arXiv subjects

Elizabeth A. Stuart

Publications and source records attributed to Elizabeth A. Stuart.

At least 37 records · Page 2Linked to original sources

arXiv2024

Practical challenges in mediation analysis: A guide for applied researchers

Mediation analysis is a statistical approach that can provide insights regarding the intermediary processes by which an intervention or exposure affects a given outcome. Mediation analyses rose to prominence, particularly in social science research, with the publication of the seminal paper by Baron and Kenny and is now commonly applied in many research disciplines, including health services research. Despite the growth in popularity, applied researchers may still encounter challenges in terms of conducting mediation analyses in practice. In this paper, we provide an overview of conceptual and methodological challenges that researchers face when conducting mediation analyses. Specifically, we discuss the following key challenges: (1) Conceptually differentiating mediators from other third variables, (2) Extending beyond the single mediator context, (3) Identifying appropriate datasets in which measurement and temporal ordering supports the hypothesized mediation model, (4) Selecting mediation effects that reflect the scientific question of interest, (5) Assessing the validity of underlying assumptions of no omitted confounders, (6) Addressing measurement error regarding the mediator, and (7) Clearly reporting results from mediation analyses. We discuss each challenge and highlight ways in which the applied researcher can approach these challenges.

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arXiv2023

Identification of complier and noncomplier average causal effects in the presence of latent missing-at-random (LMAR) outcomes: a unifying view and choices of assumptions

The study of treatment effects is often complicated by noncompliance and missing data. In the one-sided noncompliance setting where of interest are the complier and noncomplier average causal effects (CACE and NACE), we address outcome missingness of the \textit{latent missing at random} type (LMAR, also known as \textit{latent ignorability}). That is, conditional on covariates and treatment assigned, the missingness may depend on compliance type. Within the instrumental variable (IV) approach to noncompliance, methods have been proposed for handling LMAR outcome that additionally invoke an exclusion restriction type assumption on missingness, but no solution has been proposed for when a non-IV approach is used. This paper focuses on effect identification in the presence of LMAR outcome, with a view to flexibly accommodate different principal identification approaches. We show that under treatment assignment ignorability and LMAR only, effect nonidentifiability boils down to a set of two connected mixture equations involving unidentified stratum-specific response probabilities and outcome means. This clarifies that (except for a special case) effect identification generally requires two additional assumptions: a \textit{specific missingness mechanism} assumption and a \textit{principal identification} assumption. This provides a template for identifying effects based on separate choices of these assumptions. We consider a range of specific missingness assumptions, including those that have appeared in the literature and some new ones. Incidentally, we find an issue in the existing assumptions, and propose a modification of the assumptions to avoid the issue. Results under different assumptions are illustrated using data from the Baltimore Experience Corps Trial.

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arXiv2023

Shared Control Individuals in Health Policy Evaluations with Application to Medical Cannabis Laws

Health policy researchers often have questions about the effects of a policy implemented at some cluster-level unit, e.g., states, counties, hospitals, etc. on individual-level outcomes collected over multiple time periods. Stacked difference-in-differences is an increasingly popular way to estimate these effects. This approach involves estimating treatment effects for each policy-implementing unit, then, if scientifically appropriate, aggregating them to an average effect estimate. However, when individual-level data are available and non-implementing units are used as comparators for multiple policy-implementing units, data from untreated individuals may be used across multiple analyses, thereby inducing correlation between effect estimates. Existing methods do not quantify or account for this sharing of controls. Here, we describe a stacked difference-in-differences study investigating the effects of state medical cannabis laws on treatment for chronic pain management that motivated this work, discuss a framework for estimating and managing this correlation due to shared control individuals, and show how accounting for it affects the substantive results.

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arXiv2023

Comparison of Methods that Combine Multiple Randomized Trials to Estimate Heterogeneous Treatment Effects

Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials allows for the combination of datasets with unconfounded treatment assignment to better estimate heterogeneous treatment effects. This paper discusses several non-parametric approaches for estimating heterogeneous treatment effects using data from multiple trials. We extend single-study methods to a scenario with multiple trials and explore their performance through a simulation study, with data generation scenarios that have differing levels of cross-trial heterogeneity. The simulations demonstrate that methods that directly allow for heterogeneity of the treatment effect across trials perform better than methods that do not, and that the choice of single-study method matters based on the functional form of the treatment effect. Finally, we discuss which methods perform well in each setting and then apply them to four randomized controlled trials to examine effect heterogeneity of treatments for major depressive disorder.

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arXiv2023

Multiple imputation for propensity score analysis with covariates missing at random: some clarity on within and across methods

In epidemiology and social sciences, propensity score methods are popular for estimating treatment effects using observational data, and multiple imputation is popular for handling covariate missingness. However, how to appropriately use multiple imputation for propensity score analysis is not completely clear. This paper aims to bring clarity on the consistency (or lack thereof) of methods that have been proposed, focusing on the within approach (where the effect is estimated separately in each imputed dataset and then the multiple estimates are combined) and the across approach (where typically propensity scores are averaged across imputed datasets before being used for effect estimation). We show that the within method is valid and can be used with any causal effect estimator that is consistent in the full-data setting. Existing across methods are inconsistent, but a different across method that averages the inverse probability weights across imputed datasets is consistent for propensity score weighting. We also comment on methods that rely on imputing a function of the missing covariate rather than the covariate itself, including imputation of the propensity score and of the probability weight. Based on consistency results and practical flexibility, we recommend generally using the standard within method. Throughout, we provide intuition to make the results meaningful to the broad audience of applied researchers.

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arXiv2023

Choosing the Causal Estimand for Propensity Score Analysis of Observational Studies

Matching and weighting methods for observational studies involve the choice of an estimand, the causal effect with reference to a specific target population. Commonly used estimands include the average treatment effect in the treated (ATT), the average treatment effect in the untreated (ATU), the average treatment effect in the population (ATE), and the average treatment effect in the overlap (i.e., equipoise population; ATO). Each estimand has its own assumptions, interpretation, and statistical methods that can be used to estimate it. This article provides guidance on selecting and interpreting an estimand to help medical researchers correctly implement statistical methods used to estimate causal effects in observational studies and to help audiences correctly interpret the results and limitations of these studies. The interpretations of the estimands resulting from regression and instrumental variable analyses are also discussed. Choosing an estimand carefully is essential for making valid inferences from the analysis of observational data and ensuring results are replicable and useful for practitioners.

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arXiv2023

Identifying Optimal Methods for Addressing Confounding Bias When Estimating the Effects of State-Level Policies

Background: Policy evaluation studies that assess how state-level policies affect health-related outcomes are foundational to health and social policy research. The relative ability of newer analytic methods to address confounding, a key source of bias in observational studies, has not been closely examined. Methods: We conducted a simulation study to examine how differing magnitudes of confounding affected the performance of four methods used for policy evaluations: (1) the two-way fixed effects (TWFE) difference-in-differences (DID) model; (2) a one-period lagged autoregressive (AR) model; (3) augmented synthetic control method (ASCM); and (4) the doubly robust DID approach with multiple time periods from Callaway-Sant'Anna (CSA). We simulated our data to have staggered policy adoption and multiple confounding scenarios (i.e., varying the magnitude and nature of confounding relationships). Results: Bias increased for each method: (1) as confounding magnitude increases; (2) when confounding is generated with respect to prior outcome trends (rather than levels), and (3) when confounding associations are nonlinear (rather than linear). The AR and ASCM have notably lower root mean squared error than the TWFE model and CSA approach for all scenarios; the exception is nonlinear confounding by prior trends, where CSA excels. Coverage rates are unreasonably high for ASCM (e.g., 100%), reflecting large model-based standard errors and wide confidence intervals in practice. Conclusions: Our simulation study indicated that no single method consistently outperforms the others. But a researcher's toolkit should include all methodological options. Our simulations and associated R package can help researchers choose the most appropriate approach for their data.

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arXiv2023

Methods for Integrating Trials and Non-Experimental Data to Examine Treatment Effect Heterogeneity

Estimating treatment effects conditional on observed covariates can improve the ability to tailor treatments to particular individuals. Doing so effectively requires dealing with potential confounding, and also enough data to adequately estimate effect moderation. A recent influx of work has looked into estimating treatment effect heterogeneity using data from multiple randomized controlled trials and/or observational datasets. With many new methods available for assessing treatment effect heterogeneity using multiple studies, it is important to understand which methods are best used in which setting, how the methods compare to one another, and what needs to be done to continue progress in this field. This paper reviews these methods broken down by data setting: aggregate-level data, federated learning, and individual participant-level data. We define the conditional average treatment effect and discuss differences between parametric and nonparametric estimators, and we list key assumptions, both those that are required within a single study and those that are necessary for data combination. After describing existing approaches, we compare and contrast them and reveal open areas for future research. This review demonstrates that there are many possible approaches for estimating treatment effect heterogeneity through the combination of datasets, but that there is substantial work to be done to compare these methods through case studies and simulations, extend them to different settings, and refine them to account for various challenges present in real data.

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arXiv2023

Causal mediation analysis: From simple to more robust strategies for estimation of marginal natural (in)direct effects

This paper aims to provide practitioners of causal mediation analysis with a better understanding of estimation options. We take as inputs two familiar strategies (weighting and model-based prediction) and a simple way of combining them (weighted models), and show how a range of estimators can be generated, with different modeling requirements and robustness properties. The primary goal is to help build intuitive appreciation for robust estimation that is conducive to sound practice. A second goal is to provide a "menu" of estimators that practitioners can choose from for the estimation of marginal natural (in)direct effects. The estimators generated from this exercise include some that coincide or are similar to existing estimators and others that have not previously appeared in the literature. We note several different ways to estimate the weights for cross-world weighting based on three expressions of the weighting function, including one that is novel; and show how to check the resulting covariate and mediator balance. We use a random continuous weights bootstrap to obtain confidence intervals, and also derive general asymptotic variance formulas for the estimators. The estimators are illustrated using data from an adolescent alcohol use prevention study.

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arXiv2022

Methodological considerations for estimating policy effects in the context of co-occurring policies

Understanding how best to estimate state-level policy effects is important, and several unanswered questions remain, particularly about the ability of statistical models to disentangle the effects of concurrently enacted policies. In practice, many policy evaluation studies do not attempt to control for effects of co-occurring policies, and this issue has not received extensive attention in the methodological literature to date. In this study, we utilized Monte Carlo simulations to assess the impact of co-occurring policies on the performance of commonly-used statistical models in state policy evaluations. Simulation conditions varied effect sizes of the co-occurring policies and length of time between policy enactment dates, among other factors. Outcome data (annual state-specific opioid mortality rate per 100,000) were obtained from 1999-2016 National Vital Statistics System (NVSS) Multiple Cause of Death mortality files, thus yielding longitudinal annual state-level data over 18 years from 50 states. When co-occurring policies are ignored (i.e., omitted from the analytic model), our results demonstrated that high relative bias (>85%) arises, particularly when policies are enacted in rapid succession. Moreover, as expected, controlling for all co-occurring policies will effectively mitigate the threat of confounding bias; however, effect estimates may be relatively imprecise (i.e., larger variance) when policies are enacted in near succession. Our findings highlight several key methodological issues regarding co-occurring policies in the context of opioid-policy research yet also generalize more broadly to evaluation of other state-level policies, such as policies related to firearms or COVID-19, showcasing the need to think critically about co-occurring policies that are likely to influence the outcome when specifying analytic models.

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arXiv2022

Clarifying causal mediation analysis: Effect identification via three assumptions and five potential outcomes

Causal mediation analysis is complicated with multiple effect definitions that require different sets of assumptions for identification. This paper provides a systematic explanation of such assumptions. We define five potential outcome types whose means are involved in various effect definitions. We tackle their mean/distribution's identification, starting with the one that requires the weakest assumptions and gradually building up to the one that requires the strongest assumptions. This presentation shows clearly why an assumption is required for one estimand and not another, and provides a succinct table from which an applied researcher could pick out the assumptions required for identifying the causal effects they target. Using a running example, the paper illustrates the assembling and consideration of identifying assumptions for a range of causal contrasts. For several that are commonly encountered in the literature, this exercise clarifies that identification requires weaker assumptions than those often stated in the literature. This attention to the details also draws attention to the differences in the positivity assumption for different estimands, with practical implications. Clarity on the identifying assumptions of these various estimands will help researchers conduct appropriate mediation analyses and interpret the results with appropriate caution given the plausibility of the assumptions.

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arXiv2021

Estimating subgroup effects in generalizability and transportability analyses

Methods for extending -- generalizing or transporting -- inferences from a randomized trial to a target population involve conditioning on a large set of covariates that is sufficient for rendering the randomized and non-randomized groups exchangeable. Yet, decision-makers are often interested in examining treatment effects in subgroups of the target population defined in terms of only a few discrete covariates. Here, we propose methods for estimating subgroup-specific potential outcome means and average treatment effects in generalizability and transportability analyses, using outcome model-based (g-formula), weighting, and augmented weighting estimators. We consider estimating subgroup-specific average treatment effects in the target population and its non-randomized subset, and provide methods that are appropriate both for nested and non-nested trial designs. As an illustration, we apply the methods to data from the Coronary Artery Surgery Study to compare the effect of surgery plus medical therapy versus medical therapy alone for chronic coronary artery disease in subgroups defined by history of myocardial infarction.

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arXiv2021

Teacher Mental Health During the COVID-19 Pandemic: Informing Policies to Support Teacher Well-being and Effective Teaching Practices

While there is an emergence of research investigating the educational impacts of the COVID-19 pandemic, empirical studies assessing teacher mental health throughout the pandemic have been scarce. Using a large national dataset, the current study first compared mental health outcomes during the pandemic between pK-12 teachers and professionals in other occupations. Further, we compared the prevalence of mental health outcomes between in-person and remote teachers (n = 131,154). Findings indicated teachers reported greater mental health concerns than those in other professions, and that remote teachers reported significantly higher levels of distress than those teaching in-person. Policy implications are discussed, with a focus on providing support to meet the evolving needs of teachers.

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arXiv2021

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($α_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $α_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

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arXiv2021

Moving beyond the classic difference-in-differences model: A simulation study comparing statistical methods for estimating effectiveness of state-level policies

State-level policy evaluations commonly employ a difference-in-differences (DID) study design; yet within this framework, statistical model specification varies notably across studies. Motivated by applied state-level opioid policy evaluations, this simulation study compares statistical performance of multiple variations of two-way fixed effect models traditionally used for DID under a range of simulation conditions. While most linear models resulted in minimal bias, non-linear models and population-weighted versions of classic linear two-way fixed effect and linear GEE models yielded considerable bias (60 to 160%). Further, root mean square error is minimized by linear AR models when examining crude mortality rates and by negative binomial models when examining raw death counts. In the context of frequentist hypothesis testing, many models yielded high Type I error rates and very low rates of correctly rejecting the null hypothesis (< 10%), raising concerns of spurious conclusions about policy effectiveness. When considering performance across models, the linear autoregressive models were optimal in terms of directional bias, root mean squared error, Type I error, and correct rejection rates. These findings highlight notable limitations of traditional statistical models commonly used for DID designs, designs widely used in opioid policy studies and in state policy evaluations more broadly.

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arXiv2021

Center-specific causal inference with multicenter trials: reinterpreting trial evidence in the context of each participating center

In multicenter randomized trials, when effect modifiers have a different distribution across centers, comparisons between treatment groups that average over centers may not apply to any of the populations underlying the individual centers. Here, we describe methods for reinterpreting the evidence produced by a multicenter trial in the context of the population underlying each center. We describe how to identify center-specific effects under identifiability conditions that are largely supported by the study design and when associations between center membership and the outcome may be present, given baseline covariates and treatment ("center-outcome associations"). We then consider an additional condition of no center-outcome associations given baseline covariates and treatment. We show that this condition can be assessed using the trial data; when it holds, center-specific treatment effects can be estimated using analyses that completely pool information across centers. We propose methods for estimating center-specific average treatment effects, when center-outcome associations may be present and when they are absent, and describe approaches for assessing whether center-specific treatment effects are homogeneous. We evaluate the performance of the methods in a simulation study and illustrate their implementation using data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial.

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arXiv2021

Consistency between household and county measures of K-12 onsite schooling during the COVID-19 pandemic

The academic, socioemotional, and health impacts of school policies throughout the COVID-19 pandemic have been a source of many important questions that require accurate information about the extent of onsite schooling that has been occurring throughout the pandemic. This paper investigates school operational status data sources during the COVID-19 pandemic, comparing self-report data collected nationally on the household level through a Facebook-based survey with data collected at district and county levels throughout the country. The percentage of households reporting in-person instruction within each county is compared to the district and county data at the state and county levels. The results show high levels of consistency between the sources at the state level and for large counties. The consistency levels across sources support the usage of the Facebook-based COVID-19 Symptom Survey as a source to answer questions about the educational experiences, factors, and impacts related to K-12 education across the nation during the pandemic.

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arXiv2021

Global Trends and Predictors of Face Mask Usage During the COVID-19 Pandemic

Background: Guidelines and recommendations from public health authorities related to face masks have been essential in containing the COVID-19 pandemic. We assessed the prevalence and correlates of mask usage during the pandemic. Methods: We examined a total of 13,723,810 responses to a daily cross-sectional representative online survey in 38 countries who completed from April 23, 2020 to October 31, 2020 and reported having been in public at least once during the last seven days. The outcome was individual face mask usage in public settings, and the predictors were country fixed effects, country-level mask policy stringency, calendar time, individual sociodemographic factors, and health prevention behaviors. Associations were modelled using survey-weighted multivariable logistic regression. Findings: Mask-wearing varied over time and across the 38 countries. While some countries consistently showed high prevalence throughout, in other countries mask usage increased gradually, and a few other countries remained at low prevalence. Controlling for time and country fixed effects, sociodemographic factors (older age, female gender, education, urbanicity) and stricter mask-related policies were significantly associated with higher mask usage in public settings, while social behaviors considered risky in the context of the pandemic (going out to large events, restaurants, shopping centers, and socializing outside of the household) were associated with lower mask use. Interpretation: The decision to wear a face mask in public settings is significantly associated with sociodemographic factors, risky social behaviors, and mask policies. This has important implications for health prevention policies and messaging, including the potential need for more targeted policy and messaging design.

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