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Thromb Haemost 2013; 109(03): 497-503
DOI: 10.1160/TH12-10-0715
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

William M. O’Neil
1   LA-SER Group, Montreal, Canada
,
Sharon A. Welner
1   LA-SER Group, Montreal, Canada
,
Gregory Y. H. Lip
2   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
› Author Affiliations Financial support: This research was made possible by an unrestricted research grant from Boehringer Ingelheim.
Further Information

Publication History

Received: 01 October 2012

Accepted after minor revision: 09 January 2012

Publication Date:
29 November 2017 (online)

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Summary

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54–1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73–2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Keywords

Metaanalysis - coagulation inhibitors - management of disease - thrombosis - clinical studies

 

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