Design characteristics of Sequential Multiple Assignment Randomized Trials (SMARTs) for human health: a scoping review of studies between 2009-2024

  1. Nikki L. B. Freeman
  2. Sydney E. Browder
  3. Bryce T. Rowland
  4. Emily P. Jones
  5. Margaret Hoch
  6. Alice H. Kim
  7. Christina W. Zhou
  8. Anna R. Kahkoska
  9. Katharine L. McGinigle
  10. Anastasia Ivanova
  11. Michael R. Kosorok
  12. Kevin J. Anstrom
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Abstract

Objective

To characterize the reporting practices of sequential multiple assignment randomized trials (SMARTs) in human health research.

Design

Scoping review of protocol and primary analysis papers describing SMARTs published between January 2009 and January 2024.

Background

SMARTs are innovative trial designs that allow for multiple stages of randomization to treatment based on a patient’s responses to previous treatments. They are uniquely designed to develop sequential adaptive interventions (dynamic treatment regimes) to support clinical decision-making over time. Previous reviews have identified inconsistencies in how the design, implementation, and results have been reported in published studies. A comprehensive assessment of SMART reporting practices is lacking, and necessary for developing standardized SMART-specific reporting guidelines.

Methods

We systematically searched multiple databases for SMART-related protocol and primary analysis papers published between January 2009 and January 2024. Title, abstract, and full-text screenings were performed by pairs of reviewers, with disagreements resolved by consensus. Data extraction included study characteristics, design elements, and analytic approaches for embedded or tailored dynamic treatment regimes (DTRs). Results were synthesized qualitatively and presented descriptively.

Results

From 5486 screened studies, 88 (59 protocols, 29 primary analyses) met inclusion criteria. Most studies targeted adults (62.7% protocols, 58.6% primary analyses) and were primarily conducted in the United States. Behavioral and mental health constituted the most frequent therapeutic domain. While intervention descriptions and re-randomization criteria were consistently reported, operational characteristics such as blinding (protocols: 64.4%, primary analyses: 69.0%) and randomization details (protocols: 88.1%, primary analyses: 75.9%) were inconsistently documented. Only 48.3% of primary analyses evaluated embedded DTRs, and none explored tailored DTRs.

Conclusions

Despite the increased adoption of SMART designs, substantial reporting variability persists. Most primary analyses underutilize the capability of SMARTs to generate data for developing dynamic treatment regimes. SMART-specific standardized reporting guidelines can help accelerate the scientific and clinical impact of SMARTs.

Strengths and limitations of this study

Strengths

  • This is the most comprehensive review of SMARTs in human health to date, spanning studies published since SMARTS were introduced, and over a 15-year period (2009–2024).

  • Rigorous methodology, including dual independent screening and extraction, enhances the reliability of the findings.

  • The granularity of our assessment of design elements provides specific targets for developing SMART reporting guidelines.

Limitations

  • This study only included protocol and primary analysis papers, missing SMARTs described in trial registries alone as well as analyses of SMARTs in secondary analysis papers.

  • This review included only English-language publications, potentially missing relevant studies published in other languages

  • This review did not assess the quality of the included SMARTs themselves, focusing instead on reporting practices.

Article activity feed

  1. Version published to 10.1101/2025.06.06.25329149v1 on medRxiv