title: Regression models for multiple outcomes in large epidemiologic studies.
abstract: In situations in which one cannot specify a single primary outcome, epidemiologic analyses often examine multiple associations between outcomes and explanatory covariates or risk factors. To compare alternative approaches to the analysis of multiple outcomes in regression models, I used generalized estimating equations (GEE) models, a multivariate extension of generalized linear models, to incorporate the dependence among the outcomes from the same subject and to provide robust variance estimates of the regression coefficients. I applied the methods in a hospital-population-based study of complications of surgical anaesthesia, using GEE model fitting and quasi-likelihood score and Wald tests. In one GEE model specification, I allowed the associations between each of the outcomes and a covariate to differ, yielding a regression coefficient for each of the outcome and covariate combinations; I obtained the covariances among the set of outcome-specific regression coefficients for each covariate from the robust 'sandwich' variance estimator. To address the problem of multiple inference, I used simultaneous methods that make adjustments to the test statistic p-values and the confidence interval widths, to control type I error and simultaneous coverage, respectively. In a second model specification, for each of the covariates I assumed a common association between the outcomes and the covariate, which eliminates the problem of multiplicity by use of a global test of association. In an alternative approach to multiplicity, I used empirical Bayes methods to shrink the outcome-specific coefficients toward a pooled mean that is similar to the common effect coefficient. GEE regression models can provide a flexible framework for estimation and testing of multiple outcomes.
authors.affiliation: Samuel Lunenfeld Research Institute, University of Toronto, Canada. bull@mshri.on.ca
authors.forename: S B
authors.initials: SB
authors.lastname: Bull
mesh_terms: D000758:Anesthesia / Q000009:adverse effects / Q000706:statistics & numerical data; D000777:Anesthetics / Q000009:adverse effects; D001499:Bayes Theorem; D015982:Bias; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015986:Confounding Factors, Epidemiologic; D006801:Humans; D007431:Intraoperative Complications / Q000453:epidemiology; D016013:Likelihood Functions; D017063:Outcome Assessment, Health Care; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D000777:Anesthetics