New directions in adaptive designs

Abstract

In any sequential medical experiment on a cohort of human beings, there is an ethical imperative to provide the best possible medical care for the individual patient. This ethical imperative may be compromised if a randomization scheme involving 50-50 allocation is used as accruing evidence begins to favor (albeit not yet conclusively) one experimental therapy over another. Adaptive designs have long been proposed to remedy this situation. An adaptive design seeks to skew assignment probabilities to favor the treatment performing best thus far in the study, proportionately to the magnitude of the treatment effect.

Current researchers in adaptive designs are attempting to provide physicians with a wide choice of design options, and to address practical and ethical concerns within a rigorous mathematical framework. This paper focuses on several broad families of designs, including urn models, random walk rules and other rules. Numerous examples are given along with applications, dose-response studies, clinical trials for efficacy and combined toxicity-efficacy studies.