I-SPY2

An adaptive clinical trial is a clinical trial that evaluates a medical device or treatment by observing participant outcomes (and possibly other measures, such as side-effects) on a prescribed schedule, and modifying parameters of the trial protocol in accord with those observations. The adaptation process generally continues throughout the trial, as prescribed in the trial protocol. Modifications may include dosage, sample size, drug undergoing trial, patient selection criteria and "cocktail" mix. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained. Importantly, the trial protocol is set before the trial begins; the protocol pre-specifies the adaptation schedule and processes.

The aim of an adaptive trial is to more quickly identify drugs or devices that have a therapeutic effect, and to zero in on patient populations for whom the drug is appropriate. A key modification is to adjust dosing levels. Traditionally, non-adverse patient reactions are not considered until a trial is completed.

In 2004, a Strategic Path Initiative was introduced by the United States’ Food and Drug Administration (FDA) to modify the way drugs travel from lab to market. This initiative aimed at dealing with the high attrition levels observed in the clinical phase. It also attempted to offer flexibility to investigators to find the optimal clinical benefit without affecting the study's validity. Adaptive clinical trials initially came under this regime.

The FDA issued draft guidance on adaptive trial design in 2010. In 2012, the President's Council of Advisors on Science and Technology (PCAST) recommended that FDA "run pilot projects to explore adaptive approval mechanisms to generate evidence across the lifecycle of a drug from the premarket through the postmarket phase." While not specifically related to clinical trials, the Council also recommended that FDA "make full use of accelerated approval for all drugs meeting the statutory standard of addressing an unmet need for a serious or lifethreatening disease, and demonstrating an impact on a clinical endpoint other than survival or irreversible morbidity, or on a surrogate endpoint, likely to predict clinical benefit."

In the 2007–2009 period, the Department of Biostatistics at the M. D. Anderson Cancer Center was running 89 Bayesian adaptive trials, 36% of the total designed by the faculty.

The FDA adaptive trial design guidance [1] is a 50-page document covering 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.” Attempts have been made to excerpt the guidance and make it more accessible [2].

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