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Risk of bias among included RCTs was assessed using the following criteria: adequacy of allocation concealment, blinding of subjects and clinicians to treatment groups, blinding during outcome adjudication (for studies reporting neurological outcomes in addition to mortality), use of an intention-to-treat analysis, loss to follow-up, and baseline differences in important prognostic variables.
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Inter-rater agreement for adjudication of study quality was calculated using Cohen's κ statistic.
The Event Adjudication Committee consisting of three independent physicians will adjudicate events for study objectives and document event classifications.
However, there was a trend for studies without blinding of outcome adjudication (OR = 0.28, 95%CI 0.17 to 0.46) to show a greater effect than studies with blinding of outcome adjudication (OR = 0.50, 95%CI 0.32 to 0.77) with the test for heterogeneity between subgroups p = 0.09 (Additional file 3).
For studies reporting neurological outcomes, we also required outcome adjudication to have been performed in a blinded fashion.
Less than half (44%) of studies undertook independent adjudication for the diagnosis of sepsis while 68% provided microbiological data.
We post all relevant patient records devoid of personal identifiers (ie, case report forms and X-rays) on a specially designed, password-protected website for study adjudication.
Inter-rater agreement for study quality adjudication was excellent (κ=0.87).
With regard to the diagnostic uncertainty that is common in any large-scale study, best attempts were made for the proper classification of fatal and non-fatal strokes with the opportunity for adjudication among the study investigators.
The methods of accrual and adjudication for this prospective cohort have been previously described [36].
AR also performed expert adjudication for ambiguous results.
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