The FDA adaptive trial design guidance in a nutshell - A review in Q&A format for decision makers

The FDA adaptive trial design guidance (1) is a thoughtful but lengthy document that explains on 50 pages wide-ranging and important topics “such as ... what aspects of adaptive design trials (i.e., clinical, statistical, regulatory) call for special consideration, ... when to interact with FDA while planning and conducting adaptive design studies, ... what information to include in the adaptive design for FDA review, and ... issues to consider in the evaluation of a completed adaptive design study.” [20-24]. The advice in the guidance is often misinterpreted, misquoted or ignored. This is unfortunate because an appropriate use of adaptive designs could increase the chances of success in drug development programs. Decision makers rely on the advice of regulatory affairs professionals and statisticians to interpret the guidance. Unfortunately, many clinical trial statisticians and regulatory professionals only have a rudimentary understanding of the guidance, presumably because the document is somewhat inscrutable for both audiences, too ‘regulatory’ for statisticians, too ‘statistical’ for regulatory people. This digest was therefore written with three goals in mind: 1) Make the content of the guidance more accessible through a question & answer format, 2) shorten the content from 50 to 10 pages by excerpting the most important dictums, and 3) keep fidelity to the original guidance by frequent use of direct quotes with reference to the respective lines in the original FDA guidance where the quote can be found in square brackets.