Use of Sequential Multiple Assignment Randomized Trials (SMARTs) in oncology: systematic review of published studies

Sequential multiple assignments randomized trials (SMARTs) are a type of experimental design where patients may be randomised multiple times according to pre-specified decision rules. The present work investigates the state-of-the-art of SMART designs in oncology, focusing on the discrepancy between the available methodological approaches in the statistical literature and the procedures applied within cancer clinical trials. A systematic review was conducted, searching PubMed, Embase and CENTRAL for protocols or reports of results of SMART designs and registrations of SMART designs in clinical trial registries applied to solid tumour research. After title/abstract and full-text screening, 33 records were included. Fifteen were reports of trials' results, four were trials' protocols and fourteen were trials' registrations. The study design was defined as SMART by only one out of fifteen trial reports. Conversely, 13 of 18 study protocols and trial registrations defined the study design SMART. Furthermore, most of the records considered each stage separately in the analysis, without considering treatment regimens embedded in the trial. SMART designs in oncology are still limited. Study powering and analysis is mainly based on statistical approaches traditionally used in single-stage parallel trial designs. Formal reporting guidelines for SMART designs are needed.

Automated summary

Sequential multiple assignments randomized trials (SMARTs) are an experimental design in which patients are randomized multiple times according to pre-specified decision rules. This study investigates the current state of SMART designs in oncology and identifies a discrepancy between the statistical literature and actual procedures used in cancer clinical trials. A systematic review found that SMART designs in oncology are still limited and there is a need for formal reporting guidelines.