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 |
Some concerns |
Protocol: "A statistician not directly involved in the analysis of the study results will prepare the folded paper. The schedule will be provided to the pharmacist and sealed envelopes containing the treatment allocation to assign to each participant. Participants will be expected to pick a folded paper out of 60 folded papers which gives them an equal chance of belonging to any of three arms."
Comment: Allocation sequence random. Unclear allocation concealment (i.e., unclear if opaque envelopes and if sequential). |
Deviations from intervention |
Some concerns |
Report: "We conducted a translational proof of concept (PoC) randomized,
double blind placebo controlled dose response trial"
"The study was a proof of concept (PoC), double blind, randomized controlled trial" Protocol: "This is designed as a double-blind trial. The tablets for the three arms of the study will look alike and labeled ABC." "The 3mg tablets will be used meaning those to receive 6mg will have 2 tablets and those to receive 12mg will have 4 tablets." With blinding, the drugs will be labeled as assigned by the statistician. The data will be entered against the label of the drug being taken. The name of the drug will only be revealed at the end of the study after data has been collated. Comment: There is conflicting information between the report and its protocol. In the report, no placebo is described beyond the brief mention in the abstract. Patients in the control arm received Lopinavir/Ritonavir, which was not allowed for patients in the Ivermectin arms. Although described as a double-blind trial, patients could have been aware of the treatment assignment due to the number of tablet given. Furthermore, because lopinavir/ritonavir was not allowed for patients in the ivermectin arms, this treatment difference likely compromised the blinding of physicians and study personnel. No participant cross-over. Although administration of corticosteroids were reported and balanced between groups, there was no information on administration of another co-intervention of interest, biologics. Hence, little to no information on deviations that arose due to the trial context. According to the protocol, the intention to treat analysis method was used. As we are assessing the effect of assignment to intervention, this method is considered appropriate. Risk assessed to be some concerns for the outcomes: Mortality (D28). Time to viral negative conversion. |
Missing outcome data |
Low |
Comment: 63 patients randomized; 62 patients analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to viral negative conversion. |
Measurement of the outcome |
Low |
Comment: Unclear blinding; no information on blinding of outcome assessor.
Mortality and viral negative conversion are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to viral negative conversion. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry were available.
Mortality was not an outcome pre-specified in the protocol or registry but we consider the reporting of this outcome acceptable as mortality should be reported even if not planned. Time to viral negative conversion was pre-specified as reported. Serious adverse events were pre-specified as reported. 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: Mortality (D28). Time to viral negative conversion. |
Overall risk of bias |
Some concerns |