Trial NCT04790786
Publication OPTIMISE-C19 - Huang D, JAMA Netw Open (2022) (published paper)
Primary outcome on the report: Hospital-free days up to day 28 after mAb treatment. This outcome was an ordinal end point, with death as the worst outcome (labeled as −1) followed by the length of time alive and free of hospitalization, such that the best outcome would be 28 hospital-free days. If a patient had intervening days free of hospitalization and was then rehospitalized, the patient was given credit for the intervening days as free of hospitalization.

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: “Randomization was triggered when clinicians entered into the electronic medical record a generic mAb referral order. When the patient's medical record number was entered and the randomize button was clicked (by a centralized mAb operations team member at infusion centers and by a pharmacist at EDs), a random mAb was generated. The patient's randomized treatment was automatically recorded in the data and analytics team database.”
Comment: Allocation sequence 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: Mortality (D28). Hospitalization or death.
Missing outcome data
Some concerns 		Comment: 4530 participants randomized; 3558 (79%) participants analyzed.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: proportions that were excluded from analysis were not reported per group; overall, 879 did not receive infusion (285 Declined, 183 Undetermined reason, 152 Could not be contacted, 116 Scheduled but not infused, etc.), 14 received bamlanivimab and etesevimab, and 79 received subcutaneous treatment.
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome.
Risk assessed to be some concerns for the outcomes: Mortality (D28). Hospitalization or death.
Measurement of the outcome
Low 		Quote: “This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached.” 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). Hospitalization or death.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan, and prospective registry were available (registry dated March 10, 2021).
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). Hospitalization or death.
Overall risk of bias
Some concerns