Accounting for extent of non-compliance when estimating treatment effects on an ordinal outcome in randomized clinical trials

在随机临床试验中,估计治疗对有序结果的影响时,应考虑不依从性的程度。

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Abstract

BACKGROUND: In randomized clinical trials (RCTs) with non-compliance, evaluating the causal effects of interventions would lead to a more precise estimation of treatment effect when the estimand of interest is the effect of treatment amongst compliers. While there is a large body of literature addressing the issue of non-compliance for continuous, binary, and time-to-event outcomes, this issue is seldom discussed for ordinal outcomes. METHODS: In this paper, we consider one-sided non-compliance. We introduce an extension of the inverse probability weighting (IPW) method for handling non-compliance involving an ordinal outcome by fully utilizing the information of non-compliance and defining it as a categorical variable to describe the extent of non-compliance. This is in contrast to the usual convention where compliance is regarded as a binary variable. We provide the identification and asymptotic distribution of the proposed method. We compare the proposed method (IPW_Dnew) with intention-to-treat (ITT), per protocol (PP), instrumental variable (IV), and IPW method via a simulation study and real-life data from the JOBS II intervention trial and the IMMACULATE trial. RESULTS: Simulation results demonstrate that the proposed method performs better than other methods in terms of bias, coverage, mean squared error, power and Type I error under various scenarios, particularly in situations with selection bias and partial compliance. In the empirical study, a substantial estimate of partial compliance by IPW_Dnew implies that there may be a partial compliance effect. CONCLUSION: For ordinal outcome in the presence of non-compliance, we suggest using the proposed method to estimate the causal effect of treatment amongst compliers and partial compliers, especially when there exists selection bias.

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