title: Estimation of survival distributions of treatment policies in two-stage randomization designs in clinical trials.
abstract: 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.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. jared_lunceford@merck.com
authors.forename: Jared K
authors.initials: JK
authors.lastname: Lunceford
authors.forename: Marie
authors.initials: M
authors.lastname: Davidian
authors.forename: Anastasios A
authors.initials: AA
authors.lastname: Tsiatis
mesh_terms: 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
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor