Spline-based semiparametric projected generalized estimating equation method for panel count data.

We propose to analyze panel count data using a spline-based semiparametric projected generalized estimating equation (GEE) method with the proportional mean model E(N(t)|Z) = Λ(0)(t) e(β(0)(T)Z). The natural logarithm of the baseline mean function, logΛ(0)(t), is approximated by a monotone cubic B-spline function. The estimates of regression parameters and spline coefficients are obtained by projecting the GEE estimates into the feasible domain using a weighted isotonic regression (IR). The proposed method avoids assuming any parametric structure of the baseline mean function or any stochastic model for the underlying counting process. Selection of the working covariance matrix that accounts for overdispersion improves the estimation efficiency and leads to less biased variance estimations. Simulation studies are conducted using different working covariance matrices in the GEE to investigate finite sample performance of the proposed method, to compare the estimation efficiency, and to explore the performance of different variance estimates in presence of overdispersion. Finally, the proposed method is applied to a real data set from a bladder tumor clinical trial.