8. ROB table: tocilizumab vs standard care(SC)/placebo. Time to WHO score 7 or above.
| Study | 1.Randomisation |
2.Deviations from intervention |
3.Missing outcome data |
4.Measurement of the outcome |
5.Selection of the reported results |
Overall risk of bias |
| Hermine CORIMUNO‐19 2020 | Low | Some concerns 1 | Low | Low | Low | Some concerns |
| Salama EMPACTA 2020 | Low | Some concerns 2 | Low | Low | Low | Some concerns |
| Stone 2020 | Low | Low | Low | Low | Low | Low |
1 Quote: “Open‐label study” Comment: unblinded study.
Deviations from intended intervention arising because of the study context: 3 participants in the treatment group did not receive study drug. Administration of co‐interventions of interest (antivirals, corticosteroids and biologics) were reported. The proportions of participants receiving antivirals and steroids were imbalanced between 2 arms (> 10% absolute difference between the 2 arms) for steroids. This deviation could affect the outcome and was not balanced. Nevertheless, this domain was rated as Some Concerns as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. Participants were analysed according to their randomised groups for the outcome. Of note, 1 vs 0 participants were excluded from the analysis because of consent withdrawal. Nevertheless, we consider the analysis appropriate to estimate the effect of assignment to intervention.
2 Quote: “double‐blind, placebo‐controlled trial.” “A site blinding plan was established at each site to identify which personnel would be blinded or unblinded at a site level. A pharmacy manual and specific training in addition to completion of a site blinding plan was provided to each site. Each site had an unblinded pharmacist that randomized the participant and prepared and labeled study medication in the same method for both tocilizumab and placebo. The remainder of the study team was blinded to treatment assignment. There was no communication during the study between unblinded and blinded members. In addition, there was an unblinded medical monitor available to answer questions from the unblinded site staff. Placebo was not provided and consisted of an unaltered saline infusion bag, the same as would be used to prepare tocilizumab. The volume of tocilizumab diluted in saline appears colorless and matches saline.”
Comment: Blinded study. Participants were blinded. Carers were probably blinded. Participants were analysed according to their randomised groups for the outcome. Of note, 10 vs 1 participants were excluded from the analysis post‐randomisation because they did not receive the drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this time‐to‐event outcome. There was probably no substantial impact of failure to analyse participants according to their randomised groups