Bias was reduced in an open-label trial through the removal of subjective elements from the outcome definition.

Abstract

OBJECTIVE: To determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment. STUDY DESIGN AND SETTING: 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. RESULTS: 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%. CONCLUSION: 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.