Estimation of risk ratio in a noncompliance randomized clinical trial with trichotomous dose levels

Abstract

In randomized clinical trials (RCTs), we may come across the situation in which some patients do not fully comply with their assigned treatment. For an experimental treatment with trichotomous levels, we derive the maximum likelihood estimator (MLE) of the risk ratio (RR) per level of dose increase in a RCT with noncompliance. We further develop three asymptotic interval estimators for the RR. To evaluate and compare the finite sample performance of these interval estimators, we employ Monte Carlo simulation. When the number of patients per treatment is large, we find that all interval estimators derived in this paper can perform well. When the number of patients is not large, we find that the interval estimator using Wald’s statistic can be liberal, while the interval estimator using the logarithmic transformation of the MLE can lose precision. We note that use of a bootstrap variance estimate in this case may alleviate these concerns. We further note that an interval estimator combining interval estimators using Wald’s statistic and the logarithmic transformation can generally perform well with respect to the coverage probability, and be generally more efficient than interval estimators using bootstrap variance estimates when RR>1. Finally, we use the data taken from a study of vitamin A supplementation to reduce mortality in preschool children to illustrate the use of these estimators.