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: “Randomisation was performed using permuted block randomisation with varying block sizes ranging from 4 to 8. Generation of randomisation numbers was done by the study biostatistician, who did not have contact with participants. The biostatistician printed individual randomisation numbers with their corresponding treatment assignment and placed each number in an opaque envelope. Each enrolled participant was asked to pick the envelope on top of the batch.
Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Open label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: 6 patients in the SOC arm withdrew because they wanted the study treatment (not reported whether they received it); 6 in the CCP+SOC arm withdrew before transfusion, 1 was not transfused because of stock out and 1 died prior to transfusion. No information on administration of co-interventions of interest: antivirals and biologics. Corticosteroids were reported and were administered slightly more frequently in the SOC alone arm (52.2% vs. 65.7%). Hence, no information on whether deviations arose because of the trial context. 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). Incidence of viral negative conversion (D7). Time to viral negative conversion. Adverse events. |
| Missing outcome data |
Low |
Comment: 136 participants randomized; 122 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 6 patients in the SOC arm withdrew because they wanted the study treatment (not reported whether they received it); 6 in the CCP arm withdrew before transfusion, 1 was not transfused because of stock out and 1 died prior to transfusion. The risk of bias due to deviations from the interventions has been taken into account in domain 2. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. 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, VIRAL NEGATIVE CONVERSION and TIME TO VIRAL NEGATIVE CONVERSION Observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. 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 |
Low |
Comment: The prospective registry was available (dated September 9, 2020).
Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Adverse events |
| Overall risk of bias |
Some concerns |