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 an interactive web response system and a randomization schedule prepared by unblinded biostatisticians.” "Participants, personnel, and outcome assessors were blinded to treatment allocation for the duration of the study. CT-P59 and placebo were supplied in identical vials identified by a study drug number. Designated unblinded personnel prepared the study drug for infusion."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Low |
Quote: “Participants, personnel, and outcome assessors were blinded to treatment allocation for the duration of the study. CT-P59 and placebo were supplied in identical vials identified by a study drug number. Designated unblinded personnel prepared the study drug for infusion."
Comment: Blinded study (participants and personnel/carers) Participants were not analyzed according to their randomized groups for the outcome. Of note, 1 participant randomized to the control group was analyzed in an intervention group. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
Missing outcome data |
Low |
Comment: 327 participants randomized; 325 participants analyzed for mortality, adverse events and serious adverse events outcomes; 307 participants analyzed for viral negative conversion.
MORTALITY, ADVERSE and SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 20 patients were excluded as they were found not to be RT-PCR positive at baseline. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). |
Measurement of the outcome |
Low |
Quote: "Quote: “Participants, personnel, and outcome assessors were blinded to treatment allocation for the duration of the study."
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan (SAP), and registry were available. The protocol, SAP and some registries were retrospective. The prospective EU Clinical Trials Register was consulted.
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). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
Overall risk of bias |
Low |