Sensitivity analysis for assumptions of general mediation analysis

Author(s):  
Wentao Cao ◽  
Yaling Li ◽  
Qingzhao Yu
2017 ◽  
Vol 28 (2) ◽  
pp. 515-531 ◽  
Author(s):  
Lawrence C McCandless ◽  
Julian M Somers

Causal mediation analysis techniques enable investigators to examine whether the effect of the exposure on an outcome is mediated by some intermediate variable. Motivated by a data example from epidemiology, we consider estimation of natural direct and indirect effects on a survival outcome. An important concern is bias from confounders that may be unmeasured. Estimating natural direct and indirect effects requires an elaborate series of assumptions in order to identify the target quantities. The analyst must carefully measure and adjust for important predictors of the exposure, mediator and outcome. Omitting important confounders may bias the results in a way that is difficult to predict. In recent years, several methods have been proposed to explore sensitivity to unmeasured confounding in mediation analysis. However, many of these methods limit complexity by relying on a handful of sensitivity parameters that are difficult to interpret, or alternatively, by assuming that specific patterns of unmeasured confounding are absent. Instead, we propose a simple Bayesian sensitivity analysis technique that is indexed by four bias parameters. Our method has the unique advantage that it is able to simultaneously assess unmeasured confounding in the mediator–outcome, exposure–outcome and exposure–mediator relationships. It is a natural Bayesian extension of the sensitivity analysis methodologies of VanderWeele, which have been widely used in the epidemiology literature. We present simulation findings, and additionally, we illustrate the method in an epidemiological study of mortality rates in criminal offenders from British Columbia.


Author(s):  
Anita Lindmark

AbstractCausal mediation analysis is used to decompose the total effect of an exposure on an outcome into an indirect effect, taking the path through an intermediate variable, and a direct effect. To estimate these effects, strong assumptions are made about unconfoundedness of the relationships between the exposure, mediator and outcome. These assumptions are difficult to verify in a given situation and therefore a mediation analysis should be complemented with a sensitivity analysis to assess the possible impact of violations. In this paper we present a method for sensitivity analysis to not only unobserved mediator-outcome confounding, which has largely been the focus of previous literature, but also unobserved confounding involving the exposure. The setting is estimation of natural direct and indirect effects based on parametric regression models. We present results for combinations of binary and continuous mediators and outcomes and extend the sensitivity analysis for mediator-outcome confounding to cases where the continuous outcome variable is censored or truncated. The proposed methods perform well also in the presence of interactions between the exposure, mediator and observed confounders, allowing for modeling flexibility as well as exploration of effect modification. The performance of the method is illustrated through simulations and an empirical example.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anita Lindmark ◽  
Bo Norrving ◽  
Marie Eriksson

Abstract Background Although it has been established that low socioeconomic status is linked to increased risk of death after stroke, the mechanisms behind this link are still unclear. In this study we aim to shed light on the relationship between income level and survival after stroke by investigating the extent to which differences in stroke severity account for differences in survival. Methods The study was based on patients registered in Riksstroke (the Swedish stroke register) with first time ischemic stroke (n = 51,159) or intracerebral hemorrhage (n = 6777) in 2009–2012. We used causal mediation analysis to decompose the effect of low income on 3-month case fatality into a direct effect and an indirect effect due to stroke severity. Since causal mediation analysis relies on strong assumptions regarding residual confounding of the relationships involved, recently developed methods for sensitivity analysis were used to assess the robustness of the results to unobserved confounding. Results After adjustment for observed confounders, patients in the lowest income tertile had a 3.2% (95% CI: 0.9–5.4%) increased absolute risk of 3-month case fatality after intracerebral hemorrhage compared to patients in the two highest tertiles. The corresponding increase for case fatality after ischemic stroke was 1% (0.4–1.5%). The indirect effect of low income, mediated by stroke severity, was 1.8% (0.7–2.9%) for intracerebral hemorrhage and 0.4% (0.2–0.6%) for ischemic stroke. Unobserved confounders affecting the risk of low income, more severe stroke and case fatality in the same directions could explain the indirect effect, but additional adjustment to observed confounders did not alter the conclusions. Conclusions This study provides evidence that as much as half of income-related inequalities in stroke case fatality is mediated through differences in stroke severity. Targeting stroke severity could therefore lead to a substantial reduction in inequalities and should be prioritized. Sensitivity analysis suggests that additional adjustment for a confounder of greater impact than age would be required to considerably alter our conclusions.


2021 ◽  
Vol 12 ◽  
Author(s):  
Davood Tofighi

Mediation analysis relies on an untestable assumption of the no omitted confounders, which posits that an omitted variable that confounds the relationships between the antecedent, mediator, and outcome variables cannot exist. One common model in alcohol addiction studies is a nonrandomized latent growth curve mediation model (LGCMM), where the antecedent variable is not randomized, the two covarying mediators are latent intercept and slope modeling longitudinal effect of the repeated measures mediator, and an outcome variable that measures alcohol use. An important gap in the literature is lack of sensitivity analysis techniques to assess the effect of the violation of the no omitted confounder assumption in a nonrandomized LGCMM. We extend a sensitivity analysis technique, termed correlated augmented mediation sensitivity analysis (CAMSA), to a nonrandomized LGCMM. We address several unresolved issues in conducting CAMSA for the nonrandomized LGCMM and present: (a) analytical results showing how confounder correlations model a confounding bias, (b) algorithms to address admissible values for confounder correlations, (c) accessible R code within an SEM framework to conduct our proposed sensitivity analysis, and (d) an empirical example. We conclude that conducting sensitivity analysis to ascertain robustness of the mediation analysis is critical.


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