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: "This open-label, randomized clinical trial was designed to evaluate
the efficacy and safety of IFN β-1b in the treatment of patients with CoVID-19" "Patients were randomly recruited (1:1) to the IFN group or the control group. The method of randomization was the permuted block randomization (6 patients per block) "A biostatistician who was not involved in patients’ care did this process" Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study (participants and personnel/carers).
Deviations from intended intervention arising because of the study context: No participant cross-over. No information on co-interventions of interest, biologics. Administration of antivirals and corticosteroids were reported. Hence, no information on whether deviations arose because of the trial context. MORTALITY, WHO SCORE 7 AND ABOVE 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). WHO score 7 and above (D28). TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 7 vs 7 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: Time to clinical improvement. |
| Missing outcome data |
Some concerns |
Comment: 80 eligible participants randomized, 66 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: withdrew consent (3 vs 4), enrolled in another trial (0 vs 3), discontinued IFN (4 vs 0) Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (equal proportion of missingness between arms) Risk assessed to be some concerns for outcomes: Mortality (D28). Time to clinical improvement. 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). 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). TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as at least 2 points improvement on a 6-category scale) 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: Time to clinical improvement. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available, though the authors stated they will include them as supplementary material. The registry was available and utilized.
MORTALITY, WHO SCORE 7 AND ABOVE Outcomes were taken from the "Clinical outcome" endpoint that was registered and then reported in the paper as "Clinical status". However, the timepoints do not correspond. In the registry it is "end of treatment" and in the paper it is "at day 7, 14 and 28". 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 outcomes: Mortality (D28). WHO score 7 and above (D28). TIME TO CLINICAL IMPROVEMENT 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: Time to clinical improvement. |
| Overall risk of bias |
Some concerns |