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: "The trial participants were randomly assigned
(in a 1:1 ratio) to receive subcutaneous REGENCOV
at a total dose of 1200 mg (600 mg each of
casirivimab and imdevimab) or placebo and were
stratified according to age and to the results of
local diagnostic tests to detect SARS-CoV-2." (report)
"Subjects will be randomized in a 1:1 ratio to receive REGN10987+REGN10933 or placebo according to a central randomization scheme provided by an interactive web response system (IWRS) to the designated study pharmacist (or qualified designee). Randomization will be performed by individual study subjects, not by households. All subjects randomized will be given a household identification number in the case that multiple members of the same household are enrolled and receive study drug. This ensures that any correlation among subjects within the same household may be considered in the statistical analysis." (protocol) Comment: Allocation sequence probably random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. Co-interventions not reported. |
| Deviations from intervention |
Low |
Quote: "randomized, double-blind, placebo-controlled trial"
Comment: Blinded study (participants and personnel/carers) Participants were analyzed according to their randomized groups for the outcome. Of note, 214 vs 194 participants were excluded after randomization due to SARS-CoV-2 PCR positive or undetermined and 269 vs 293 because they were seropositive or sero-undetermined (seronegative mFAS-A population), according to protocol. This outcome population was pre-defined prior to database unblinding. This is an ineligibility exclusion and was considered appropriate to estimate the effect of assignment to preventive intervention. Risk assessed to be low for the outcome: Confirmed COVID-19. Symptomatic confirmed COVID-19. |
| Missing outcome data |
Low |
Comment: 2475 participants randomized; 1505 participants analyzed for efficacy.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: SARS-CoV2 PCR positive or undetermined (214 vs 194), seropositive or sero-undetermined (269 vs 293) [all avvounted for in domain 2] Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcome: Confirmed COVID-19. Symptomatic confirmed COVID-19. |
| 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: Confirmed COVID-19. Symptomatic confirmed COVID-19. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (30 June 2020).
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: Confirmed COVID-19. Symptomatic confirmed COVID-19. |
| Overall risk of bias |
Low |