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: “Randomization was performed using an interactive web response system, and a randomization schedule was prepared by
unblinded biostatisticians.”
Comment: Allocation sequence random No information on allocation concealment Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “Participants, personnel, and outcome assessors were blinded to treatment allocation for the duration of the study”
Comment: Blinded study (participants and personnel/carers) Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Of note, 1 patient randomized to the placebo group was incorrectly given a study drug that partially contained regdanvimab; they were analyzed according to their randomized group for ITT and ITTI analyses, however they were included in the regdanvimab 40 mg/kg group for safety analyses. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 327 participants randomized; 307 participants analyzed for efficacy; 327 participants analyzed for safety.
HOSPITALIZATION OR DEATH. MORTALITY. VIRAL NEGATIVE CONVERSION. WHO SCORE 7 AND ABOVE. Data not available for all or nearly all participants randomized for efficacy. No evidence that the result is not biased. Reasons: 5 vs. 8 vs. 7 were found not to have confirmed COVID-19 by PCR at study entry and were excluded from efficacy analyses. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome due to similar proportions and reasons between groups. Risk assessed to be some concerns for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). ADVERSE AND SERIOUS ADVERSE EVENTS. Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (EudraCT Sept 14, 2020).
Outcome 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 outcome: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |