BackgroundPersonalizing medical care is becoming increasingly popular, particularly mental health care. There is growing interest in formalizing medical decision making based on evolving patient symptoms in an evidence-based manner. To determine optimal sequencing of treatments, the sequences themselves must be studied; this may be accomplished by using a sequential multiple assignment randomized trial (SMART). It has been hypothesized that SMART studies may improve participant retention and generalizability.MethodsWe examine the hypotheses that SMART studies are more generalizable and have better retention than traditional randomized clinical trials via a case study of a SMART study of antipsychotic medications. We considered the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, comparing the trial participant characteristics and overall retention to those of comparable trials found via a review of all related trials conducted from 2000 onwards.ResultsA MEDLINE search returned 6435 results for primary screening; ultimately, 48 distinct trials were retained for analysis. The study population in CATIE was similar to, although perhaps less symptomatic than, the study populations of traditional randomized clinical trials (RCTs), suggesting no large gains in generalizability despite the pragmatic nature of the trial. However, CATIE did see good month-by-month retention.ConclusionsSMARTs offer the possibility of studying treatment sequences in a way that a series of traditional RCTs cannot. SMARTs may offer improved retention; however, this case study did not find evidence to suggest greater generalizability using this trial design.Trial registrationClinicalTrials.gov NCT00014001. Registered on 6 April 2001.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1368-3) contains supplementary material, which is available to authorized users.