Trial NCT04678739
Publication Mohiuddin Chowdhury ATM, Front pharmacol (2022) (published paper)
Primary outcome on the report: Primary outcome was unclear. "Treatment outcomes were measured as follows: time to clinical improvement, defined as the time from randomization to NEWS-2 score (National Early Warning Score 2) of ≤2 as maintained for 24 h; mortality rate; duration of ICU stay; total period of hospitalization; the rate of oxygen use; time to clinical failure; NEWS-2 score on discharge; and the percentage of lung recovery on CT of the chest (the difference value of the CT involvement of lung pathology during admission and at the time of discharge)."

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 chosen and included in the study. Then, they were divided into two study groups (A and B) by using an odd–even ratio of 1:1 applied to the hospital registration number.
Comment: Allocation sequence probably random.
No information on allocation concealment
Deviations from intervention
Some concerns 		Quote: “Open-label"
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
No participant cross-over.
No information on administration of co-interventions of interest: biologics (other than tocilizumab). Antivirals and corticosteroids were the intervention.
Hence, no information on whether deviations arose because of the trial context.
Our analysis for the 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). Clinical improvement (D28). WHO score 7 and above (D28).
Missing outcome data
Low 		Comment: 208 participants randomized; 205 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28).
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
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28).

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: WHO score 7 and above (D28).

CLINICAL IMPROVEMENT
Clinical improvement (discharge alive from hospital) requires clinical judgement and could be affected by knowledge of intervention receipt, but it is not considered likely to in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Clinical improvement (D28).
Selection of the reported results
Some concerns 		Comment: The registry was retrospective (dated December 22, 2020).

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).

CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE.
No information on whether the result was selected from multiple outcome measurements or analyses of the data.
No information on whether the trial was analyzed as pre-specified.
Risk assessed to be some concerns for the outcome: Clinical improvement (D28). WHO score 7 and above (D28).
Overall risk of bias
Some concerns