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: “Central Internet-based systems to randomly assign patients to receive either therapeutic- dose anticoagulation with unfractionated or low-molecular-weight heparin or usual-care pharmacologic thromboprophylaxis in an openlabel
fashion.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: The comparison was therapeutic-dose anticoagulation with heparin versus usual care prophylactic anticoagulation. Thus both arms received anticoagulation, with some in each group recieving similar regimens.11.6% of the intervention group received the control. 0.9% of the control received the intervention. No information on administration of co-interventions of interest: antivirals and corticosteroids and biologics. Hence, no information on whether deviations arose because of the trial context 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 some concerns for the outcomes: Mortality (D60 or more). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). |
| Missing outcome data |
Low |
Comment: 2245 participants randomized; 2226 participants analyzed for mortality (D60 and more), 2219 for clinical improvement, 2231 for WHO score 7 and above.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. Clinical improvement (D28). WHO score 7 and above (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, TIME TO DEATH Mortality is an observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. WHO SCORE 7 AND ABOVE For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcome: WHO score 7 and above (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as survival to discharge) 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 outcome: Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The protocol (prospective core protocol dated July 10th, 2019 and retrospective pandemic appendix to core protocol dated May 18th, 2020), statistical analysis plan (retrospective, dated 5th January) and trial registries (retrospective) were available.
NORTALITY, TIME TO DEATH Outcome 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 (D60 or more). Time to death. CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE Outcome not pre-specified No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |