Project description:Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided.
Project description:BackgroundAttrition in cohort studies challenges causal inference. Although inverse probability weighting (IPW) has been proposed to handle attrition in association analyses, its relevance has been little studied in this context. We aimed to investigate its ability to correct for selection bias in exposure-outcome estimation by addressing an important methodological issue: the specification of the response model.MethodsA simulation study compared the IPW method with complete-case analysis (CCA) for nine response-mechanism scenarios (3 missing at random - MAR and 6 missing not at random - MNAR). Eighteen response models differing by the type of variables included were assessed.ResultsThe IPW method was equivalent to CCA in terms of bias and consistently less efficient in all scenarios, regardless of the response model tested. The most effective response model included only the confounding factors of the association model.ConclusionOur study questions the ability of the IPW method to correct for selection bias in situations of attrition leading to missing outcomes. If the method is to be used, we encourage including only the confounding variables of the association of interest in the response model.
Project description:Objective Using a novel mediation method that presents unbiased results even in the presence of exposure-mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce. Methods Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50-64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE). Results Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37-1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15-1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27-1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health. Conclusions Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.
Project description:Inverse probability-weighted estimators are widely used in applications where data are missing due to nonresponse or censoring and in the estimation of causal effects from observational studies. Current estimators rely on ignorability assumptions for response indicators or treatment assignment and outcomes being conditional on observed covariates which are assumed to be measured without error. However, measurement error is common for the variables collected in many applications. For example, in studies of educational interventions, student achievement as measured by standardized tests is almost always used as the key covariate for removing hidden biases, but standardized test scores may have substantial measurement errors. We provide several expressions for a weighting function that can yield a consistent estimator for population means using incomplete data and covariates measured with error. We propose a method to estimate the weighting function from data. The results of a simulation study show that the estimator is consistent and has no bias and small variance.
Project description:Two methods from the potential outcomes framework - inverse propensity weighting (IPW) and sequential G-estimation - were evaluated and compared to linear regression for estimating the mediated effect in a two-wave design with a randomized intervention and continuous mediator and outcome. Baseline measures of the mediator and outcome can be considered confounders of the follow-up mediator - outcome relation for which adjustment is necessary to eliminate bias. To adjust for baseline measures of the mediator and outcome, IPW uses stabilized inverse propensity weights whereas sequential G-estimation uses regression adjustment. Theoretical differences between the models are described, and Monte Carlo simulations compared the performance of linear regression; IPW without weight truncation; IPW with weights truncated at the 1st/99th, 5th/95th, and 10th/90th percentiles; and sequential G-estimation. Sequential G-estimation performed similarly to linear regression, but IPW provided a biased estimate of the mediated effect, lower power, lower confidence interval coverage, and higher mean squared error. Simulation results show that IPW failed to fully adjust the follow-up mediator - outcome relation for confounding due to the baseline measures. We then compared the mediated effect estimates using data from a randomized experiment evaluating a steroid prevention program for high school athletes. Implications and future directions are discussed.
Project description:The win ratio method has received much attention in methodological research, ad hoc analyses, and designs of prospective studies. As the primary analysis, it supported the approval of tafamidis for the treatment of cardiomyopathy to reduce cardiovascular mortality and cardiovascular-related hospitalization. However, its dependence on censoring is a potential shortcoming. In this article, we propose the inverse-probability-of-censoring weighting (IPCW) adjusted win ratio statistic (i.e., the IPCW-adjusted win ratio statistic) to overcome censoring issues. We consider independent censoring, common censoring across endpoints, and right censoring. We develop an asymptotic variance estimator for the logarithm of the IPCW-adjusted win ratio statistic and evaluate it via simulation. Our simulation studies show that, as the amount of censoring increases, the unadjusted win proportions may decrease greatly. Consequently, the bias of the unadjusted win ratio estimate may increase greatly, producing either an overestimate or an underestimate. We demonstrate theoretically and through simulation that the IPCW-adjusted win ratio statistic gives an unbiased estimate of treatment effect.
Project description:Evaluation of impact of potential uncontrolled confounding is an important component for causal inference based on observational studies. In this article, we introduce a general framework of sensitivity analysis that is based on inverse probability weighting. We propose a general methodology that allows both non-parametric and parametric analyses, which are driven by two parameters that govern the magnitude of the variation of the multiplicative errors of the propensity score and their correlations with the potential outcomes. We also introduce a specific parametric model that offers a mechanistic view on how the uncontrolled confounding may bias the inference through these parameters. Our method can be readily applied to both binary and continuous outcomes and depends on the covariates only through the propensity score that can be estimated by any parametric or non-parametric method. We illustrate our method with two medical data sets.
Project description:Inverse probability weighting can be used to correct for missing data. New estimators for the weights in the nonmonotone setting were introduced in 2018. These estimators are the unconstrained maximum likelihood estimator (UMLE) and the constrained Bayesian estimator (CBE), an alternative if UMLE fails to converge. In this work we describe and illustrate these estimators, and examine performance in simulation and in an applied example estimating the effect of anemia on spontaneous preterm birth in the Zambia Preterm Birth Prevention Study. We compare performance with multiple imputation (MI) and focus on the setting of an observational study where inverse probability of treatment weights are used to address confounding. In simulation, weighting was less statistically efficient at the smallest sample size and lowest exposure prevalence examined (nā=ā1500, 15% respectively) but in other scenarios statistical performance of weighting and MI was similar. Weighting had improved computational efficiency taking, on average, 0.4 and 0.05 times the time for MI in R and SAS, respectively. UMLE was easy to implement in commonly used software and convergence failure occurred just twice in >200ā000 simulated cohorts making implementation of CBE unnecessary. In conclusion, weighting is an alternative to MI for nonmonotone missingness, though MI performed as well as or better in terms of bias and statistical efficiency. Weighting's superior computational efficiency may be preferred with large sample sizes or when using resampling algorithms. As validity of weighting and MI rely on correct specification of different models, both approaches could be implemented to check agreement of results.
Project description:This article discusses the augmented inverse propensity weighted (AIPW) estimator as an estimator for average treatment effects. The AIPW combines both the properties of the regression-based estimator and the inverse probability weighted (IPW) estimator and is therefore a "doubly robust" method in that it requires only either the propensity or outcome model to be correctly specified but not both. Even though this estimator has been known for years, it is rarely used in practice. After explaining the estimator and proving the double robustness property, I conduct a simulation study to compare the AIPW efficiency with IPW and regression under different scenarios of misspecification. In 2 real-world examples, I provide a step-by-step guide on implementing the AIPW estimator in practice. I show that it is an easily usable method that extends the IPW to reduce variability and improve estimation accuracy.[Box: see text].
Project description:As one of causal inference methodologies, the inverse probability weighting (IPW) method has been utilized to address confounding and account for missing data when subjects with missing data cannot be included in a primary analysis. The transdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathological and epidemiological methods, and takes advantages of improved understanding of pathogenesis to generate stronger biological evidence of causality and optimize strategies for precision medicine and prevention. Disease subtyping based on biomarker analysis of biospecimens is essential in MPE research. However, there are nearly always cases that lack subtype information due to the unavailability or insufficiency of biospecimens. To address this missing subtype data issue, we incorporated inverse probability weights into Cox proportional cause-specific hazards regression. The weight was inverse of the probability of biomarker data availability estimated based on a model for biomarker data availability status. The strategy was illustrated in two example studies; each assessed alcohol intake or family history of colorectal cancer in relation to the risk of developing colorectal carcinoma subtypes classified by tumor microsatellite instability (MSI) status, using a prospective cohort study, the Nurses' Health Study. Logistic regression was used to estimate the probability of MSI data availability for each cancer case with covariates of clinical features and family history of colorectal cancer. This application of IPW can reduce selection bias caused by nonrandom variation in biospecimen data availability. The integration of causal inference methods into the MPE approach will likely have substantial potentials to advance the field of epidemiology.