Response adaptive intervention allocation in stepped-wedge cluster randomized trials.
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Grayling, M. J., Wason, J. M., & Villar, S. S. (2022). Response adaptive intervention allocation in stepped-wedge cluster randomized trials.. Stat Med https://doi.org/10.1002/sim.9317
BACKGROUND: Stepped-wedge cluster randomized trial (SW-CRT) designs are often used when there is a desire to provide an intervention to all enrolled clusters, because of a belief that it will be effective. However, given there should be equipoise at trial commencement, there has been discussion around whether a pre-trial decision to provide the intervention to all clusters is appropriate. In pharmaceutical drug development, a solution to a similar desire to provide more patients with an effective treatment is to use a response adaptive (RA) design. METHODS: We introduce a way in which RA design could be incorporated in an SW-CRT, permitting modification of the intervention allocation during the trial. The proposed framework explicitly permits a balance to be sought between power and patient benefit considerations. A simulation study evaluates the methodology. RESULTS: In one scenario, for one particular RA design, the proportion of cluster-periods spent in the intervention condition was observed to increase from 32.2% to 67.9% as the intervention effect was increased. A cost of this was a 6.2% power drop compared to a design that maximized power by fixing the proportion of time in the intervention condition at 45.0%, regardless of the intervention effect. CONCLUSIONS: An RA approach may be most applicable to settings for which the intervention has substantial individual or societal benefit considerations, potentially in combination with notable safety concerns. In such a setting, the proposed methodology may routinely provide the desired adaptability of the roll-out speed, with only a small cost to the study's power.
RESEARCH ARTICLE, RESEARCH ARTICLES, adaptive design, clinical trial, interim analysis, multi‐stage, sequential allocation
Medical Research Council (MC_UU_00002/15, MC_UU_00002/6)
External DOI: https://doi.org/10.1002/sim.9317
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333232