Estimation of survival distributions of treatment policies in two-stage randomization designs in clinical trials.
Some clinical trials follow a design where patients are randomized to a primary therapy at entry followed by another randomization to maintenance therapy contingent upon disease remission. Ideally, analysis would allow different treatment policies, i.e., combinations of primary and maintenance therapy if specified up-front, to be compared. Standard practice is to conduct separate analyses for the primary and follow-up treatments, which does not address this issue directly. We propose consistent estimators for the survival distribution and mean restricted survival time for each treatment policy in such two-stage studies and derive large-sample properties. The methods are demonstrated on a leukemia clinical trial data set and through simulation.
Lunceford
Jared K
JK
Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. jared_lunceford@merck.com
Davidian
Marie
M
Tsiatis
Anastasios A
AA
D000368:Aged; D003198:Computer Simulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
D016178:Granulocyte-Macrophage Colony-Stimulating Factor