| Bias | Author's judgement | Support for judgement |
| Confounding |
Serious |
The model controlles for age, sex,severity and the following review comordidities: diabetes, hypertension, obesity. Also controlles for ischemic heart failure and cancer. Ethnicity/socioeconmic status, immunosupression not controlled for. Some patients start treatment after 48 hours (withing three days of hospitalsation and there was no adjustment for this time- varying confounding. |
| Selection of participants into the study |
Moderate |
Quote: "Day 3 from hospital admission was set as a landmark time point: those who died, were intubated or discharged from the hospital before day 3 were excluded, while patients were included in the tocilizumab/methylprednisolone treatment group if the treatment was started within 3 days from hospital admission (see Fig 1). Authors decided to start follow up on day 3 for both groups to avoid the case of immortal bias. Although they excluded patients who had outcome within the first 3 days, these excluded patients would happen in both groups. So this exclusion is unlikely to be related to interventions. |
| Intervention classification |
Low |
Participants receiving study treatment within three days from hospitaisation were included in the treatment group.Participants treated with study drugs after three days from hospitalization were included in the SOC group. Quote: "The outcomes of patients treated with tocilizumab/methylprednisolone were compared to data from consecutive patients admitted to our hospital for COVID-19 pneumonia who received only SOC, mainly because they were admitted before the routine use of tocilizumab/ methylprednisolone (control group)" "Within the cohort of 130 treated patients, 45 (34.6%) received methylprednisolone, 29 (22.3%) tocilizumab and 56 (43.1%) combined therapy" "Data were collected from hospital information system by a standard based automatic procedure and stored in an online database with pseudo-anonymization features suitable for secondary use of clinical data" "Controls were identified through this prospectively collected database of hospital-admitted COVID-19 patients" Comments: Observational study, Tocilizumab was added in case of systemic inflammation or rapid respiratory function deterioration, and methylprednisolone was used according to COVID-19 protocol in place "20 patients receiving treatment afte day 3 from hospitalization were included in the control (ie, SOC) group, but excluded from sensitivity analysis" |
| Deviation from intended intervention |
Serious |
Quote: 20 patients that were treated with tocilizumab/methylprednisolone after 3 days from hospitalization were included in the SOC group. Comment: Deviation from intended intervention beyond what would be expected in usual practice and likely to have affected the outcome. |
| Missing data |
Low |
Comment: Survival analysis included 196 patients (130 treatement group and 66 in SOC group) as per figures 2 and 4. Risk assessed to be low for outcomes: mortality and need of mechanical ventilation, AE/SAE |
| Measurements of outcomes |
Low |
Outcome assessors were likely aware of the intervention received however the outcomes 'Time to death or mechanical ventilation' are objective observer-reported outcomes not involving judgement. Risk assessed to be low for outcomes: Time to death or mechanical ventilation. Adverse events included both laboratory and clinical assessment. |
| Selection of the reported results |
Moderate |
Comment: The outcomes are clearly defined in the Methods section. There is no a-priori registered protocol or statistical analysis plan available Risk assessed to be moderate for the outcome: time to mechanical ventilation or death, AE/SAE |