| Bias | Author's judgement | Support for judgement |
| Confounding |
Moderate |
Comment: The confounders of interest (age, sex, comorbidities, severity, insurance) were controlled for in the propensity score model (see “Variables assessed” section; the variables included in the propensity score model are listed in the Supplementary file, Table S2; see Table 1 for baseline differences in confounders). See sections “Data sources” and “Variables assessed” for measures used by the authors |
| Selection of participants into the study |
Serious |
Comment: Follow up begins after the first 24 hours after arrival at the emergency room. Patients are classified as receiving HCQ if they received HCQ at baseline (defined as the first 24 hours after arrival at the emergency room) or during the follow-up period. Therefore, some patients might receive HCQ before the start of the follow up (prevalent users) and this time interval wasn’t included in the analysis (risk of lead time bias). For patients who received HCQ after baseline, the time period in which they did not receive HCQ should be classified in the non-exposed group (risk of immortal time bias). |
| Intervention classification |
Low |
Quote: “Patients were defined as receiving hydroxychloroquine if they were receiving it at study baseline or received it during the follow-up period before intubation or death. Study baseline was defined as 24 hours after arrival at the emergency department.).” Comment: data were collected from clinic records. Treatment groups were classified using clearly defined criteria. |
| Deviation from intended intervention |
NI |
Comment: The information reported is inadequate to assess whether there are deviations from the intended intervention beyond what would be expected in usual practice. For example, the authors present only baseline data for the administration of co-interventions (e.g., azithromycin). It is unclear how many participants per arm received these co-interventions during follow-up. Inadequate information to assess risk for the outcomes: WHO clinical improvement scale 7 or above. |
| Missing data |
Low |
Comment: No participants were excluded due to missing data. Risk assessed to be low for the outcomes: WHO clinical improvement scale score 7 or above. Time to WHO score 7 and above |
| Measurements of outcomes |
Low |
Comment: WHO clinical improvement scale 7 or above is an observer-reported outcome involving clinical decision-making. It could theoretically have been influenced by knowledge of the intervention received by the participants, but this is unlikely in the pandemic context. Risk assessed to be low for the outcomes: WHO clinical improvement scale score 7 or above. Time to WHO score 7 and above |
| Selection of the reported results |
Moderate |
Comment: The outcomes and analyses are clearly defined in the Methods section. Planned subgroup/sensitivity analysis results are reported. There is no a-priori registered protocol or statistical analysis plan available. Risk assessed to be moderate for the outcomes: WWHO clinical improvement scale score 7 or above. Time to WHO score 7 and above |