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Table 3 Examination of Identifiability Assumptions for Causal Mediation Analysis

From: Implementation and reporting of causal mediation analysis in 2015: a systematic review in epidemiological studies

References No unmeasured exposure-outcome confounders No unmeasured mediator-outcome confounders No unmeasured exposure-mediator confounders No mediator-outcome confounder affected by the exposure
Acknowledged assumption Empirical analyses or sensitivity analyses Acknowledged assumption Empirical analyses or sensitivity analyses Acknowledged assumption Empirical analyses or sensitivity analyses Acknowledged assumption Empirical analyses or sensitivity analyses
Studies estimating controlled direct effects only
 Banack et al. [26] Not reported Unmeasured confounder cardiorespiratory-fitness
Estimates of the direct effect of cardiorespiratory fitness on mortality from well-established literature. No literature on estimates of prevalence differences of unmeasured confounder—so a range of 10–90 % was considered
Not applicable
 Mendola et al. [33] Not reported Unmeasured confounder maternal infection
Estimates of the direct effect of maternal infection on neonatal outcome ranged from 2 to 10. Prevalence differences of unmeasured confounder—so a range of 1–99 % was considered. Whether this was done because no literature was available on which to base the sensitivity analyses was not reported
Not applicable
 Messerlian et al. [34] It is unclear if they were addressing this concern although additional pre-specified stratum- specific with different reference categories and exposure groups were used for sensitivity analyses Stratified analyses “triangulated” those derived from marginal structural models. It is unclear if they were addressing this concern Not applicable
 Rao et al. [36] Unmeasured confounder situation that unmeasured confounders could be correlated with exposure, mediator, and outcome were considered. Using parameters, such as γ (conditional increase in risk for oral cancer), P1 (prevalence in smokers/chewers/drinkers), and P2 (prevalence among non-smokers/non-chewers/non-drinkers) were specified. The bias introduced by unmeasured confounders that may entirely invalidate the controlled direct effect was calculated Unmeasured confounder considered with the exposure-outcome relationship Not applicable
Studies estimating natural direct and indirect effects
 D’Amelio et al. [27] Randomized controlled trial-not applicable a Not reported Randomized controlled trial-not applicable a No sensitivity analyses, but adjusted for biomarkers that were unbalanced between the two treatment groups at baseline
 Freeman et al. [28] Randomized controlled trial-not applicable No sensitivity analyses, but adjusted for baseline confounders; can’t rule out Randomized controlled trial-not applicable Not reported
 Jackson et al. [29] Showed risk factors by antipsychotic group No sensitivity analyses, but adjusted for many risk factors; cannot rule out residual confounding No sensitivity analysis, but residual confounding (i.e. delirium) at baseline that could bias the total and indirect effects upwards was acknowledged No sensitivity analyses, but conducted stratified analyses by mediators to provide qualitative evidence for whether or not the association between mediator and mortality is modified by antipsychotic type
 Louwies et al. [31] X No sensitivity analyses, but adjusted for confounders in Table 1, except day of the week X Not reported X Not reported X Not reported
 Lu et al. [32] Excluded first 3 years of follow-up to reduce the influence of baseline confounders
Restricted the analysis to never-smokers to better control for confounding by smoking
Unmeasured confounder
Common cause of metabolic mediators and coronary heart disease (e.g. family history, genetic factors, residual confounding due to measurement error in diet and physical activity). Sensitivity analyses done with two scenarios: (1) mild confounding (increased hazard ratio by factor of 1.1 and prevalence 20 % for normal weight/25 % for overweight/obese); and (2) strong confounding (increased hazard ratio by factor of 1.8 and prevalence of 45 % for normal weight and 40 % for overweight/obese)
Restricted the analysis to never-smokers to better control for confounding by smoking Not reported
 Raghavan et al. [35] X Not reported X No sensitivity analyses, but mediation analysis was conducted with all three metabolic mediators
(CIR, HOMA-IR and MSS) together
X No sensitivity analyses, but mediation analysis was conducted with all three metabolic mediators
(CIR, HOMA-IR and MSS) together
X Not reported
 Song et al. [37] No sensitivity analysis, but included all the covariates that may confound the relationship No sensitivity analysis, but included all the covariates that may confound the relationship No sensitivity analysis, but included all the covariates that may confound the relationship Sensitivity analysis was conducted through excluding BMI, a mediator-outcome confounder that is possibly affected by the exposure (low birth weight)
 Xie et al. [38] X Not reported X Not reported X Not reported X Not reported
Effects not identified
 Kositsawat et al. [30] X Not reported X Not reported X Not reported X Not reported
  1. CIR beta cell corrected insulin response; HOMA-IR homeostatic model assessment for insulin resistance; MSS metabolic syndrome score
  2. aIdentifiability assumptions were not specifically mentioned in the article but appeared to have appropriate references