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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"]
["2021-04-13 13.38","Gharbaran 2020 Mortality","VP, NS, KLC, CK, SJV",1,"Ghabaran","Convalescent plasma","standard of care (supportive care, oxygen, antibiotics)","All-cause mortality at hospital discharge & time-to event mortality","OR: 0.95 (95% CI: 0.20 to 4.67)","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","small differences, but trial was stopped after assignment of 86 of 426 planned participants and the differences do not suggest a problem with randomization","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Open-lable ","NI","All patients received assigned intervention, but co-interventions not described. \r\nQuote: \"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for\r\nCOVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nUnclear whether treatments were balanced across arms. ","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"Y","Data available for all participants (86/86)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 86 participants randomized.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurements between groups ","Y","open-label","N","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The outcome assessors aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement or that the measurement differed between intervention groups.",null,null,"Y","in accordance with a pre-specified analysis plan ","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","PN","Preplanned primary endpoint measured and reported as planned at protocol stage. Adjusted and unadjusted analyses provided.","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Some concerns","Some concerns","For the mortality outcomes, there is a low risk of bias from the randomization process, due to missing outcome data, in measurement of the outcome and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions.","Towards null "]
["2021-04-13 13.38","Li 2020 Mortality","VP, NS","Li","Li","Conventional treatment with convalescent plasma","Conventional treatment alone","Mortality at day 28 and time to event",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Quote: \"Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone (control group) (Figure 1). The randomization was stratified based on the severity of COVID-19 (severe or life-threatening) and a randomization schedule was generated using block randomization with block size of 4 for each type of COVID-19 by SAS software.\"\r\nQuote: \"This random number will connect the subject to the designated treatment group (experimental group or control group) for treatment. [...] Staff responsible for randomization will only be responsible for the assignment of random groups and will not be involved in any specific trial operations.\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were block randomized via computer-generated random numbering in a 1:1 ratio to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Quote: \"open-label\"","PN","All patients received assigned intervention; co-interventions not balanced across arms, but no evidence for a protocol deviation and no deviations due to trial context.","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Mortality at day 28: nearly all participants (51 out of 52 in plasma group and 50 out of 51 in control group) Mortality (time to event): For all participants (52 in plasma group and 51 in control group) ","NA",null,"NA",null,"NA",null,"Low","Low","Mortality at day 28: Data for this outcome was available for nearly all participants randomized, a total of 101 out of 103 participants were included in the analysis.\r\nMortality (time to event): Data for this outcome was available for all 103 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurements between groups","N","Quote: \"To avoid assessment bias, the evaluation of clinical outcomes was performed by an investigator who was blind to the study group allocation.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were not aware of the intervention received.",null,null,"Y","In accordance with analysis plan available","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"mortality at up to day 28\", all the domains have a low risk of bias.\r\nFor the outcome \"mortality (time to event)\", all the domains have a low risk of bias."]
["2021-04-13 11.46","Avendano Sola mortality","MB,VP",null,"Avendano Sola ","intravenously administered CP (single infusion) + SOC","SOC","Mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Randomization among the two arms will be 1:1 and will be stratified per center.\r\nThe randomization process has been developed using the RERAND system integrated within the RDC Onsite ECRF system based on Oracle.","PN","There were no relevant between-group differences at baseline suggesting a problem with randomization","Low","Low","Participants were randomized through a web-based eCRF system (ORACLE clinical) in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Because this is an open label trial","N","\"1 did not receive CP due to absence of AB0 blood group compatible plasma\" -->but this is not because of trial context\r\nOf the patients randomized to receive plasma, 37 (97.4%) received treatment as assigned.","NA",null,"NA",null,"Y","Intention to treat analysis was performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All 81 participants available for all randomized were analysed(although some were lost to follow-up, withdrew consent).","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 81 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no difference in measurements between groups ","PY","open label trial","N","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","The trial protocol and SAP were not available, but some supplementary material was provided on methods and the trial registry was available. From the trial registry we could compare the outcomes planed and reported and there were no inconsistencies for the mortality at day 29 assessment.","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For the outcome \"mortality at up to day 28\", there is a low risk of bias for all the domains. "]
["2021-04-13 13.39","Simonovich Mortality","VP,MK","Simonovich",null,"CP","Placebo","Mortality at day 28 and time to event",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","random list will be generated in blocks of variable size, stratified\r\nfor each of the participating centers. Recruitment will be consecutive until the proposed sample\r\nsize is reached. A list of random numbers will be drawn up for each of the participating centers,\r\nconsigning the assignment to the branch \"Intervention\" (Convalescent Plasma) or \"Placebo\"\r\n(saline solution).\r\nThis list will remain hidden from both the doctors and nurses in charge of the assistance of each\r\nparticipant.","PN","small differences in baseline characterisctics; e.g. patients with COPD, patients on critical care unit, but probably not due to problems with randomisation process","Low","Low","Participants were randomized through a randomization program (REDCap) in a 2:1 ratio to receive either convalescent plasma or a placebo. The allocation sequence was random and concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","double-blinded; \r\nQuote: \"The intervention will remain blind to the research subjects and to the research team throughout the entire protocol. The transfusional medicine team and the persons in charge of the statistical analysis will not be blind regarding the assignment of the branch to which the patients have been randomized.\"\r\nQuote: \"Since the plasma solution is slightly opaque,\r\nthe container and IV line will be covered with a colored sleeve to maintain the masking.\"\r\n","NA",null,"NA",null,"NA",null,"Y","Yes, an intention to treat analysis was used ","NA",null,"Low","Low","Both participants and carers and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","From the 334 participants randomized, only 1 patient in control group did not receive intervention due to withdrawal of consent after randomisation and was excluded from analysis","NA",null,"NA",null,"NA",null,"Low","Low","From the 334 participants randomized data was available for 228 participants in the convalescent plasma group and 105 participants in the placebo group. The data of  one participant in control group was missing, due to withdrawal of consent after randomisation and therefore the participant was excluded from the analysis.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","No differences in measurements between intervention groups","PN","Quote: \"The intervention will remain blind to the research subjects and to the research team throughout the entire protocol. The transfusional medicine team and the persons in charge of the statistical analysis will not be blind regarding the assignment of the branch to which the patients have been randomized.\"","NA",null,"NA",null,"Low","Low","Mortality is an objective outcome measure, appropriately measured and it is unlikely that the measurement differed between intervention groups. The outcome assessors were probably not aware of the intervention received. ",null,null,"Y","Protocol available and the outcome was analyse in accordance to this. ","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"mortality\", all the domains have a low risk of bias."]
["2021-04-13 11.06","Libster 2020 Mortality","VP, MB","Libster 2020",null,"CP","Placebo","All-cause mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","The randomization of participating subjects will be conducted by the person in charge of randomizing the study using an electronic system. Once the patient is randomized, the person in charge of the allocation will communicate with a member of the Transfusion Medicine Central Team in the study who will remove the opaque bag treatment indicated in the freezer of the Central Laboratory.","PN","There are no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized using an electronic system numbering to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","PY","Neither the patient nor the researchers will have knowledge of the administered treatment, conducting a double-blind study. The unblinded team will keep a record of the product assignments and their administrations that will be kept confidential.","N","There were no deviations due to trial context.","NA",null,"NA",null,"Y","Intention to treat analysis was done ","NA",null,"Low","Low","The participants were unaware of their assigned intervention and those delivering the intervention were aware of intervention assigned during the trial, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All 160 out of 160 participants were analysed","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 160 participants randomized.",null,null,"N","The event probably did not occur in discharged patients, but the outcome was measured as described in trial registry","N","no difference in measurement between groups","PN","\"Neither the patient nor the researchers will have knowledge of the administered treatment, conducting a double-blind study\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were probably unaware of the intervention received.",null,null,"Y","Measured as defined at protocol stage: Mortality due to COVID-19 up to 15 days or, thereafter, up to a maximum of 2 5 days after the administration of treatment if continued hospitalization","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For this outcome \" all-cause mortality\", there is a low risk of bias for all the domains."]
["2021-04-13 13.31","Agarwal 2020, mortality","CI, MK, CK",1,"Agarwal 2020","convalescent plasma and BSC","Best standard of care (BSC)","Mortality at 28 days & at hospital discharge","risk ratio= 1.04 (95% CI, 0.66 to 1.63)","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","\"An independent biostatistician from the Indian Council Medical Research-National Institute of Epidemiology, Chennai, India, generated the randomisation sequence using the RALLOC module in STATA v.14 \"\r\n\"A stratified block randomisation strategy was used to allocate participants in a 1:1 ratio to receive either convalescent plasma with the best standard of care (intervention arm) or best standard of care alone (control arm).\"","PN","There were no important difference in characteristics between groups, except for some comorbidities, especially diabetes mellitus.\" There were also small differences in concomitant treatments; probably not due to problems with randomisation process","Low","Low","The allocation sequence was random and concealed and there were no differences between intervention groups suggesting a problem with the randomization process.",null,null,"Y","Y","The study used an open label design, which can always be prone to some bias, but the open label design was probably a good choice for this kind of trial. \r\n\"Because our study used an open label design, it was susceptible to anchoring bias of the treating doctors in outcme ascertainment\"","PY","5 patients in CP arm, and 4 in control arm did not receive intervention allocated intervention because of withdrawal of consent; could be due to awareness of intervention 3 patients in control group received CP instead","PN","Comment: Share of participants who did not receive the allocated intervention was relatively low (11/464).","NA",null,"Y","\"We performed an intention-to-treat analysis after imputing the missing composite outcomes for progression to severe disease or mortality.\"","NA",null,"Some concerns","Some concerns","Five participants in convalescent plasma arm and four in control arm did not receive the allocated intervention and this is probably a deviation from the intended intervention that arose because of the trial context. The analysis was appropriate.",null,null,"Y","Data was available for nearly all participants (for exact numbers, see general notes below)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome \"Mortality at 28 days\" was available for 453 out of 464 participants. Data of six participants in the convalescent plasma arm and of five participants in the control arm were missing.\r\nData for this outcome \"Mortality at hospital discharge\" was available for 451 out of 464 participants. Data of eight participants in the convalescent plasma arm and of five participants in the control arm were missing. \r\n \r\n\r\n\r\n\r\n",null,null,"N","Measured as described in trial registry","N","no differences in measurements between groups\r\n","Y","open label","PN","The knowledge of intervention received could not have affected outcome measurement.","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.\r\n\r\n",null,null,"Y","The statistical analysis plan and protocol were not available yet, we could compare the planned and reported outcome with the trial registry. The registry mentioned \"All cause mortality at 28 days or progression to severe diseas\".","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced the result \"mortality at 28 days\" was analysed in accordance with the predefined outcomes stated in the trial registration. For the outcome \"mortality at hospital discharge\", there was no information on whether the data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration, as the data was provided on request by the study investigators. \r\n",null,null,"Some concerns","Some concerns","For this outcome \"mortality\", there is a low risk of bias from the randomization process, missing outcome data, measurement of the outcome and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions."]
["2021-04-12 12.14","AlQahtani 2020, mortality","VP, CI","AlQahtani ",null,"convalescent plasma","SOC","Mortality at day 28",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The study will randomise the patients to one of 2 groups randomised by computer. The number of patients in each group will be the same and they will have an equal chance of being in either arm of the study. Randomisation code will be provided by RCSI Bahrain to be administered in the local environment.\r\n\"Following informed consent and screening, the patients were block randomised (in blocks of 4) by computer-generated random numbering to either the standard therapy or CP arms\"","PN","There are no major differences between groups in baseline characteristics, except for Ferritin level (much higher in Plasma group) and Steroids (more in Control group) \"The CP group showed higher ferritin levels (p=0.049); however, respiratory indices did not differ. There were more men than women, reflecting the demographics of the workforce in Bahrain\"\r\nSteroids: \" at the time of the study this evidence was not known and hence steroids were used at the discretion of the physicians\"\r\nHowever, these differences do not suggest a problem with the randomization process. ","Low","Low","Participants were block randomized by computer-generated random numbering in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","small differences in co-interventions, but probably not due to trial context","NA",null,"NA",null,"Y","Intention to treat analysis","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All the 40 patients ramdonized were included in die analysis. ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 40 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry and in the protocol","N","No differences in measurements between groups ","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.\r\n\r\n\r\n\r\n",null,null,"N","Timepoint of outcome measurement not pre-specified in study protocol","PN","Chosen timepoint established overtime in COVID trials. Preplanned primary endpoint measured and reported as planned at protocol stage","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","Some concerns","Some concerns","Mortality at day 28: The data that produced this result was not analysed in accordance with the predefined outcomes stated in the protocol, as the time point of the outcome measurement was not pre-specified in the  study protocol. \r\n",null,null,"Some concerns","Some concerns","\r\nFor the outcome \"mortality\", there are some concerns for bias in selection of reported results. However, for all the other domains, there is a low risk of bias. "]
["2021-04-12 12.16","AlQahtani 2020, mortality 2","VP, CI","AlQahtani ",null,"CP ","SOC","Mortality at hospital discharge (on request)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The study will randomise the patients to one of 2 groups randomised by computer. The number of patients in each group will be the same and they will have an equal chance of being in either arm of the study. Randomisation code will be provided by RCSI Bahrain to be administered in the local environment.\r\n\"Following informed consent and screening, the patients were block randomised (in blocks of 4) by computer-generated random numbering to either the standard therapy or CP arms\"","PN","There are no major differences between groups in baseline characteristics, except for Ferritin level (much higher in Plasma group) and Steroids (more in Control group) \"The CP group showed higher ferritin levels (p=0.049); however, respiratory indices did not differ. There were more men than women, reflecting the demographics of the workforce in Bahrain\"\r\nSteroids: \" at the time of the study this evidence was not known and hence steroids were used at the discretion of the physicians\"\r\nHowever, these differences do not suggest a problem with the randomization process. ","Low","Low","Participants were block randomized by computer-generated random numbering in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","Small differences in co-intervention, but probably not due to trial context. ","NA",null,"NA",null,"Y","Intention-to treat analysis performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All the 40 patients ramdonized were included in die analysis. ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 40 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","No differences in measurement between groups","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"NI","no information on whether the data that produced this result was analysed in accordance with the predefined protocol, as the data was provided on request by the study investigators. ","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Some concerns","Low","For this outcome, there was no information on whether the data that produced this result was analysed in accordance with the predefined protocol, as the data was provided on request by the study investigators. ",null,null,"Low","Low","For the outcome \"All-cause mortality at hospital discharge\" all the other domains were at low risk of bias. "]
["2021-04-13 11.48","Bajpai 2020, mortality","SV, CI",5,"Bajpai 2020","Convalescent plasma","Fresh frozen plasma (FFP) ","Mortality (at 28-day)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"The randomization was done by using block randomization method with varying block sizes by an independent statistician. The allocation concealment was done by using Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method.\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were block randomized with concealed allocation using the Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method, to receive either convalescent plasma or standard plasma. There are no baseline differences that would suggest a problem with randomisation.\r\n\r\n",null,null,"Y","Y","this was an open label trial ","N","\"in both groups, one patient became RT-PCR negative for SARS-CoV-2 on the day of plasma transfusion\" but this is not because of trial context\r\n\"Thirty-one patients underwent randomization out of which 15 were assigned to receive convalescent plasma with standard care and 16 to FFP with standard care. However, in both groups, one patient became \"RT-PCR negative for SARS-CoV-2 on the day of plasma transfusion. Thus, a total of 14 patients received COPLA and 15 received FFP\"","NA",null,"NA",null,"Y","An intention to treat analysis was done. ","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Nearly all participants, 29 out of 31: \"in both groups, one patient became RT-PCR negative for SARS-CoV-2 on the day of plasma transfusion.\" ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for nearly all participants randomized, in total 29 out of 31 participants (2 participants became PCR negative on the day of plasma transfusion).",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in the outcome measurements between groups ","Y","open label","N","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","The trial protocol and SAP were not available, but the trial registry. From the trial registry we could compare the outcomes planed and reported and there was no inconsistency\r\n-->\"The secondary outcome measures included mortality at day 28\" , and in the trial register mortality is stated also at day 28 ","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For this outcome \"mortality at day 28\", there is a low risk of bias for all the domains. "]
["2021-04-13 13.40","Ray 2020, mortality","CI, MK",7,"Ray 2020","CP","SOC","mortality (30day and time to event)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","NI","Registry: \"Computer generated randomization\" \r\nIn the report it is not clearly described how patients were randomized and no clear information on soncealment was given: \"Patients  fulfilling  the  inclusion  criteria  were  randomized  into  either  the  SOC  arm  receiving  only  the  standard  of  care  therapy,  as  per  current  advisory,  or  in  to  the  CPT group\"\r\n\r\nRegistry: Concealment: Case Record Numbers\"\r\n","PN","Baseline characteristics table missing/not reported. According to the text and a figure on age, the characteristics between groups might be similarly distributed.","Some concerns","Some concerns","Participants were probably allocated randomly to either the standard of care group alone or standard of care with convalescent plasma group and there were no further information given on the randomization process. There is no information on the allocation concealment, the trial registry only indicates concealment through \"Case Record Numbers\". There were no baseline imbalances that would suggest a problem with randomisation.",null,null,"Y","Y","open label and further information is not given","N","There is no flow chart available in the report but, \"All  patients  recruited  in  CPT  arm  received  two  transfusions  of  200ml  ABO-matched  convalescent  plasma  on  two  successive  days,  first  one  being  on  the  day  on  enrolment,  except  for  one  patient  who  succumbed  before he  could  be  transfused with second unit\"","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"PY"," there is no flow-chart available in the report, but based on the text, they mention that 80 participants were randomized and 80 were analysed","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 80 participants randomized.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","No differences in measurements between groups","Y","open label","N","The outcome mortality is objective and its assessment cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","No protocol was available. Only trial registry was available. \r\nThe outcome mortality (time to event) was not described in the registry. The outcome mortality (30 day) was mentioned in the registry. ","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","Mortality at day 28: The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration. Time to event: The data that produced this result was not analysed in accordance with the predefined outcomes stated in the trial registration. The \"time-to-event\" measurement for mortality was not mentioned in the trial registry. ",null,null,"Some concerns","Some concerns","For the outcome \"mortality at up to day 28\" in this study, there is a low risk of bias due to deviations from intended interventions, due to missing outcome data, in measurement of the outcome and in selection of the reported result . There are some concerns for bias from the randomization process.\r\nFor the outcome \"mortality (time to event)\", there is a low risk of bias due to deviations from intended interventions, due to missing outcome data and in measurement of the outcome. There are some concerns for bias in selection of the reported result and from the randomization process."]
["2021-04-13 11.34","Horby 2021, Mortality","CI, VP","Horby 2021",null,"CP","SOC","28-day mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Eligible and consenting patients were allocated in a ratio of 1:1:1\". \"Randomisation was web-based simple (unstratified) randomisation with allocation concealment\"\r\n\"As a platform trial and in a factorial design, patients could be simultaneously randomised to other treatment groups\"","PN","There were nobaseline differences between intervention groups suggesting a problem with the randomization process.","Low","Low","Participants were randomized through web-based simple randomization with allocation concealment in a 1:1:1 ratio to a platform trial in a factorial design, receiving either convalescent plasma in addition to the standard therapy or standard of care alone. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label: \"Participants and local study staff were not masked to the allocated treatment\"\r\nBUT: \"The trial steering committee, investigators, and all other  individuals involved in the trial were masked to outcome data during the trial.\"","N","No, only \"Several of these treatment arms were added to or removed from the protocol over the period that convalescent plasma was evaluated\", but no deviations due to trial context","NA",null,"NA",null,"Y","intention-to-treat comparison","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","all randomised participants were evaluated (5795 out of 5795 in the plasma arm and 5763 of 5763 in the control arm)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 11,558 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in the protocol","N","no differences in measurement between groups","PN","\"The trial steering committee, investigators, and all other  individuals involved in the trial were masked to outcome data during the trial.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were probably not aware of the intervention received.",null,null,"Y","The result analysed were in accordance to the Protocol and statistical analysis plan available","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"28-day mortality\", there was a low risk of bias for all the domains. \r\nFor the outcome \"mortality (time to event)\", there was a low risk of bias for all the domains. "]
["2021-04-12 18.28","O’Donnell 2021, mortality","CI, VP","O’Donnell 2021",null,"CP","normal plasma","28-day mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Enrolled participants were randomized in a 2:1 ratio to receive either convalescent plasma or control plasma using a web-based randomization platform; treatment assignments were generated using randomly permuted blocks of different sizes. \"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were block randomized using a web-based randomization platform in a 2:1 ratio to receive either convalescent plasma or standard plasma and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","Quote (study protocol): \"The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment.\"\r\n\r\nQuote (preprint publication): \"The clinical teams directly managing patients and the trial clinicians who adjudicated clinical status and determined 28-day outcomes were blinded to treatment allocation. The hospital blood bank at each site and the clinical research teams who completed case record forms and performed other study specific procedures were not blinded; this was done to prevent errors in treatment allocation.\"","NA",null,"NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","All participants were analysed: 223 of 223 randomized","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 223 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","N","\"The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were unaware of the intervention received.",null,null,"Y","In accordance with the trial registry available. ","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For the outcome \"28-day mortality\", there is a low risk of bias for all the domains. "]
["2021-04-13 13.40","Horby 2021, Clinical status","CI, VP","Horby 2021",null,"CP","SOC","Clinical worsening: need for IMV ",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Eligible and consenting patients were allocated in a ratio of 1:1:1\". \"Randomisation was web-based simple (unstratified) randomisation with allocation concealment\"\r\n\"As a platform trial and in a factorial design, patients could be simultaneously randomised to other treatment groups\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low",null,null,null,"Y","Y","open-label: \"Participants and local study staff were not masked to the allocated treatment\"","N","No, only \"Several of these treatment arms were added to or removed from the protocol over the period that convalescent plasma was evaluated\", but no deviations due to trial context.","NA",null,"NA",null,"Y","Intention to treat analysis performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data for this outcome was available for all participants not on invasive mechanical ventilation at baseline (10,901 out of 11,558 participants randomized)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all participants not on invasive mechanical ventilation at baseline, a total of 10,901 out of 11,558 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in the protocol. Outcome:\"among patients not on invasive mechanical ventilation at baseline, the composite endpoint of death or need for invasive mechanical ventilation\" -->clear defined based on WHO 7 point scale\r\n","N","no differences in measurement between groups","PN","\"The trial steering committee, investigators, and all other  individuals involved in the trial were masked to outcome data during the trial.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were probably not aware of the intervention received.",null,null,"Y","Protocol and SAP available. For outcome \"need for MV\" there is no inconsistency.\r\n","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"Need for invasive mechanical ventilation\", there was a low risk of bias for all the domains. "]
["2021-04-13 13.41","Horby 2021, Clinical status 2","CI, VP","Horby 2021",null,"CP","SOC","Clinical improvement: Liberation from IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Eligible and consenting patients were allocated in a ratio of 1:1:1\". \"Randomisation was web-based simple (unstratified) randomisation with allocation concealment\"\r\n\"As a platform trial and in a factorial design, patients could be simultaneously randomised to other treatment groups\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized through web-based simple randomization with allocation concealment in a 1:1:1 ratio to a platform trial in a factorial design, receiving either convalescent plasma in addition to the standard therapy or standard of care alone. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label: \"Participants and local study staff were not masked to the allocated treatment\"","N","No, only \"Several of these treatment arms were added to or removed from the protocol over the period that convalescent plasma was evaluated\", but no deviations due to trial context.","NA",null,"NA",null,"Y","intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data for this outcome was available for all participants requiring invasive mechanical ventilation at baseline, which was 617 out of 11,558 participants randomized. ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all participants requiring invasive mechanical ventilation at baseline, which was 617 out of 11,558 participants randomized. ",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in the protocol","N","no differences in measurement between groups","PN","\"The trial steering committee, investigators, and all other  individuals involved in the trial were masked to outcome data during the trial.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were probably not aware of the intervention received.",null,null,"Y","In accordance with protocol: Liberation from IMV reported as defined at protocol stage: \"Successful cessation of invasive mechanical ventilation will be defined as removal of invasive mechanical ventilation within (and survival to) 28 days after randomisation. A time-to-event analysis will be used to compare each treatment group with the no additional treatment group using the log-rank test, as described above. The rate ratio and its confidence interval will be estimated from the log-rank observed minus expected statistic and its variance, and Kaplan-Meier curves will be drawn.\"\r\n","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"Weaning or liberation from invasive mechanical ventilation\", there was a low risk of bias for all the domains. "]
["2021-04-13 13.30","Agarwal 2020, clinical worsening","CI, VP","Agarwal 2020",null,"CP","SOC","Need for IMV",null,"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","National Institute of Epidemiology, Chennai, India, generated the randomisation sequence using the RALLOC module in STATA v.14 \"\r\n\"A stratified block randomisation strategy was used to allocate participants in a 1:1 ratio to receive either convalescent plasma with the best standard of care (intervention arm) or best standard of care alone (control arm).\"","PN","There were no important difference in characteristics between groups, except for some comorbidities, especially diabetes mellitus. To account for the latter and for the different locations of the participating hospitals, they adjusted the risk ratio for \"trial sites and presence of diabetes mellitus\".","Low","Low","The allocation sequence was random and concealed and there were no differences between intervention groups suggesting a problem with the randomization process.",null,null,"Y","Y","Open label","PY","5 patients in CP arm, and 4 in control arm did not receive intervention allocated intervention because of withdrawal of consent; could be due to awareness of intervention 3 patients in control group received CP instead","PN","Comment: Share of participants who did not receive the allocated intervention was relatively low (11/464).","NA",null,"PN","\"A per protocol analysis was performed for secondary outcomes.\" \r\n","PN","Only a small number of participants were not analysed: From the 464 patients randomized, around 451 were included in outcome data anlysis. ","Some concerns","Some concerns","Five participants in convalescent plasma arm and four in control arm did not receive the allocated intervention and this is probably a deviation from the intended intervention that arose because of the trial context. According to the study, a per protocol analysis was performed for this secondary outcome, but there was no potential for a substantial impact (on the result) of the failure to analyse randomized participants.",null,null,"Y","Only a small number of participants were not analysed: From the 464 patients randomized, around 451 were included in outcome data anlysis. ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for 451 out of 451 participants included in the per protocol analysis. Data of eight participants in the convalescent plasma arm and of five participants in the control arm were missing.\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurements between groups ","Y","open label trial ","PN","The knowledge of intervention received could not have affected outcome measurement.","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.\r\n\r\n\r\n\r\n",null,null,"PN","Comment: The statistical analysis plan and protocol were not available yet, but we could compare the planned and reported outcome with the trial registry. In the trial registry, the outcome \"need for invasive ventilation\" was not pre-specified.","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Some concerns","Some concerns","There was a trial register entry, which provided details of the pre-specified outcomes, but \"need for invasive ventilation\" was not pre-specified at trial registration.\r\n\r\n",null,null,"Some concerns","Some concerns","\r\nFor this outcome \"Clinical worsening: Need for invasive mechanical ventilation\", there is a low risk of bias from the randomization process, missing outcome data and measurement of the outcome. However, there are some concerns for bias due to deviations from intended interventions and for bias in selection of the reported result."]
["2021-04-12 11.41","AlQahtani 2020, clinical worsening","CI, VP","AlQahtani 2020",null,"CP","SoC","Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","Quote: \"Following informed consent and screening, the patients were block randomised (in blocks of 4) by computer-generated random numbering to either the standard therapy or CP arms\"\r\n\r\nQuote: \"The number of patients in each group will be the same and they will have an equal chance of being in either arm of the study. Randomisation code will be provided by RCSI Bahrain to be administered in the local environment.\"","PN","Comment: There are no major differences in baseline characteristics between groups , except for Ferritin level (much higher in Plasma group) and Steroids (more in Control group)\r\nQuote: Concerning Steroids: \" (...)at the time of the study this evidence was not known and hence steroids were used at the discretion of the physicians\". However, there are no differences suggesting a problem with the randomization process. ","Low","Low","Participants were block randomized by computer-generated random numbering in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","There were small differences in co-interventions, but this was probably not due to trial context. ","NA",null,"NA",null,"Y","Intention-to-treat analysis was performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All 40 participants randomized, were included in the analysis","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 40 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in the protocol","N","no differences in measurements between groups ","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PN","The assessment of the outcome cannot be influenced by the knowledge of intervention received, as it would not change the fact of being dead or alive","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","result analysed in accordance with a pre-specified analysis plan and protocol","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","PN","Preplanned primary endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For the outcome \"Need for invasive mechanical ventilation\", there was a low risk of bias for all the domains. "]
["2021-04-13 13.42","Simonovich 2020, Clinical worsening","CI, VP","Simonovich 2020",null,"CP","Placebo","Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","PlasmAr was a double-blind, placebo-controlled trial\r\n\"Eligible participants were randomly assigned in a 2:1 ratio to receive either convalescent plasma or placebo.\"\r\n\"Eligible patients underwent treatment allocation and concealment through a randomization program (REDCap) and were assigned in a 2:1 ratio\r\nto receive either a single administration of Covid-19 convalescent plasma or placebo (normal saline solution) in addition to standard treatment.\"","PN","There were small differences in baseline characterisctics; e.g. patients with COPD, patients on critical care unit, but probably not due to problems with randomisation process","Low","Low","Participants were randomized through a randomization program (REDCap) in a 2:1 ratio to receive either convalescent plasma or a placebo. The allocation sequence was random and concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","Quote: \"The intervention will remain blind to the research subjects and to the research team throughout the entire protocol. \r\nQuote: \"Since the plasma solution is slightly opaque, the container and IV line will be covered with a coloured sleeve to maintain the masking.\"","NA",null,"NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and carers and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","Out of 334 participants, 333 were analysed. ","NA",null,"NA",null,"NA",null,"Low","Low","From the 334 participants randomized data was available for 228 participants in the convalescent plasma group and 105 participants in the placebo group. The data of  one participant in control group was missing, due to withdrawal of consent after randomisation and therefore the participant was excluded from the analysis.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described ","N","No differences in measurement between groups","N","\"The intervention will remain blind to the research subjects and to the research team throughout the entire protocol\"","NA",null,"NA",null,"Low","Low","The outcome measurement is an appropriate measure and it is unlikely that the measurement differed between intervention groups. The outcome assessors were  not aware of the intervention received. \r\n",null,null,"Y","In accordance with the available protocol","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. \r\n\r\n",null,null,"Low","Low","For the outcome \"Clinical worsening: Need for invasive mechanical ventilation\", all the domains have a low risk of bias."]
["2021-04-12 17.55","Bajpai 2020, clinical worsening","CI, VP","Bajpai",null,"CP","standard plasma","need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"The randomization was done by using block randomization method with varying block sizes by an independent statistician. The allocation concealment was done by using Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method.\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were block randomized with concealed allocation using the Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method, to receive either convalescent plasma with standard of care or standard plasma (fresh frozen plasma) with standard of care. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","This is an open-label trial.","N","No deviations due to trial context","NA",null,"NA",null,"Y","Intention to treat was done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Nearly all participants, 29 out of 31: \"in both groups, one patient became RT-PCR negative for SARS-CoV-2 on the day of plasma transfusion.\" ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for nearly all participants randomized, in total 29 out of 31 participants (2 participants became PCR negative on the day of plasma transfusion).",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","Y","open label","N","The assessment of the outcome could not have been influenced by knowledge of intervention received.","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For this outcome \"Clinical worsening: Need for invasive mechanical ventilation\", there is a low risk of bias for all the domains. "]
["2021-04-13 13.13","Gharbaran 2020, liberattion from oxygen","CI, VP","Gharbharan ",null,"CP","SoC","liberation from supplemental oxygen",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record); Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","small differences, but trial wasParticipants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation. stopped after enrollment of 86 of 426 planned participants","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label","NI","\"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for COVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nComment: Unclear whether treatments were balanced across arms. \r\n","NA",null,"NA",null,"Y","Intention to treat analysis was performed","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"Y","Data for this outcome was available for 77 out of 86 participants randomized. ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all participants requiring any supplemental oxygen or ventilator support at baseline, being 77 out of 86 participants randomized. ",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol","N","no differences in measurements between groups","Y","this was an open label trial","N","The assessment of the outcome could not have been influenced by knowledge of intervention received","NA",null,"Low","Low","The outcome assessors aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement or that the measurement differed between intervention groups.",null,null,"Y","Yes, reported in the protocol as well: Impact of 300ml convP on weaning from oxygen therapy","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. \r\n",null,null,"Some concerns","Some concerns","For the outcome \"liberation from supplemental oxygen\", there is a low risk of bias from the randomization process, due to missing outcome data, in measurement of the outcome and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions."]
["2021-04-13 13.13","Gharbaran 2020 liberation from IVM","VP, CI","Gharbharan 2020",null,"CP","SoC","Liberation from IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record); Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","small differences, but trial was stopped after enrollment of 86 of 426 planned participants","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label","NI","\"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for COVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nComment: Unclear whether treatments were balanced across arms. \r\n","NA",null,"NA",null,"Y","AN intention to treat analysis was done","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"Y","Data for this outcome was available for 13 out of 86 participants randomized (all 13 participants requiring invasive mechanical ventilation at baseline)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all participants requiring invasive mechanical ventilation at baseline, which was 13 out of 86 participants randomized. ",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol","N","no differences in measurements between groups ","Y","This was an open lable trial","N","The assessment of the outcome could not have been influenced by knowledge of intervention received","NA",null,"Low","Low","The outcome assessors aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement or that the measurement differed between intervention groups.",null,null,"NI","Data obtained on request","NI","Data obtained on request","NI","Data obtained on request","Some concerns","Low","There was no information on whether the data that produced this result was analysed in accordance with a pre-specified analysis plan, as the data was provided on request by the study investigators. ",null,null,"Some concerns","Some concerns","For the outcome \"liberation from invasive mechanical ventilation\", there is a low risk of bias from the randomization process, due to missing outcome data, in measurement of the outcome and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions."]
["2021-04-13 13.18","Gharbaran 2020 Clinical Improvement","VP, NS, KLC, CK, SJV",1,"Ghabaran","Convalescent plasma","supportive care, oxygen, antibiotics)","Clinical improvement",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record); Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Open-lable","NI","All patients received assigned intervention, but co-interventions not described. \r\nQuote: \"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for\r\nCOVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nUnclear whether treatments were balanced across arms. ","NA",null,"NA",null,"Y","An intention to treat analysis was done","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"Y","Data for this outcome was available for all participants randomized (100%) ","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all participants randomized. ",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol, with 8 point WHO clinical progression scale","PN","no differences in measurements between groups ","Y","opene label trial","NI","we do not have enough information whether the knowledge of intervention received could have affected outcome measurement, but it is unlikely.","N",null,"Some concerns","Some concerns","The outcome assessors aware of the intervention received and we do not have enough information whether the knowledge of intervention received could have affected outcome measurement, but it is unlikely. The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. ",null,null,"PY","Results only provided for day 15 in pre-print article, but authors provided data for day 30 upon request. analysed in accordance with a pre-specified analysis plan","PN","Preplanned endpoint measured and reported as planned at protocol stage\r\nadjusted and unadjusted results rovided","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Some concerns","Some concerns"]
["2021-04-12 16.16","Li 2020 Clinical Improvement","VP, NS",2,"Li","Conventional treatment with convalescent plasma","Conventional treatment alone","Clinical improvement",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Quote: \"Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone (control group) (Figure 1). The randomization was stratified based on the severity of COVID-19 (severe or life-threatening) and a randomization schedule was generated using block randomization with block size of 4 for each type of COVID-19 by SAS software.\"\r\nQuote: \"This random number will connect the subject to the designated treatment group (experimental group or control group) for treatment. [...] Staff responsible for randomization will only be responsible for the assignment of random groups and will not be involved in any specific trial operations.\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were block randomized via computer-generated random numbering in a 1:1 ratio to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Quote: \"open-lable\"","PN","All patients received assigned intervention; co-interventions not balanced across arms, but no evidence for a protocol deviation and no deviations due to trial context","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data for this outcome was available for all 103 participants randomized.","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 103 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","N","Quote: \"To avoid assessment bias, the evaluation of clinical outcomes was performed by an investigator who was blind to the study group allocation.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were not aware of the intervention received.",null,null,"N","result analysed not in accordance with a pre-specified analysis plan availbale or protocol, time points added. Post-hoc analyses probably done after unblinded outcome data were available for analysis. \r\nQuote: \"A post hoc analysis was added to compare rates of improvement at days 7, 14, and 28.\"","NI",null,"Y","Quote: \"A post hoc analysis was added to compare rates of improvement at days 7, 14, and 28.\"","High","Low","Post-hoc analyses probably done after unblinded outcome data were available for analysis. However, time points were prioritised by WHO and COMET-initiative after the study was set up. Conducting post-hoc analyses according to WHO/ COMET- recommendations was probably not done by choosing particulare results to present a specific view of the data. Assessor's judgement therefore deviates from algorithm result. ",null,null,"Low","Low","For this outcome, all the domains have a low risk of bias."]
["2021-04-13 13.51","Agarwal 2020, Improvement of clinical symptoms","CI, ED","Agarwal 2020",null,"convalescent plasma and BSC","Best standard of care","Clinical status (data provided by authors)","NR","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","National Institute of Epidemiology, Chennai, India, generated the randomisation sequence using the RALLOC module in STATA v.14 \"\r\n\"A stratified block randomisation strategy was used to allocate participants in a 1:1 ratio to receive either convalescent plasma with the best standard of care (intervention arm) or best standard of care alone (control arm).\"","PN","there were no differences between intervention groups suggesting a problem with the randomization process.","Low","Low","The allocation sequence was random and concealed and there were no differences between intervention groups suggesting a problem with the randomization process.",null,null,"Y","Y","The study used an open label design","PY","5 patients in CP arm, and 4 in control arm did not receive intervention allocated intervention because of withdrawal of consent; could be due to awareness of intervention 3 patients in control group received CP instead","PN","Comment: Share of participants who did not receive the allocated intervention was relatively low (11/464).","NA",null,"PN","\"A per protocol analysis was performed for secondary outcomes.\" ","PN","Only a small number of participants were not analysed: From the 464 patients randomized, around 451 were included in outcome data anlysis. ","Some concerns","Some concerns","Five participants in convalescent plasma arm and four in control arm did not receive the allocated intervention and this is probably a deviation from the intended intervention that arose because of the trial context. The analysis was not appropriate (per protocol analysis), but there was no potential for a substantial impact on the results. ",null,null,"Y","From the 464 patients randomized, 451 were included in outcome data anlysis. \r\n\r\n8/235 lost to follow up in CP group; 5/229 in control group","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for 451 participants out of 464 participants randomized.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry. The WHO 8 point ordincal scale was used, which is comparable to the WHO 10 point clinical improvement scale\r\nQuote: \"WHO ordinal scale scores for clinical improvement\". \"we compared clinical improvement on the World Health Organization ordinal scale on days 0, 1, 3, 5, 7, 14, and 28 between the two study arms\"","N","no differences in measurements between groups","Y","open label","PN","The knowledge of intervention received could not have affected outcome measurement.","NA",null,"Low","Low","\r\nThe measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.\r\n\r\n",null,null,"NI","\"The WHO ordinal scale was not mentioned in the initial study protocol but was added midway through the trial as we thought it would be a key endpoint in future meta-analyses.\" \r\nAlso: we got the final data for this outcome on request from the authors.","NI","we got the final data for this outcome on request from the authors","NI","we got the final data for this outcome on request from the authors","Some concerns","Low","There was no information on whether the data that produced this result was analysed in accordance with a pre-specified trial registration, as the data was provided on request by the study investigators.",null,null,"Low","Low","For this outcome, there is a low risk of bias arising from the randomization process and due to missing outcome data, in measurement of the outcome and in the in selection of the reported result. But, there are some concerns for bias due to deviations from intended interventions. "]
["2021-04-12 13.42","Avendano-Sola 2020, clinical status","CI, MB",10,"Avendano-Sola 2020","Convalescent plasma","SOC","clinical status (at day 7, 15 & 29)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","Yes: \"Patients were registered, after giving informed consent to participate, in a web-based eCRF (ORACLE clinical), their baseline clinical data collected and then randomly assigned 1:1 to the investigational treatment, stratified by study site.\"\r\nThe randomization process has been developed using the RERAND system integrated within the RDC Onsite ECRF system based on Oracle.\r\n","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized through a web-based eCRF system (ORACLE clinical) in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Because this is an open label trial.","N","\"1 did not receive CP due to absence of AB0 blood group compatible plasma\" -->but this is not because of trial context\r\nOf the patients randomized to receive plasma, 37 (97.4%) received treatment as assigned.","NA",null,"NA",null,"Y","Intention to treat analysis was performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data for this outcome was available for all 81 participants randomized.","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 81 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry. The outcome is: proportion of patients in categories 5, 6 or 7 at day 15 and at day 29\r\n\"The patient’s clinical status was recorded using the seven-category ordinal COVID-19 scale: 1, not hospitalized, no limitations on activities; 2, not hospitalized, limitation on activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, on non-invasive ventilation or high flow oxygen devices; 6, hospitalized, on invasive mechanical ventilation or ECMO and 7, death.\"","PN","no differences in measurement between groups","PY","open label trial","PN","The outcome assessment was probably not influenced by the knowledge of intervention received\r\n","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","The trial protocol and SAP were not available, only some supplementary material is provided on methods and trial registry. From the trial registry we could compare the outcomes planed and reported and there were no inconsistencies. It was planned to measure the time to category 5, 6 or 7 of the ordinal scale up to day 29.\r\n","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","Low","Low","The trial protocol and SAP were not available, only some supplementary material is provided on methods and trial registry. From the trial The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.\r\n",null,null,"Low","Low","For the outcome there is a low risk of bias for all the domains. \r\n\r\n"]
["2021-04-13 11.20","Libster 2020, Development of severe","CI, VP","Libster ",null,"CP","SOC","Development of severe symptoms: need for invasive mechanical ventilation",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","The randomization of participating subjects will be conducted by the person in charge of randomizing the study using an electronic system. Once the patient is randomized, the person in charge of the allocation will communicate with a member of the Transfusion Medicine Central Team in the study who will remove the opaque bag treatment indicated in the freezer of the Central Laboratory.","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized using an electronic system numbering to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","PY","Neither the patient nor the researchers will have knowledge of the administered treatment, conducting a double-blind study. The unblinded team will keep a record of the product assignments and their administrations that will be kept confidential.","N","no deviations due to trial context","NA",null,"NA",null,"Y","Intention to treat analysis was performed","NA",null,"Low","Low","The participants were unaware of their assigned intervention and those delivering the intervention were aware of intervention assigned during the trial, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All 160 out of 160 participants were analysed","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 160 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol","N","no differences in measurement between groups","PN","\"Neither the patient nor the researchers will have knowledge of the administered treatment, conducting a double-blind study\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were probably unaware of the intervention received.",null,null,"Y","accordance with a pre-specified analysis plan","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For this outcome \"Development of severe symptoms\", there is a low risk of bias for all the domains."]
["2021-04-13 14.00","Gharbaran 2020 Safety","VP, NS, KLC, CK, SJV",1,null,"Convalescent plasma","SoC","Safety",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-lable","NI","All patients received assigned intervention, but co-interventions not described. \r\nQuote: \"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for\r\nCOVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nUnclear whether treatments were balanced across arms. ","NA",null,"NA",null,"Y","An intention to treat analysis was done","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"N","Only reported for intervention group","N","We found no evidence","Y","The investigators could have intended to only identify, collect and report adverse events from the intervention group and on purpose not collect adverse events of the control group.","PY",null,"High","High","Data for this outcome was available only for the intervention group randomized. There no evidence that the result was not biased by missing outcome data and it is likely that missingness in the outcome depended on its true value.",null,null,"NI","Measurement not described","Y","Only transfusion-related AEs were measured; therefore only in the intervention group","NA",null,"NA",null,"NA",null,"High","High","The method of measuring the outcome was not reported or described and could have differed between groups. ",null,null,"Y","in accordance with a pre-specified analysis plan ","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"High","High","For the outcome \"safety\" there is a low risk of bias from the randomization process and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions and high risk of bias due to missing outcome data, in measurement of the outcome "]
["2021-04-13 13.54","Li 2020 Safety","VP, NS",2,null,"Conventional treatment with convalescent plasma","conventional treatment alone","Safety",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Quote: \"Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone (control group) (Figure 1). The randomization was stratified based on the severity of COVID-19 (severe or life-threatening) and a randomization schedule was generated using block randomization with block size of 4 for each type of COVID-19 by SAS software.\"\r\nQuote: \"This random number will connect the subject to the designated treatment group (experimental group or control group) for treatment. [...] Staff responsible for randomization will only be responsible for the assignment of random groups and will not be involved in any specific trial operations.\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were block randomized via computer-generated random numbering in a 1:1 ratio to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","Quote: \"open-lable\"","PN","All patients received assigned intervention; co-interventions not balanced across arms, but no evidence for a protocol deviation and no deviations due to trial context","NA",null,"NA",null,"N","Only transfusion-related adverse events reported","PN","Only transfusion-related adverse events reported, and from the plasma group, all the participants were included in the safety analysis","Some concerns","High","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate. But no appropriate analysis was perfomed, only transfusion-related adverse events were reported, but there was no potential for substantial impact on the results",null,null,"N","Only reported for intervention group (52 participants)","N","No specific evidence could be found.","Y","The investigators could have intended to only identify, collect and report adverse events from the intervention group and on purpose not collect adverse events of the control group. ","PY",null,"High","High","Data for this outcome was available only for the intervention group randomized. There no evidence that the result was not biased by missing outcome data and it is likely that missingness in the outcome depended on its true value.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","Y","Only transfusion-related AEs were measured; therefore only in the intervention group","NA",null,"NA",null,"NA",null,"High","High","The measurement of the outcome was appropriate and the measurment differed between intervention groups. ",null,null,"Y","accordance with a pre-specified analysis plan","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"High","High","For the safety outcome, there is a high risk of bias due to missing outcomes, measurement of the outcome and selection of reported results. "]
["2021-04-13 11.40","Avendano-Sola 2020, safety","MB, CI",10,"Avendano-Sola 2020","Convalescent plasma in addition to standard treatment","SOC","safety (grade 3 & 4 AEs and serious AEs)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","Yes: \"Patients were registered, after giving informed consent to participate, in a web-based eCRF (ORACLE clinical), their baseline clinical data collected and then randomly assigned 1:1 to the investigational treatment, stratified by study site.\"\r\n\r\n","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized through a web-based eCRF system (ORACLE clinical) in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","This is an open label trial.","N","\"1 patient did not receive CP due to absence of AB0 blood group compatible plasma\" (Of the patients randomized to receive plasma, 37 (97.4%) received treatment as assigned)-->but this is not because of trial context","NA",null,"NA",null,"Y","Intention to treat analysis performed.","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","All 81 participants available for all randomized were analysed(although some were lost to follow-up, withdrew consent).","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 81 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry. Clinical and laboratory tests performed, but choice of these tests and AE to focus on might have been subjective: \"Serious adverse events (AE), grade 3 or 4 AE and infusion related AE (within 24 hours after administration) were collected. Investigators were instructed to actively monitor for the appearance of predefined AE of Special enhancement of infection)\"\r\nInfusion-related adverse reactions will be recorded by a trained Hemovigilance nurse or physician, according to the Active 24h quarantine Hemovigilance Program","N","no differences in measurement between groups","PY","open label trial","PN","The outcome assessment was probably not influenced by the knowledge of intervention received","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","The trial protocol and SAP were not available, only some supplementary material is provided on methods and trial registry. From the trial registry we could compare the outcomes planed and reported and there was no inconsistencies for safety assessment\r\n","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.\r\n\r\n",null,null,"Low","Low","For this outcome \"Grade 3 and 4 adverse events\", there is a low risk of bias for all the domains. \r\nFor this outcome \"Serious adverse events\", there is a low risk of bias for all the domains. "]
["2021-04-13 11.42","Simonovich 2020, safety","VP, CI","Simonovich 2020","Simonovich","Convalescent plasma","Placebo (saline)","Any grade, AEs 3+4, SAEs",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","PlasmAr was a double-blind, placebo-controlled trial\r\n\"Eligible participants were randomly assigned in a 2:1 ratio to receive either convalescent plasma or placebo.\"\r\n\"Eligible patients underwent treatment allocation and concealment through a randomization program (REDCap) and were assigned in a 2:1 ratio\r\nto receive either a single administration of Covid-19 convalescent plasma or placebo (normal saline solution) in addition to standard treatment.\"","PN","There were small differences in baseline characterisctics; e.g. patients with COPD, patients on critical care unit, but probably not due to problems with randomisation process","Low","Low","Participants were randomized through a randomization program (REDCap) in a 2:1 ratio to receive either convalescent plasma or a placebo. The allocation sequence was random and concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","double-blinded; Quote: \"The intervention will remain blind to the research subjects and to the research teamthroughout the entire protocol. The transfusional medicine team and the persons in charge ofthe statistical analysis will not be blind regarding the assignment of the branch to which thepatients have been randomized.\"Quote: \"Since the plasma solution is slightly opaque,the container and IV line will be covered with a colored sleeve to maintain the masking.\"","NA",null,"NA",null,"NA",null,"Y","Safety population: ITT performed on both groups (CP and placebo group)","NA",null,"Low","Low","Both participants and carers and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.\r\n",null,null,"Y","For any grade AE: neraly all the participants were analysed (332 out of 334)\r\nFor grade 3 and 4: nearyl all partcicipants were analysed (333 out of 334)","NA",null,"NA",null,"NA",null,"Low","Low","From the 334 participants randomized, data was available for 228 participants in the convalescent plasma group and 104 participants in the placebo group. For any grade AE: The data of two participants in control group was missing, of which one missing participants was due to withdrawal of consent after randomisation and therefore that participant was excluded from the analysis.\r\nFor grade 3 & 4 and SEAs: From the 334 participants randomized, data was available for 228 participants in the convalescent plasma group and 105 participants in the placebo group.  The data of  one participant in control group was missing, due to withdrawal of consent after randomisation and therefore the participant was excluded from the analysis.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry/protocol: \"Patients were clinically followed for a period of 30 days after enrollment. In case of earlier hospital discharge, a phone based follow up was scheduled in order to look up for clinical outcomes and adverse events until day 30, in compliance with current healthcare protection policies. Adverse events were registered and reported on an ongoing basis.\"","PN","no differences in measurements between groups ","N","\r\nResearchers were blinded to the intervention. ","NA",null,"NA",null,"Low","Low","The outcome measurement is an appropriate measure and it is unlikely that the measurement differed between intervention groups. The outcome assessors were  not aware of the intervention received. ",null,null,"Y","outcome analysed in accordance with available protocol ","PN","Quote: \"For secondary outcome #9 (adverse events / serious adverse events)...percentage of adverse events and severe adverse events. ...\" Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Low","Low","For this outcome \"Any grade adverse events\", there is a low risk of bias for all the domains. \r\nFor this outcome \"Grade 3 and 4 adverse events\", there is a low risk of bias for all the domains. \r\nFor this outcome \"Serious adverse events\", there is a low risk of bias for all the domains. "]
["2021-04-12 17.05","AlQahtani 2020, safety","CI, ED, VP","AlQahtani 2020",null,"CP","SOC","Safety (grade 3 and 4 on request)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record); “Grey literature” (e.g. unpublished thesis)","Y","Y","Quote: \"Following informed consent and screening, the patients were block randomised (in blocks of 4) by computer-generated random numbering to either the standard therapy or CP arms\"\r\n\r\nQuote: \"The number of patients in each group will be the same and they will have an equal chance of being in either arm of the study. Randomisation code will be provided by RCSI Bahrain to be administered in the local environment.\"","PN","Comment: There are no major differences in baseline characteristics between groups , except for Ferritin level (much higher in Plasma group) and Steroids (more in Control group)\r\nHowever, there were no differences suggesting a problem with randomization","Low","Low","Participants were block randomized by computer-generated random numbering in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open label\r\nQuote: \"Patients and clinicians were not blinded to the treatment given\"","PN","Comment: There were small differences in co-interventions, but this was probably not due to trial context. ","NA",null,"NA",null,"Y","Intention to treat analysis performed","NA",null,"Low","Low","open label\r\nQuote: \"Patients and clinicians were not blinded to the treatment given\"\r\nBoth participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data available for all the participants randomized (40 out of 40 participants)","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 40 participants randomized.",null,null,"NI","The data was obtained on request, so we cannot check whether the measuring method of the outcome was appropriate or not. ","NI","We have no information whether the measurement differend between groups.","Y","open label: \"Patients and clinicians were not blinded to the treatment given\"","PY","The knowledge of intervention received could have affected safety outcome assessments, as there are different assessments methods and criteria possible for safety. \r\n","PN",null,"Some concerns","Some concerns","There is no information available on whether the method of measuring the outcome was appropriate or whether the measurement could have differed between groups , as the data was provided on request by the study investigator and for safety different measurements are possible. The outcome assessors were aware of the intervention received, which is why the knowledge of intervention received could have affected safety outcome assessments, but this is unlikely.  \r\n\r\n\r\n\r\n",null,null,"NI","data obtained on request","NI","data obtained on request","NI","data obtained on request","Some concerns","Low","For this outcome, there was no information on whether the data that produced this result was analysed in accordance with the predefined protocol, as the data was provided on request by the study investigators. ",null,null,"Some concerns","Some concerns","For the outcome \"Grade 3 and 4 adverse events\", there is a low risk of bias arising from the randomization process, due to deviations from intended interventions, due to missing outcome data and in the in selection of the reported result. But, there are some concerns for bias in measurement of the outcome. \r\n\r\n\r\n\r\n"]
["2021-04-13 10.18","O’Donnell 2021, safety","CI, VP","O’Donnell 2021",null,"CP","normal plasma","safety: any grade AEs and SAEs",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Enrolled participants were randomized in a 2:1 ratio to receive either convalescent plasma or control plasma using a web-based randomization platform; treatment assignments were generated using randomly permuted blocks of different sizes. \"","PN","There are no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were block randomized using a web-based randomization platform in a 2:1 ratio to receive either convalescent plasma or standard plasma and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","Quote (study protocol): \"The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment.\"\r\n\r\nQuote (preprint publication): \"The clinical teams directly managing patients and the trial clinicians who adjudicated clinical status and determined 28-day outcomes were blinded to treatment allocation. The hospital blood bank at each site and the clinical research teams who completed case record forms and performed other study specific procedures were not blinded; this was done to prevent errors in treatment allocation.\"","NA",null,"NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","Nearly all  participants: 147/150 in convalescent plasma group and 72/73 in the standard plasma group","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for nearly all (219 out of 223) participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","N","\"The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were unaware of the intervention received.",null,null,"Y","in accordance with a pre-specified trial registry","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For the outcome \"any adverse events\", there is a low risk of bias for all the domains. \r\nFor the outcome \"serious adverse events\", there is a low risk of bias for all the domains. "]
["2021-04-13 13.46","Agarwal 2020, safety","CI, ED, VP",1,"Agarwal 2020","convalescent plasma and BSC","Best standard of care","Safety (grade 3 and 4 on request)","not reported","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","National Institute of Epidemiology, Chennai, India, generated the randomisation sequence using the RALLOC module in STATA v.14 \"\r\n\"A stratified block randomisation strategy was used to allocate participants in a 1:1 ratio to receive either convalescent plasma with the best standard of care (intervention arm) or best standard of care alone (control arm).\"","PN","There were no important difference in characteristics between groups, except for some comorbidities, especially diabetes mellitus. To account for the latter and for the different locations of the participating hospitals, they adjusted the risk ratio for \"trial sites and presence of diabetes mellitus\".","Low","Low","The allocation sequence was random and concealed and there were no differences between intervention groups suggesting a problem with the randomization process.",null,null,"Y","Y","The study used an open label design, which can always be prone to some bias, but the open label design was probably a good choice for this kind of trial. \r\n\"Because our study used an open label design, it was susceptible to anchoring bias of the treating doctors in outcome ascertainment\"","PY","5 patients in CP arm, and 4 in control arm did not receive intervention allocated intervention because of withdrawal of consent; could be due to awareness of intervention 3 patients in control group received CP instead","PN","Comment: Share of participants who did not receive the allocated intervention was relatively low (11/464).","NA",null,"PY","Data obtained on request ","NA",null,"Some concerns","Some concerns","Five participants in convalescent plasma arm and four in control arm did not receive the allocated intervention and this is probably a deviation from the intended intervention that arose because of the trial context. There is no information on whether the analysis was appropriate.",null,null,"Y","Data from 451 out of 464 participants randomized","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for 451 participants out of 464 participants randomized and the data of eight participants in the convalescent plasma arm and of five participants in the control arm were missing.\r\n\r\n",null,null,"NI","Safety data obtained on request","PN","no difference in measurements bwteen groups","Y","open label","PY","The knowledge of intervention received could have affected outcome measurement, but it is unlikely. ","PN",null,"Some concerns","Some concerns","There was no information on the method of measuring for this outcome, as the data was provided on request by the study investigator. The outcome assessors were aware of the intervention received and the knowledge of intervention received could have affected outcome measurement, but it is probably not likely. ",null,null,"NI","Not planned in the registry, but safety data was obtained on request","NI","safety data was obtained on request","NI","safety data was obtained on request","Some concerns","Low","There was no information on whether the data that produced this result was analysed in accordance with a pre-specified analysis plan, as the data was provided on request by the study investigators. \r\n\r\n",null,null,"Some concerns","Some concerns","For the outcome \"Grade 3 and 4 adverse events\" , there is a low risk of bias arising from the randomization process and due to missing outcome data and in the in selection of the reported result. But, there are some concerns for bias due to deviations from intended interventions and in measurement of the outcome. "]
["2021-04-13 12.58","Avendano-Sola 2020, viral clearance","MB, CI",10,"Avendano-Sola 2020","CP","SOC","viral clearance (day 3, 7, 15)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Yes: \"Patients were registered, after giving informed consent to participate, in a web-based eCRF (ORACLE clinical), their baseline clinical data collected and then randomly assigned 1:1 to the investigational treatment, stratified by study site.\"\r\n\r\n","PN","No baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized through a web-based eCRF system (ORACLE clinical) in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open label","N","\"1 did not receive CP due to absence of AB0 blood group compatible plasma\" -->but this is not because of trial context","NA",null,"NA",null,"Y","Intention to treat analysis performed","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"N","\"Not all patients had their samples collected at all scheduled timepoints.\"\r\nFor viral clearance day 3: Data for this outcome was not available for all participants randomized, but only for 68 out of 81 participants. \r\nFor viral clearance day 7: Data for this outcome was not available for all participants randomized, but only for 56 out of 81 participants. \r\nFor viral clearance day 15: Data for this outcome was not available for all participants randomized, but only for 62 out of 81 participants.","PN","There is no evidence that the result was not biased by missing outcome data.","N","it is unlikely that the missingness of outcome data depended on its true value.","NA",null,"Low","Low","For viral clearance day 3: Data for this outcome was not available for all participants randomized, but only for 68 out of 81 participants. \r\nFor viral clearance day 7: Data for this outcome was not available for all participants randomized, but only for 56 out of 81 participants.\r\nFor viral clearance day 15: Data for this outcome was not available for all participants randomized, but only for 62 out of 81 participants.\r\nOnly 79.7% of serial scheduled samples in the plasma group and 66.54% in the control group were obtained, but it is unlikely that the missingness of outcome data depended on its true value.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry \"Negativization over time of RT-PCR on serial oro/naso pharyngeal swabs (all patients).\" --> This is quite objective, so no judgement possible","N","no diffferences in measurement between groups","PY","Open-label trial","N","The assessment of the outcome has probably not been influenced by knowledge of intervention received","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","Comment: The trial protocol and SAP were not available, but some supplementary material was provided on methods and the trial registry was available. From the trial registry we could compare the outcomes planed and reported and there were no inconsistencies for viral clearance at day 3, 8 and 15.","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","\r\nFor the outcome \"viral clearance\", there is a low risk of bias for all the domains."]
["2021-04-13 13.00","Li 2020, viral clearance","CI, MB",3,"Li 2020","Convalescent plasma ","SOC","viral clearance (day 3)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone (control group)\"\r\n\"The randomization was stratified based on the severity of COVID-19 (severe or life-threatening) and a randomization schedule was generated using block randomization with block size of 4 for each type of COVID-19 by SAS software.\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were block randomized via computer-generated random numbering in a 1:1 ratio to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","\"open-label\"\r\n\"Patients and clinicians were not masked to treatment assignment.\"\r\n","PN","Slightly different standard of care treatments were given between the intervention and control group. \r\n\"Interpretation is limited by early termination of the trial, which\r\nmay have been underpowered to detect a clinically important difference.\" \r\n\"The last patient enrolled in this study was on March 27, 2020, and\r\nfor the next 3 days, we were not able to recruit more patients and did not have any recruitment targets. \" -->not because of trial context","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"PN","Only assessed for 47 out of 52 participants (CP group) and 40 out of 51 participants (SOC groups)\r\n- CP group: 41/47 events is greater than n of patients missing (5)\r\n- Control group: 15/40 events is not much greater than n of patients missing (11)\r\n","PN","No evidence could be found. ","PN"," it is unlikely that the missingness in the outcome could depend on its true value.","NA",null,"Low","Low","Data for this outcome was not available for all, or nearly all, participants randomized (47/52 participants in plasma group and 40/51 participants in control group) and there is no evidence that the result was not biased by missing outcome data. However, it is unlikely that the missingness in the outcome could depend on its true value.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurements between groups","N","\"To avoid assessment bias, the evaluation of clinical outcomes was performed by an investigator who was blind to the study group allocation\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were not aware of the intervention received.",null,null,"Y","In accordance with a pre-specified analysis plan ","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol\r\n\r\n",null,null,"Low","Low","For the outcome \"viral clearance\", there is a low risk of bias in all the domains."]
["2021-04-13 12.51","Agarwal 2020, viral clearance","VP, CI","Agarwal 2020",null,"Convalescent plasma ","SOC","viral clearance (day 3 and day 7)","binary","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","National Institute of Epidemiology, Chennai, India, generated the randomisation sequence using the RALLOC module in STATA v.14 \"\r\n\"A stratified block randomisation strategy was used to allocate participants in a 1:1 ratio to receive either convalescent plasma with the best standard of care (intervention arm) or best standard of care alone (control arm).\"\r\nStratification was by sites; block randomisation was done with unequal\r\nblock sizes. \r\n\"investigators screened the participants for recruitment and contacted a member of the central trial coordinating team to receive the randomisation sequence, ensuring concealment of allocation.\"","PN","There were no important difference in characteristics between groups, except for some comorbidities, especially diabetes mellitus. There were also small differences in concomitant treatments; probably not due to problems with randomisation process","Low","Low","The allocation sequence was random and concealed and there were no differences between intervention groups suggesting a problem with the randomization process.",null,null,"Y","Y","\r\n\"Because our study used an open label design, it was susceptible to anchoring bias of the treating doctors in outcome ascertainment\"","PY","5 patients in CP arm, and 4 in control arm did not receive intervention allocated intervention because of withdrawal of consent; could be due to awareness of intervention 3 patients in control group received CP instead","PN","Comment: Share of participants who did not receive the allocated intervention was relatively low (11/464).","NA",null,"PN","\"A per protocol analysis was performed for secondary outcomes in 451 participants.\" ","PN","There was no potential for substantial impact on the result. ","Some concerns","Some concerns","Five participants in convalescent plasma arm and four in control arm did not receive the allocated intervention, which could be due to awareness of the intervention, as this trial was open-label. According to the study, a per protocol analysis was performed for this secondary outcome, but there was no potential for a substantial impact (on the result) of the failure to analyse randomized participants.",null,null,"N","Viral clearance day 3: 367 out of 451 patients analysed (assessed for 184/235 patients in CP arm and 183/229 patients in control arm)\r\nViral clearance day 7: Data for this outcome was available for 342 out of 451\r\n-->n of events much greater than n of pat with missing data","N","there is no evidence that the result was not biased by missing outcome data. ","Y","It is not likely that missingness in the outcome depended on its true value. ","PN",null,"Some concerns","Some concerns","Viral clearance at day 3: Data for this outcome was available for 367 out of 451 participants included in the per protocol analysis. Data of 51 participants in the convalescent plasma arm and of 46 participants in the control arm were missing and there is no evidence that the result was not biased by missing outcome data. However, there it is not likely that missingness in the outcome depended on its true value. Viral clearance dat day 7: Data for this outcome was available for 342 out of 451 participants included in the per protocol analysis and there is no evidence that the result was not biased by missing outcome data. However, there it is not likely that missingness in the outcome depended on its true value. ",null,null,"NI","The method of measuring of the outcome was no described/not reported: \"To assess viral clearance, we compared the proportion of participants negative for SARS-CoV-2 RNA between the trial arms on days 3 and 7\" -->BUT, unclear how outcome was measured","PY","Yes, the measurement of the outcome could have differed between intervention groups","NA",null,"NA",null,"NA",null,"High","High","There was no information on whether the method of measuring the outcome was inappropriate, as it was unclear how the outcome was exactly measured and the measurement could have differed between intervention groups.",null,null,"Y","The statistical analysis plan and protocol were not available yet, we could compare the planned and reported outcome with the trial registry. The registry mentioned \"to measure the change in RNA levels (Ct values) of SARS-CoV-2 from RT-PCR transfusion\" at day 0, 3 and 7.","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.\r\n",null,null,"High","High","For this outcome \"viral clearance\", there is a low risk of bias from the randomization process and in selection of the reported result, there are some concerns for bias due to deviations from intended interventions and due to missing outcome data. However, there is a high risk in measurement of the outcome."]
["2021-04-12 17.30","Hamdy Salman 2020, viral clearance","CI, SV",8,"Hamdy Salman 2020","CP","SOC","Viral clearance (day3)",null,"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","\"Using website software, enrolled patients were randomized in a 2:1 ratio to receive standard therapy alone, versus receiving standard therapy plus plasm of recovered COVID-19 individuals. Treatment allocation were assigned using randomized block design to provide symmetrically distributed base on key outcome-related characteristics.\"","PN","There are no baseline differences that would suggest a problem with randomisation.","Low","Low","Participants were block randomized using website software in a 2:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","PN","\"clinical data were monitored by the attending team, that was not aware of the research scheme. Radiological reports and laboratory parameter were registered by the administrative staff who was unaware of research protocol. The blood bank staff was blinded to group assignment. Patients were blinded to the intervention.\"","NA",null,"NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and carers and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","All the particpants randomized were analysed, 30 out of 30 participants","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 30 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry \"viral negative seroconversion detected by Nasopharyngeal/oropharyngeal SARSCoV-2 by RNA, assayed RT-PCR, throughout the 5 days study period. \"","N","no differences in measurement between groups","N","\"Radiological reports and laboratory parameter were registered by the administrative staff who was unaware of research protocol\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were unaware of the intervention received.",null,null,"PN","No protocol or statistical plan available, but trial registry. We could compare the outcomes planned and reported. There were some inconsistencies with this outcome, in the trial registry the nasopharyngeal/oropharyngeal swab in 5-days period is not mentioned, but reported in the journal article. Only the primary outcomes are reported in the registry.","NI","Not reported in the trial registry","NI","Not reported in the trial registry","Some concerns","Some concerns","The data that produced this result was not analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Some concerns","Some concerns","For this outcome \" viral clearance at day 3\", there is a low risk of bias from the randomization process, due to deviations from intended interventions, due to missing outcome data and in measurement of the outcome. However, there are some concerns for bias in selection of the reported result.\r\n"]
["2021-04-13 11.55","Simonovich 2020, time to discharge","CI, ED","Simonovich 2020",null,"CP","Placebo","time to discharge from hospital",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","PlasmAr was a double-blind, placebo-controlled trial\r\n\"Eligible participants were randomly assigned in a 2:1 ratio to receive either convalescent plasma or placebo.\"\r\n\"Eligible patients underwent treatment allocation and concealment through a randomization program (REDCap) and were assigned in a 2:1 ratio\r\nto receive either a single administration of Covid-19 convalescent plasma or placebo (normal saline solution) in addition to standard treatment.\"","PN","There were small differences in baseline characterisctics; e.g. patients with COPD, patients on critical care unit, but probably not due to problems with randomisation process","Low","Low","Participants were randomized through a randomization program (REDCap) in a 2:1 ratio to receive either convalescent plasma or a placebo. The allocation sequence was random and concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"N","N","Comment: This trial was double-blinded.\r\nQuote: \"The intervention will remain blind to the research subjects and to the research team throughout the entire protocol. \r\nQuote: \"Since the plasma solution is slightly opaque, the container and IV line will be covered with a coloured sleeve to maintain the masking.\"","NA",null,"NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and carers and people delivering the intervention were unaware of the assigned intervention received and the analysis was appropriate.",null,null,"Y","nearly all participant were analysed: 333 out of 334","NA",null,"NA",null,"NA",null,"Low","Low","From the 334 participants randomized data was available for 228 participants in the convalescent plasma group and 105 participants in the placebo group. The data of one participant in control group was missing, due to withdrawal of consent after randomisation and therefore the participant was excluded.\r\n\r\n\r\n",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol","N","no differences in measurement between groups","N","\"The statistical team and the person in charge of transfusional medicine will be unblinded to intervention. The rest of the researchers will remain blinded to the intervention branches of the study.\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were unaware of the intervention received.\r\n\r\n\r\n",null,null,"Y","In accordance with Protocol available: \"Time from intervention to discharge from hospital (in days).\"","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. \r\n",null,null,"Low","Low","For the outcome \"time to discharge from hospital \", all the domains have a low risk of bias."]
["2021-04-12 16.19","Li 2020, time to discharge","CI, ED","Li 2020",null,"CP","SOC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone (control group)\"\r\n\"The randomization was stratified based on the severity of COVID-19 (severe or life-threatening) and a randomization schedule was generated using block randomization with block size of 4 for each type of COVID-19 by SAS software.\"","PN","There were no baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were block randomized via computer-generated random numbering in a 1:1 ratio to receive standard treatment coupled with convalescent plasma transfusion or standard treatment alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","\"open-label\"\r\n\"Patients and clinicians were not masked to treatment assignment.\"\r\n","PN","Comment: All the patients received their assigned intervention.\r\n\r\nComment: The co-interventions were not balanced across arms, but there There was no evidence for a protocol deviation of trial context","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","Data for this outcome was available for all 103 participants randomized.","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 103 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","N","\"To avoid assessment bias, the evaluation of clinical outcomes was performed by an investigator who was blind to the\r\nstudy group allocation\"","NA",null,"NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were not aware of the intervention received.",null,null,"Y","In accordance with Protocol available","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol.",null,null,"Low","Low","For this outcome, all the domains have a low risk of bias.\r\n"]
["2021-04-13 12.14","Gharbaran 2020 time to discharge","CI, VP","Gharbaran 2020 ","Gharbaran 2020 ","CP","SOC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Trial protocol; Statistical analysis plan (SAP); Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","Quote: \"Patients were randomly assigned via a web-based system at a 1:1 ratio to the currentstandard of care at each hospital with or without the addition of 300ml of ConvP\"","PN","small differences, but trial was stopped after enrollment of 86 of 426 planned participants","Low","Low","Participants were randomized via a web-based system in a 1:1 ratio to the current standard of care at each hospital with or without the addition of convalescent plasma. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label","NI","All patients received assigned intervention, but co-interventions not described. \r\nQuote: \"Off-label use of EMA-approved drugs (e.g. chloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, anakinra) as a treatment for\r\nCOVID-19 was allowed in hospitals were this was part of the standard of care\"\r\nUnclear whether treatments were balanced across arms. ","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Some concerns","Some concerns","Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention, as insufficient information was provided on whether treatments were balanced across arms. The analysis was appropriate.",null,null,"Y","all participans were analysed: 86 out of 86","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 86 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial protocol","N","no diffferences in measurement between groups","Y","This was an open label trial","N","The outcome assessment could not be influenced by the knowledge of intervention received.","NA",null,"Low","Low","The outcome assessors aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement or that the measurement differed between intervention groups.",null,null,"Y","analysed in accordance with a pre-specified analysis plan ","PN","Preplanned endpoint measured and reported as planned at protocol stage","PN","Preplanned endpoint measured and reported as planned at protocol stage","Low","Low","The data that produced this result was analysed in accordance with the pre-specified analysis plan and the outcome was reported as planned in the protocol. ",null,null,"Some concerns","Some concerns","For this outcome, there is a low risk of bias from the randomization process, due to missing outcome data, in measurement of the outcome and in selection of the reported result. However, there are some concerns for bias due to deviations from intended interventions."]
["2021-04-13 12.21","Ray 2020, time to discharge","CI, CI","Ray 2020",null,"CP","SoC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","PY","NI","Registry: \"Computer generated randomization\" \r\nIn the report it is not clearly described how patients were randomized and no clear information on soncealment was given: \"Patients  fulfilling  the  inclusion  criteria  were  randomized  into  either  the  SOC  arm  receiving  only  the  standard  of  care  therapy,  as  per  current  advisory,  or  in  to  the  CPT group\"\r\n\r\nRegistry: Concealment: Case Record Numbers\"\r\n","PN","Baseline characteristics table missing/not reported. According to the text and a figure on age, the characteristics between groups might be similarly distributed.","Some concerns","Some concerns","Participants were probably allocated randomly to either the standard of care group alone or standard of care with convalescent plasma group and there were no further information given on the randomization process. There is no information on the allocation concealment, the trial registry only indicates concealment through \"Case Record Numbers\". There were no baseline imbalances that would suggest a problem with randomisation.",null,null,"Y","Y","open-label","N","There is no flow chart available in the report but, \"All  patients  recruited  in  CPT  arm  received  two  transfusions  of  200ml  ABO-matched  convalescent  plasma  on  two  successive  days,  first  one  being  on  the  day  on  enrolment,  except  for  one  patient  who  succumbed  before he  could  be  transfused with second unit\" -->so no deviations due to trial context","NA",null,"NA",null,"Y","an intention to treat analysis was done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","for all participants: 80 out of 80","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 80 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurement between groups","Y","This was an open label trial ","N","The assessment of the outcome could not be influenced by knowledge of intervention received","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","in accordance with trial registry","PN","Preplanned endpoint measured and reported as planned at trial registration stage","PN","Preplanned endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Some concerns","Some concerns","For the outcome \"time to discharge from hospital\" in this study, there is a low risk of bias due to deviations from intended interventions, due to missing outcome data, in measurement of the outcome and in selection of the reported result . There are some concerns for bias from the randomization process."]
["2021-04-13 11.58","Avendano Sola, time to discharge","VP, CI","Avendano-Sola",null,"CP","SoC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Y","Y","\"Patients were registered, after giving informed consent to participate, in a web-based eCRF (ORACLE clinical), their baseline clinical data collected and then randomly assigned 1:1 to the investigational treatment, stratified by study site.\"","PN","No baseline differences between intervention groups suggesting a problem with the randomization process","Low","Low","Participants were randomized through a web-based eCRF system (ORACLE clinical) in a 1:1 ratio to receive either convalescent plasma in addition to the standard therapy or standard of care alone and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation.",null,null,"Y","Y","open-label","N","Quote: \"1 did not receive CP due to absence of AB0 blood group compatible plasma\" \r\nComment: This was probably not because of trial context.","NA",null,"NA",null,"Y","Intention to treat analysis done","NA",null,"Low","Low","Both participants and those delivering the intervention were aware of intervention received, but there were no deviations from intended interventions and the analysis was appropriate.",null,null,"Y","all participants: 81 out of 81","NA",null,"NA",null,"NA",null,"Low","Low","Data for this outcome was available for all 81 participants randomized.",null,null,"N","The outcome measurement is an appropriate measure and was measured as described in trial registry","N","no differences in measurements between groups","PY","Open label trial","N","The assessment of the outcome could not been influenced by knowledge of intervention received","NA",null,"Low","Low","The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement.",null,null,"Y","in accordance with trial registry","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","PN","Preplanned primary endpoint measured and reported as planned at trial registration stage","Low","Low","The data that produced this result was analysed in accordance with the predefined outcomes stated in the trial registration.",null,null,"Low","Low","For the outcome \"time to discharge from hospital\", there is a low risk of bias for all the domains."]

{"sheet":"Summary","index":2,"n_rows":41,"n_cols":27,"rows_kept":41,"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"]
["Gharbaran 2020 Mortality","VP, NS, KLC, CK, SJV",1,"Ghabaran","Convalescent plasma","standard of care (supportive care, oxygen, antibiotics)","All-cause mortality at hospital discharge","OR: 0.95 (95% CI: 0.20 to 4.67)","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Low","Some concerns",null,null,null,"Assignment to intervention (the 'intention-to-treat' effect)"]
["Li 2020 Mortality","VP, NS",2,"Li","Conventional treatment with convalescent plasma","Conventional treatment alone","Mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",null,null,null,"Total number of study = 40"]
["Avendano Sola mortality","MB,VP",null,"Avendano Sola ","intravenously administered CP (single infusion) + SOC","SOC","Mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",null,null,null,"Low risk",95,72.5,85,85,92.5,55]
["Simonovich Mortality","VP,MK","Simonovich",null,"CP","Placebo","Mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",null,null,null,"Some concerns",0,22.5,7.5,7.5,7.5,30]
["Libster 2020 Mortality","VP,MB","Libster 2020",null,"CP","Placebo","All-cause mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",null,null,null,"High risk",5,5,7.5,7.5,0,15]
["Agarwal 2020, mortality","CI, MK, CK",1,"Agarwal 2020","convalescent plasma and BSC","Best standard of care (BSC)","Mortality at 28 days","risk ratio= 1.04 (95% CI, 0.66 to 1.63)","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Low","Some concerns",null,null,null,"Adhering to intervention (the 'per-protocol' effect)"]
["AlQahtani 2020, mortality","VP, CI","AlQahtani ",null,"convalescent plasma","Control SOC","Mortality (day 28)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Some concerns","Some concerns",null,null,null,"Total number of study = 0"]
["Bajpai 2020, mortality","SV, CI",5,"Bajpai 2020","Convalescent plasma","Fresh frozen plasma (FFP) ","Mortality (28-day)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",null,null,null,"Low risk"]
["Ray 2020, mortality","CI, MK",7,"Ray 2020","CP","SOC","mortality (30day and time to event)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"High","Low","Low","Low","Low","High",null,null,null,"Some concerns"]
["Gharbaran 2020 Clinical Improvement","VP, NS, KLC, CK, SJV",1,"Ghabaran","Convalescent plasma","supportive care, oxygen, antibiotics)","Clinical improvement",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Some concerns","Low","Some concerns",null,null,null,"High risk"]
["Li 2020 Clinical Improvement","VP, NS",2,"Li","Conventional treatment with convalescent plasma","Conventional treatment alone","Clinical improvement",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Avendano-Sola 2020, clinical status","CI, MB",10,"Avendano-Sola 2020","Convalescent plasma","SOC","clinical status (at day 7, 15 & 29)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Gharbaran 2020 Safety","VP, NS, KLC, CK, SJV",1,null,"Convalescent plasma","SoC","Safety",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","High","High","Low","High"]
["Li 2020 Safety","VP, NS",2,null,"Conventional treatment with convalescent plasma","conventional treatment alone","Safety",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","High","High","High","Low","High"]
["Avendano-Sola 2020, safety","MB, CI",10,"Avendano-Sola 2020","Convalescent plasma in addition to standard treatment","SOC","safety (AE/SAE/Infusion related AE)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Simonovich 2020, safety","VP, CI","Simonovich 2020","Simonovich","Convalescent plasma","Placebo (saline)","AEs 3+4, SAEs",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Avendano-Sola 2020, viral clearance","MB, CI",10,"Avendano-Sola 2020","CP","SOC","viral clearance (day 3, 7, 15)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Li 2020, viral clearance","CI, MB",3,"Li 2020","Convalescent plasma ","SOC","viral clearance (day 3)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Some concerns","Low","Low","Some concerns"]
["Agarwal 2020, viral clearance","VP, CI","Agarwal 2020",null,"Convalescent plasma ","SOC","viral clearance (day 3)","binary","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","High","High","High","Low","High"]
["Hamdy Salman 2020, viral clearance","CI, SV",8,"Hamdy Salman 2020","CP","SOC","Viral clearance (day3)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Some concerns","Some concerns"]
["AlQahtani 2020, safety","CI, ED, VP","AlQahtani 2020",null,"CP","SOC","Safety (grade 3 and 4 on request)",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Some concerns","Some concerns","Low","Some concerns"]
["Agarwal 2020, safety","CI, ED, VP",1,"Agarwal 2020","convalescent plasma and BSC","Best standard of care","Safety (grade 3 and 4 on request)","not reported","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Some concerns","Some concerns","Low","Some concerns"]
["Simonovich 2020, time to discharge","CI, ED","Simonovich 2020",null,"CP","Placebo","time to discharge from hospital",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Agarwal 2020, Improvement of clinical symptoms","CI, ED","Agarwal 2020",null,"convalescent plasma and BSC","Best standard of care","Clinical status (data provided by authors)","NR","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Li 2020, time to discharge","CI, ED","Li 2020",null,"CP","SOC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Gharbaran 2020 time to discharge","CI, VP","Gharbaran 2020 ","Gharbaran 2020 ","CP","SOC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Low","Some concerns"]
["Ray 2020, time to discharge","CI, CI","Ray 2020",null,"CP","SoC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"High","Low","Low","Low","Low","High"]
["Horby 2021, Mortality","CI, VP","Horby 2021",null,"CP","SOC","28-day mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Horby 2021, Clinical status","CI, VP","Horby 2021",null,"CP","SOC","Clinical status: IMV ",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Horby 2021, Clinical status 2","CI, VP","Horby 2021",null,"CP","SOC","Clinical status: Liberation from IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Agarwal 2020, clinical worsening","CI, VP","Agarwal 2020",null,"CP","SOC","Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Some concerns","Some concerns"]
["AlQahtani 2020, clinical worsening","CI, VP","AlQahtani 2020",null,"CP","SoC","Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","High"]
["Simonovich 2020, Clinical worsening","CI, VP","Simonovich 2020",null,"CP","Placebo","Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Bajpai 2020, clinical worsening","CI, VP","Bajpai",null,"CP","standard plasma","need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Gharbaran 2020, liberattion from oxygen","CI, VP","Gharbharan ",null,"CP","SoC","liberation from supplemental oxygen",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Low","Some concerns"]
["Gharbaran 2020 liberation from IVM","VP, CI","Gharbharan 2020",null,"CP","SoC","Liberation from IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Some concerns","Low","Low","Low","Some concerns"]
["O’Donnell 2021, mortality","CI, VP","O’Donnell 2021",null,"CP","normal plasma","28-day mortality",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["O’Donnell 2021, clinical worsening","CI, VP","O’Donnell 2021",null,"CP","Normal plasma","clinical worsening: Need for IMV",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["O’Donnell 2021, safety","CI, VP","O’Donnell 2021",null,"CP","normal plasma","SAEs",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Avendano Sola, time to discharge","VP, CI","Avendano-Sola",null,"CP","SoC","Time to hospital discharge",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]

{"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"]