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: “A stratified permuted block randomization procedure with a 1:1 ratio, with blocks of variable sizes and stratification for clinical sites,was generated by using Stata version 16.1 (StataCorp). Eligible patients underwent web-based treatment allocation through REDcap platform. The Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) managed the randomization of patients and the database of the study through the creation of electronic case report forms on the REDCap secure web application.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Antivirals and corticosteroids were reported and balanced between groups. Biologics were the intervention. Hence, no deviations arose because of the trial context. Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Of note, 9 (treatment)/ 5 (control) participants were excluded from the analysis post-randomization because 1/3 withdrew informed consent; 8/2 did not receive the treatment due to: 4/0 lack of compatible plasma, 1/1 medical decision, 3/1 patient refusal. Risk assessed to be low for the outcomes: Mortality (D28). WHO score 7 and above (D28). Adverse events. |
| Missing outcome data |
Low |
Comment: 487 participants randomized; 487 participants analyzed for adverse and severe adverse events; 471 participants analyzed for mortality (D28); 470 participants analyzed for WHO score 7 and above (D28).
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). WHO score 7 and above (D28). 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 Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). WHO SCORE 7 AND ABOVE For this outcome, 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). 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 outcome: Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol (dated May 18, 2020), statistical analysis plan (dated May 18, 2020), supplementary material and retrospective registry (dated January 20, 2021).
Outcomes pre-specified. Results were 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 (D28). WHO score 7 and above (D28). Adverse events. |
| Overall risk of bias |
Some concerns |