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: "Eligible and consenting adult patients were assigned in a 1:1 ratio to either usual standard of care or usual standard of care plus aspirin using web-based simple (unstratified)
randomisation with allocation concealed until after randomisation"
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: "Participants and local study staff were not masked to the allocated treatment. The trial steering committee, investigators, and all other individuals involved in the trial were masked to outcome data during the trial."
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: Administration of co-interventions of interest, biologics, antivirals and corticosteroids, reported and balanced between groups. 210 of 7457 (3%) usual care patients who completed follow-up received aspirin. 6587 of 7290 patients with completed follow-up at time of analysis allocated to aspirin received aspirin. Overall, the deviation was too small to affect the outcome. Data for the outcome were analyzed using 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: Mortality (D28). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 14,892 participants randomized; 14,892 participants analyzed (with completed follow up data for 14,747).
Data available for all or nearly all participants randomized (>99%). Of note, 23 vs 19 participants withdrew consent. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge alive) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan (prospective, dated November 1st, 2021) and registry (prospective, dated May 11th, 2020) were available.
Outcomes pre-specified. 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). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |