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: "subjects were randomized 1:1 into treatment arm or standard of care (SOC) control arm. Author M.G., the randomizing investigator, used a web-based computer-generated randomization (A study [IVIG] group, B control [SOC] group) in blocks of 10 (https://www.sealedenvelope.com/simple-ran-domiser/v1/lists). When the randomization list was generated, M.G. placed the codes into individual sealed and sequentially numbered envelopes. The batch of sealed envelopes was stacked in sequential order and retained in a locked drawer in the Investigational Research Pharmacy. After informed consent was obtained from a potential study subject, M.G. obtained the next numbered envelope (i.e., #001, #002, #003, etc.) to obtain the A, B randomization code for treatment arm allocation" Comment: Allocation sequence random. Unclear allocation concealment (no information on opaque envelopes). |
| 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. Administration of all co-interventions of interest were reported: antivirals, corticosteroids and biologics. Corticosteroid administration: 16/17 vs. 10/17 in the intervention vs control arms. The rest were balanced. This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. 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 low for outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 34 participants randomized; 33 participants analyzed.
Data available for all or nearly all participants randomized. Of note, 1 subject immediately deemed unevaluable by the principal investigator due to a high risk of bacterial superinfection. Risk assessed to be low for outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| 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 outcome: 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 outcome: WHO score 7 and above (D28). SERIOUS ADVERSE EVENTS Death was the only serious adverse event reported, therefore no judgement was involved. Risk assessed to be low for the outcome: Serious adverse events. CLINICAL IMPROVEMENT Clinical improvement (defined as discharged from hospital on room air/no O2) 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). ADVERSE EVENTS The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The registry was available but retrospective (dated June 2nd, 2020).
CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE 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). Adverse events. Serious adverse events. MORTALITY Mortality outcome was not pre-specified, 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). |
| Overall risk of bias |
Some concerns |