Improved Methods and Selecting Classification Types for Time-Dependent Covariates in the Marginal Analysis of Longitudinal Data

Generalized estimating equations (GEE) are popularly utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless an independence working correlation structure is employed. Moreover, in this case regression parameter estimation can be very inefficient because not all valid moment conditions are incorporated within the corresponding estimating equations. Therefore, approaches using the generalized method of moments or quadratic inference functions have been proposed for utilizing all valid moment conditions. However, we have found that such methods will not always provide valid inference and can also be improved upon in terms of finite-sample regression parameter estimation. Therefore, we propose a modified GEE approach and a selection method that will both ensure the validity of inference and improve regression parameter estimation. In addition, these modified approaches assume the data analyst knows the type of time-dependent covariate, although this likely is not the case in practice. Whereas hypothesis testing has been used to determine covariate type, we propose a novel strategy to select a working covariate type in order to avoid potentially high type II error rates with these hypothesis testing procedures. Parameter estimates resulting from our proposed method are consistent and have overall improved mean squared error relative to hypothesis testing approaches. Finally, for some real-world examples the use of mean regression models may be sensitive to skewness and outliers in the data. Therefore, we extend our approaches from their use with marginal quantile regression to modeling the conditional quantiles of the response variable. Existing and proposed methods are compared in simulation studies and application examples