Risk of bias for analysis 1.5 Serious adverse events.
| Study | Bias | |||||||||||
| Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
| Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
| Angus 2020 | Low risk of bias | Participants were randomised to each locally available group using balanced assignment. Participants were randomly assigned via a computer software program to each locally available group using proportional assignment (e.g., 1:1 if 2 groups available and 1:1:1 if 3 groups available) Protocol: The RAR will occur centrally as part of the computerised randomisation process. Sites will receive the allocation status and will not be informed of the randomisation proportions. Each region will maintain its own computer‐based randomisation program that is accessed by sites in that region but the RAR proportions will be determined by a SAC and provided monthly to the administrator of each region's randomisation program who will update the RAR proportions Baseline characteristics were similar across groups. |
Some concerns | Participants and clinicians were aware of the assigned treatment. Further 15% of the participants in the no hydrocortisone group received hydrocortisone, and although we deem it rather unlikely that a larger part of these deviations arose from the experimental context, we see some concerns. | High risk of bias | Since data were not adjusted for competing risk of death in the presence of a relevant death rate, risk of bias is high. | Low risk of bias | The measurement method was appropriate. | Low risk of bias | Protocol and SAP available. | High risk of bias | Because of the issue of competing risk of death all data for this outcome might not be available. There was no adjustment in the analysis for competing risk of death. |
| Angus 2020 | Low risk of bias | Participants were randomised to each locally available group using balanced assignment. Participants were randomly assigned via a computer software program to each locally available group using proportional assignment (e.g., 1:1 if 2 groups available and 1:1:1 if 3 groups available) Protocol: The RAR will occur centrally as part of the computerised randomisation process. Sites will receive the allocation status and will not be informed of the randomisation proportions. Each region will maintain its own computer‐based randomisation program that is accessed by sites in that region but the RAR proportions will be determined by a SAC and provided monthly to the administrator of each region's randomisation program who will update the RAR proportions Baseline characteristics were similar across groups. |
Some concerns | Participants and clinicians were aware of the assigned treatment. Further 15% of the participants in the no hydrocortisone group received hydrocortisone, and although we deem it rather unlikely that a larger part of these deviations arose from the experimental context, we see some concerns. | High risk of bias | Since data were not adjusted for competing risk of death in the presence of a relevant death rate, risk of bias is high. | Low risk of bias | The measurement method was appropriate. | Low risk of bias | Protocol and SAP available. | High risk of bias | Because of the issue of competing risk of death all data for this outcome might not be available. There was no adjustment in the analysis for competing risk of death. |
| Tomazini 2020 | Low risk of bias | Randomisation was performed through an online web‐based system using computer‐generated random numbers and blocks of 2 and 4, unknown to the investigators, and was stratified by centre. The group treatment was disclosed to the investigator only after all information regarding patient enrolment was recorded in the online system. Baseline characteristics were well‐balanced between groups. |
Some concerns | 25 deviations from protocol in the intervention arm (16.55%); 1 patient received a corticosteroid other than dexamethasone. In the control arm, 52 patients received corticosteroids, of which 14 were protocol deviations (9.4%). | High risk of bias | Unknown amount of missing data because of competing risk, and no analysis to adjust for this was made. | Low risk of bias | The measurements were similar between groups. | Low risk of bias | The protocol and statistical analysis plan were available. Outcomes reported as prespecified. | High risk of bias | Occurrence of non‐terminal events can be precluded by death as a competing risk. Without adjustment this leads to high risk of bias, so overall we judged high risk of bias. |