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["Basic information",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 1. Randomization process",null,null,null,null,null,null,null,null,null,"Domain 2. Deviations from intended interventions",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 3. Mising outcome data",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 4. Measurement of the outcome",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 5. Selection of the reported result",null,null,null,null,null,null,null,null,null,null,"Domain 6. Overall Bias"]
["Time","Unique ID","Assessor","Study ID","Reference","Experimental","Comparator","Outcome","Results","Aim","Effect of adhering to intervention?","Weight","Sources","1.1","1.2","Note for 1.1&1.2","1.3","Note for 1.3","1.0 Algorithm result","1.0 Assessor's Judgement","1.0 General note","1.0 Optional Question","1.0 Note for optional question","2.1","2.2","Note for 2.1&2.2","2.3","Note for 2.3","2.4","Note for 2.4","2.5","Note for 2.5","2.6","Note for 2.6","2.7","Note for 2.7","2.0 Algorithm result","2.0 Assessor's Judgement","2.0 General Notes","2.0 Optional Question","2.0 Note for optional question","3.1","Note for 3.1","3.2","Note for 3.2","3.3","Note for 3.3&3.4","3.4","Note for 3.4 (not use)","3.0 Algorithm result","3.0 Assessor's judgement","3.0 Gerenal notes","3.0 Optional Question","3.0 Note for optional question","4.1","Note for 4.1","4.2","Note for 4.2","4.3","Note for 4.3","4.4","Note for 4.4&4.5","4.5","Note for 4.5 (not use)","4.0 Algorithm result","4.0 Assessor's Judgement","4.0 General note","4.0 Optional Question","4.0 Note for optional question","5.1","Note for 5.1","5.2","Note for 5.2","5.3","Note for 5.3","5.0 Algorithm result","5.0 Assessor's Judgement","5.0 General note","5.0 Optional Question","5.0 Note for optional question","Algorithm's overall Judgement","Assessor's overall Judgement","6.0 General Note","6.0 Optional Question","6.0 Note for optional question"]
["2021.07.08 15.45","Angus 2020 mortality","Kopp/Griesel/Wagner","NCT02735707",null,"hydrocortisone","no hydrocortisone","in-hospital deaths","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 (eg, 1:1 if 2 groups available and 1:1:1 if 3 groups available)\r\n\r\nProtocol: 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 computerbased 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 randomization program who will update the RAR proportions.","N","Baseline characteristics were similar across groups","Low","Low","The allocation sequence was random because of using a computer software program. Further the allocation was concealed because the randomisation process was conducted centrally. There were no baseline differences between the groups. All this leads us to the following judgement for domain 1: Low",null,null,"Y","Y","open-label design (clinician and patient awareness of study assignment)","Y","15% of the participants in the no hydrocortisone group received hydrocortisone\r\n\r\ndifferent standard of care in the different hospitals","PY","Yes, it is likely that the deviations have affected the outcome","N","No, the deviations weren't balanced between groups. ","Y","ITT analysis was used","NA",null,"High","Some concerns","Participants and clinicians were aware of the assigned treatment. Further 15% of the participants in the no hydrocortisone group received hydrocortisone. All this leads us to the following judgement for domain 2: Some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","Y","The data was available for all participants. 238 were randomised and 238 were analysed.","NA",null,"NA",null,"NA",null,"Low","Low","Since the data were available for all participants, we arrive at the following assessment of domain 3: Low",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Assessors were aware of the assigned treatment","PN","Mortality is an observer-reported outcome not involving judgement.","NA",null,"Low","Low","The measurements were similar betwenn groups. So we assessed the domain 4 with low. ",null,null,"Y","The trial protocol and the SAP were available. ","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Low","Low","The data were in accordance with the protocol and the SAP, so that we assessed domain 5 with low. ",null,null,"Some concerns","Some concerns","Overall judged some concerns due to protocol deviations. "]
["2021.07.09 10.21","Angus 2020 SAE","Kopp/Griesel/Wagner","NCT02735707",null,"hydrocortisone","no hydrocortisone","Serious adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 (eg, 1:1 if 2 groups available and 1:1:1 if 3 groups available)\r\n\r\nProtocol: 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 computerbased 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 randomization program who will update the RAR proportions.","N","Baseline characteristics were similar across groups","Low","Low","The allocation sequence was random because of using a computer software program. Further the allocation was concealed because the randomisation process was conducted centrally. There were no baseline differences between the groups. All this leads us to the following judgement for domain 1: Low",null,null,"Y","Y","open-label design (clinician and patient awareness of study assignment)","Y","15% of the participants in the no hydrocortisone group received hydrocortisone\r\n\r\ndifferent standard of care in the different hospitals","PY","Yes, it is likely that the deviations have affected the outcome","N","No, the deviations weren't balanced between groups","Y","ITT analysis was used","NA",null,"High","Some concerns","Participants and clinicians were aware of the assigned treatment. Further 15% of the participants in the no hydrocortisone group received hydrocortisone. All this leads us to the following judgement for domain 2: Some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available","N","The trialists have not provided an analysis or information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value.\r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome","PY",null,"High","High","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.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Assessors were aware of the assigned treatment","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. \r\n",null,null,"Y","The trial protocol and the SAP were available. ","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Low","Low","The data were in accordance with the protocol and the SAP, so that we assessed domain 5 with low. ",null,null,"High","High","Overall judged high due missing outcome data."]
["2021.07.09 10.21","Corral-Gudino 2021 mortality","Kopp/Griesel/Wagner","EUCTR2020-001934-37",null,"methylprednisolone","standard of care","mortality at day 28","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","Patients were randomised based on a spreadsheet that transformed every medical record number into a group allocation using a concealed mathematical formula.","PN","A single item (age) showed statistically significant difference, but none of the others including preconditions and biomarkers for disease severity.","Some concerns","Some concerns","We judged the domain some concerns due to missing information about the allocation concealment. ",null,null,"Y","Y","open label design (participants and clinicians are aware of the assignment)","N","There were no deviations from the intended intervention","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Participants and clinicians were aware of the assigned treatment. The intention-to-treat-analysis was used to estimate the effect of the assignment to intervention. All this leads us to the following judgement for domain 2: Low.",null,null,"Y","64 participants were randomised and 64 were analysed","NA",null,"NA",null,"NA",null,"Low","Low","Since the data were available for all participants, we arrive at the following assessment of domain 3: Low",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","Mortality is an observer-reported outcome not involving judgement.","NA",null,"Low","Low","The measurements were similar between groups. So we assessed the domain 4 with low. ",null,null,"N","Outcome was registered in Eudra-CT as in-hospital mortality but reported as 28d-mortality in the supplemental material.","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Some concerns","Some concerns","Outcome was registered in Eudra-CT as in-hospital mortality but reported as 28d-mortality in the supplemental material. So we assessed the domain 5 with some concerns. \r\n\r\n",null,null,"Some concerns","Some concerns","Overall judged some concerns due to selection of reported results and the randomisation process."]
["2021.07.07 13.24","Corral-Gudino 2021 AE","Kopp/Griesel/Wagner","EUCTR2020-001934-37",null,"methylprednisolone","standard of care","Adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","Patients were randomised based on a spreadsheet that transformed every medical record number into a group allocation using a concealed mathematical formula.","PN","A single item (age) showed statistically significant difference, but none of the others including preconditions and biomarkers for disease severity.","Some concerns","Some concerns","We judged the domain some concerns due to missing information about the allocation concealment.",null,null,"Y","Y","open label design (participants and clinicians are aware of the assignment)","N","No, there were no deviations from the intendend intervention","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Participants and clinicians were aware of the assigned treatment. The intention-to-treat-analysis was used to estimate the effect of the assignment to intervention. All this leads us to the following judgement for domain 2: Low.",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome","PY",null,"High","High","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.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"PN","Thresholds, definitions, and time points were called \"pre-specified\" in the journal publication but not available in the Eudra-CT registration. Statistical analysis plan not published.","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Some concerns","Some concerns","Thresholds, definitions, and time points were called \"pre-specified\" in the journal publication but not available in the Eudra-CT registration. Statistical analysis plan not published. So we assessed the domain 5 with some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.07 13.25","Corral-Gudino 2021 Hospital acquired infections","Kopp/Griesel/Wagner","EUCTR2020-001934-37",null,"methylprednisolone","standard of care","nosocomial infection","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","Patients were randomised based on a spreadsheet that transformed every medical record number into a group allocation using a concealed mathematical formula.","PN","A single item (age) showed statistically significant difference, but none of the others including preconditions and biomarkers for disease severity.","Some concerns","Some concerns","We judged the domain some concerns due to missing information about the allocation concealment. ",null,null,"Y","Y","open label design (participants and clinicians are aware of the assignment)","N","No, there were no deviations from the intendend intervention","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Participants and clinicians were aware of the assigned treatment. The intention-to-treat-analysis was used to estimate the effect of the assignment to intervention. All this leads us to the following judgement for domain 2: Low.",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value\r\n \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome","PY",null,"High","High","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.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"PN","Thresholds, definitions, and time points were called \"pre-specified\" in the journal publication but not available in the Eudra-CT registration. Statistical analysis plan not published.","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Some concerns","Some concerns","Thresholds, definitions, and time points were called \"pre-specified\" in the journal publication but not available in the Eudra-CT registration. Statistical analysis plan not published. So we assessed the domain 5 with some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.07 10.40","Dequin 2020 mortality","Kopp/Griesel/Wagner","NCT02517489",null,"hydrocortisone","placebo","21-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was centralised and performed electronically.\r\n\r\nAllocation sequences were generated in a 1:1 ratio by a computer-generated random number using a blocking schema.","N","There were no baseline differences between the groups.","Low","Low","The allocation sequence was random and concealed because it was centralised and electronically performed by a computer-generated number using a blocking scheme. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain low. ",null,null,"N","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Patients and clinicians weren't aware of the assigned treatment. For estimating the effect of the assigned intervention the intention-to-treat analysis was used. We judged this domain low. ",null,null,"Y","149 participants were randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"Low","Low","The measurements were similar between groups, so that we judged this domain low.",null,null,"N","Protocol and SAP are available. But 21-day mortality was a post hoc outcome.","PN","There is only one possible way in which outcome domain can be measured: looking at how many have died after 21 days","PN","There is only one possible way in which the outcome data can be analysed","Some concerns","Some concerns","Because 21-day mortality was a post hoc outcome we judged this domain some concerns.",null,null,"Some concerns","Some concerns","Overall judged some concerns due to selection of reported results."]
["2021.07.07 13.26","Dequin 2020 need for IMV","Kopp/Griesel/Wagner","NCT02517489",null,"hydrocortisone","placebo","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was centralised and performed electronically.\r\n\r\nAllocation sequences were generated in a 1:1 ratio by a computer-generated random number using a blocking schema.","N","There were no baseline differences between the groups.","Low","Low","The allocation sequence was random and concealed because it was centralised and electronically performed by a computer-generated number using a blocking scheme. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain low. ",null,null,"N","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Patients and clinicians weren't aware of the assigned treatment. For estimating the effect of the assigned intervention the intention-to-treat analysis was used. We judged this domain low. ",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"N","Protocol and SAP are available. But status at day 21 mechanical ventilation was a post hoc outcome.","PN","There is only one possible way in which outcome domain can be measured: looking at how many have needed mechanical ventilation after 21 days","PN","There is only one possible way in which the outcome data can be analysed","Some concerns","Some concerns","Because status at day 21 mechanical ventilation was a post hoc outcome we judged this domain some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.07 13.27","Dequin 2020 AE","Kopp/Griesel/Wagner","NCT02517489",null,"hydrocortisone","placebo","Adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was centralised and performed electronically.\r\n\r\nAllocation sequences were generated in a 1:1 ratio by a computer-generated random number using a blocking schema.","N","There were no baseline differences between the groups.","Low","Low","The allocation sequence was random and concealed because it was centralised and electronically performed by a computer-generated number using a blocking scheme. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain low. ",null,null,"N","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Patients and clinicians weren't aware of the assigned treatment. For estimating the effect of the assigned intervention the intention-to-treat analysis was used. We judged this domain low. ",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"Y","Protocol and SAP are available","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data were analysed in accordance with a pre-specified analysis plan we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.07 13.28","Dequin 2020 HAI","Kopp/Griesel/Wagner","NCT02517489",null,"hydrocortisone","placebo","hospital-acquired infections","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was centralised and performed electronically.\r\n\r\nAllocation sequences were generated in a 1:1 ratio by a computer-generated random number using a blocking schema.","N","There were no baseline differences between the groups.","Low","Low","The allocation sequence was random and concealed because it was centralised and electronically performed by a computer-generated number using a blocking scheme. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain low. ",null,null,"N","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Patients and clinicians weren't aware of the assigned treatment. For estimating the effect of the assigned intervention the intention-to-treat analysis was used. We judged this domain low. ",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","Protocol: Patients, investigators and careproviders will be blinded for the patient-arm","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"Y","Protocol and SAP are available","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data were analysed in accordance with a pre-specified analysis plan we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.08 15.45","Edalatifard 2020 need for IMV","Kopp/Griesel/Wagner","IRCT20200404046947N1",null,"methylprednisolone","standard of care","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","The patients were randomly allocated in a 1:1 ratio by block randomisation method","N","there were no baseline differences which suggest a problem with the randomisation process","Some concerns","Some concerns","The allocation sequence was random because of using a block randomisation. But there were no information about the concealing of the allocation sequence. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain some concerns. ",null,null,"N","Y","participents were not aware of the assigned intevention\r\n\r\nPhysicians and clinicians team know about the medicine and intervention groups. ","Y","6 patients in the control group received the intervention drug (17%)","Y","The deviations were likely to have affected the outcome.","N","The deviations were not balanced between groups.","Y","ITT was used; 6 patients in the control group were not included in the analysis because of deviations from the protocol \r\n","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns. ","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Outcome assessor were unblinded.","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","Some concerns","Some concerns","Because neither the protocol nor the SAP were available, we judged this domain some concerns.",null,null,"High","High","Overall judged high risk of bias because of missing outcome data."]
["2021.07.08 15.45","Edalatifard 2020 AE","Kopp/Griesel/Wagner","IRCT20200404046947N1",null,"methylprednisolone","standard of care","Adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","The patients were randomly allocated in a 1:1 ratio by block randomization method","N","there were no baseline differences which suggest a problem with the randomisation process","Some concerns","Some concerns","The allocation sequence was random because of using a block randomisation. But there were no information about the concealing of the allocation sequence. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain some concerns. ",null,null,"N","Y","participents were not aware of the assigned intevention\r\n\r\nPhysicians and clinicians team know about the medicine and intervention groups. ","Y","6 patients in the control group received the intervention drug (17%)","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT was used; 6 patients in the control group were not included in the analysis because of deviations from the protocol \r\n","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","unblinded","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","Some concerns","Some concerns","Because neither the protocol nor the SAP were available, we judged this domain some concerns.",null,null,"High","High","Overall judged high because of missing outcome data."]
["2021.07.08 15.45","Edalatifard 2020 HAI","Kopp/Griesel/Wagner","IRCT20200404046947N1",null,"methylprednisolone","placebo","hospital-acquired infections","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","The patients were randomly allocated in a 1:1 ratio by block randomization method","N","there were no baseline differences which suggest a problem with the randomisation process","Some concerns","Some concerns","The allocation sequence was random because of using a block randomisation. But there were no information about the concealing of the allocation sequence. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain some concerns. ",null,null,"N","Y","participents were not aware of the assigned intevention\r\n\r\nPhysicians and clinicians team know about the medicine and intervention groups. ","Y","6 patients in the control group received the intervention drug (17%)","PY","The deviations were likely to have affected the outcome.","N","The deviations were not balanced between groups.","Y","ITT was used; 6 patients in the control group were not included in the analysis because of deviations from the protocol \r\n","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","unblinded","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","Some concerns","Some concerns","Because neither the protocol nor the SAP were available, we judged this domain some concerns.",null,null,"High","High","Overall judged high because of missing outcome data."]
["2021.07.08 15.45","Horby 2020 mortality","Kopp/Griesel/Wagner","NCT04381936",null,"dexamethasone","standard of care","28-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was performed with the use of a web-based system with concealment of the trial-group assignment","N","no baseline differences","Low","Low","The allocation sequence was random and concealed because of using a web-based system with concealment. Further there were no baseline differences between the groups, so that we judged this domain low.",null,null,"Y","Y","Patients and local members of the trial staff were aware of the assigned treatments.\r\n","Y","8% of the participants in the control group received dexamethasone","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT was used","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns. ","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","Y","6425 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","Mortality is an observer-reported outcome not involving judgement.","NA",null,"Low","Low","The measurements were similar between groups. So we assessed the domain 4 with low. ",null,null,"Y","Protocol and SAP are available","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data were analysed in accordance with a pre-specified analysis plan we judged this domain low.",null,null,"Some concerns","Some concerns","Overall judged some concerns due to deviations from the intended intervention in the control group."]
["2021.07.08 15.45","Horby 2020 need for dialysis","Kopp/Griesel/Wagner","NCT04381936",null,"dexamethasone","standard of care","Need for dialysis","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","Randomisation was performed with the use of a web-based system with concealment of the trial-group assignment","N","no baseline differences","Low","Low","The allocation sequence was random and concealed because of using a web-based system with concealment. Further there were no baseline differences between the groups, so that we judged this domain low.",null,null,"Y","Y","Patients and local members of the trial staff were aware of the assigned treatments.\r\n","Y","8% of the participants in the control group received dexamethasone","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT was used","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","Protocol and SAP are available","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","The outcome was pre-specified in the SAP, so we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.09 10.25","Jamaati 2021 mortality","Kopp/Griesel/Wagner","IRCT20151227025726N17",null,"dexamethasone","standard of care","28-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The selected patients were allocated to either the dexamethasone group or the control group by block randomization. Ten blocks were generated by the Online Randomizer website.","PY","Pulmonary disease was highly significantly more prevalent in the control group. Additionally, baseline level of respiratory support was not reported so that we can only assume the most likely circumstance, i.e. that no support beyond oxygen insufflation had been given until randomisation.","Some concerns","Some concerns","The participants were allocated by block randomisation generated by a online randomiser website. In the control group pulmonary disease were more prevalent than in the intervention group. We judged this domain some concerns. ",null,null,"NI","NI","There is no information whether participants and people delivering the intervention were aware of intervention received","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","We judged this domain low due to no protocol deviations and usage of ITT.",null,null,"Y","50 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","Mortality is an observer-reported outcome not involving judgement.","NA",null,"Low","Low","The measurements were similar between groups. So we assessed the domain 4 with low. ",null,null,"NI","Trial registered after recruitment stop. No analysis plan published beyond registry entry.","NI","Trial registered after recruitment stop. No analysis plan published beyond registry entry.","NI","Trial registered after recruitment stop. No analysis plan published beyond registry entry.","Some concerns","Some concerns","We judged this domain some concerns because there were no protocol or SAP available and the trial was registered after recruitment stop.",null,null,"Some concerns","Some concerns","Overall judged some concerns due to the randomisation process and the selection of reported results."]
["2021.07.07 13.34","Jamaati 2021 need for IMV","Kopp/Griesel/Wagner","IRCT20151227025726N17",null,"dexamethasone","standard of care","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The selected patients were allocated to either the dexamethasone group or the control group by block randomisation. Ten blocks were generated by the Online Randomizer website.","PY","group. Additionally, baseline level of respiratory support was not reported so that we can only assume the most likely circumstance, i.e. that no support beyond oxygen insufflation had been given until randomisation.","Some concerns","Some concerns","The participants were allocated by block randomisation generated by a online randomiser website. In the control group pulmonary disease were more prevalent than in the intervention group. We judged this domain some concerns. ",null,null,"NI","NI","There is no information whether participants and people delivering the intervention were aware of intervention received","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","We judged this domain low due to no protocol deviations and usage of ITT.",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"NI","No protocol and SAP available. ","NI","No protocol and SAP available. ","NI","No protocol and SAP available. ","Some concerns","Some concerns","We judged this domain some concerns because there were no protocol or SAP available.",null,null,"High","High","Overall judged hifh risk of bias due to missing outcome data."]
["2021.07.12 14.17","Jeronimo 2020 mortality","Kopp/Griesel/Wagner","NCT04343729",null,"methylprednisolone","placebo","28-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","An independent statistician prepared an electronically generated randomisation list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomised by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number.","N","There were no major differences in baseline characteristics between the intervention and placebo groups","Low","Low","Because the randomisation was electronically generated via software, the randomisation list was only accessible to non-blinded pharmacists and no major baseline differences were present, we judged this domain low.",null,null,"N","Y","The list with the randomised participants was accessible only to non-blinded pharmacists. \r\n\r\nNon-blinded pharmacists prepared the dilutions in the wards and distributed syringes labelled as MP/placebo to the nursing staff\r\n\r\n","Y","Intervention group: 14 excluded before starting treatment, 1 excluded after starting treatment\r\n\r\nControl group: 5 excluded before starting treatment, 3 excluded after starting treatment","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","Intention-to-treat (excluded only patients who had withdrawn informed consent)","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","Y","416 participants randomised and 416 participants analysed.","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","It is an observer-reported outcome not involving judgement.","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups,",null,null,"Y","Protocol and statistical plan available. Data analysed and presented according to a pre-specified plan.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because of the availability of the protocol and the SAP, we judged this domain low.",null,null,"Some concerns","Some concerns","Overall we judged some concern due to protocol deviations."]
["2021.07.12 15.26","Jeronimo 2020 need for dialysis","Kopp/Griesel/Wagner","NCT04343729",null,"methylprednisolone","placebo","Need for dialysis","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","An independent statistician prepared an electronically generated randomisation list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomised by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number.","N","There were no major differences in baseline characteristics between the intervention and placebo groups","Low","Low","Because the randomisation was electronically generated via software, the randomisation list was only accessible to non-blinded pharmacists and no major baseline differences were present, we judged this domain low.",null,null,"N","Y","The list with the randomised participants was accessible only to non-blinded pharmacists. \r\n\r\nNon-blinded pharmacists prepared the dilutions in the wards and distributed syringes labelled as MP/placebo to the nursing staff\r\n\r\n","Y","Intervention group: 14 excluded before starting treatment, 1 excluded after starting treatment\r\n\r\nControl group: 5 excluded before starting treatment, 3 excluded after starting treatment","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","Intention-to-treat (excluded only patients who had withdrawn informed consent)","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available\r\n","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\n\r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"Y","Protocol and statistical plan available. Data analysed and presented according to a pre-specified plan.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because of the availability of the protocol and the SAP, we judged this domain low.",null,null,"High","High","Overall judged high due to missing outcome data. "]
["2021.07.12 15.23","Jeronimo 2020 viral clearance","Kopp/Griesel/Wagner","NCT04343729",null,"methylprednisolone","placebo","presence of viral RNA in the naso-/oropharyngeal swab on day 7","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","An independent statistician prepared an electronically generated randomisation list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomised by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number","N","There were no major differences in baseline characteristics between the intervention and placebo groups","Low","Low","Because the randomisation was electronically generated via software, the randomisation list was only accessible to non-blinded pharmacists and no major baseline differences were present, we judged this domain low.",null,null,"N","Y","The list with the randomised participants was accessible only to non-blinded pharmacists. \r\n\r\nNon-blinded pharmacists prepared the dilutions in the wards and distributed syringes labelled as MP/placebo to the nursing staff\r\n\r\n","Y","Intervention group: 14 excluded before starting treatment, 1 excluded after starting treatment\r\n\r\nControl group: 5 excluded before starting treatment, 3 excluded after starting treatment","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups. ",null,null,"Y","Protocol and statistical plan available. Data analysed and presented according to a pre-specified plan.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because of the availability of the protocol and the SAP, we judged this domain low.",null,null,"High","High","Overall judged high due to missing outcome data."]
["2021.07.07 10.45","Tang 2021 mortality","Kopp/Griesel/Wagner","NCT04273321",null,"methylprednisolone","placebo","30-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Randomisation was stratified by the statistician of the leading site, who produced computer-generated block randomisation lists with a block size of 4 patients.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated block randomisation, we judged this domain low.",null,null,"N","Y","the participants were blinded and the physicians were aware of the treatment assignment","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of no protocol deviations and using the ITT analysis, we judged this domain low.",null,null,"Y","86 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","the data collection and end point judgement were blinded, and the statisticians were also blinded during the statistical analysis. ","NA",null,"NA",null,"Low","Low","The measurements were similar between groups, we judged this domain low.",null,null,"PY","30-day mortality as pre-specified in the trial registration was not explicitly reported, but could reliably derived from a synopsis of fulltext, figures, and supplemental material.","PN","The analysis for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Low","Low","30-day mortality as pre-specified in the trial registration was not explicitly reported, but could reliably derived from a synopsis of fulltext, figures, and supplemental material. That's why we judged this domain low.",null,null,"Low","Low","All domains were rated low risk of bias. "]
["2021.07.07 13.38","Tang 2021 AE","Kopp/Griesel/Wagner","NCT04273321",null,"methylprednisolone","placebo","Adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Randomisation was stratified by the statistician of the leading site, who produced computer-generated block randomisation lists with a block size of 4 patients.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated block randomisation, we judged this domain low.",null,null,"N","Y","the participants were blinded and the physicians were aware of the treatment assignment","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of no protocol deviations and using the ITT analysis, we judged this domain low.",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","the data collection and end point judgement were blinded, and the statisticians were also blinded during the statistical analysis. ","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"N","Endpoint including its subitems were not named in NCT registration.","NI","Endpoint including its subitems were not named in NCT registration.","NI","Endpoint including its subitems were not named in NCT registration.","Some concerns","Some concerns","Because this outcome wasn't named in the register entry, we juged this domain some concerns.",null,null,"High","High","Overall judged high risk of due to missing outcome data."]
["2021.07.07 13.39","Tang 2021 HAI","Kopp/Griesel/Wagner","NCT04273321",null,"methylprednisolone","placebo","hospital-acquired infections","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Randomisation was stratified by the statistician of the leading site, who produced computer-generated block randomisation lists with a block size of 4 patients.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated block randomisation, we judged this domain low.",null,null,"N","Y","the participants were blinded and the physicians were aware of the treatment assignment","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of no protocol deviations and using the ITT analysis, we judged this domain low.",null,null,"N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","the data collection and end point judgement were blinded, and the statisticians were also blinded during the statistical analysis. ","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"N","Endpoint was not named in NCT registration.","N","Endpoint was not named in NCT registration.","N","Endpoint was not named in NCT registration.","Some concerns","Some concerns","Because this outcome wasn't named in the register entry, we juged this domain some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.08 15.45","Tomazini 2020 mortality","Kopp/Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","28-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrollment was recorded in the online system.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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 corticosteriods, of which 14 were protocol deviations (9.4%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","Y","299 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment","PN","Mortality is an observer-reported outcome not involving judgement","NA",null,"Low","Low","The measurements were similar between groups, we judged this domain low.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"Some concerns","Some concerns","Overall judged some concerns because of protocol deviations."]
["2021.07.08 15.46","Tomazini 2020 ventilator-free days","Kopp/Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","ventilator-free days","continuous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrollment was recorded in the online system.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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 corticosteriods, of which 14 were protocol deviations (9.4%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","Y","299 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because data is available for all participants we judged this domain low.",null,null,"N","The method was appropriate (measuring days)","PN","Specified definition (alive and free from mechanical ventilation). The measurement as similar between groups.","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","The measurement was similar between groups, so that we judged this domain low.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"Some concerns","Some concerns","Overall judged some concerns because of protocol deviations."]
["2021.07.08 15.46","Tomazini 2020 SAE","Kopp/Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","Serious adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrollment was recorded in the online system.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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 corticosteriods, of which 14 were protocol deviations (9.4%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.08 15.46","Tomazini 2020 AE","Kopp/Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","Adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrollment was recorded in the online system.","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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 corticosteriods, of which 14 were protocol deviations (9.4%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.08 15.46","Tomazini 2020 HAI","Kopp/Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","hospital-acquired infections","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrolment was recorded in the online system","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.09 10.26","Ranjbar 2021 mortality","Kopp/Griesel/Wagner","IRCT20200204046369N1",null,"methylprednisolone","dexamethasone","28-day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","Y","Random allocation using the block randomisation method was performed in all four branches of the strata, based on two prognostic factors such as age (< 55 and ≥55) and disease severity based on O2 saturation (<85 and ≥85)\r\n \r\nThe patient, assessor, and analyzer in the two groups did not have access to the randomisation list and type of administered drug (Triple blind).","N","no major differences in the baseline characteristics","Low","Low","Because of block randomisation, concealed allocation and no major differences between the two groups, we judged this domain low.",null,null,"N","N","The patient, assessor, and analyser in the two groups did not have access to the randomization list and type of administered drug (Triple blind)","NA",null,"NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of blinded patients and care providers and using the ITT analysis, we judged this domain low.",null,null,"Y","86 participants randomised and analysed","NA",null,"NA",null,"NA",null,"Low","Low","Because of no missing data, we judged this domain low.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","The patient, assessor, and analyser in the two groups did not have access to the randomisation list and type of administered drug (Triple blind)","NA",null,"NA",null,"Low","Low","The measurements were similar between groups, we judged this domain low.",null,null,"NI","Protocol and SAP not available","NI","Protocol and SAP not available","NI","Protocol and SAP not available","Some concerns","Some concerns","Because protocol and SAP are not available, we judged this domain some concerns.",null,null,"Some concerns","Some concerns","Overall judged some concerns due to the selection of the reported results."]
["2021.07.07 13.42","Ranjbar 2021 need IMV","Kopp/Griesel/Wagner","IRCT20200204046369N1",null,"methylprednisolone","dexamethasone","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","Y","Random allocation using the block randomisation method was performed in all four branches of the strata, based on two prognostic factors such as age (< 55 and ≥55) and disease severity based on O2 saturation (<85 and ≥85)\r\n \r\nThe patient, assessor, and analyser in the two groups did not have access to the randomisation list and type of administered drug (Triple blind).","N","no major differences in the baseline characteristics","Low","Low","Because of block randomisation, concealed allocation and no major differences between the two groups, we judged this domain low.",null,null,"N","N","The patient, assessor, and analyser in the two groups did not have access to the randomization list and type of administered drug (Triple blind)","NA",null,"NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of blinded patients and care providers and using the ITT analysis, we judged this domain low.",null,null,"N","Because of the competing risk of death it is possible that not all data were available","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","N","The patient, assessor, and analyser in the two groups did not have access to the randomisation list and type of administered drug (Triple blind)","NA",null,"NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"NI","Protocol and SAP not available","NI","Protocol and SAP not available","NI","Protocol and SAP not available","Some concerns","Some concerns","Because protocol and SAP are not available, we judged this domain some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.09 10.27","Edalatifard 2020 mortality","Griesel/Wagner","IRCT20200404046947N1",null,"methylprednisolone","standard of care","60 day mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","The patients were randomly allocated in a 1:1 ratio by block randomization method","N","there were no baseline differences which suggest a problem with the randomisation process","Some concerns","Some concerns","The allocation sequence was random because of using a block randomisation. But there were no information about the concealing of the allocation sequence. Further there were no baseline differences that suggest a problem with the randomisation process. We judged this domain some concerns. ",null,null,"N","Y","participents were not aware of the assigned intevention\r\n\r\nPhysicians and clinicians team know about the medicine and intervention groups. ","Y","6 patients in the control group received the intervention drug (17%)","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT was used; 6 patients in the control group were not included in the analysis because of deviations from the protocol \r\n","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","The data were requested from the authors because the follow up time was not clearly visible from the publication.","PN",null,"PN",null,"NA",null,"Low","Low","We judged this domain low. We requested the data from the authors, because the follow-up time was not clear stated in the publication.",null,null,"N","The method was appropriate (measuring events)","PN","The measurements were similar between groups","Y","Outcome assessor were unblinded.","N","mortality is an observer-reported outcome not involving judgement","NA",null,"Low","Low","The measurements were similar between groups, we judged this domain low.",null,null,"NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","NI","Neither the protocol nor statistical analysis plan were available","Some concerns","Some concerns","Because neither the protocol nor the SAP were available, we judged this domain some concerns.",null,null,"Some concerns","Some concerns","Overall judged some concerns due to the randomisation process, protocol deviations and the selection of the reported results. "]
["2021.07.12 15.18","Jeronimo 2020 need for IMV","Griesel/Wagner","NCT04343729",null,"methylprednisolone","placebo","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","An independent statistician prepared an electronically generated randomisation list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomised by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number.","N","There were no major differences in baseline characteristics between the intervention and placebo groups","Low","Low","Because the randomisation was electronically generated via software, the randomisation list was only accessible to non-blinded pharmacists and no major baseline differences were present, we judged this domain low.",null,null,"N","Y","The list with the randomised participants was accessible only to non-blinded pharmacists. \r\n\r\nNon-blinded pharmacists prepared the dilutions in the wards and distributed syringes labelled as MP/placebo to the nursing staff\r\n\r\n","Y","Intervention group: 14 excluded before starting treatment, 1 excluded after starting treatment\r\n\r\nControl group: 5 excluded before starting treatment, 3 excluded after starting treatment","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","Intention-to-treat (excluded only patients who had withdrawn informed consent)","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","We requested the data from the study authors, because this outcome was not reported.\r\n\r\nBecause of the competing risk of death it is possible that not all data were available","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low the measurements were similar between groups.",null,null,"PY","Data was kindly sent in upon request.","NI","Data was not pre-specified in the protocol","NI","Data was not pre-specified in the protocol","Some concerns","Some concerns","Because of sending in the requested data and data was not pre-specified in the protocol, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.12 15.19","Jeronimo 2020 liberation from IMV","Griesel/Wagner","NCT04343729",null,"methylprednisolone","placebo","liberation from IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","An independent statistician prepared an electronically generated randomisation list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomised by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number.","N","There were no major differences in baseline characteristics between the intervention and placebo groups","Low","Low","Because the randomisation was electronically generated via software, the randomisation list was only accessible to non-blinded pharmacists and no major baseline differences were present, we judged this domain low.",null,null,"N","Y","The list with the randomised participants was accessible only to non-blinded pharmacists. \r\n\r\nNon-blinded pharmacists prepared the dilutions in the wards and distributed syringes labelled as MP/placebo to the nursing staff\r\n","Y","Intervention group: 14 excluded before starting treatment, 1 excluded after starting treatment\r\n\r\nControl group: 5 excluded before starting treatment, 3 excluded after starting treatment","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","Intention-to-treat (excluded only patients who had withdrawn informed consent)","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns.","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","We requested the data from the study authors, because this outcome was not reported.\r\n\r\nBecause of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"PY","Data was kindly sent in upon request.","NI","Data was not pre-specified in the protocol","NI","Data was not pre-specified in the protocol","Some concerns","Some concerns","Because of sending in the requested data and was not pre-specified in the protocol, we judged this domain some concerns.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.07 13.45","Corral-Gudino 2021 Need fir IMV","Griesel/Wagner","EUCTR2020-001934-37",null,"methylprednisolone","standard of care","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s)","Y","NI","Patients were randomised based on a spreadsheet that transformed every medical record number into a group allocation using a concealed mathematical formula.","PN","A single item (age) showed statistically significant difference, but none of the others including preconditions and biomarkers for disease severity.","Some concerns","Some concerns","We judged the domain some concerns due to missing information about the allocation concealment.",null,null,"Y","Y","open label design (participants and clinicians are aware of the assignment)","N","All patients received assigned intervention; co-interventions not balanced across arms, but there were no deviations from the intended intervention due to trial context.","NA",null,"NA",null,"Y","ITT","NA",null,"Low","Low","Because of no protocol deviations and usage of ITT, we judged this domain low.",null,null,"N","We requested the data from the authors, because it was not reported.\r\n\r\nBecause of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n","PY",null,"High","High","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.",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","NI",null,"PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"PY","Data was kindly sent in upon request.","NI","Data was not pre-specified in the protocol","NI","Data was not pre-specified in the protocol","Some concerns","Some concerns","Data was kindly sent in upon request and was not pre-specified in the protocol. So we judged this domain some concerns. \r\n\r\n",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.08 15.47","Tomazini 2020 Liberation from IMV","Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","Liberation from IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrolment was recorded in the online system","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns. ","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]
["2021.07.09 10.27","Tomazini 2020 Need for IMV","Griesel/Wagner","NCT04327401",null,"dexamethasone","standard of care","Need for IMV","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP)","Y","Y","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 center. The group treatment was disclosed to the investigator only after all information regarding patient enrolment was recorded in the online system","N","Baseline characteristics were well balanced between groups","Low","Low","Because of computer-generated randomisation, concealed allocation and balanced baseline characteristics, we judged this domain low.",null,null,"Y","Y","Patients were not blinded for the assigned treatment\r\n\r\nPhysicians were not blinded for the assigned treatment","Y","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%).","PY","The deviations were likely to have affected the outcome","N","The deviations were not balanced between groups","Y","ITT","NA",null,"High","Some concerns","Due to protocol deviations we judged this domain some concerns. ","Towards null ","As the study is meant to detect a positive effect of corticosteroids, participants in the control group receiving the experimental medication lead to expected bias towards null. Hence we only see a slight tendency of under-estimating the effect but there is no increase in the risk to mistakingly introduce a medication for its beneficial effect.","N","Because of the competing risk of death it is possible that not all data were available ","N","The trialists have not provided an analysis  or  information to show there is no problem","PY","The missingness of this outcome is likely to be influenced by its true value \r\nIf the data are unavailable because of competing risks from other outcomes e.g. patients have died then this is likely to be related to the outcome\r\n\r\n","PY",null,"High","High","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.\r\n\r\n",null,null,"N","The method was appropriate (measuring events)","N","The measurements were similar between groups","Y","Individuals who assessed the outcomes were not blinded for the assigned treatment. ","PN","The knowledge of the received intervention is unlikely to have affected the assessment of the outcome. ","NA",null,"Low","Low","We judged this domain low because the measurements were similar between groups.",null,null,"Y","The protocol and statistical analysis plan were available. Outcomes reported as prespecified.","N","The analysis for this result was prespecified in the protocol","N","The analysis for this result was prespecified in the protocol","Low","Low","Because the data was analysed in accordance with a pre-specified analysis plan, we judged this domain low.",null,null,"High","High","Overall judged high risk of bias due to missing outcome data."]

{"sheet":"Summary","index":2,"n_rows":11,"n_cols":27,"rows_kept":11,"cut":false,"hidden":false,"merged":[]}
["Unique ID","Reviewer","Study ID","Reference","Experimental","Comparator","Outcome","Result","Aim","Effect of adhering to intervention?","Weight","Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias",null,null,null,null,"Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Assignment to intervention (the 'intention-to-treat' effect)"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Total number of study = 0"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Low risk"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Some concerns"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"High risk"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Adhering to intervention (the 'per-protocol' effect)"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Total number of study = 0"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Low risk"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Some concerns"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"High risk"]

{"sheet":"Figure (ITT)","index":3,"n_rows":1,"n_cols":13,"rows_kept":1,"cut":false,"hidden":false,"merged":[]}
["Intention-to-treat","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]

{"sheet":"Figure (PP)","index":4,"n_rows":1,"n_cols":13,"rows_kept":1,"cut":false,"hidden":false,"merged":[]}
["Per-protocol","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]

{"sheet":"Print (ITT)","index":5,"n_rows":0,"n_cols":0,"rows_kept":0,"cut":false,"hidden":false,"merged":[]}

{"sheet":"Print (PP)","index":6,"n_rows":0,"n_cols":0,"rows_kept":0,"cut":false,"hidden":false,"merged":[]}

{"sheet":"Check","index":7,"n_rows":0,"n_cols":0,"rows_kept":0,"cut":false,"hidden":false,"merged":[]}

{"sheet":"Print_format (PP)","index":8,"n_rows":32,"n_cols":6,"rows_kept":32,"cut":false,"hidden":true,"merged":[[31,1,31,3],[21,0,26,0],[21,1,21,3],[22,1,22,3],[26,1,26,3],[23,1,23,3],[25,1,25,3],[24,1,24,3],[29,1,29,3],[27,0,30,0],[27,1,27,3],[28,1,28,3],[30,1,30,3],[14,1,14,3],[15,1,15,3],[16,0,20,0],[16,1,16,3],[17,1,17,3],[18,1,18,3],[20,1,20,3],[19,1,19,3],[18,5,19,5],[24,5,25,5],[4,1,4,3],[5,0,8,0],[5,1,5,3],[5,5,6,5],[6,1,6,3],[7,1,7,3],[8,1,8,3],[9,5,10,5],[10,1,10,3],[11,1,11,3],[12,1,12,3],[13,1,13,3],[9,0,15,0],[9,1,9,3]]}
["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","adhering to intervention (the 'per-protocol' effect)","The effect of adhering to intervention…"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1 Were participants aware of their assigned intervention during the trial?"]
[null,"2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important non-protocol interventions balanced across intervention groups?"]
[null,"2.4. [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?"]
[null,"2.5. [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?"]
[null,"2.6. If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

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["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

{"sheet":"Function Tab","index":10,"n_rows":12,"n_cols":19,"rows_kept":12,"cut":false,"hidden":true,"merged":[]}
[null,"Journal article(s)","NA","Yes",null,"1.1 Was the allocation sequence random?",null,"2.1 Were participants aware of their assigned intervention during the trial?","2.1 Were participants aware of their assigned intervention during the trial?",null,"3.1 Were data for this outcome available for all, or nearly all, participants randomized?","Individually Randomized, Parallel Group Trials","4.1 Was the method of measuring the outcome inappropriate?","assignment to intervention (the 'intention-to-treat' effect)","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,null,"occurance of non-protocol interventions"]
["NA","Trial protocol","Favours experimental ","No (Please include reasons in the note)","Y","1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?","Low","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,"3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data?",null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?","adhering to intervention (the 'per-protocol' effect)","5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,null,"failures in implementing the intervention that could have affected the outcome"]
["Y","Statistical analysis plan (SAP)","Favours comparator ",null,"PY","1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?","High","2.3 [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important nonprotocol interventions balanced across intervention groups?","2.3 If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the trial context?",null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,"4.3 If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study participants?",null,"5.3 ... multiple eligible analyses of the data?",null,null,null,"non-adherence to their assigned intervention by trial participants"]
["PY","Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Towards null ",null,"PN",null,"Some concerns","2.4 [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?","2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
["PN","Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Away from null ",null,"N",null,null,"2.5 [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?","2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
["N","“Grey literature” (e.g. unpublished thesis)","Unpredictable",null,"NI",null,null,"2.6 If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?","2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
["NI","Conference abstract(s) about the trial",null,null,null,null,null,null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
[null,"Research ethics application"]
[null,"Grant database summary (e.g. NIH RePORTER, Research Councils UK Gateway to Research)"]
[null,"Personal communication with trialist"]
[null,"Personal communication with the sponsor"]