| Bias | Author's judgement | Support for judgement |
| Confounding |
Moderate |
Comment: The following review confounders (Age, Gender, Comorbidities, Severity) were controlled for in the propensity score model. Review confounders socio-economic status, ethnicity and site-effects were not recorded from the database nor controlled for. All 17 hospitals were in Madrid. Other non-review comorbidities (Lung Dx, CKDx, CCF, IHDx) were recorded and included in the model. |
| Selection of participants into the study |
Serious |
Quote: We excluded 99 patients because they died, were discharged, or were transferred to a different hospital within 24 hours after admission to the emergency department. Comment: It is unclear when start of follow up (T0) began. It seems to be admission date. It is also unclear when start of intervention occurred for all patients. They do report a median (IQR) for first dose. Quote: The first dose was administered at a median time of 4 (IQR 3 5) days from inpatient admission. » Comment: For patients who received Tocilizumub after T0, 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 |
Comment: Information collected from a dataset. Quote: "The dataset collects the different interactions in the COVID-19 treatment process including detailed information on diagnoses, treatments, admissions, intensive care unit (ICU) admissions, diagnostic imaging tests, laboratory results, discharge or death, and diagnostic and procedural records coded according to the International Statistical Classification of Disease and Related Health Problems (ICD-10) classification." |
| Deviation from intended intervention |
Moderate |
Comment: The information reported is inadequate to assess whether there are deviations from the intended intervention beyond what would be expected in usual practice. Review co-interventions were administered but no per arm proportions reported. They did perform a planned exploratory sensitivity analysis stratified by CRP. |
| Missing data |
Moderate |
Comment: n=79 treated and n=739 controls were excluded due to missing data of which n=28 and n=123 had the outcome mortality. Quote: The characteristics of the individuals not included due to missing data in the information required for the statistical modelling strategy are shown in Table S1 in the Supplement. |
| Measurements of outcomes |
Low |
Comment: Observer-reported outcome (death). Risk assessed to be low for the outcomes: time to death. |
| Selection of the reported results |
Moderate |
Comment: The outcomes and analyses are clearly defined in the Methods section. There is no a-priori registered protocol or statistical analysis plan available. Risk assessed to be low for the outcomes: time to death. |