Matched survival data in a co-twin control design.

When using the co-twin control design for analysis of event times, one needs a model to address the possible within-pair association. One such model is the shared frailty model in which the random frailty variable creates the desired within-pair association. Standard inference for this model requires independence between the random effect and the covariates. We study how violations of this assumption affect inference for the regression coefficients and conclude that substantial bias may occur. We propose an alternative way of making inference for the regression parameters by using a fixed-effects models for survival in matched pairs. Fitting this model to data generated from the frailty model provides consistent and asymptotically normal estimates of regression coefficients, no matter whether the independence assumption is met.