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: “Using an interactive web response system, eligible patients were randomized 1:1 to receive a single intravenous infusion of sotrovimab 500 mg or an equal volume of saline placebo over 1 hour on day 1."
Comment: Allocation sequence probably random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote from article: "double-blind, placebo-controlled, multicenter randomized clinical trial." Quote from registry: “Quadruple blinding (Participant, Care Provider, Investigator, Outcomes Assessor)". Quote: “Study pharmacists reconstituted and dispensed all study medications within equal time frames to maintain blinding.” Comment: Blinded study (participants and personnel/carers) HOSPITALIZATION OR DEATH, MORTALITY, WHO SCORE 7 AND ABOVE, AE, SAE 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. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Mortality (D60 or more). WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 469 vs 461 participants were excluded from the analysis post-randomization for unknown reasons. This will be accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
HOSPITALIZATION OR DEATH, MORTALITY D28, WHO SCORE 7 ANDA BOVE
Comment: 1057 participants randomized; 1057 participants analyzed. Of note, 6 vs 2 participants did not receive intervention as randomized, 10 v 12 withdrawn from study during follow-up Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). WHO score 7 and above (D28). MORTALITY D60, AE, SAE Comment: 1057 randomized; 1049 participants analyzed. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Comment: 1057 randomized; 127 participants analyzed. Data not available for all or nearly all participants randomized. Reasons: unknown Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportions of missing data between arms) Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| 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). Mortality (D60 or more). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events |
| Selection of the reported results |
Some concerns |
Comment: The registry and supplementary material with changes to the protocol/statistical analysis plan were available. Earliest version of registry dated September 9, 2020. Randomization of study participants began August 27, 2020, thus the registry was likely published before unblinded data was available for analysis.
MORTALITY, HOSPITALIZATION OR DEATH, WHO SCORE 7 AND ABOVE, AE, SAE 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 outcome: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Incidence of viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Outcome not pre-specified (different timepoint) No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| Overall risk of bias |
Some concerns |