Trial NCT04575597
Publication MOVe-OUT - Caraco Y, N Engl J Med Evidence (2021) (published paper)
Primary outcome on the report: Adverse event (AE) data collection by the investigator from the time of randomization through 14 days after cessation of treatment, physical examinations (including vital signs), and laboratory tests (hematology and chemistry).; The proportion of participants who were hospitalized and/or died from any cause through day 29.

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: "Participants were randomly assigned 1:1:1:1 using an interactive response technology system to receive 200, 400, or 800mg of molnupiravir or placebo twice daily for 5 days and followed through day 29. Participants were stratified (with a block size of four, the minimum block size for a four-group trial) by symptom onset (up to [and including] 5 days, >5 days) and by being at increased risk for severe illness from Covid-19 (yes, no)."
Comment: Allocation sequence random.
Allocation sequence probably concealed.
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote: "Participants, investigators, and study staff (except unblinded site pharmacists) remain blinded to allocation assignment until study completion."
Comment: Blinded study (participants and personnel/carers)

HOSPITALIZATION OR DEATH, 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 low for the outcomes: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 302 participants randomized; 299 participants analyzed.
Data available for nearly all participants randomized.
Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). 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: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol, statistical analysis plan (dated September 14, 2020), and registry (October 5, 2020) were available.

HOSPITALIZATION OR DEATH. AVERSE EVENTS. SERIOUS ADVERSE EVENTS
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: Hospitalization or death. Adverse events. Serious adverse events.

MORTALITY
Mortality outcome was not pre-specified in the protocol or 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 outcomes: Mortality (D28).
Overall risk of bias
Low