Methods for estimating mediation effect in survival analysis: Does weight loss mediate the undernutrition-mortality relationship in the older adults?

摘要

The influence of undernutrition on mortality and other adverse outcomes through the mechanism of unintentional weight loss in older adults is often assumed, but the analytic methods to test these mediation mechanisms are not well-developed, and the need for methodological advances in this area motivated this program of research. We first examined the test-retest reliability and predictive validity of self-reported caloric intake as a measure of undernutrition. Acceptable reliability was observed, consistent with previous reports, but the evidence for predictive validity was inconsistent and self-reported caloric intake deficiency was not found to be related to observed weight loss. We then extended the existing mediation methods in survival analysis by conducting a simulation study to further investigate the properties of two mediation effect calculation methods under the condition when censored data is present. Our findings from examination of product of coefficients method did not show a clear pattern in terms of bias with different specifications of hazard rate, mortality rate and amount of censoring. However we did find point estimates with increasing hazard rate have shown the smallest standard error and mean square error, followed by the constant and decreased hazard rates. The comparison between two mediation effect methods showed there is evidence that two methods can lead to substantially different estimates and inferential conclusions under the impact of hazard rate, mortality rate and amount of censoring. Generally speaking, the product of coefficient method performs better than the other under most of scenarios with moderate sample size, and two methods become less distinguishable when sample size increases to be 1000. Further, we also applied this improved method to a population of older adults and our findings indicated that the causal relationship between certain risk factors and mortality are mediated by weight loss. Finally, we have contributed a novel input to the research of examining mediation effects in the context of survival analysis with censored data and have made recommendation regarding the choice between two methods under difference scenarios.