Mixture models for the joint distribution of repeated measures and event times.
Many long-term clinical trials collect both a vector of repeated measurements and an event time on each subject; often, the two outcomes are dependent. One example is the use of surrogate markers to predict disease onset or survival. Another is longitudinal trials which have outcome-related dropout. We describe a mixture model for the joint distribution which accommodates incomplete repeated measures and right-censored event times, and provide methods for full maximum likelihood estimation. The methods are illustrated through analysis of data from a clinical trial for a new schizophrenia therapy; in the trial, dropout time is closely related to outcome, and the dropout process differs between treatments. The parameter estimates from the model are used to make a treatment comparison after adjusting for the effects of dropout. An added benefit of the analysis is that it permits using the repeated measures to increase efficiency of estimates of the event time distribution.
Hogan
J W
JW
Center for Statistical Sciences, Brown University, Providence, RI 02912, USA.
Laird
N M
NM
D000465:Algorithms; D002986:Clinical Trials as Topic / Q000379:methods*; D016001:Confidence Intervals; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D008137:Longitudinal Studies; D015233:Models, Statistical; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000188:drug therapy; D013997:Time Factors