title: Inference on treatment effects from a randomized clinical trial in the presence of premature treatment discontinuation: the SYNERGY trial.
abstract: The Superior Yield of the New Strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) was a randomized, open-label, multicenter clinical trial comparing 2 anticoagulant drugs on the basis of time-to-event endpoints. In contrast to other studies of these agents, the primary, intent-to-treat analysis did not find evidence of a difference, leading to speculation that premature discontinuation of the study agents by some subjects may have attenuated the apparent treatment effect and thus to interest in inference on the difference in survival distributions were all subjects in the population to follow the assigned regimens, with no discontinuation. Such inference is often attempted via ad hoc analyses that are not based on a formal definition of this treatment effect. We use SYNERGY as a context in which to describe how this effect may be conceptualized and to present a statistical framework in which it may be precisely identified, which leads naturally to inferential methods based on inverse probability weighting.
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, USA. mzhangst@umich.edu
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Anastasios A
authors.initials: AA
authors.lastname: Tsiatis
authors.forename: Marie
authors.initials: M
authors.lastname: Davidian
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000465:Algorithms; D003198:Computer Simulation; D023381:Endpoint Determination; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D057194:Intention to Treat Analysis; D015233:Models, Statistical; D009010:Monte Carlo Method; D009026:Mortality; D015337:Multicenter Studies as Topic; D011336:Probability; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D017984:Enoxaparin; D006493:Heparin
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