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, non-hospitalized adults with mild COVID19 were randomized to receive either molnupiravir 800 mg (200 mg x 4 capsules administered orally every 12 hours for 5 days) with SOC or SOC alone.” [Report] Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized [registry]”
Comment: Allocation sequence random /probably random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context 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). Incidence of viral negative conversion (D7). Clinical improvement (D28). Time to clinical improvement. WHO score 7 or above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 1220 participants randomized; 1216 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Incidence of viral negative conversion (D7). Clinical improvement (D28). Time to clinical improvement. WHO score 7 or above (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, VIRAL NEGATIVE CONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). HOSPITALIZATION OR DEATH, WHO SCORE 7 AND ABOVE For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: Hospitalization or death. WHO score 7 and above (D28). (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as decrease of at least 2 points on the 11-point WHO scale) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement. ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry was available (dated 05/07/2021)
HOSPITALIZATION OR DEATH. CLINICAL IMPROVEMENT. TIME TO CLINICAL IMPROVEMENT 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. Clinical improvement (D28). Time to clinical improvement. MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably 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). VIRAL NEGATIVE CONVERSION. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS Outcome not pre-specified for viral negative conversion, WHO score 7 and above (D28), adverse events. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |