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: "Sentinel dosing was undertaken for each dose level, where the first 2 participants in each cohort were randomized 1:1 to bamlanivimab and placebo. Following a safety and tolerability review at 24 hours postdosing, subsequent participants were randomized to the remaining treatment allocations, 5 to bamlanivimab and 1 to placebo. Assignment to study intervention was determined using an interactive web-response system, and the blinded site staff were responsible for administering the study drug to the patients."
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Low |
Quote: "Investigator and patient-blind trial. Assignment to study intervention was determined using an interactive web-response system, and the blinded site staff were responsible for administering the study drug to the patients."
Comment: Blinded study (participants and personnel/carers) Our analysis for the binary outcomes 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: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Missing outcome data |
High |
Comment: 26 participants randomized; 24 participants analyzed; 5 (19%) missing data
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 2/6 (33%) vs 2/7 vs 0/6 vs 1/7 participants withdrawn/lost to follow-up, including 2 withdrawn before intervention. Missingness could depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome due to different proportions of missing data between arms. Risk assessed to be high for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). 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: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry (dated June 2, 2020) were available.
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: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Overall risk of bias |
High |