Five questions to consider before conducting a stepped wedge trial

James R Hargreaves, Andrew J Copas, Emma Beard, David Osrin, James J Lewis, Calum Davey, Jennifer A Thompson, Gianluca Baio, Katherine L Fielding, Audrey Prost

Researchers should consider five questions before starting a stepped wedge trial. Why are you planning one? Researchers sometimes think that stepped wedge trials are useful when there is little doubt about the benefit of the intervention being tested. However, if the primary reason for an intervention is to measure its effect, without equipoise there is no ethical justification for delaying implementation in some clusters. By contrast, if you are undertaking pragmatic research, where the primary reason for rolling out the intervention is for it to exert its benefits, and if phased implementation is inevitable, a stepped wedge trial is a valid option and provides better evidence than most non-randomized evaluations. What design will you use? Two common stepped wedge designs are based on the recruitment of a closed or open cohort. In both, individuals may experience both control and intervention conditions and you should be concerned about carry-over effects. In a third, continuous-recruitment, short-exposure design, individuals are recruited as they become eligible and experience either control or intervention condition, but not both. How will you conduct the primary analysis? In stepped wedge trials, control of confounding factors through secular variation is essential. 'Vertical' approaches preserve randomization and compare outcomes between randomized groups within periods. 'Horizontal' approaches compare outcomes before and after crossover to the intervention condition. Most analysis models used in practice combine both types of comparison. The appropriate analytic strategy should be considered on a case-by-case basis. How large will your trial be? Standard sample size calculations for cluster randomized trials do not accommodate the specific features of stepped wedge trials. Methods exist for many stepped wedge designs, but simulation-based calculations provide the greatest flexibility. In some scenarios, such as when the intracluster correlation coefficient is moderate or high, or the cluster size is large, a stepped wedge trial may require fewer clusters than a parallel cluster trial. How will you report your trial? Stepped wedge trials are currently challenging to report using CONSORT principles. Researchers should consider how to demonstrate balance achieved by randomization and how to describe trends for outcomes in both intervention and control clusters.