Trial NCT04362176
Publication PassITON - Self WH, Chest (2022) (published paper)
Primary outcome on the report: Clinical status (illness severity) 14 days after study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score)

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: “Using a centralized, web-based Research Electronic Data Capture (REDCap) platform, enrolled patients were randomized in a 1:1 ratio to COVID-19 convalescent plasma or placebo stratified by site, sex, and age.”
Comment: Allocation sequence random. Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote: “Patients, investigators, outcome assessors, and treating providers remained blinded.”
Comment: Blinded study (participants and personnel/carers).

MORTALITY. CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS
Our analysis for the binary outcomes 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). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.

TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT
Participants were analyzed according to their randomized groups for the time-to-event outcomes.
Of note, 8 vs 6 participants were excluded from the analysis post-randomization because they withdrew consent however this will be assessed in domain 3 as missing data.
Risk assessed to be low for the outcomes: Time to death. Time to clinical improvement.
Missing outcome data
Low 		Comment: 974 participants randomized; 960 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events.
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: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan and prospective registry were available.
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). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Overall risk of bias
Low