Statistical methods for handling compliance in randomized controlled trials of device interventions: a systematic review

Objectives: We aimed to review the extent to which analysis of randomized controlled trials (RCTs) of device interventions includes methods to handle compliance to the study intervention as described in the protocol.Study Design and Setting: We conducted a systematic review of the statistical methods used to handle compliance to a device inter-vention when estimating the effect of the device compared to another intervention in RCTs. We searched Embase, MEDLINE, PsychInfo, and the Cochrane Central Register of Controlled Trials. We sought to evaluate what methods were used and how using these methods impacted the estimate of the effect size.Results: One hundred fifty eight RCTs were identified for inclusion, of which only 21 (13%) described using a method to account for compliance to the device intervention, consisting of alternative analysis populations such as per-protocol, modified intention-to-treat, or as-treated, alongside a primary intention-to-treat analysis. No causal inference methods were used. Fourteen (9%) studies included compli-ance as a factor in the analysis and investigated its effect on outcomes.Conclusion: Although some studies consider methods to handle compliance, causal inference methods have not been well adopted in the analysis of device trials. An increased awareness of the applications of statistical methods to adjust for compliance is needed. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/lice nses/by-nc-nd/4.0/).