Regression models for multiple outcomes in large epidemiologic studies

Stat Med. 1998 Oct 15;17(19):2179-97. doi: 10.1002/(sici)1097-0258(19981015)17:19<2179::aid-sim921>3.0.co;2-l.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia / adverse effects
  • Anesthesia / statistics & numerical data
  • Anesthetics / adverse effects
  • Bayes Theorem
  • Bias
  • Cardiovascular Diseases / epidemiology
  • Confounding Factors, Epidemiologic
  • Humans
  • Intraoperative Complications / epidemiology
  • Likelihood Functions
  • Outcome Assessment, Health Care*
  • Regression Analysis*
  • Risk Factors

Substances

  • Anesthetics