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[null,null,null,null,null,null,null,"V8 update:"]
[null,null,null,null,null,null,null,"*Added judgement-level comment in the summary table"]
[null,null,null,null,null,null,null,"*Removed \"Double click on this column…\" label in the comments after enter"]
[null,null,null,null,null,null,null,"*Corrected spelling mistakes"]

{"sheet":"Results","index":1,"n_rows":15,"n_cols":85,"rows_kept":15,"cut":false,"hidden":false,"merged":[[0,0,0,12],[0,13,0,22],[0,80,0,83],[0,23,0,40],[0,41,0,53],[0,54,0,68],[0,69,0,79]]}
["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. Missing 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"]
["2021.10.13 11.10","Clemency 2021 All-cause mortality","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","all-cause mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Although there were around 5% of participants lost to follow-up, it seems not probable that the outcome has been affected relevantly by those dropouts.",null,null,"N","study visit on day 30.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, scheduled contact at day 30.",null,null,"Y","This endpoint was pre-specified in the trial protocol and SAP.","PN","There were no multiple eligible outcome measurements of that outcome.","PN","Analysis was conducted as planned.","Low","Low","We judged this domain low due to pre-specification of the outcome.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 11.11","Clemency 2021 Admission to hospital or death ","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","admission to hospital or death","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Although there were around 5% of participants lost to follow-up, it seems not probable that the outcome has been affected relevantly by those dropouts.",null,null,"N","study visit on day 30.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, scheduled contact at day 30.",null,null,"Y","This endpoint was the primary outcome before starting that study. Due to low event rates, a primary outcome based on symptom resolution was chosen rather than one based on emergency department visits or hospital admission after preliminary data demonstrated substantially lower than expected rates of emergency department visits or hospitalizations among study participants.","PN","There were no multiple eligible outcome measurements of that outcome.","PN","Analysis was conducted as planned.","Low","Low","We judged this domain low due to pre-specification of the outcome.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 11.12","Clemency 2021 all initial symptoms resolved (asymptomatic) at day 14","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","all initial symptoms resolved (asymptomatic) at day 14","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Although there were around 5% of participants lost to follow-up, it seems not probable that the outcome has been affected relevantly by those dropouts.",null,null,"N","eDiary and contact on days 2, 4, 6, 8, 10, 12, 14, 21 ± 2 days, study visit on day 30 ± 2 days. other contacts at day 37 ± 4 days and day 60 ± 7 days to collect follow-up safety and outcome data.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, as the combination of structured contacts and eDiary provided a high probability that the outcome would be detected.",null,null,"N","This endpoint was not pre-specified in the trial protocol and added only 9 April 2021 (after having completed the trial for month).","PY","As the endpoint was added to the trial registration after completing the trial there were multiple elegible outcome measurements.","PY","As the endpoint was added to the trial registration after completing the trial there were multiple elegible analyses of the data.","High","High","We judged this domain high due to a subsequent addition of this outcome to the trial protocol month after having completed the trial.",null,null,"High","High","Overall, we judged high risk of bias due to subsequent addition of this outcome (probably during the analysis process). "]
["2021.10.13 11.13","Clemency 2021 all initial symptoms resolved (asymptomatic) at day 30","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","all initial symptoms resolved (asymptomatic) at day 30","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Although there were around 5% of participants lost to follow-up, it seems not probable that the outcome has been affected relevantly by those dropouts.",null,null,"N","eDiary and contact on days 2, 4, 6, 8, 10, 12, 14, 21 ± 2 days, study visit on day 30 ± 2 days. other contacts at day 37 ± 4 days and day 60 ± 7 days to collect follow-up safety and outcome data.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, as the combination of structured contacts and eDiary provided a high probability that the outcome would be detected.",null,null,"N","This endpoint was not pre-specified in the trial protocol and added only 9 April 2021 (after having completed the trial for month).","PY","As the endpoint was added to the trial registration after completing the trial there were multiple elegible outcome measurements.","PY","As the endpoint was added to the trial registration after completing the trial there were multiple elegible analyses of the data.","High","High","We judged this domain high due to a subsequent addition of this outcome to the trial protocol month after having completed the trial.",null,null,"High","High","Overall, we judged high risk of bias due to subsequent addition of this outcome (probably during the analysis process). "]
["2021.10.13 11.14","Clemency 2021 adverse events","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Some adverse events lead to trial discontinuation. But they had been reported, so we do not assume, that the ~5% \"lost to follow up\" affected the outcome.",null,null,"N","eDiary and contact on days 2, 4, 6, 8, 10, 12, 14, 21 ± 2 days, study visit on day 30 ± 2 days. other contacts at day 37 ± 4 days and day 60 ± 7 days to collect follow-up safety and outcome data.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, as the combination of structured contacts and eDiary provided a high probability that the outcome would be detected.",null,null,"Y","Although pre-specified in the trial protocol, SAE were not reported, although there were hospitalisations (so there must have been SAE).","PN","The assessment of SAE was planned in the SAP, but not reported. AE were assessed as planned.","PN","Analysis was conducted as planned.","Low","Low","We judged this domain low due to pre-specification of the outcome.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 11.15","Clemency 2021 infections","Fischer/Wagner","NCT04377711",null,"ciclesonide","placebo","infections","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","PY","Quote: The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in  blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment. ","PN","Baseline characteristics were well balanced between groups, except for diabetes mellitus type 2 with 11% vs 4% and asthma 9% vs 4%  (intervention vs control). We suppose this was by chance.","Low","Low","We judged this domain low as the randomisation process was adequate because it is done remotely and moreover consider concealment adequate. Slight baseline differences were most likely due to chance.",null,null,"PN","PN","double blinded study design","NA",null,"NA",null,"NA",null,"Y","ITT was used","NA",null,"Low","Low","Deviations were balanced and most likely not due to the trial context in this double-blinded trial.",null,null,"PY","The whole ITT was analysed, although there were 5% lost to follow up (11 participants in the ciclesonide group and 9 participants in the placebo group).","NA",null,"NA",null,"NA",null,"Low","Low","Although there were around 5% of participants lost to follow-up, it seems not probable that the outcome has been affected relevantly by those dropouts.",null,null,"N","eDiary and contact on days 2, 4, 6, 8, 10, 12, 14, 21 ± 2 days, study visit on day 30 ± 2 days. other contacts at day 37 ± 4 days and day 60 ± 7 days to collect follow-up safety and outcome data.","N","It is unlikely the outcome measurement has differed. ","PN","placebo-controlled study","NA",null,"NA",null,"Low","Low","We judged low risk of bias, as the combination of structured contacts and eDiary provided a high probability that the outcome would be detected.",null,null,"Y","This endpoint was pre-specified in the trial protocol and SAP.","PN","There were no multiple eligible outcome measurements of that outcome.","PN","Analysis was conducted as planned.","Low","Low","We judged this domain low due to pre-specification of the outcome.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 12.21","Ramakrishnan 2021 all-cause mortality","Griesel/Wagner","NCT04416399",null,"budesonide","standard care","all-cause mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The randomisation sequence was created using a random number generation function and allocation to each group was done through block randomisation in a 1:1 ratio","N","Baseline characteristics were well balanced between groups","Low","Low","Stratified block randomization, sequence held in secure network location at Oxford University, characteristics incl. SARS-CoV-2 status are well balanced.",null,null,"Y","Y","open-label trial","PN","Only low number of participants in the intervention group 1 (1%)and in the control group 3 (4%) withdrew consent due to allocation.","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","Only low number of participants in the intervention group 1 (1%)and in the control group 3 (4%) withdrew consent due to allocation.",null,null,"Y","Less than 10 percent missing, balanced between groups.","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low due to small number of missing data.",null,null,"N","The method was appropriate (measuring events) and time points for assessment pre-specified. All-cause mortality can easily be assessed.","N","The measurements were similar between groups","Y","open-label trial","N","Mortality 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,"PN","Analysis plan is available. Outcome was not pre-specified ","NI","Post-hoc extraction by the review team, not pre-specified.","NI","The analysis for this result was not prespecified in the protocol","Some concerns","Some concerns","We judged some concerns because the outcome was not pre-specified. ",null,null,"Some concerns","Some concerns","Overall we judged some concerns due to selective reporting\t\t\t\t"]
["2021.10.13 12.21","Ramakrishnan 2021 mean time to recovery (days)","Fischer/Wagner","NCT04416399",null,"budesonide","standard care","mean time to recovery (days)","continuous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The randomisation sequence was created using a random number generation function and allocation to each group was done through block randomisation in a 1:1 ratio","N","Baseline characteristics were well balanced between groups","Low","Low","Stratified block randomization, sequence held in secure network location at Oxford University, characteristics incl. SARS-CoV-2 status are well balanced.",null,null,"Y","Y","open-label trial","PN","Only low number of participants in the intervention group 1 (1%)and in the control group 3 (4%) withdrew consent due to allocation.","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","Only low number of participants in the intervention group 1 (1%)and in the control group 3 (4%) withdrew consent due to allocation.",null,null,"Y","Less than 10 percent missing, balanced between groups.","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low due to small number of missing data.",null,null,"PN","Quote: \"All participants not admitted to hospital had daily telephone checks with the COVID hub general practitioner team.\"","PY","It is unclear when patients were consiered recovered.",null,"NA","NA",null,"NA",null,"High","High","We judged this domain high due to the unanswered question when the participants were considered recovered.  ",null,null,"PN","Analysis plan was only released together with results. Study registration did not clarify how the outcome would be assessed. But the patient information sheet included a detailled description of the visits and telephone calls.","PN","daily telephone assessment and four visits were planned","PN","The analysis for this result was not prespecified in the protocol","Some concerns","Some concerns","We judged this domain some concerns because the outcome was not pre-specified.",null,null,"High","High","Overall we judged high risk of bias due to measurement of the outcome."]
["2021.10.13 13.31","Yu 2021 all-cause mortality","Fischer/Griesel","ISRCTN86534580",null,"budesonide","standard care","all-cause mortality","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Web based Sortition. Exact generation of the randomization sequence is not worded in the preprint. Allocation sequence was intimated to GP and patient via email/letter, but there was no independant body to allocate intervention. It was the same member of the trial team.","N","Baseline characteristics were well balanced between groups","Low","Low","Participants were randomized via web-based Sortition and the allocation sequence was intimated to GP and patient via email/letter. There are no baseline differences that would suggest a problem with randomization",null,null,"Y","Y","open-label trial","N","All participants received assigned intervention","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","We judged risk of bias low because there were no reported deviations from intended interventions.",null,null,"PY","Quote: \"At the time of data-extraction for this updated analysis on March 25, 2021, 892/961 (92.8%) of all those randomized to budesonide had the opportunity to contribute data for the complete 28 days follow up\"","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low because it is not likely that missingness in the outcome depended on its true value.",null,null,"PN","healthcare use outcome data was collected from general practice and hospital records","PN","All measurements were done in the same way for each group.","Y","open-label trial","PN","Mortality is an observer-reported outcome not involving judgement. 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","Analysis plan: hospitalisation and/or death as co-primary outcome","PN","The outcome measurement for this result was prespecified in the protocol","PN","The analysis for this result was prespecified in the protocol","Low","Low","We judged this domain low due to pre-specification of the outcome.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 13.31","Yu 2021 Admission to hospital or death","Daniel/Nair/Wagner","ISRCTN86534580",null,"budesonide","standard care","Admission to hospital or death","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Web based Sortition. Exact generation of the randomization sequence is not worded in the preprint. Allocation sequence was intimated to GP and patient via email/letter, but there was no independant body to allocate intervention. It was the same member of the trial team.","N","Baseline characteristics were well balanced between groups","Low","Low","Participants were randomized via web-based Sortition and the allocation sequence was intimated to GP and patient via email/letter. There are no baseline differences that would suggest a problem with randomization",null,null,"Y","Y","open-label trial","N","All participants received assigned intervention","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","We judged risk of bias low because there were no reported deviations from intended interventions.",null,null,"PY","Quote: \"At the time of data-extraction for this updated analysis on March 25, 2021, 892/961 (92.8%) of all those randomized to budesonide had the opportunity to contribute data for the complete 28 days follow up\"","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low because it is not likely that missingness in the outcome depended on its true value.",null,null,"N","The outcome measurement is an appropriate measure (measuring events)","N","The measurements were similar between groups","Y","open-label trial","N","Mortality is an observer-reported outcome not involving judgement. 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 is available and outcome pre-specified","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, so that we assessed domain 5 low.",null,null,"Low","Low","Overall, we judged low risk of bias. "]
["2021.10.13 13.31","Yu 2021 all initial symptoms resolved (asymptomatic) at day 14","Griesel/Daniel/Nair/Wagner","ISRCTN86534580",null,"budesonide","standard care","all initial symptoms resolved (asymptomatic) at day 14","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Web based Sortition. Exact generation of the randomization sequence is not worded in the preprint. Allocation sequence was intimated to GP and patient via email/letter, but there was no independant body to allocate intervention. It was the same member of the trial team.","N","Baseline characteristics were well balanced between groups","Low","Low","Participants were randomized via web-based Sortition and the allocation sequence was intimated to GP and patient via email/letter. There are no baseline differences that would suggest a problem with randomization",null,null,"Y","Y","open-label trial","N","All participants received assigned intervention","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","We judged risk of bias low because there were no reported deviations from intended interventions.",null,null,"PY","Quote: \"At the time of data-extraction for this updated analysis on March 25, 2021, 892/961 (92.8%) of all those randomized to budesonide had the opportunity to contribute data for the complete 28 days follow up\"","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low because it is not likely that missingness in the outcome depended on its true value.",null,null,"N","A daily symptom diary is an appropriate measurement for time until self-reported recovery","N","All measurements were done in the same way for each group.","Y","open-label trial","Y","Time to first self-reported recovery was patient-reported – participants were aware that they were receiving / not receiving the intervention. It was subjective assessment.","Y",null,"High","High","Missing placebo control could introduce relevant confounding to subjective self-assessment of this endpoint.",null,null,"Y","Protocol is available and outcome pre-specified","PN","Available but prespecified.","PN","Available but prespecified.","Low","Low","No source of bias detected in domain 5.",null,null,"High","High","Likely placebo effect in assessing the outcome introduces high risk of bias towards the experimental."]
["2021.10.13 13.32","Yu 2021 Quality of life","Daniel/Nair","ISRCTN86534580",null,"budesonide","standard care","Quality of life","continuous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Web based Sortition. Exact generation of the randomization sequence is not worded in the preprint. Allocation sequence was intimated to GP and patient via email/letter, but there was no independant body to allocate intervention. It was the same member of the trial team.","N","Baseline characteristics were well balanced between groups","Low","Low","Participants were randomized via web-based Sortition and the allocation sequence was intimated to GP and patient via email/letter. There are no baseline differences that would suggest a problem with randomization",null,null,"Y","Y","open-label trial","N","All participants received assigned intervention","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","We judged risk of bias low because there were no reported deviations from intended interventions.",null,null,"PY","Quote: \"At the time of data-extraction for this updated analysis on March 25, 2021, 892/961 (92.8%) of all those randomized to budesonide had the opportunity to contribute data for the complete 28 days follow up\"","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low because it is not likely that missingness in the outcome depended on its true value.",null,null,"N","Baseline, day 14 and day 28 data collected","N","All measurements were done in the same way for each group.","Y","open-label trial","Y","Patient-reported","Y",null,"High","High","Favours intervention if patient had the knowledge that inhaled corticosteroids could improve symptoms",null,null,"Y","Master analysis plan, time to first self-reported recovery was added later. However this happened before interim analysis","PN","analysed by pre-specified method - only one scale","PN","The analysis for this result was prespecified in the protocol","Low","Low","No source of bias detected in domain 5.",null,null,"High","High","Overall judged high risk of bias since the knowledge of intervention could influence patient reported outcome."]
["2021.10.13 13.54","Yu 2021 serious adverse events","Daniel/Nair","ISRCTN86534580",null,"budesonide","standard care","serious adverse events","dichotomous","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Web based Sortition. Exact generation of the randomization sequence is not worded in the preprint. Allocation sequence was intimated to GP and patient via email/letter, but there was no independant body to allocate intervention. It was the same member of the trial team.","N","Baseline characteristics were well balanced between groups","Low","Low","Participants were randomized via web-based Sortition and the allocation sequence was intimated to GP and patient via email/letter. There are no baseline differences that would suggest a problem with randomization",null,null,"Y","Y","open-label trial","N","All participants received assigned intervention","NA",null,"NA",null,"Y","modified ITT","NA",null,"Low","Low","We judged risk of bias low because there were no reported deviations from intended interventions.",null,null,"PY","Quote: \"At the time of data-extraction for this updated analysis on March 25, 2021, 892/961 (92.8%) of all those randomized to budesonide had the opportunity to contribute data for the complete 28 days follow up\"","NA",null,"NA",null,"NA",null,"Low","Low","We judged this domain low because it is not likely that missingness in the outcome depended on its true value.",null,null,"N","Daily diary entry, also from GP records","N","All measurements were done in the same way for each group.","Y","open-label trial","Y","Patient-reported","Y",null,"High","High","Favours intervention since the other arm had no placebo or drug.",null,null,"Y","Master analysis plan, time to first self-reported recovery was added later. However this happened before interim analysis","PN","SAE reporting was well defined and followed protocol","PN","Data presented as it is","Low","Low","No source of bias detected in domain 5.",null,null,"High","High","Overall judged high risk of bias since the knowledge of intervention could influence patient reported outcome."]

{"sheet":"Summary","index":2,"n_rows":11,"n_cols":33,"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","Comment for randomization process","Deviations from intended interventions","Comment for deviations from intended interventions","Missing outcome data","Comment for missing outcome data","Measurement of the outcome","Comment for measurement of the outcome","Selection of the reported result","Comment for selection of the reported result","Overall Bias","Comment for 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,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,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,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,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,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,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,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,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,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,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"]

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{"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"]