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: "After giving informed consent to participate, patients were registered in a web-based electronic Case Report Form (eCRF) performed with ORACLE clinical. After baseline clinical data were recorded and plasma availability confirmed, patients were randomized using a centralized system embedded in the eCRF that ensures allocation concealment. Randomization list was 1:1 ratio, stratified by study site with variable block size multiple of 2 elements and generated using the RERAND system integrated within the eCRF" Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "open-label"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: 1 patient did not receive the intervention due to absence of AB0 blood group compatible plasma. Administration of co-interventions of interest (antivirals, corticosteroids and biologics) were balanced between the two arms. Hence, deviations did not arise 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. Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 350 participants randomized, 350 participants analyzed.
Of note, missing data included withdrawn consent and lost to follow up The flow chart of the study shows 8 patients who did not reach end of study, day 28) (3 vs 5) However, data were available for nearly all participants randomized. Risk assessed to be low for outcomes: Mortality (D28). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Appropriate method of outcome measurement.
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). TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as one point improvement on ordinal scale) 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: Time to clinical improvement. SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that 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: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were available but retrospective (dated September 20th, 2020). The prospective version of the registry (dated April 10th, 2020) was available and utilized.
MORTALITY, SAE 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). Serious adverse events. WHO SCORE 7 AND ABOVE, TIME TO CLINICAL IMPROVEMENT Outcomes not pre-specified. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Time to clinical improvement. WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |