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: “COnV-ert: Eligible patients who provided written informed consent were randomly assigned (1:1) using a computer-generated random-number list. CoV-Early: Eligible patients were randomized using an online randomization tool incorporated in the eCRF (ALEA). The allocation code was mailed to the transfusion lab of the hospital. They provided the study team with one unit of convalescent or control plasma. Masking of investigators and the patient was done by the transfusion lab with the use of a non-transparent concealment bag around the plasma unit."
Comment: Allocation sequence random Allocation concealment probably random. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “Double-blinded. COnV-ert: [infusions were] covered with opaque tubular bags for blinding investigators and patients.
Cov-Early: Masking of investigators and the patient was done by the transfusion lab with the use of a non-transparent concealment bag around the plasma unit."
Comment: Blinded study (participants and personnel/carers). 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, 8 treatment vs 7 control participants were excluded from the analysis post-randomization because they did not receive the intervention (n=7) or placebo (n=5), or because they were <50 years of age (1 vs 2). This will be accounted for in domain 3. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| Missing outcome data |
Low |
Comment: 797 participants randomized; 782 participants analyzed.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| Selection of the reported results |
Low |
Comment: A summary protocol of the included RCTs and the individual RCT registrie were available (dated Oct 19, 2020 and Nov 9, 2020).
Outcome 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 outcome: Mortality (D28). Hospitalization or death. Clinical improvement (D28). WHO score 7 and above (D28). |
| Overall risk of bias |
Low |