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Clinical Studies

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

British Journal of Cancer volume 128, pages 1177–1188 (2023) Cite this article

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Abstract

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.

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Acknowledgements

The work was part of a research project developed in the context of the Master’s Programme in Epidemiology of the University of Turin.

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The authors received no specific funding for this work.

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Author notes

  1. These authors jointly supervised this work: Giulia Lorenzoni, Elisabetta Petracci.

Authors and Affiliations

  1. Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Padova, Italy

    Giulia Lorenzoni, Ileana Baldi & Dario Gregori

  2. Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy

    Elisabetta Petracci, Emanuela Scarpi & Oriana Nanni

Authors
  1. Giulia Lorenzoni
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  2. Elisabetta Petracci
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  3. Emanuela Scarpi
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  4. Ileana Baldi
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  5. Dario Gregori
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  6. Oriana Nanni
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Contributions

GL designed the work, acquired the data, interpreted the results, drafted the work; EP acquired the data, interpreted the results, drafted the work; ES acquired the data and revised the manuscript; IB designed the work, revised the manuscript; DG conceived the work, revised the manuscript; ON conceived the work, revised the manuscript. All authors approved the final version and agreed to be accountable for all aspects of the work.

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Correspondence to Dario Gregori.

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Lorenzoni, G., Petracci, E., Scarpi, E. et al. Use of Sequential Multiple Assignment Randomized Trials (SMARTs) in oncology: systematic review of published studies. Br J Cancer 128, 1177–1188 (2023). https://doi.org/10.1038/s41416-022-02110-z

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