|Bias||Author's judgement||Support for judgement|
|Quote: “The randomization was performed by permuted block randomization and block sizes of 2, 4 and 6 used randomly. The statistician prepared a list of numbers for randomization. Sequentially numbered opaque envelopes were prepared according to the list and envelopes were delivered to the clinical investigators. The statistician that performed randomization and analysis was unaware regarding to treatment and follow-up of patients.”
Comment: Allocation sequence random. Allocation concealment unclear (sealing of envelopes).
|Deviations from intervention||
|Comment: Unblinded study. (patients and physicians)
No participant cross-over.
Administration of all co-interventions of interest were reported: antivirals, biologics, corticosteroids.
Imbalance in corticosteroid administration (61.9% vs 43.6% in the intervention vs control arms) and biologic administration (35.7% vs 25.6% in the intervention vs control arms).
Data were analyzed using per protocol analysis, hence inappropriate to estimate the effect of assignment
Substantial impact of failure to analyze participants in randomized group since 4 known deaths occurred in excluded patients.
|Missing outcome data||
|Comment: 92 patients randomized; 81 patients analyzed.
Seven patients in the control arm were excluded. Reason: entered another trial.
Missingness is likely to be due to its true value, and related to the outcome.
Four patients in the intervention arm were excluded. Reason: died before finishing the first week treatment (i.e., received <3 doses of IFN).
The reason for missing data is associated with the outcome for mortality. Although we do not agree with the reason for exclusion of these participants, for our review, since the event is known, we do not consider it missing data for Mortality outcome (total missing data still >5% of population; 7/92 participants). For the other outcomes, it is considered missing data (total missing data 11/92; >5% of population)
Risk assessed to be high for the outcomes: Mortality. Time to death. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above.
|Measurement of the outcome||
|Comment: Unblinded study (outcome assessor).
Mortality is an observer-measured outcome not involving judgement. 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: Mortality. Time to death. WHO score 7 and above.
Time to clinical improvement (defined as time to at least 2-point improvement in ordinal scale or discharge) and WHO score 6 and above require 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: Time to clinical improvement. WHO score 6 and above.
|Selection of the reported results||
|Comment: The protocol and statistical analysis plan were not available. The registry was available.
Time to clinical improvement was listed in the registry as "Response to treatment" and reported as the primary outcome in the publication. WHO score 6 and above and WHO score 7 and above were also specified in the registry as it was measured using data from the ordinal scale of "Response to treatment" outcome and reported in the published article.
Result was not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for outcome: Time to clinical improvement. WHO score 6 and above. WHO score 7 and above.
Mortality outcome was not listed in the registry but reported as a secondary outcome in the publication.
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: Mortality. Time to death.
|Overall risk of bias||