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: "Randomization was performed using a secure, central, interactive, web-based response system (eSOCDAT). Crizanlizumab or saline placebo was prepared by the site pharmacist who was unblinded; after crizanlizumab or placebo was prepared, the study treatment was blinded by using darkened bags"
Comment: Allocation sequence random. Allocation sequence concealed. |
Deviations from intervention |
Low |
Quote: "double-blind" (report) "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (registry)
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. (br/>Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 54 participants randomized; 52 participants analyzed for clinical improvement (discharge); 50 participants analyzed for safety; 42 participants analysed for mortality and WHO score 7 or above.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 2 vs. 2 did not receive intervention, 3 vs. 5 had missing blood draw. Not likely that missingness depended on the true value of the outcome because reasons and proportions of missing data were similar between arms. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). 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). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and trial registry were available (dated 17 June 2020).
Outcomes were 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). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |