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Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding.

ABSTRACT: It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.

SUBMITTER: Ding P

PROVIDER: S-EPMC4890130 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding.

Ding Peng P Vanderweele Tyler J TJ

Biometrika 20160430 2

It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique ...[more]

PMID: 27279672

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Project description:BackgroundAlthough 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.MethodsThe 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.ResultsAfter 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.ConclusionsThis 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.

Dataset Information

Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding.

Publications

Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding.

Similar Datasets

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