Adaptive treatment strategies in chronic disease.

An adaptive treatment strategy (ATS) is a rule for adapting a treatment plan to a patient's history of previous treatments and the response to those treatments. The ongoing management of chronic disease defines an ATS, which may be implicit and hidden or explicit and well-specified. The ATS is characterized by the use of intermediate, early markers of response to dynamically alter treatment decisions, in order to achieve a favorable ultimate outcome. We illustrate the ATS concept and describe how the effect of initial treatment decisions depends on the performance of subsequent decisions at later stages. We show how to compare two or more ATSs, or to determine an optimal ATS, using a sequential multiple assignment randomized (SMAR) trial. Designers of clinical trials might find the ATS concept useful in improving the efficiency and ecological relevance of clinical trials.