Preclinical research is widely criticized for its wastage of test animals. In Germany alone 1,368,447 mice and 255,449 rats were sacrificed for animal experiments in 2017 [1]. The recently established Charité 3R center tries to address growing concerns in society about this practice. “3R” is an animal protection principle and stands for “Replace”, “Reduce” and “Refine”. Adaptive study designs could contribute to the efforts to reduce the number of animals used in preclinical trials.

The need for a great deal of test animals is particularly high in multi-group studies, e.g. dose finding studies with many treatment arms (dose levels).

In the talk, we will propose an adaptive two-stage design that has a greater statistical power than the single stage designs usually used in preclinical research. The gain of power could be used to save animals needed for the experiment.

Following ideas from [2] the study design allows dropping groups after the first stage (at least one) and stopping for futility.

Preclinical trials often lack power. That could be one reason why translation of promising preclinical findings into clinical application often fails (c.f. [3] for a discussion of this issue in neurological stroke research). Designs that are more powerful could be an answer to many needs. However, they are scarcely used in practice since they require additional efforts and the need for statistical consulting in the planning phase. In the talk, we discuss how to improve the user friendliness of such designs such that they can find their way into application eventually.

Finally, we give an example of an application of the method to a real world neuroprotection study in the middle cerebral artery occlusion (MCAO) model of ischemic stroke.

The authors declare that they have no competing interests.

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