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: “Patients were randomised using a web-based system with a 1:1 allocation ratio. Randomisation sequence was performed by a computer program in blocks of six and was not stratified.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Open-label. Physicians, patients, and individuals who assessed the outcomes were not blinded for the assigned treatment.”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: 32 of 102 assigned to low-dose dexamethasone received high-dose. This was allowed by the trial protocol after clinical worsening. Administration of co-interventions of interest - biologics and antivirals - were reported and balanced between groups. Corticosteroids were the intervention. 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). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). |
| Missing outcome data |
Some concerns |
Comment: 200 participants randomized; 200 participants analyzed for mortality, clinical improvement and WHO Score 7 and above at day 28; 182 participants analyzed for mortality day 60.
MORTALITY (D28). CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). MORTALITY (D60) Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: lost to follow up. Missingness could depend on the true value of the outcome. No reason to suspect that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Mortality (D60 or more). |
| 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 Mortality is an observer-reported outcomesnot involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). WHO SCORE 7 AND ABOVE For WHO score 7 and above, 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 (defined as discharge) 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). |
| Selection of the reported results |
Some concerns |
Comment: The registry was available (dated January 27, 2021).
MORTALITY (D28) 28-day mortality 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 outcome: Mortality (D28). MORTALITY (D60). CLINIAL IMPROVEMENT. WHO SCORE 7 AND ABOVE Outcomes not pre-specified in the registry. 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: Mortality (D60). Clinical improvement (D28). WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |