Dataset Information

Multiply robust causal inference with double-negative control adjustment for categorical unmeasured confounding.

ABSTRACT: Unmeasured confounding is a threat to causal inference in observational studies. In recent years, the use of negative controls to mitigate unmeasured confounding has gained increasing recognition and popularity. Negative controls have a long-standing tradition in laboratory sciences and epidemiology to rule out non-causal explanations, although they have been used primarily for bias detection. Recently, Miao and colleagues have described sufficient conditions under which a pair of negative control exposure and outcome variables can be used to identify non-parametrically the average treatment effect (ATE) from observational data subject to uncontrolled confounding. We establish non-parametric identification of the ATE under weaker conditions in the case of categorical unmeasured confounding and negative control variables. We also provide a general semiparametric framework for obtaining inferences about the ATE while leveraging information about a possibly large number of measured covariates. In particular, we derive the semiparametric efficiency bound in the non-parametric model, and we propose multiply robust and locally efficient estimators when non-parametric estimation may not be feasible. We assess the finite sample performance of our methods in extensive simulation studies. Finally, we illustrate our methods with an application to the post-licensure surveillance of vaccine safety among children.

SUBMITTER: Shi X

PROVIDER: S-EPMC7768794 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Multiply robust causal inference with double-negative control adjustment for categorical unmeasured confounding.

Shi Xu X Miao Wang W Nelson Jennifer C JC Tchetgen Eric J Tchetgen EJT

Journal of the Royal Statistical Society. Series B, Statistical methodology 20200122 2

Unmeasured confounding is a threat to causal inference in observational studies. In recent years, the use of negative controls to mitigate unmeasured confounding has gained increasing recognition and popularity. Negative controls have a long-standing tradition in laboratory sciences and epidemiology to rule out non-causal explanations, although they have been used primarily for bias detection. Recently, Miao and colleagues have described sufficient conditions under which a pair of negative contr ...[more]

PMID: 33376449

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Project description:BackgroundFour models are commonly used to adjust for energy intake when estimating the causal effect of a dietary component on an outcome: 1) the "standard model" adjusts for total energy intake, 2) the "energy partition model" adjusts for remaining energy intake, 3) the "nutrient density model" rescales the exposure as a proportion of total energy, and 4) the "residual model" indirectly adjusts for total energy by using a residual. It remains underappreciated that each approach evaluates a different estimand and only partially accounts for confounding by common dietary causes.ObjectivesWe aimed to clarify the implied causal estimand and interpretation of each model and evaluate their performance in reducing dietary confounding.MethodsSemiparametric directed acyclic graphs and Monte Carlo simulations were used to identify the estimands and interpretations implied by each model and explore their performance in the absence or presence of dietary confounding.ResultsThe "standard model" and the mathematically identical "residual model" estimate the average relative causal effect (i.e., a "substitution" effect) but provide biased estimates even in the absence of confounding. The "energy partition model" estimates the total causal effect but only provides unbiased estimates in the absence of confounding or when all other nutrients have equal effects on the outcome. The "nutrient density model" has an obscure interpretation but attempts to estimate the average relative causal effect rescaled as a proportion of total energy. Accurate estimates of both the total and average relative causal effects may instead be derived by simultaneously adjusting for all dietary components, an approach we term the "all-components model."ConclusionsLack of awareness of the estimand differences and accuracy of the 4 modeling approaches may explain some of the apparent heterogeneity among existing nutritional studies. This raises serious questions regarding the validity of meta-analyses where different estimands have been inappropriately pooled.

Project description:BackgroundSelection bias and unmeasured confounding are fundamental problems in epidemiology that threaten study internal and external validity. These phenomena are particularly dangerous in internet-based public health surveillance, where traditional mitigation and adjustment methods are inapplicable, unavailable, or out of date. Recent theoretical advances in causal modeling can mitigate these threats, but these innovations have not been widely deployed in the epidemiological community.ObjectiveThe purpose of our paper is to demonstrate the practical utility of causal modeling to both detect unmeasured confounding and selection bias and guide model selection to minimize bias. We implemented this approach in an applied epidemiological study of the COVID-19 cumulative infection rate in the New York City (NYC) spring 2020 epidemic.MethodsWe collected primary data from Qualtrics surveys of Amazon Mechanical Turk (MTurk) crowd workers residing in New Jersey and New York State across 2 sampling periods: April 11-14 and May 8-11, 2020. The surveys queried the subjects on household health status and demographic characteristics. We constructed a set of possible causal models of household infection and survey selection mechanisms and ranked them by compatibility with the collected survey data. The most compatible causal model was then used to estimate the cumulative infection rate in each survey period.ResultsThere were 527 and 513 responses collected for the 2 periods, respectively. Response demographics were highly skewed toward a younger age in both survey periods. Despite the extremely strong relationship between age and COVID-19 symptoms, we recovered minimally biased estimates of the cumulative infection rate using only primary data and the most compatible causal model, with a relative bias of +3.8% and -1.9% from the reported cumulative infection rate for the first and second survey periods, respectively.ConclusionsWe successfully recovered accurate estimates of the cumulative infection rate from an internet-based crowdsourced sample despite considerable selection bias and unmeasured confounding in the primary data. This implementation demonstrates how simple applications of structural causal modeling can be effectively used to determine falsifiable model conditions, detect selection bias and confounding factors, and minimize estimate bias through model selection in a novel epidemiological context. As the disease and social dynamics of COVID-19 continue to evolve, public health surveillance protocols must continue to adapt; the emergence of Omicron variants and shift to at-home testing as recent challenges. Rigorous and transparent methods to develop, deploy, and diagnosis adapted surveillance protocols will be critical to their success.

Dataset Information

Multiply robust causal inference with double-negative control adjustment for categorical unmeasured confounding.

Publications

Multiply robust causal inference with double-negative control adjustment for categorical unmeasured confounding.

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