A class of semiparametric transormation frailty models with application to estimating treatment effects and heterogenity in aids clinical traials

Muitivariate failure time data are common in medical research; com¬monly used statistical models for such correlated failure-time data include frailty and marginal models. Both types of models most often assume pro¬portional hazards (Cox, 1972); but the Cox model may not fit the data well This article presents a class of linear transformation frailty models that in¬cludes, as a special case, the proportional hazards model with frailty. We then propose approximate procedures to derive the best linear unbiased es¬timates and predictors of the regression parameters and frailties. We apply the proposed methods to analyze results of a clinical trial of different dose levels of didansine (ddl) among HIV-infected patients who were intolerant of zidovudine (ZDV). These methods yield estimates of treatment effects and of frailties corresponding to patient groups defined by clinical history prior to entry into the trial.