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: “Participants were randomly assigned to Lambda or placebo using a 1:1 REDCAP-based computer-generated randomization scheme that stratified by age ( 50 and < 50 years old) and sex. A password-protected electronic spreadsheet containing the randomization allocation, along with the code used to generate the allocation and seed used in the random number generation, was stored on secure servers at Stanford.” "The study medication/placebo syringe was dispensed by the Stanford Investigational Pharmacist"
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Low |
Quote: "single-blind" "Lambda and placebo syringes were identically labeled but differed in the appearance of the needle hub. Since the nurse administering the medication might see syringe differences, the study was not strictly “double-blind” even though all participants and investigators were blinded to treatment arm."
Comment: It is unlikely that this lack of blinding (of the study nurse) would have led to deviations (by patients or staff) from the intended intervention. Two participants, after randomization, inadvertently were injected with the incorrect syringe. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context. Our analysis for the outcome 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: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Time to viral negative conversion. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 120 patients randomized; 120 patients analyzed.
Data available for nearly all participants randomized. Of note, 2 vs 2 participants withdrew from study. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Time to viral negative conversion. 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 likely blinded). Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Time to viral negative conversion. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The retrospective protocol and statistical analysis plan were available. The prospective registry (consulted up to version dated April 23rd, 2020) was utilized.
TIME TO VIRAL NEGATIVE CONVERSION 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: Time to viral negative conversion. MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably 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). HOSPITALIZATION OR DEATH. ADVERSE AND SERIOUS ADVERSE EVENTS. Outcome not pre-specified in the registry. 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: Hospitalization or death. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |