Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Patients were assigned in a 1:1:1 ratio to either usual standard of care, usual standard of care plus REGEN-COV or usual standard of care plus convalescent plasma (until 15 January 2021), using web-based simple (unstratified) randomisation with allocation concealed until after randomization.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: Among patients with a completed follow-up form, 90% allocated to REGEN-COV received the treatment compared with <1% allocated to usual care. Deviation too small to affect the outcome. Administration of co-interventions of interest was reported and balanced between groups: biologics, antivirals and corticosteroids. Hence, deviations did not arise because of the trial context. Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 9785 participants randomized; 9785 participants analyzed.
Of note, 28 vs 18 participants withdrew consent Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registries were available (NCT04381936 May 11 2020, EudraCT 2020-001113-21 March 19 2020, ISRCTN50189673 April 2 2020).
Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |