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Regulatory Guidance Documents on Adaptive Designs: An Industry Perspective

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Practical Considerations for Adaptive Trial Design and Implementation

Part of the book series: Statistics for Biology and Health ((SBH))

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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 confirmatory 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 reflection paper by EMA (Reflection paper on methodological issues in confirmatory clinical trials with flexible design and analysis plan (draft CHMP/EWP/2459/02, 23-Mar-2006), 2007) and the draft guidance by FDA (Adaptive design clinical trials for drug and biologics draft guidance, 2010).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.

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Correspondence to José Pinheiro .

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Pinheiro, J. (2014). Regulatory Guidance Documents on Adaptive Designs: An Industry Perspective. In: He, W., Pinheiro, J., Kuznetsova, O. (eds) Practical Considerations for Adaptive Trial Design and Implementation. Statistics for Biology and Health. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1100-4_2

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