| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
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: Treatment sequence random and allocation concealed. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study.
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. Outcome data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
34 randomized; 33 analyzed. Data unavailable in <5% of population. Risk assessed to be low for outcomes: Mortality. Incidence of clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study.
Mortality is an observer-reported outcome not involving judgement. Death was the only serious adverse event reported, therefore no judgement was involved. WHO score 7 and above is an outcome that reflects decisions made by the intervention provider. However, we consider that the assessment of these outcomes cannot possibly be influenced by knowledge of the intervention assignment. Risk assessed to be low for outcomes: Mortality. WHO score 7 and above. Serious adverse events. Clinical improvement (definition is discharged from hospital on room air/no O2) reflects a decision made by the intervention provider where the assessment could possibly be influenced by knowledge of the intervention assignment however we did not consider this likely in the context of a pandemic. For WHO score 6 and above, although the assessment could also possibly be influenced by knowledge of the intervention assignment, we also did not consider this likely to have happened in the context of a pandemic. Adverse events may contain both clinically- and laboratory-detected outcomes, therefore it can be influenced by knowledge of the intervention assignment, but is not likely to. Risk assessed to be some concerns for outcomes: Incidence of clinical improvement. WHO score 6 and above. Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were not available. The registry was available and utilized.
None of the outcomes in this review were registered nor reported as outcomes in the paper. Results was not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality. Incidence of clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |