Within-trial data borrowing for sequential multiple assignment randomized trials

The Sequential Multiple Assignment Randomized Trial (SMART) is a complex trial design that involves randomizing a single participant multiple times in a sequential manner. This results in the branching nature of a SMART, which represents several distinct groups defined by different combinations of treatments, response statuses, etc. A SMART can then answer various scientific questions of interest, eg, the optimal dynamic treatment regime (DTR) for treating a chronic illness, what intervention to offer first, and what intervention to offer to nonresponders (or suboptimal responders). However, the analysis of a SMART can suffer from low precision, as the potentially widely branching structure can lead to reduced sample sizes in some groups of interest. In this paper, we propose a novel analysis method for a SMART in which dynamic borrowing is used to borrow strength across groups with similar expected outcomes, thus providing increased precision for the estimation of the expected outcomes of DTRs. We apply our method to a SMART evaluating various weight loss strategies using a binary endpoint of clinically significant weight loss and show by simulation that our method can improve the precision of the estimated expected outcome of a DTR, aid in the identification of the optimal DTR, and produce a clustering analysis of DTRs embedded in a SMART.

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Publication Details

Journal
Biostatistics
Published
2024-12-31
DOI
https://doi.org/10.1093/biostatistics/kxaf003
Primary Topic
Statistical Methods in Clinical Trials
Type
article
Field-Weighted Citation Impact
0.00

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article

Within-trial data borrowing for sequential multiple assignment randomized trials

Brian Paul Hobbs, Joseph S. Koopmeiners, David M. Vock, Ales Kotalik et al.
Biostatistics
Statistical Methods in Clinical Trials
article

Within-trial data borrowing for sequential multiple assignment randomized trials

Brian Paul Hobbs, Joseph S. Koopmeiners, David M. Vock, Ales Kotalik, Nancy E. Sherwood
article en

Abstract

The Sequential Multiple Assignment Randomized Trial (SMART) is a complex trial design that involves randomizing a single participant multiple times in a sequential manner. This results in the branching nature of a SMART, which represents several distinct groups defined by different combinations of treatments, response statuses, etc. A SMART can then answer various scientific questions of interest, eg, the optimal dynamic treatment regime (DTR) for treating a chronic illness, what intervention to offer first, and what intervention to offer to nonresponders (or suboptimal responders). However, the analysis of a SMART can suffer from low precision, as the potentially widely branching structure can lead to reduced sample sizes in some groups of interest. In this paper, we propose a novel analysis method for a SMART in which dynamic borrowing is used to borrow strength across groups with similar expected outcomes, thus providing increased precision for the estimation of the expected outcomes of DTRs. We apply our method to a SMART evaluating various weight loss strategies using a binary endpoint of clinically significant weight loss and show by simulation that our method can improve the precision of the estimated expected outcome of a DTR, aid in the identification of the optimal DTR, and produce a clustering analysis of DTRs embedded in a SMART.

BiostatisticsVol. 26(1)
University of Minnesota (US), The University of Texas at Austin (US)
National Institutes of Health, National Heart, Lung, and Blood Institute
Openalex Percentile: Top 73%
Statistical Methods in Clinical Trials
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