Table 2.
Risk‐of‐Bias Assessment of Original Randomized Controlled Trials
| Trial | ARISTOTLE7 | ENGAGE AF8 | RE‐LY5 | ROCKET AF6 |
|---|---|---|---|---|
| Random sequence generation (selection bias) |
Low risk Quote: “Each subject will be randomly assigned to 1 of 2 treatment groups in a 1:1 ratio by the Interactive Voice Response System (IVRS).” Comment: probably done |
Low risk Quote: “Patients were randomly assigned, in a 1:1:1 ratio. Randomization was performed with the use of a central, 24‐hour, interactive, computerized response system.” Comment: probably done |
Low risk Quote: “The patients were randomized by a central randomization service, through an interactive voice response system (IVRS).” Comment: probably done |
Low risk Quote: “Treatment allocation is randomized using a blinded, central telephonic Interactive Voice Response System.” Comment: probably done |
| Allocation concealment (selection bias) |
Low risk Quote: “Randomization schedules will be generated and kept by Bristol‐Myers Squibb (BMS)” Comment: probably done |
Low risk Quote: “Randomization was performed with the use of a central, 24‐hour, interactive, computerized response system” Comment: probably done |
Low risk Quote: “Randomization service located at the Coordinating Centre at Population Health Research Institute (PHRI) in Hamilton, Canada” Comment: probably done |
Low risk To effect concealment of randomization, treatment allocation is randomized using a blinded, central telephonic Interactive Voice Response System Comment: probably done |
| Blinding of participants and personnel (performance bias) |
Low risk Quote: “double‐blind, double‐dummy, parallel‐arm study” Comment: probably done |
Low risk Quote: “double‐blind, double‐dummy trial” Comment: probably done |
High risk Quote: “open‐label, randomized trial with blinded evaluation of all outcomes”Comment: probably done |
Low risk Quote: “double‐blind, double‐dummy, randomized trial” Comment: probably done |
| Blinding of outcome assessment (detection bias) |
Low risk Quote: “double blind” Comment: probably done |
Low risk Quote: “double‐blind, double‐dummy trial” Comment: probably done |
Low risk Quote: “open‐label, randomized trial with blinded evaluation of all outcomes” Comment: probably done |
Low risk Quote: “double‐blind, double‐dummy, randomized trial” Comment: probably done |
| Incomplete outcome data (attrition bias) |
Low risk Comment: <1% patients lost follow‐up |
Low risk Comment: 0.5% incomplete information on the primary end point |
Low risk Comment: 0.11% lost to follow‐up |
Low risk Comment: 0.22% lost to follow‐up |
| Selective reporting (reporting bias) |
Low risk Comment: study protocol is available, and all of the study's prespecified outcomes of interest in the review have been reported in the prespecified way |
Low risk Comment: study protocol is available, and all of the study's prespecified outcomes of interest in the review have been reported in the prespecified way |
Low risk Comment: study protocol is not available, but the published reports clearly include all expected outcomes, including those that were prespecified |
Low risk Comment: study protocol is not available, but the published reports clearly include all expected outcomes, including those that were prespecified |
| Other potential bias |
Low risk Comment: study seems to be free of other sources of bias |
Low risk Comment: study seems to be free of other sources of bias |
Low risk Comment: study seems to be free of other sources of bias |
Low risk Comment: study seems to be free of other sources of bias |
ARISTOTLE indicates Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; ENGAGE AF, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation; RE‐LY, Randomized Evaluation of Long‐Term Anticoagulation Therapy; ROCKET AF, Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.