| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote from the protocol: "The study will randomize participants 1:1 to placebo or investigational product. If additional arms are added to or dropped from the trial, randomization will proceed with an equal probability of assignment to each of the remaining arms. Randomization will be stratified by: Site; Severity of illness at enrollment (Severe disease: requiring mechanical ventilation or oxygen, a SpO2 ? 94% on room air, or tachypnea (respiratory rate ? 24 breaths/min); Mild-moderate disease: SpO2 > 94% and respiratory rate < 24 breaths/min without supplemental oxygen)." "Enrollment and randomization of subjects is done online using the enrollment module of Advantage eClinical®. Eligible subjects will be randomized and assigned in a 1:1 ratio to either remdesivir or placebo, with stratification by site and disease severity (Mild/Moderate disease or Severe disease). The randomization is based on a variable blocked scheme to provide an approximately balanced allocation to the treatment groups during the study. If arms are added or removed later in thestudy, randomization will continue in an equal allocation manner." Comment: The allocation sequence was concealed. Allocation sequence random. Baseline imbalances appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "The treatment will be prepared by the licensed pharmacist and administered by an unblinded study nurse. All follow-up safety and efficacy evaluations will be performed by blinded clinic staff."
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. Data were analyzed by using intent-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 1062 patients randomized; 1062 patients analyzed.
Data available for all patients. Risk assessed to be low for the outcomes: Mortality. Time to death. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "All follow-up safety and efficacy evaluations will be performed by blinded clinic staff".
Method of measuring outcome not inappropriate. Measurement or ascertainment of outcome not different between groups. Outcome assessors blinded. Risk assessed to be low for the outcomes: Mortality. Time to death. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were available.
Data presented and analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality. Time to death. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |