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 (protocol): “Consecutive consenting COVID-19+ patients will be recruited as participants, who will be randomized equally to camostat mesylate or placebo using a permuted-block design with variable
block size. Actual treatment assignment will be double-blind, concealed from the investigators and the participants. The YCCI statistical group (YCAS) will generate the randomization scheme
and provide it to the pharmacy.”
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Low |
Quote: “Double-blind. The study pharmacy prepared study drug by over-encapsulation with an identically prepared placebo.”
Comment: Blinded study (participants and personnel/carers) HOSPITALIZATION OR DEATH. MORTALITY. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. Our analysis for the binary 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). Adverse events. Serious adverse events. INCIDENCE OF VIRAL NEGATIVE CONVERSION. Participants were analyzed according to their randomized groups for the outcome. Of note, 12 vs 9 participants were excluded from analysis for unknown reason. This will be taken into account in ROB3. We considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 70 participants randomized; 70 participants analyzed (ITT), 67 with 3 consent withdrawals. 47 participants analyzed (Incidence of viral negative conversion).
HOSPITALIZATION OR DEATH. MORTALITY. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events. INCIDENCE OF VIRAL NEGATIVE CONVERSION. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Unknown. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| 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: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol (dated April 5, 2020), statistical analysis plan and prospective registry (dated April 20, 2020) were available.
Outcomes reported were pre-specified in the registry and/or protocol. 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: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |