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 ConCOVID study was designed as a nationwide multicenter open-label randomized clinical trial...assigned via a
web-based system ALEA at a 1 : 1 ratio to the current SoC with or without the
addition of 300 mL ConvP."
Quote from protocol: "All eligibility criteria will be checked with a checklist at the time of randomization. Patients will be randomized without stratificiation with the use of an online randomization system using blocks of 4 and 2 in ALEA. Each patient will be given a unique patient study number (a sequence number by order of enrolment in the trial). Patient study number and result of randomization will be given immediately by the online registration database and confirmed by email" Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "open-label"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. No information on any co-interventions of interest were reported: antivirals, biologics, corticosteroids. Hence, no information on whether deviations arose because of the trial context. 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 some concerns for the outcomes: Mortality (D60 or more). Clinical improvement (D28). Serious adverse events. |
| Missing outcome data |
Low |
Quote: "At that time, all 86 patients had been followed for at least 15 days after inclusion and 75 and 32 for at least 30 and 60 days respectively"
Comment: 86 participants randomized, 86 participants analyzed for Clinical improvement (D28) and Serious adverse events. 32 participants analyzed for Mortality (D60 or more). Clinical improvement (D28). Serious adverse events. Data available or all or nearly all participants randomized. Risk assessed to be low for the outcomes: Clinical improvement (D28). Serious adverse events. Mortality (D60 or more). Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: on going study. Particpants had not reached the follow up timepoint. Missingness could not depend on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Mortality (D60 or more) |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D60 or more). Clinical improvement (defined as Improvement on the 8-point WHO COVID-19 disease severity scale from inclusion to day 15) requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on serious adverse events that may contain both clinically- and laboratory-detected events. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The retrospecitve protocol statistical analysis plan (dated May 11th, 2020) and registry (considered as prospective, since only 2 days delay, dated April 10th, 2020) were available.
Mortality was pre-specified in the registry. Results were not selected from multiple outcome measurements or analyses of the data. Trial probably analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D60 or more). Clinical improvement and serious adverse events were not pre-specified by the April 15th update of the registry (start of trial April 8th, 2020). 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 outcomes: Clinical improvement (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |