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 |
Report: "We are conducting an ongoing operationally seamless
(continual enrollment), multicenter, randomized,
double-blind, placebo-controlled, phase 1–3
clinical trial" Supplementary Appendix: "In the Phase 2 study, randomization was stratified by: • Presence/absence of coronavirus disease 2019 (Covid-19) symptoms (i.e., symptomatic versus asymptomatic cohort) • Country • Risk factors for hospitalization due to Covid-19 (no risk factors for hospitalization due to Covid-19 versus ≥1 risk factor for hospitalization due to Covid-19)" Protocol: “Patients will be randomized according to a central randomization scheme using an interactive web response system (IWRS).” Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “Study patients, the principal investigators, and study site personnel (with the exception of the unblinded pharmacist at each site) will remain blinded to all randomization assignments throughout the study. The Regeneron medical/study director, study monitor, and any other Regeneron and contract research organization (CRO) personnel who are in regular contact with the study site will remain blinded to all patient randomization assignments in all phases of the study.”
Comment: Blinded study (participants and personnel/carers). 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 outcome: Serious adverse events. |
| Missing outcome data |
Low |
Comment: 275 participants randomized; 269 participants analyzed for safety.
Data available for nearly all participants randomized. Risk assessed to be low for the outcome: Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Methods of measuring the outcomes appropriate.
Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcome: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (dated May 29th, 2020), statistical analysis plan and study registry (dated June 8th, 2020) were available.
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 outcome: Serious adverse events. |
| Overall risk of bias |
Low |