Clinical trial designs for more rapid proof-of-principle and approval

This chapter reviews and proposes clinical trial design innovations that will hopefully not only accelerate the drug development process, but also improve upon its success rate. The promise of more targeted, rationally designed drugs has unfortunately not resulted in more new agents being approved for routine clinical use. A recent review found that oncology is one of the worst therapeutic areas in terms of attrition rates. There are many compounds that have entered pivotal Phase III trials and subsequently have not been approved. Most prominent amongst these in terms of oncology drug development are biomarker development, streamlining clinical trials through novel designs, and the use of bioinformatics. Parallel to the FDA's Critical Path Initiative is the European Agency for the Evaluation of Medicinal Products' (EMEA) initiative – the Innovative Medicines Initiative (IMI or InnoMed) –, which aims to foster public–private collaborations to accelerate drug development. In the battle against attrition for drug development in oncology, it may help to be armed with trial designs and techniques that can help not only to accelerate the process, but also to reduce the failure rate.