Response adaptive intervention allocation in stepped‐wedge cluster randomized trials

摘要

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.