| 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 (patients and physicians/carers). Data were analyzed appropriately for the effect of assignment to intervention; participants analyzed according to their randomized assignment. |
| Missing outcome data |
Low |
Comment: 275 patients randomized; 269 patients analyzed for safety.
Data available for > 95% of population. Risk assessed to be low for the outcomes: Mortality. 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 outcomes: Mortality. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and study registry were available.
Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for outcomes: Mortality. Serious adverse events. |
| Overall risk of bias |
Low |