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: “Enrolled subjects were randomized 1:1 to study drug or placebo and followed for 30 days. Randomization was stratified by age (>60 years old) and study site.”
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "Subjects and investigators were blinded to the treatment assignment, but in cases of rapid COVID-19 progression meeting our primary endpoint, or at the request of the treating physician, we allowed for subject unblinding."
Comment: Partially-blinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Administration of co-interventions of interest: antivirals, corticosteroids and biologics were mentioned but it was unclear whether they were balanced between groups (no information). Considerable proportions of patients received cointerventions as part of other clinical trials. Hence, no information on whether deviations arose because of the trial context. MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, ADVERSE EVENTS Data for the outcome were analyzed using 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). Adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 30 vs 31 participants were excluded from the analysis post-randomization due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 128 participants randomized; 128 participants analyzed.
VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: No follow-up PCR performed (30 vs 31) Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (same reason and proportion of missingness between arms) Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). MORTALITY Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: lost to follow-up (14 vs 11) Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (same reason and proportion of missingness between arms) Risk assessed to be some concerns for the outcome: Mortality (D28). CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: unknown (7 vs 4) No information on whether missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportion of missingness between arms). Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). WHO score 7 and above (D28). ADVERSE EVENTS Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: unknown (11 vs 7) No information on whether missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportion of missingness between arms). Risk assessed to be some concerns for the outcome: 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: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available. The registry would have been prospective "but due to administrative delays during COVID-19, the NYU Office of Science and Research submitted the registration to Clinicaltrials.gov on April 27, 2020." For the purpose of selective reporting and due to reasons given, we considered the data presented in the registry.
MORTALITY, VIRAL NEGATIVE CONVERSION Outcomes pre-specified. Result was not selected from multiple outcome measurements nor multiple analyses of the data. Trial was analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE Different timepoint 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: Clinical improvement (D28). WHO score 7 and above (D28). ADVERSE EVENTS Outcome not pre-specified. 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: Adverse events. |
| Overall risk of bias |
Some concerns |