New concepts for approval of drugs in oncology beyond randomized clinical studies

Background In recent years a large number of biomarker-stratified targeted and immunological treatment procedures were introduced in oncology. Higher efficacy has been shown in subgroups of patients with these drugs compared to the standard of care; however, due to the low numbers of patients within some subgroups confirmatory phase III trials are sometimes not feasible and the proof-of-principle is increasingly shifted towards early study phases. The approval authorities in the USA and the European Union have recognized these difficulties and established new instruments to accelerate and simplify drug approval. This development is accompanied by innovative trial designs that can provide relevant data for drug approval in early study phases. Objective Summary and discussion of innovative trial designs and approval procedures in oncology. Material and methods A systematic search was carried out in the medical literature database PubMed () for articles on "approval procedures" and "trial designs" in oncology as well as the websites of the European Medicines Agency (EMA), the US Food and Drug Administration (FDA) and the Federal Institute for Drugs and Medical Devices (Bundesamt fur Arzneimittel und Medizinprodukte, BfArM). Results and discussion A growing number of drugs are being approved within accelerated approval procedures in oncology. The FDA programs, such as the "breakthrough designation" and the "accelerated approval" procedures have been especially successful. Systematic analyses revealed that the time to the first use in patients was significantly shortened. Based on new designs, such as basket trials, approvals were granted in the USA for histology-independent personalized treatment for patient subgroups. Despite these achievements, criticism has arisen concerning the sometimes preliminary nature of data on safety and efficacy on which accelerated approval is based.