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: "Hospitalized patients with Covid-19 were randomly
assigned in a 1:1 ratio to receive either
LY-CoV555 or matching placebo.
Randomization was stratified according
to the trial pharmacy, since each pharmacy
could serve more than one trial site. LY-CoV555
or placebo was administered as a single intravenous
infusion over a 1-hour period. The infusion
was prepared by trial pharmacists. All other personnel,
including investigators and research staff,
clinical staff, and patients, were unaware of the
trial-group assignments."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote (report): “The infusion was prepared by trial pharmacists. All other personnel, including investigators and research staff, clinical staff, and patients, were unaware of the trial-group assignments.”
Quote (protocol): “blinding of the participant and clinical staff will be achieved by placing a colored sleeve over the infusion bags used for investigational agents and placebos” Comment: Blinded study (participants and personnel/carers). MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, SERIOUS ADVERSE EVENTS Data for the outcome were analyzed using 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). Mortality (D60 or more). Clinical improvement (D60 or more). WHO score 7 and above (D28). Serious adverse events. TIME TO DEATH, TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 6 vs 6 participants were excluded from the analysis post-randomization because they did not receive the drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Time to death. Time to clinical improvement. |
| Missing outcome data |
Low |
Comment: 326 participants randomized; 314 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). WHO score 7 and above (D28). Time to clinical improvement. 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). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective protocol (dated July 27, 2020) and trial registry (dated August 06, 2020) were available. The statistical analysis plan was also available (dated October 06, 2020).
MORTALITY, TIME TO DEATH, TIME TO CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, SERIOUS ADVERSE EVENTS 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 outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. CLINICAL IMPROVEMENT Outcome not pre-specified No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D60 or more). |
| Overall risk of bias |
Some concerns |