Identification of confounder in epidemiologic data contaminated by measurement error in covariates

Abstract Background Common methods for confounder identification such as directed acyclic graphs (DAGs), hypothesis testing, or a 10 % change-in-estimate (CIE) criterion for estimated associations may not be applicable due to (a) insufficient knowledge to draw a DAG and (b) when adjustment for a tru...

Full description

Bibliographic Details
Main Authors: Paul H. Lee, Igor Burstyn
Format: Article
Language:English
Published: BMC 2016-05-01
Series:BMC Medical Research Methodology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12874-016-0159-6
_version_ 1818583886512259072
author Paul H. Lee
Igor Burstyn
author_facet Paul H. Lee
Igor Burstyn
author_sort Paul H. Lee
collection DOAJ
description Abstract Background Common methods for confounder identification such as directed acyclic graphs (DAGs), hypothesis testing, or a 10 % change-in-estimate (CIE) criterion for estimated associations may not be applicable due to (a) insufficient knowledge to draw a DAG and (b) when adjustment for a true confounder produces less than 10 % change in observed estimate (e.g. in presence of measurement error). Methods We compare previously proposed simulation-based approach for confounder identification that can be tailored to each specific study and contrast it with commonly applied methods (significance criteria with cutoff levels of p-values of 0.05 or 0.20, and CIE criterion with a cutoff of 10 %), as well as newly proposed two-stage procedure aimed at reduction of false positives (specifically, risk factors that are not confounders). The new procedure first evaluates potential for confounding by examination of correlation of covariates and applies simulated CIE criteria only if there is evidence of correlation, while rejecting a covariate as confounder otherwise. These approaches are compared in simulations studies with binary, continuous, and survival outcomes. We illustrate the application of our proposed confounder identification strategy in examining the association of exposure to mercury in relation to depression in the presence of suspected confounding by fish intake using the National Health and Nutrition Examination Survey (NHANES) 2009–2010 data. Results Our simulations showed that the simulation-determined cutoff was very sensitive to measurement error in exposure and potential confounder. The analysis of NHANES data demonstrated that if the noise-to-signal ratio (error variance in confounder/variance of confounder) is at or below 0.5, roughly 80 % of the simulated analyses adjusting for fish consumption would correctly result in a null association of mercury and depression, and only an extremely poorly measured confounder is not useful to adjust for in this setting. Conclusions No a prior criterion developed for a specific application is guaranteed to be suitable for confounder identification in general. The customization of model-building strategies and study designs through simulations that consider the likely imperfections in the data, as well as finite-sample behavior, would constitute an important improvement on some of the currently prevailing practices in confounder identification and evaluation.
first_indexed 2024-12-16T08:12:24Z
format Article
id doaj.art-bb72f08ed3264fdbbe5ae64a213fec5d
institution Directory Open Access Journal
issn 1471-2288
language English
last_indexed 2024-12-16T08:12:24Z
publishDate 2016-05-01
publisher BMC
record_format Article
series BMC Medical Research Methodology
spelling doaj.art-bb72f08ed3264fdbbe5ae64a213fec5d2022-12-21T22:38:20ZengBMCBMC Medical Research Methodology1471-22882016-05-0116111810.1186/s12874-016-0159-6Identification of confounder in epidemiologic data contaminated by measurement error in covariatesPaul H. Lee0Igor Burstyn1School of Nursing, PQ433, Hong Kong Polytechnic UniversityDepartment of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel UniversityAbstract Background Common methods for confounder identification such as directed acyclic graphs (DAGs), hypothesis testing, or a 10 % change-in-estimate (CIE) criterion for estimated associations may not be applicable due to (a) insufficient knowledge to draw a DAG and (b) when adjustment for a true confounder produces less than 10 % change in observed estimate (e.g. in presence of measurement error). Methods We compare previously proposed simulation-based approach for confounder identification that can be tailored to each specific study and contrast it with commonly applied methods (significance criteria with cutoff levels of p-values of 0.05 or 0.20, and CIE criterion with a cutoff of 10 %), as well as newly proposed two-stage procedure aimed at reduction of false positives (specifically, risk factors that are not confounders). The new procedure first evaluates potential for confounding by examination of correlation of covariates and applies simulated CIE criteria only if there is evidence of correlation, while rejecting a covariate as confounder otherwise. These approaches are compared in simulations studies with binary, continuous, and survival outcomes. We illustrate the application of our proposed confounder identification strategy in examining the association of exposure to mercury in relation to depression in the presence of suspected confounding by fish intake using the National Health and Nutrition Examination Survey (NHANES) 2009–2010 data. Results Our simulations showed that the simulation-determined cutoff was very sensitive to measurement error in exposure and potential confounder. The analysis of NHANES data demonstrated that if the noise-to-signal ratio (error variance in confounder/variance of confounder) is at or below 0.5, roughly 80 % of the simulated analyses adjusting for fish consumption would correctly result in a null association of mercury and depression, and only an extremely poorly measured confounder is not useful to adjust for in this setting. Conclusions No a prior criterion developed for a specific application is guaranteed to be suitable for confounder identification in general. The customization of model-building strategies and study designs through simulations that consider the likely imperfections in the data, as well as finite-sample behavior, would constitute an important improvement on some of the currently prevailing practices in confounder identification and evaluation.http://link.springer.com/article/10.1186/s12874-016-0159-6Causal effectChange-in-estimateConfoundingSimulationModel-selectionEpidemiology
spellingShingle Paul H. Lee
Igor Burstyn
Identification of confounder in epidemiologic data contaminated by measurement error in covariates
BMC Medical Research Methodology
Causal effect
Change-in-estimate
Confounding
Simulation
Model-selection
Epidemiology
title Identification of confounder in epidemiologic data contaminated by measurement error in covariates
title_full Identification of confounder in epidemiologic data contaminated by measurement error in covariates
title_fullStr Identification of confounder in epidemiologic data contaminated by measurement error in covariates
title_full_unstemmed Identification of confounder in epidemiologic data contaminated by measurement error in covariates
title_short Identification of confounder in epidemiologic data contaminated by measurement error in covariates
title_sort identification of confounder in epidemiologic data contaminated by measurement error in covariates
topic Causal effect
Change-in-estimate
Confounding
Simulation
Model-selection
Epidemiology
url http://link.springer.com/article/10.1186/s12874-016-0159-6
work_keys_str_mv AT paulhlee identificationofconfounderinepidemiologicdatacontaminatedbymeasurementerrorincovariates
AT igorburstyn identificationofconfounderinepidemiologicdatacontaminatedbymeasurementerrorincovariates