G-estimation and artificial censoring: problems, challenges, and applications.

In principle, G-estimation is an attractive approach for dealing with confounding by variables affected by treatment. It has rarely been applied for estimation of the effects of treatment on failure-time outcomes. Part of this is due to artificial censoring, an analytic device which considers some subjects who actually were observed to fail as if they were censored. Artificial censoring leads to a lack of smoothness in the estimating function, which can pose problems in variance estimation and in optimization. It also can lead to failure to have solutions to the usual estimating functions, which then raises questions about the appropriate criteria for optimization. To improve performance of the optimization procedures, we consider approaches for reducing the amount of artificial censoring, propose the substitution of smooth for indicator functions, and propose the use of estimating functions scaled to a measure of the information in the data; we evaluate performance of these approaches using simulation. We also consider appropriate optimization criteria in the presence of information loss due to artificial censoring. We motivate and illustrate our approaches using observational data on the effect of erythropoietin on mortality among subjects on hemodialysis.