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Objective To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes.Design Systematic review of trials with both blinded and non-blinded assessment of the same binary outcome. For each trial we calculated the ratio of the odds ratios-the odds ratio from non-blinded assessments relative to the corresponding odds ratio from blinded assessments. A ratio of odds ratios <1 indicated that non-blinded assessors generated more optimistic effect estimates than blinded assessors. We pooled the individual ratios of odds ratios with inverse variance random effects meta-analysis and explored reasons for variation in ratios of odds ratios with meta-regression. We also analysed rates of agreement between blinded and non-blinded assessors and calculated the number of patients needed to be reclassified to neutralise any bias.Data Sources PubMed, Embase, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press, and Google Scholar.Eligibility criteria for selecting studies Randomised clinical trials with blinded and non-blinded assessment of the same binary outcome. ResultsWe included 21 trials in the main analysis (with 4391 patients); eight trials provided individual patient data. Outcomes in most trials were subjective-for example, qualitative assessment of the patient's function. The ratio of the odds ratios ranged from 0.02 to 14.4. The pooled ratio of odds ratios was 0.64 (95% confidence interval 0.43 to 0.96), indicating an average exaggeration of the non-blinded odds ratio by 36%. We found no significant association between low ratios of odds ratios and scores for outcome subjectivity (P=0.27); non-blinded assessor's overall involvement in the trial (P=0.60); or outcome vulnerability to non-blinded patients (P=0.52). Blinded and non-blinded assessors agreed in a median of 78% of assessments (interquartile range 64-90%) in the 12 trials with available data. The exaggeration of treatment effects associated with non-blinded assessors was induced by the misclassification of a median of 3% of the assessed patients per trial (1-7%).Conclusions On average, non-blinded assessors of subjective binary outcomes generated substantially biased effect estimates in randomised clinical trials, exaggerating odds ratios by 36%. This bias was compatible with a high rate of agreement between blinded and non-blinded outcome assessors and driven by the misclassification of few patients.

This study provides empirical evidence of pronounced bias due to lack of patient blinding in complementary/alternative randomized clinical trials with patient-reported outcomes.