Data for sequential decisions
Murphy and colleagues suggest that sound sequential decisions follow from observing important clinical outcomes that mark "critical decision points." From this, they indicate, decisions are made to optimally treat the disorder, maximize function, and minimize the burden of illness. In the typical dilemma of a patient's symptoms improving but not fully remitting, the clinician confronts the choice of switching to a different treatment, with risk of losing the initial benefit or increasing adverse effects, or maintaining the marginally successful treatment in hope that more improvement will occur with time.
"Adaptive treatment strategies, treatment algorithms, and expert systems provide a framework for operationalizing these key clinical decisions," Murphy and colleagues explain. "By operationalizing these decisions, they can be studied and improved upon, with the aim of reducing inappropriate variance in treatment delivery while retaining appropriate flexibility to tailor these decisions to individual patients."1
Murphy and colleagues suggest that studies based on the Sequential Multiple Assignment Randomized Trial (SMART) design,5,6 which uses multiple randomizations at each critical decision point, are more likely to inform sequential decisions than traditional randomized clinical trials. They note that these studies are not confirmatory, however, and may not involve a control condition. Murphy and colleagues also indicate that several SMART design trials may be necessary to fully inform an adaptive treatment strategy and that the validity of that strategy may need further testing against alternatives in a confirmatory randomized clinical trial.
The STAR*D study does not appear to be an exception to these characteristics. Despite enrolling 4041 patients over a 7-year period, there was a lack of differences between treatments at levels 2, 3, and 4, which, Nelson remarks, "leaves us without a roadmap to guide treatment selection and leaves us wanting more."
The characteristics of psychiatric illness, however, "motivate the development of adaptive treatment strategies," Murphy and colleagues declare. "Addressing tactical questions concerning the length of time to wait for treatment response and the choice of subsequent treatment are crucial in this endeavor."