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Given the double blind adjudication, it can be reasonably expected that the calculated relative risk of direct comparisons would have provided an unbiased estimate.
We assessed three key domains of internal validity, concealment of allocation, blind adjudication of outcomes, and the inclusion of all randomised participants in the analysis according to the intention to treat principle (see supplementary appendix).
Fifty six trials (56%) reported blind adjudication of clinical outcomes, and for 69 trials (69%) we were able to include all randomised patients into the analysis according to the intention to treat principle.
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Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.
However, blinded adjudication of test interpretation and diagnoses was not performed in any of the studies.
Definite and probable STs were defined according to the Academic Research Consortium (ARC) 16 and diagnosed by the authors without blinded adjudication.
However, the pre-specified design of the present meta-analysis involved prospective and blinded adjudication of CV events, which should strengthen the validity of the current findings.
Major adverse cardiovascular events (MACE; a composite of total cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) were evaluated and classified by an independent, blinded adjudication committee.
All identified potential CV events subsequently went through treatment-blinded adjudication by independent reviewers at the Duke Clinical Research Institute (DCRI; Durham, NC; 8 studies) or the Montreal Heart Institute (MHI; Montreal, QC, Canada; 12 studies).
Two investigators (BC, KT) independently appraised the potential risk of bias in trials according to the Cochrane Collaboration guidelines (adequate sequence generation, allocation concealment, blinded adjudication of events) 12; discrepancies were resolved by discussion with a third investigator (EPN).
Independent blinded adjudication boards were formed to ensure a consistent, accurate, and unbiased assessment of the following AEs of interest: VTEs, stroke, transient ischemic attack (TIA), and breast cancer.
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