Regulatory Guidance Documents on Adaptive Designs: An Industry Perspective

W. He et al. (eds.), Practical Considerations for Adaptive Trial Design and Implementation, Statistics for Biology and Health, DOI 10.1007/978-1-4939-1100-4_2, © Springer Science+Business Media New York 2014 Abstract Adaptive designs have the potential to be a transformative methodology in clinical drug development, but acceptance by regulatory agencies is a prerequisite for their broader adoption and success, especially in the context of confi rmatory studies. Both FDA and EMA have published guidance documents focusing on adaptive designs, which have been neither discouraging nor clearly supportive of the approach in their assessments and recommendations. As a result, the interpretation of the regulatory position on adaptive designs also has been mixed, with some citing the guidance documents as evidence that health authorities do not accept adaptive designs, while others mentioning the same documents as indication that regulators support their use in drug development, when properly planned, conducted, and analyzed. This chapter reviews and discusses the two main regulatory documents on adaptive designs issued by the time this book was published: the refl ection paper by EMA (Refl ection paper on methodological issues in confi rmatory clinical trials with fl exible design and analysis plan (draft CHMP/EWP/2459/02, 23-Mar-2006), 2007) and the draft guidance by FDA (Adaptive design clinical trials for drug and biologics draft guidance, 2010). Reactions from the biopharmaceutical industry to both documents, collated by industry trade groups, are also presented and discussed.