Bias was reduced in an open-label trial through the removal of subjective elements from the outcome definition.
To determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment.



Reanalysis of an open-label trial comparing a restrictive vs. liberal transfusion strategy for gastrointestinal bleeding. The usual definition of the primary outcome, further bleeding, allows subjective clinical symptoms to be used alone for diagnosis, whereas the definition used in the trial required more objective confirmation by endoscopy. We compared treatment effect estimates for these two definitions.



Fewer subjective symptom-identified events were confirmed using more objective methods in the restrictive arm (18%) than in the liberal arm (56%), indicating differential assessment between arms. An analysis using all events (both subjective and more objective) led to an odds ratio of 0.83 (95% confidence interval [CI]: 0.50-1.37). When only events confirmed using more objective methods were included, the odds ratio was 0.50 (95% CI: 0.32-0.78). The ratio of the odds ratios was 1.66, indicating that including unconfirmed events in the definition biased the treatment effect upward by 66%.



Modifying the outcome definition to exclude subjective elements substantially reduced bias. This may be a useful strategy for reducing bias in trials that cannot blind outcome assessment.
Pragmatic Clinical Trials Unit, Centre for Primary Care and Public Health, Queen Mary University, 58 Turner Street, E1 2AB London, UK. Electronic address: b.kahan@qmul.ac.uk.
Brennan C
BC
Kahan
Comprehensive Clinical Trials Unit at UCL, UCL, Gower Street, London WC1E 6BT, UK.
Caroline J
CJ
Doré
NHS Blood and Transplant, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
Michael F
MF
Murphy
Department of Medicine, Western University and London Health Sciences Network, London, Ontario N6A 5A5, Canada; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Headington, Oxford OX3 7BN, UK.
Vipul
V
Jairath
D015982:Bias; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology* / Q000628:therapy*; D006801:Humans; D016017:Odds Ratio; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000706:statistics & numerical data*; D012107:Research Design
Bias; Blinding; Cluster-randomized; Open-label trial; Outcome assessment; Randomized controlled trial