gms | German Medical Science

Background: The demand for new treatments and developments in precision medicine remains constantly high. New findings suggest incorporating knowledge on molecular profiling by targeting aberrant genes or pathways right from the beginning of drug development. With the new perspective of precision medicine, it is no longer considered sufficient to base the treatment decision solely on the phenotype of the disease (e.g. the tumour location of an oncologic patient), but on specific biomarkers such as genetic mutations. By this, treatments become more patient-individualized, but also result in novel statistical challenges.

Methods: A relatively new approach of incorporating molecular profiling into phase II clinical trials are so-called “basket” and “umbrella” trial designs, which are sometimes summarized as “master protocols”. Master protocols cover several (sub)studies within a common study protocol thereby sharing all logistic, legal, clinical, and statistical aspects as far as possible. For example, a common biomarker-screening platform and/or a unique IT infrastructure is used. Master protocols were first established in oncology, however, they are becoming more and more popular in other medical research areas as well, e.g. in psychiatric trials. These designs have the chance to increase the efficiency of drug development and to allow developing individualized treatment approaches. However, they also come along with major open statistical challenges including multiple testing, interim analyses, the choice of optimal futility boundaries, definition of adequate go/no go criteria, unbiased quantification of treatment effects, rules for incorporating correlation and borrowing between different sub studies. The awareness of these challenges among medical researchers is not necessarily given.

Objective and Future Perspective: In this talk, we highlight the chances but also the statistical challenges of platform trials. By this, we want to initiate a discussion on what kind of evidence can be drawn from such trials and what is needed to improve the current status. By this, we try to sketch a roadmap for future methodological research.

The authors declare that they have no competing interests.

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