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: “Eligible participants were randomly assigned in a 1:1 ratio through the use of a centralized, interactive-response technology system.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. More women were randomly assigned to molnupiravir: 53.6% vs 49.0%. Post-hoc analysis adjusting for the imbalance consistent with the primary analysis. |
| Deviations from intervention |
Low |
Quote: “Participants and investigators will remain unaware of the treatment assignments until all actively enrolled participants have undergone the 7-month follow-up visit.”
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. Participants were analyzed according to their randomized groups for the outcome. Of note, 7 vs 18 participants were excluded from the efficacy analysis post-randomization because they were hospitalized before the first dose or did not receive the assigned intervention. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment:1433 participants randomized; 1408 participants analyzed for efficacy; 1381 participants analyzed for negative conversion; 1411 participants analyzed for safety.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). 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). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry (date October 5, 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 the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |