A hybrid approach to comparing parallel-group and stepped-wedge cluster-randomized trials with a continuous primary outcome when there is uncertainty in the intra-cluster correlation.

BACKGROUND/AIMS: To evaluate how uncertainty in the intra-cluster correlation impacts whether a parallel-group or stepped-wedge cluster-randomized trial design is more efficient in terms of the required sample size, in the case of cross-sectional stepped-wedge cluster-randomized trials and continuous outcome data.

METHODS

We motivate our work by reviewing how the intra-cluster correlation and standard deviation were justified in 54 health technology assessment reports on cluster-randomized trials. To enable uncertainty at the design stage to be incorporated into the design specification, we then describe how sample size calculation can be performed for cluster- randomized trials in the 'hybrid' framework, which places priors on design parameters and controls the expected power in place of the conventional frequentist power. Comparison of the parallel-group and stepped-wedge cluster-randomized trial designs is conducted by placing Beta and truncated Normal priors on the intra-cluster correlation, and a Gamma prior on the standard deviation.

RESULTS

Many Health Technology Assessment reports did not adhere to the Consolidated Standards of Reporting Trials guideline of indicating the uncertainty around the assumed intra-cluster correlation, while others did not justify the assumed intra-cluster correlation or standard deviation. Even for a prior intra-cluster correlation distribution with a small mode, moderate prior densities on high intra-cluster correlation values can lead to a stepped-wedge cluster-randomized trial being more efficient because of the degree to which a stepped-wedge cluster-randomized trial is more efficient for high intra-cluster correlations. With careful specification of the priors, the designs in the hybrid framework can become more robust to, for example, an unexpectedly large value of the outcome variance.

CONCLUSION

When there is difficulty obtaining a reliable value for the intra-cluster correlation to assume at the design stage, the proposed methodology offers an appealing approach to sample size calculation. Often, uncertainty in the intra-cluster correlation will mean a stepped-wedge cluster-randomized trial is more efficient than a parallel-group cluster-randomized trial design.