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 |
Some concerns |
Quote: "Patients were randomly grouped (2:1) into molnupiravir (n = 80) and control groups (n = 36) using a random number table."
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: No information on blinding.
Comment: Unclear blinding (unclear if participants and personnel/carers blinded). Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: corticosteroids. Antivirals and biologics were reported (excluded). Hence, no information on whether deviations arose because of the trial context. MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS 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 some concerns for the outcomes: Mortality (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 2 vs 2 participants were excluded from the analysis post-randomization because they did not comply with the protocol (inclusion criteria). 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 some concerns for the outcomes: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Low |
Comment: 116 participants randomized; 108 (93%) participants analyzed for the binary outcomes; 107 analyzed for Viral negative conversion.
MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: 1 vs 2 were excluded post-randomisation because they did not meet inclusion criteria; 2 vs 3 refused consent. Missingness could not depend on the true value of the outcome as the reason is due to outside factors. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data available for nearly all participants randomized. Of note, 4 of the 9 missing participants were addressed in domain 2; 2 vs 3 withdrew consent post-randomisation. Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). |
| 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. Unclear blinding (outcome assessor). MORTALITY, VIRAL NEGATIVE CONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28) and Incidence of viral negative conversion (D7). 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 and Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was consulted up to version dated April 25, 2022.
MORTALITY. VIRAL NEGATIVE CONVERSION 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 outcomes: Mortality (D28). Incidence of viral negative conversion (D7). ADVERSE and SERIOUS ADVERSE EVENTS Outcomes in registry noted will assess safety. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Adverse events and Serious adverse events. |
| Overall risk of bias |
Some concerns |