This JAMA Guide to Statistics and Methods explains sequential, multiple assignment, randomized trial (SMART) study designs, in which some or all participants are randomized at 2 or more decision points depending on the participant’s response to prior treatment.
An adaptive intervention is a set of diagnostic, preventive, therapeutic, or engagement strategies that are used in stages, and the selection of the intervention at each stage is based on defined decision rules. At the beginning of each stage in care, treatment may be changed by the clinician to suit the needs of the patient. Typical adaptations include intensifying an ongoing treatment or adding or switching to another treatment. These decisions are made in response to changes in the patient’s status, such as a patient’s early response to, or engagement with, a prior treatment. The patient experiences an adaptive intervention as a sequence of personalized treatments.
Adaptive interventions are necessary because, for many disorders, the optimal sequence of interventions differs among patients. Not all patients respond the same way or have the same adverse event profile; not all patients engage with treatment in the same way; many disorders have a waxing and waning course; and comorbidities arise or become more salient during the course of care. The trial by Fortney et al1 constructed a 2-stage, adaptive telecare intervention to treat complex psychiatric disorders in underserved, rural, primary care settings. The investigators used a sequential, multiple assignment, randomized trial (SMART)2 design to answer questions concerning the most effective mode of intervention delivery at 2 critical decision points in the adaptive telecare intervention.
A SMART is a type of multistage, factorial randomized trial, in which some or all participants are randomized at 2 or more decision points. Whether a patient is randomized at the second or a later decision point, and the available treatment options, may depend on the patient's response to prior treatment.
In a prototypical SMART (Figure 1), all participants are randomized at the beginning of stage 1 to treatment A or B. Those who respond continue to receive their assigned stage 1 treatment, and those who do not are rerandomized at the beginning of stage 2 to treatment C or D. SMART studies often include multiple adaptive interventions, each represented by a collection of treatment paths offered to individual patients across the multiple stages. The SMART shown in Figure 1 has 4 adaptive interventions, each based on a pair of the 6 treatment paths. One of them is: “Start with treatment A in stage 1 and assess the patient for early signs of response at the end of stage 1. If the patient is an early responder, continue treatment A in stage 2; if the patient is a nonresponder switch to treatment C in stage 2.” This could be represented as the pair (A → responder ...