Modeling concordance correlation via GEE to evaluate reproducibility

Clinical studies are often concerned with assessing whether different raters/methods produce similar values for measuring a quantitative variable. Use of the concordance correlation coefficient as a measure of reproducibility has gained popularity in practice since its introduction by Lin (1989, Biometrics 45, 255-268). Lin's method is applicable for studies evaluating two raters/two methods without replications. Chinchilli et al. (1996, Biometrics 52, 341-353) extended Lin's approach to repeated measures designs by using a weighted concordance correlation coefficient. However, the existing methods cannot easily accommodate covariate adjustment, especially when one needs to model agreement. In this article, we propose a generalized estimating equations (GEE) approach to model the concordance correlation coefficient via three sets of estimating equations. The proposed approach is flexible in that (1) it can accommodate more than two correlated readings and test for the equality of dependent concordant correlation estimates; (2) it can incorporate covariates predictive of the marginal distribution; (3) it can be used to identify covariates predictive of concordance correlation; and (4) it requires minimal distribution assumptions. A simulation study is conducted to evaluate the asymptotic properties of the proposed approach. The method is illustrated with data from two biomedical studies.