Review of draft FDA adaptive design guidance.
Recent draft Food and Drug Administration (FDA) guidelines on adaptive clinical trial design and conduct provide a useful background for both academic and industry clinical research leaders. The guidelines help to define the scope of the term "adaptive design" and clarify how adaptive designs can be a critical component of a development program. Adaptive designs are appealing because they hold the promise of conducting trials that can answer the scientific questions of interest with savings of time and resources while exposing fewer subjects to potentially risky therapies. Adaptive designs have been successfully used in clinical trials in all phases of development for many years, enabled by a variety of increasingly flexible and powerful statistical tools. Recent developments that enable adaptations based on emerging treatment differences have demonstrated potential to streamline the research enterprise, but issues remain in their implementation. Proper implementation of adaptive designs requires an adequate understanding of the inherent trade-offs that accompany their use. In exchange for potential efficiencies in resource utilization, adaptive trials suffer from limitations in scientific conclusions, complications and inefficiencies in the statistical analysis, and logistical difficulties relative to fixed sample or fixed duration trials. While scarce resources and ethical imperatives motivate serious consideration of adaptive designs, researchers should be fully aware of the advantages and disadvantages of adaptive designs and adopt them cautiously.
Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA. cook@biostat.wisc.edu
Thomas
T
Cook
David L
DL
DeMets
D015982:Bias; D002986:Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D017277:Drug Approval / Q000379:methods*; D017408:Guidelines as Topic; D006801:Humans; D015233:Models, Statistical; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome; D014481:United States