Inference on treatment effects from a randomized clinical trial in the presence of premature treatment discontinuation: the SYNERGY trial.

TitleInference on treatment effects from a randomized clinical trial in the presence of premature treatment discontinuation: the SYNERGY trial.
Publication TypeJournal Article
Year of Publication2011
AuthorsZhang, Min, Anastasios A. Tsiatis, Marie Davidian, Karen S. Pieper, and Kenneth W. Mahaffey
JournalBiostatistics
Volume12
Issue2
Pagination258-69
Date Published2011 Apr
ISSN1468-4357
KeywordsAcute Coronary Syndrome, Algorithms, Computer Simulation, Endpoint Determination, Enoxaparin, Hemorrhage, Heparin, Humans, Intention to Treat Analysis, Models, Statistical, Monte Carlo Method, Mortality, Multicenter Studies as Topic, Probability, Proportional Hazards Models, Randomized Controlled Trials as Topic, Survival Analysis, Treatment Outcome, Withholding Treatment
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.

DOI10.1093/biostatistics/kxq054
Alternate JournalBiostatistics
Original PublicationInference on treatment effects from a randomized clinical trial in the presence of premature treatment discontinuation: the SYNERGY trial.
PubMed ID20797983
PubMed Central IDPMC3062147
Grant ListP01 CA142538-01 / CA / NCI NIH HHS / United States
R01CA051962 / CA / NCI NIH HHS / United States
R37AI031789 / AI / NIAID NIH HHS / United States
R01CA085848 / CA / NCI NIH HHS / United States
P01CA142538 / CA / NCI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
R01 CA085848-11 / CA / NCI NIH HHS / United States
Project: