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[null,"Instructions for the assessment form",{"$nulls":4},"Instructions for the summary",{"$nulls":4},"Instructions for the figure",{"$nulls":4},"Instructions for generating a print view",{"$nulls":4},"Instructions for the discrepancy check"]

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["Basic information",{"$nulls":12},"Domain 1. Randomization process",{"$nulls":9},"Domain 2. Deviations from intended interventions",{"$nulls":17},"Domain 3. Mising outcome data",{"$nulls":12},"Domain 4. Measurement of the outcome",{"$nulls":14},"Domain 5. Selection of the reported result",{"$nulls":10},"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"]
["2021/04/11 09.48","Bingham 2007","Cheng","NCT00092768; NCT00092791","Rheumatology 2007;46:496–507","etorcoxib","celecoxib and placebo","APTC","The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks (data not shown).","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"         Journal article(s) with results of the trial;         Trial protocol","Y","PY","Eligible patients were randomized in a 4:4:1:1 allocation ratio to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks (part I) (Fig. 1)","N","The treatment groups in both studies were similar with respect to gender, age, race, prior medication use, pain severity and primary OA joint (Table 1). The distribution of pain scores based on medians and percentiles was also similar for all groups in both studies indicating that there were comparable proportions of subjects across pain strata (e.g. minimal, moderate, severe).","Low","High","Not mention the randomization process",null,null,"PN","PN","Eligible patients were randomized in a 4:4:1:1 allocation ratio to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks (part I) (Fig. 1)","NA",null,"NA",null,"NA",null,"Y","Safety analyses included all randomized patients who took at least one dose of study medication. ","NA",null,"Low","Low",{"$nulls":3},"Y","A total of 417 (69.6%) patients in study 1 and 419 (68.9%) patients in study\r\n2 completed the full 26-week treatment period (parts I and I).","NA",null,"NA",null,"NA",null,"Low","High","The missing rate was high",null,null,"N","Safety was monitored by clinical and laboratory assessments at study visits and patient reported adverse experiences (AEs). Pre-defined AEs of interest included discontinuation due to any AE, discontinuation due to oedema, hypertension or GI event or CHF. All potentially serious thrombotic cardiovascular (CV) AEs, deaths and serious upper GI AEs (PUBs) were adjudicated by separate, blinded expert Case Review Committees. Serious thrombotic CV AEs were confirmed and classified by vascular bed, specific event type and by the Anti-Platelet Trialists’\r\nCollaboration (APTC) criteria.","PN",null,"PN","The protocol suggested that this trial was double-blinded.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"N",null,"N",null,"Low","Low",{"$nulls":3},"High","High",null,"Towards null "]
["2021/04/10 21.01","Birbara 2006","Cheng",null,"Current Medical Research and Opinion®Vol. 22, No. 1, 2006, 199–210","rofecoxib","celecoxib and placebo","APTC","There was a significantly higher (p < 0.05) incidence of serious AEs with celecoxib than rofecoxib or placebo.","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"     Journal article(s) with results of the trial","Y","Y","Patients who met baseline eligibility criteria were randomly assigned, using a computer-generated allocation schedule, in a 2:2:1 ratio to rofecoxib 12.5mg qd, celecoxib 200mg qd, or placebo, respectively, for 6 weeks. ","N","The baseline characteristics of the patients within the rofecoxib, celecoxib, and placebo treatment groups in each study were similar (Table 2). ","Low","Low",{"$nulls":3},"N","N","A double-dummy design was used to maintain patient and investigator blinding: one tablet of rofecoxib 12.5mg and one capsule of celecoxib-matching placebo; one capsule of celecoxib 200 mg and one tablet of rofecoxib-matching placebo; or one tablet of rofecoxib\u0002matching and one capsule of celecoxib-matching placebo. ","NA",null,"NA",null,"NA",null,"Y","All patients randomized who took at least one dose of study medication, and had at least one on-treatment assessment, were included in a modified Intention\u0002to-Treat (mITT) analysis. ","NA",null,"Low","Low",{"$nulls":3},"PY",null,"NA",null,"NA",null,"NA",null,"Low","Low","脱落原因都有描述，而且所占比例不大",null,null,"N","Spontaneously reported AE data were collected at each clinic visit and assessed by the investigator with regard to intensity, seriousness, duration, relationship to study drug, and any necessary action. All serious \r\nAEs, whether or not related to the investigational protocol, were evaluated. Independent, blinded adjudication committees evaluated cardiovascular and gastrointestinal AEs.","PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/11 09.51","Cannon 2008","Cheng",null,"Arch Drug Info 2008;1:4–13","Etorcoxib, celecoxib, ibuprofen","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial","Y","Y","After clinical exams were complete, all eligible patients were randomized according to a computer\u0002generated, sponsor-supplied random allocation\r\nschedule in a 1:1:1:1 ratio to one of the following four treatments: etoricoxib 90 mg once daily, cele\u0002coxib 200 mg twice daily, ibuprofen 800 mg three times daily, or placebo. \r\nBlinding was maintained using bottles labeled with the patients’ allocation number.","N","Baseline demographics and vital signs were similar across the four treatment groups.","Low","Low","电脑产生的随机序列，且可以认为自带隐藏",null,null,"PN","PN","Blinding was maintained using bottles labeled with the patients’ allocation number.","NA",null,"NA",null,"NA",null,"Y","Analyses of clinical and laboratory adverse experiences used data from all randomized patients.","NA",null,"Low","Low",{"$nulls":3},"PN","Analyses of clinical and laboratory adverse experiences used data from all randomized patients.","N",null,"PY",null,"PN",null,"Some concerns","Some concerns","因不良事件脱落的人所占比例不少",null,null,"PN","The three nonfatal potential investigator\u0002reported thrombotic CV events that were reported in this trial were adjudicated by an external committee as part of an established adjudicationprocess for all randomized clinical trials.","PN",null,"PN","Blinding was maintained using bottles labeled with the patients’ allocation number.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/10 21.05","Clegg 2006","Cheng","NCT00032890","N Engl J Med 2006;354:795-808.","Glucosamine, chondroitin sulfate, and the two in combination ","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial;  Trial protocol","Y","Y","The randomization code list was developed by the Veterans Affairs Cooperative Studies Program Data Coordi\u0002nating Center in Hines, Illinois.  During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data.","N","The groups were well balanced at baseline (Table 1).","Low","Low","数据中心随机序列，且说了不会获得randomization codes",null,null,"PN","N","The randomization code list was developed by the Veterans Affairs Cooperative Studies Program Data Coordi\u0002nating Center in Hines, Illinois. During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data.","NA",null,"NA",null,"NA",null,"Y","Analysis of the primary outcome mea\u0002sure was conducted according to the intention to treat.","NA",null,"Low","Low",{"$nulls":3},"PN","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution. Seventy-seven serious adverse events were reported in 61 patients. Three serious adverse events were judged by the investigator to be related to study treatment.","PN","Of the patients withdrw, 59 had an adverse event.","PN","The withdraw rate of 20.5 percent did not differ significantly among the \r\ngroups and was similar to the predicted rate of 20 percent. ","NA",null,"Low","Low","脱落原因均有描述，虽且所占比例不大，但因不良事件脱落的比例可以接受，其他脱落原因似乎不会对结果造成影响",null,null,"N","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution.","PN","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution.","PN","During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/10 21.16","Conaghan 2012","Cheng","NCT007165","Rheumatology 2013;52:1303\u00021312","topical ketoprofen in transfersome gel with ketoprofen-free vehicle","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial;   Trial protocol","Y","Y","Eligible patients were randomized at B2 (according to a centre-specific assignment list generated by a random permuted block scheme) to receive treatment. Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication.","N","Demographics and baseline characteristics were similar across treatment groups.","Low","Some concerns","没有明确说明ｓｃｈｅｍｅ方案是什么",null,null,"PN","PN","Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication.","NA",null,"NA",null,"NA",null,"PY","AEs were assessed at study visits and up to 30 days after discontinuation of study drug. ","NA",null,"Low","Low",{"$nulls":3},"Y","The total number of patients in the adverse events table was in accordance with patients randomized.","NA",null,"NA",null,"NA",null,"Low","Low","脱落原因都有描述，且所占比例不大",null,null,"PN","AEs were assessed at study visits and up to 30 days after discontinuation of study drug.","PN","AEs were assessed at study visits and up to 30 days after discontinuation of study drug.","PN","Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/10 21.10","Cryer 2012","Cheng",null,null,"Celecoxib","nsNSAIDs","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","PY","Eligible patients were randomized via an interactive voice response system (1:1) in block sizes of 4 to either open-label celecoxib or an nsNSAID for 6 months.\r\nThis trial was open-label.","N","Baseline demographics were similar between treatment arms.","High","Low","系统产生随机序列",null,null,"Y","Y","This trial was open-label.","PN","Our primary outcome were objective.","NA",null,"NA",null,"Y","Safety data, physical examination, vital signs, laboratory data, and treatment-emergent adverse events were summarized.","NA",null,"Low","Low",{"$nulls":3},"PN","34.5% and　３３.９％　ｐａｔｉｅｎｔｓ　ｄｉｓｃｏｎｔｉｎｕｅｄ",null,null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"N","Safety data, physical examination, vital signs, laboratory data, and treatment-emergent adverse events were summarized.","N",null,"PY",null,"PN",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/11 09.54","Dahlberg 2009","Cheng",null,"Scand J Rheumatol 2009;38:133–14","Diclofenac, celecoxib",null,"APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial","Y","Y","Patients were randomized in a 1:1 ratio to one of the two treatment groups (celecoxib 200 mg once daily or diclofenac 50 mg twice daily) according to a computer-generated list prepared by the Biostat AS unit in Oslo, Norway. Randomization was stratified by centre with a block size of six.\r\nTo conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number.","N","No significant differences were observed between treatment groups in any demographic category.","Low","Low",{"$nulls":3},"PN","PN","Patients were randomized in a 1:1 ratio to one of the two treatment groups (celecoxib 200 mg once daily or diclofenac 50 mg twice daily) according to a computer-generated list prepared by the Biostat AS unit in Oslo, Norway. Randomization was stratified by centre with a block size of six.\r\nTo conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number.","NA",null,"NA",null,"NA",null,"Y","All randomized patients who had taken at least one dose of study medication were included in the modified intent-to-treat (m-ITT) and the safety populations.","NA",null,"Low","Low",{"$nulls":3},"PN","All randomized patients who had taken at least one dose of study medication were included in the modified intent-to-treat (m-ITT) and the safety populations.","N",null,"PY",null,"PN",null,"Some concerns","High","脱落比例太高，且因不良事件脱落的人所占比例也高",null,null,"N","Safety analyses were performed on the safety population (which was\r\nidentical to the m-ITT population).","PN",null,"PN","To conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"High","High"]
["2021/04/10 21.14","Essex 2014","Cheng",null,"International Journal of General Medicine 2014:7 227–235","Celecoxib","Naproxen, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","Y","Patients were randomized in a 2:2:1 ratio to one of three treatments, ie, celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo, according to a predetermined computer randomization schedule. Patients were assigned their randomization number based on the order in which \r\nthey enrolled in the study. \r\nBoth the investigator and patient were blinded to the study medications and to placebo, and all assessments were made by individuals who had been blinded. Each study medication had a matching placebo that was of \r\nsimilar appearance (capsule size, color, smell, and taste).","N","Baseline characteristics of the patients were similar among the treatment groups.","Low","Low","序列的产生according to a predetermined computr randomization schedule",null,null,"PN","PN","Both the investigator and patient were blinded to the study medications and to placebo, and all assessments were made by individuals who had been blinded. Each study medication had a matching placebo that was of \r\nsimilar appearance (capsule size, color, smell, and taste).","NA",null,"NA",null,"NA",null,"Y","Safety analyses were carried out in the safety population, which included all randomized patients who received at least one dose of study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","Safety analyses were carried out in the safety population, which included all randomized patients who received at least one dose of study medication.","N",null,"PY",null,"PN",null,"Some concerns","Low","脱落原因都有描述，且不良事件脱落比例可以接受，其他脱落原因似乎不会对结果造成影响",null,null,"N","General clinical safety was assessed by monitoring treatment\u0002emergent adverse events and serious adverse events and by physical examination.","PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"N",null,"N",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/10 21.18","Gibofsky 2003","Cheng",null,"ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3102–3111","Celecoxib,rofecoxib","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","Y","Upon enrollment, patients were randomly assigned to receive either celecoxib 200 mg/day, rofecoxib 25 mg/day, or placebo. Patients were instructed to take the study drug with the evening meal. Regimens were masked (double-dummied) so as to be unidentifiable to both patients and study personnel. Treatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the\r\nstudy. No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data.","N","The statistical analyses showed no differences across treatment groups with respect to demographic and medical history factors.","Low","Low","电脑产生随机序列",null,null,"N","N","Upon enrollment, patients were randomly assigned to receive either celecoxib 200 mg/day, rofecoxib 25 mg/day, or placebo. Patients were instructed to take the study drug with the evening meal. Regimens were masked (double-dummied) so as to be unidentifiable to both patients and study personnel. Treatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the\r\nstudy. No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data.","NA",null,"NA",null,"NA",null,"Y","Comparisons of safety results across treatment groups included all patients who received at least 1 dose of study medication and consisted primarily of laboratory findings and the incidences of adverse events.","NA",null,"Low","Low",{"$nulls":3},"PY",null,"NA",null,"NA",null,"NA",null,"Low","Low","脱落原因都有描述，且所占比例不大",null,null,"PN","Comparisons of safety results across treatment groups included all patients who received at least 1 dose of study medication and consisted primarily of laboratory findings and the incidences of adverse events.","N",null,"N","No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"N",null,"N",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/11 10.04","Hawel 2003","Cheng",null,"International Journal of Clinical Pharmacology and Therapeutics, Vol. 41 – No. 4/2003 (153-16)","Dexibuprofen, celecoxib",null,"APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"    Journal article(s) with results of the trial","Y","PY","only mentioned RANDOM","N","Treatment groups were comparable in age, gender, weight, height, affected body site, rea\u0002son for OA, global dimension of pain and base\u0002line WOMAC OA index scores.","Low","Some concerns","只提到ｒａｎｄｏｍｌｙ　ａｓｓｉｇｎｅｄ，没有随机序列产生的方法，不确定",null,null,"PN","PN","Exact matching placebo tablets (double dummy technique) were\r\nused to double-blind the clinical trial.\r\n","NA",null,"NA",null,"NA",null,"Y","The occurrence of adverse events and clinically relevant changes in laboratory char\u0002acteristics were analyzed descriptively.","NA",null,"Low","Low",{"$nulls":3},"PN",null,"N",null,"PY",null,"PN",null,"Some concerns","Some concerns","试验组因不良事件脱落的比例超过了１０％",null,null,"N","The occurrence of adverse events and clinically relevant changes in laboratory char\u0002acteristics were analyzed descriptively.","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/11 10.05","MacDonald 2017","Cheng",null,"European Heart Journal (2016) 0, 1–9","Celecoxib","nsNSAIDs","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial","Y","PY","(Eligible patients) were randomly assigned to switch to prescribed celecoxib (the celecoxib group) or to continue their usual prescribed nsNSAID (the nsNSAID group) using a central randomization system. ","PY",null,"Some concerns","Some concerns","没有随机序列产生的方法",null,null,"Y","Y","This trial was open-label.","N",null,"NA",null,"NA",null,"Y","These analyses were supported by a modified intention\u0002to-treat (ITT) analysis censoring on the first of death, withdrawal of consent for follow-up, or end-of-study date.","NA",null,"Low","Low",{"$nulls":3},"PN","In the prescribed celecoxib group, 50.9% withdrew from the\r\nrandomized therapy compared with 30.2% not continuing with any\r\nprescribed nsNSAID therapy.","N",null,"PY",null,"PN",null,"Some concerns","High","脱落比例很高，且没有明确的原因描述",null,null,"N","The principal method of follow-up in the SCOT was by record-link\u0002age10 (see Supplementary material online, Supplementary methods). Treatment-related adverse events and all serious adverse events reported by study sites were recorded and reconciled with the record-linkage data. ","N",null,"PY",null,"PN",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"High","High"]
["2021/04/10 21.26","McKenna 2001","Cheng",null,"J Clin Rheumatol 2001;7:151-159","Celecoxib, rofecoxib","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","PY",null,"N","There were no stastically significant differences between the three treatment groups. ","Low","Low","电脑产生随机序列",null,null,"PN","PN",null,"NA",null,"NA",null,"NA",null,"PY",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"N",null,"PN",null,"NA",null,"Low","Low",{"$nulls":3},"N","Adverse events were reported at each visit as individual events.","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/10 21.28","Nissen 2016","Cheng","NCT00346216","N Engl J Med 2016;375:2519-29.","Celecoxib","Ibuprofen, naproxen","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","PY",null,"N",null,"Low","Low",{"$nulls":3},"PN","PN","Patients were randomly assigned, in a 1:1:1 ratio, to receive celecoxib (100 mg twice a day), ibuprofen (600 mg three times a day), or naproxen (375 mg twice a day) with matching placebo.","NA",null,"NA",null,"NA",null,"Y","The investigator did both ITT and on-treatment analysis.","NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PY",null,"PN",null,"Some concerns","Some concerns","样本量很大，但失访率也大，没有明确描述所有失访原因，不好判断",null,null,"N",null,"N",null,"N","An independent committee of multidisciplinary specialists at C5Research who were unaware of the treatment assignments re\u0002viewed and adjudicated events.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"N",null,"N",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/10 21.32","Sampalis 2012","Cheng",null,"Nutrition Journal 2012, 11:21","UP446","Placebo, celecoxib","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","PY","Subjects that met the inclusion/exclusion criteria were randomly assigned to 1 of the 4 study groups (Table 1).","N","There were no statistically significant differences between the four groups with respect to demographic characteristics and baseline disease activity.","Low","Some concerns","没有明确描述随机序列的产生",null,null,"PN","PN","This was a randomized, double blind, placebo and active comparator controlled study.","NA",null,"NA",null,"NA",null,"Y",null,"NA",null,"Low","Low",{"$nulls":3},"PY","Of the 60 subjects who enrolled, 52 (87%) completed the study (Table 3).","NA",null,"NA",null,"NA",null,"Low","Low","脱落率不高，失访原因有描述，似乎不会对结果造成偏倚",null,null,"PN","Safety was measured by physical examinations.","PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/10 21.34","Sawitzke 2010","Cheng",null,"Ann Rheum Dis 2010;69:1459–1464","GS, CS, GS+CS","Placebo, celecoxib",null,null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial","Y","PY","Participants in the structural study contin\u0002ued to receive their originally assigned blinded treatment for up  to 2 years and continued to have safety monitoring and efficacy assessments as prescribed by the protocol (approximately quarterly) throughout the 2-year follow-up period. ","N","The baseline data were similar among all groups with no statis\u0002tically significant differences between them.","Low","High","没有说明随机序列如何产生,根据描述的入组方式，感觉不是真正的随机",null,null,"N","N","Participants in the structural study contin\u0002ued to receive their originally assigned blinded treatment for up  to 2 years and continued to have safety monitoring and efficacy assessments as prescribed by the protocol (approximately quarterly) throughout the 2-year follow-up period. ","NA",null,"NA",null,"NA",null,"Y","All analyses compared placebo with each of the four treatments on a modified intention-to-treat basis.","NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"Y",null,"PN",null,"Some concerns","Some concerns","没有关于脱落的相关描述",null,null,"N","Information on AEs was collected for each patient at each visit in response to an open-ended query. The reported events were assessed by the investigator at each study visit and followed up until resolution or the end of follow-up. ","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"High","High"]
["2021/04/10 21.35","Schnitzer 2011","Cheng","NCT00154219","Clin Rheumatol (2011) 30:1433–1446","Lumiracoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial;  Trial protocol","Y","Y","Patients were randomized according to a randomization list, which was computer generated by Novartis Drug Supply Management (Basel, Switzerland) using a validated system (Almedica Drug Label System). A treatment assignment was stratified by block within a center. The patient randomization numbers were generated using a block size of six.","N","Baseline demographic and background character\u0002istics were summarized in Table 1 and were comparable among the treatment groups.","Low","Low","电脑产生随机序列",null,null,"N","N","Patients were randomized according to a randomization list, which was computer generated by Novartis Drug Supply Management (Basel, Switzerland) using a validated system (Almedica Drug Label System). A treatment assignment was stratified by block within a center. The patient randomization numbers were generated using a block size of six.","NA",null,"NA",null,"NA",null,"Y","The safety and intention-to-treat (ITT) populations were identical and included all patients randomized to treatment who were exposed to the study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","The completion rate was 69%,78% and 78.9%.","N",null,"PN",null,"NA",null,"Low","Low","脱落原因有描述，且因不良事件脱落的比例可以接受，其他脱落原因似乎不会对结果造成影响",null,null,"N","Safety and tolerability were evaluated by recording adverse events (AEs) and serious adverse events (SAEs) throughout the study.","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PY",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/10 21.37","Simon 1999","Cheng",null,"JAMA November 24, 1999-- Vol 282, No.20","Celecoxib","Naproxen, Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","Y","Patients were assigned by a computer generated randomization schedual.  ","N","No significant differences were detected among treatment groups with respect to baseline characteristics.","Low","Low","电脑产生随机序列",null,null,"N","PN","All treatment regimens were fully masked.","NA",null,"NA",null,"NA",null,"Y","Efficacy analyses were based on the ITT population.","NA",null,"Low","Low",{"$nulls":3},"PN","The study was completed by 69% of total patients.","N",null,"PN",null,"NA",null,"Low","Low","因不良事件脱落的比例较低",null,null,"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2021/04/10 21.38","Smugar 2006","Cheng",null,"Current Medical Research and Opinion®","Rofecoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","Y","PY","Patients who met baseline eligibility criteria were randomly assigned in a 3:3:3:1 ratio to QD treatment with either rofecoxib 12.5 mg, rofecoxib 25 mg, celecoxib 200 mg, or matching placebos in Study 1, and in a 3:3:1 ratio to treatment with QD rofecoxib 25 mg, celecoxib 200 mg, or matching placebos in Study 2, with all treatments administered for 6 weeks.","N","Baseline demographics, patient characteristics, and pain scores were similar\r\nacross treatment groups in both studies (Tables 1 and 2).","Low","Some concerns","没有明确说明随机序列的产生",null,null,"PN","PN",null,"NA",null,"NA",null,"NA",null,"Y","A modified intent to treat analysis was employed for the analysis of efficacy and safety data.","NA",null,"Low","Low",{"$nulls":3},"PY","In both studies, approximately 85% of patients in the active treatment groups completed the 6-week study.","NA",null,"NA",null,"NA",null,"Low","Low","不良事件脱落率较低",null,null,"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2021/04/10 21.39","White 2002","Cheng",null,"Am J Cardiol 2002;89:425–430","Celecoxib","Diclofenac, Ibuprofen","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"   Journal article(s) with results of the trial","Y","Y","Patients were randomly assigned to treatments (celecoxib 400 mg twice daily [two- to fourfold greater than the maximally effective doses for rheumatoid arthritis or osteoarthritis] or a comparator NSAID, ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily) on a 2:1:1 basis by a computer\u0002generated randomization schedule. All treatment regimens were blinded and double-dummy.","Y",null,"Some concerns","Low","电脑产生随机序列",null,null,"N","N","Patients were randomly assigned to treatments (celecoxib 400 mg twice daily [two- to fourfold greater than the maximally effective doses for rheumatoid arthritis or osteoarthritis] or a comparator NSAID, ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily) on a 2:1:1 basis by a computer\u0002generated randomization schedule. All treatment regimens were blinded and double-dummy.","NA",null,"NA",null,"NA",null,"Y","Statistical analyses were con\u0002ducted on the intent-to-treat population defined in the protocol as consisting of all patients who received at\r\nleast 1 dose of assigned study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","The discontinuation number was higher than CV events.","N",null,"PN",null,"NA",null,"Low","High","脱落比例高，且因不良事件脱落的人所占比例也高",null,null,"N","In addition to potential upper gastrointestinal ulcer complications, adverse event data were collected at each visit (and as reported spontaneously) using the following question: “Since your last visit, have you experienced or do you cur\u0002rently have any symptoms that are not associated with\r\nyour arthritis?” All positive responses were recorded\r\nregardless of severity or putative relation to study drug.","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"High","High"]
["2021/04/10 21.41","Williams 2001","Cheng",null,"CLINICAL THERAPEUTICS VOL. 23, NO. 2,200l ","Celecoxib","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"  Journal article(s) with results of the trial","PY","PY",null,"N","There were no signili\u0002cant differences in baseline demographic characteristics between the treatment groups (P 2 0.300) (Table I). ","Low","Some concerns","没有随机序列的产生",null,null,"PN","PN",null,"NA",null,"NA",null,"NA",null,"Y","All randomized patients were included in the baseline analyses.","NA",null,"Low","Low",{"$nulls":3},"PN","74% completed the study.","N",null,"PN",null,"NA",null,"Low","High","脱落率２６％，且原因没有描述",null,null,"N",null,"N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"High","High"]
["2021/04/11 09.59","Wittenberg 2006","Cheng","NCT00267215","Arthritis Research & Therapy 2006, 8:R35","Lumiracoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"     Journal article(s) with results of the trial;     Trial protocol","PN","Y",null,"N","Overall, the treatment groups were balanced for baseline demographics and clinical characteristics (Table 1).","Some concerns","Some concerns","根据患者入组方式，感觉不像真随机：patients were subsequently randomly assigned",null,null,"PN","PN","Blinding was maintained by the double-dummy technique.","NA",null,"NA",null,"NA",null,"Y","All adverse events reported by the patient or discovered by the\r\ninvestigator during the study period were recorded and evalu\u0002ated in terms of seriousness, severity and potential relation\u0002ship to study medication.","NA",null,"Low","Low",{"$nulls":3},"Y","The withdrawn rate was 1.7%","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"N","All adverse events reported by the patient or discovered by the\r\ninvestigator during the study period were recorded and evalu\u0002ated in terms of seriousness, severity and potential relation\u0002ship to study medication. ","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]

{"sheet":"Summary","index":2,"n_rows":22,"n_cols":27,"rows_kept":22}
["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",{"$nulls":4},"Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias"]
["Bingham 2007","Cheng","NCT00092768; NCT00092791","Rheumatology 2007;46:496–507","etorcoxib","celecoxib and placebo","APTC","The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks (data not shown).","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"High","Low","High","Low","Low","High",{"$nulls":3},"Assignment to intervention (the 'intention-to-treat' effect)"]
["Birbara 2006","Cheng",null,"Current Medical Research and Opinion®Vol. 22, No. 1, 2006, 199–210","rofecoxib","celecoxib and placebo","APTC","There was a significantly higher (p < 0.05) incidence of serious AEs with celecoxib than rofecoxib or placebo.","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",{"$nulls":3},"Total number of study = 21"]
["Cannon 2008","Cheng",null,"Arch Drug Info 2008;1:4–13","Etorcoxib, celecoxib, ibuprofen","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Some concerns","Low","Low","Some concerns",{"$nulls":3},"Low risk",57.1,100,57.1,100,100,38.1]
["Clegg 2006","Cheng","NCT00032890","N Engl J Med 2006;354:795-808.","Glucosamine, chondroitin sulfate, and the two in combination ","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",{"$nulls":3},"Some concerns",33.3,0,19,0,0,33.3]
["Conaghan 2012","Cheng","NCT007165","Rheumatology 2013;52:1303\u00021312","topical ketoprofen in transfersome gel with ketoprofen-free vehicle","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","Low","Low","Low","Some concerns",{"$nulls":3},"High risk",9.5,0,23.8,0,0,28.6]
["Cryer 2012","Cheng",null,null,"Celecoxib","nsNSAIDs","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",{"$nulls":3},"Adhering to intervention (the 'per-protocol' effect)"]
["Dahlberg 2009","Cheng",null,"Scand J Rheumatol 2009;38:133–14","Diclofenac, celecoxib",null,"APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","High","Low","Low","High",{"$nulls":3},"Total number of study = 0"]
["Essex 2014","Cheng",null,"International Journal of General Medicine 2014:7 227–235","Celecoxib","Naproxen, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",{"$nulls":3},"Low risk"]
["Gibofsky 2003","Cheng",null,"ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3102–3111","Celecoxib,rofecoxib","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low",{"$nulls":3},"Some concerns"]
["Hawel 2003","Cheng",null,"International Journal of Clinical Pharmacology and Therapeutics, Vol. 41 – No. 4/2003 (153-16)","Dexibuprofen, celecoxib",null,"APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","Some concerns","Low","Low","Some concerns",{"$nulls":3},"High risk"]
["MacDonald 2017","Cheng",null,"European Heart Journal (2016) 0, 1–9","Celecoxib","nsNSAIDs","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","High","Low","Low","High"]
["McKenna 2001","Cheng",null,"J Clin Rheumatol 2001;7:151-159","Celecoxib, rofecoxib","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Nissen 2016","Cheng","NCT00346216","N Engl J Med 2016;375:2519-29.","Celecoxib","Ibuprofen, naproxen","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Some concerns","Low","Low","Some concerns"]
["Sampalis 2012","Cheng",null,"Nutrition Journal 2012, 11:21","UP446","Placebo, celecoxib","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","Low","Low","Low","Some concerns"]
["Sawitzke 2010","Cheng",null,"Ann Rheum Dis 2010;69:1459–1464","GS, CS, GS+CS","Placebo, celecoxib",null,null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"High","Low","Some concerns","Low","Low","High"]
["Schnitzer 2011","Cheng","NCT00154219","Clin Rheumatol (2011) 30:1433–1446","Lumiracoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Simon 1999","Cheng",null,"JAMA November 24, 1999-- Vol 282, No.20","Celecoxib","Naproxen, Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","Low","Low","Low","Low"]
["Smugar 2006","Cheng",null,"Current Medical Research and Opinion®","Rofecoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","Low","Low","Low","Some concerns"]
["White 2002","Cheng",null,"Am J Cardiol 2002;89:425–430","Celecoxib","Diclofenac, Ibuprofen","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low","Low","High","Low","Low","High"]
["Williams 2001","Cheng",null,"CLINICAL THERAPEUTICS VOL. 23, NO. 2,200l ","Celecoxib","Placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","High","Low","Low","High"]
["Wittenberg 2006","Cheng","NCT00267215","Arthritis Research & Therapy 2006, 8:R35","Lumiracoxib","Celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Some concerns","Low","Low","Low","Low","Some concerns"]

{"sheet":"Figures","index":3,"n_rows":22,"n_cols":30,"rows_kept":22}
["Studies with intention-to-treat","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","Randomization process","Deviations from intended interventions","Missing outcome data","Measurement of the outcome","Selection of the reported result","Overall",{"$nulls":4},"Studies with pre-protocol","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","Randomization process","Deviations from intended interventions","Missing outcome data","Measurement of the outcome","Selection of the reported result","Overall"]
[null,"Bingham 2007","NCT00092768; NCT00092791","etorcoxib","celecoxib and placebo","APTC",1,{"$nulls":8},"Low risk"]
[null,"Birbara 2006","NCT00032890","rofecoxib","celecoxib and placebo","APTC",1,{"$nulls":8},"Some concerns"]
[null,"Cannon 2008","NCT007165","Etorcoxib, celecoxib, ibuprofen","Placebo","APTC",1,{"$nulls":8},"High risk"]
[null,"Clegg 2006","NCT00346216","Glucosamine, chondroitin sulfate, and the two in combination ","Celecoxib, placebo","APTC",1]
[null,"Conaghan 2012","NCT00154219","topical ketoprofen in transfersome gel with ketoprofen-free vehicle","Celecoxib, placebo","APTC",1]
[null,"Cryer 2012","NCT00267215","Celecoxib","nsNSAIDs","APTC",1]
[null,"Dahlberg 2009",null,"Diclofenac, celecoxib","Naproxen, placebo","APTC",1]
[null,"Essex 2014",null,"Celecoxib","Placebo","APTC",1]
[null,"Gibofsky 2003",null,"Celecoxib,rofecoxib","nsNSAIDs","APTC",1]
[null,"Hawel 2003",null,"Dexibuprofen, celecoxib","placebo","APTC",1]
[null,"MacDonald 2017",null,"Celecoxib","Ibuprofen, naproxen","APTC",1]
[null,"McKenna 2001",null,"Celecoxib, rofecoxib","Placebo, celecoxib","APTC",1]
[null,"Nissen 2016",null,"Celecoxib","Placebo, celecoxib","APTC",1]
[null,"Sampalis 2012",null,"UP446","Celecoxib, placebo","APTC",1]
[null,"Sawitzke 2010",null,"GS, CS, GS+CS","Naproxen, Placebo","APTC",1]
[null,"Schnitzer 2011",null,"Lumiracoxib","Celecoxib, placebo","APTC",1]
[null,"Simon 1999",null,"Celecoxib","Diclofenac, Ibuprofen","APTC",1]
[null,"Smugar 2006",null,"Rofecoxib","Placebo","APTC",1]
[null,"White 2002",null,"Celecoxib","Celecoxib, placebo","APTC",1]
[null,"Williams 2001",null,"Celecoxib",null,"APTC",1]
[null,"Wittenberg 2006",null,"Lumiracoxib",null,null,1]

{"sheet":"Print 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["Unique ID","Bingham 2007","Study ID","NCT00092768; NCT00092791","Assessor","Cheng"]
["Ref or Label","Rheumatology 2007;46:496–507","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","etorcoxib","Comparator","celecoxib and placebo","Source","    Journal article(s) with results of the trial;    Trial protocol"]
["Outcome","APTC","Results","The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks (data not shown).","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","Eligible patients were randomized in a 4:4:1:1 allocation ratio to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks (part I) (Fig. 1)"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The treatment groups in both studies were similar with respect to gender, age, race, prior medication use, pain severity and primary OA joint (Table 1). The distribution of pain scores based on medians and percentiles was also similar for all groups in both studies indicating that there were comparable proportions of subjects across pain strata (e.g. minimal, moderate, severe)."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Eligible patients were randomized in a 4:4:1:1 allocation ratio to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks (part I) (Fig. 1)"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Safety analyses included all randomized patients who took at least one dose of study medication. "]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","A total of 417 (69.6%) patients in study 1 and 419 (68.9%) patients in study\r\n2 completed the full 26-week treatment period (parts I and I)."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN","The reasons for withdraws included clinical AEs."]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","Number of patients withdrawn because of lack of efficacy were similar to that because of clinical AEs."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Safety was monitored by clinical and laboratory assessments at study visits and patient reported adverse experiences (AEs). Pre-defined AEs of interest included discontinuation due to any AE, discontinuation due to oedema, hypertension or GI event or CHF. All potentially serious thrombotic cardiovascular (CV) AEs, deaths and serious upper GI AEs (PUBs) were adjudicated by separate, blinded expert Case Review Committees. Serious thrombotic CV AEs were confirmed and classified by vascular bed, specific event type and by the Anti-Platelet Trialists’\r\nCollaboration (APTC) criteria."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The protocol suggested that this trial was double-blinded."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID","Birbara 2006","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Current Medical Research and Opinion®Vol. 22, No. 1, 2006, 199–210","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","rofecoxib","Comparator","celecoxib and placebo","Source","    Journal article(s) with results of the trial"]
["Outcome","APTC","Results","There was a significantly higher (p < 0.05) incidence of serious AEs with celecoxib than rofecoxib or placebo.","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients who met baseline eligibility criteria were randomly assigned, using a computer-generated allocation schedule, in a 2:2:1 ratio to rofecoxib 12.5mg qd, celecoxib 200mg qd, or placebo, respectively, for 6 weeks. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The baseline characteristics of the patients within the rofecoxib, celecoxib, and placebo treatment groups in each study were similar (Table 2). "]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","A double-dummy design was used to maintain patient and investigator blinding: one tablet of rofecoxib 12.5mg and one capsule of celecoxib-matching placebo; one capsule of celecoxib 200 mg and one tablet of rofecoxib-matching placebo; or one tablet of rofecoxib\u0002matching and one capsule of celecoxib-matching placebo. "]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","All patients randomized who took at least one dose of study medication, and had at least one on-treatment assessment, were included in a modified Intention\u0002to-Treat (mITT) analysis. "]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN","Discontinuation rates were similar with rofecoxib and celecoxib in each \r\nstudy. Discontinuations were more common in the placebo treatment groups than the active treatment groups in both studies. The majority of patients who discontinued in all treatment groups did so because \r\nof a lack of efficacy, which occurred less often with the active treatments (approximately 5%) than with placebo (approximately 18%). There were no significant differences between treatment groups within the two \r\nstudies in discontinuation rates due to AEs."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Spontaneously reported AE data were collected at each clinic visit and assessed by the investigator with regard to intensity, seriousness, duration, relationship to study drug, and any necessary action. All serious \r\nAEs, whether or not related to the investigational protocol, were evaluated. Independent, blinded adjudication committees evaluated cardiovascular and gastrointestinal AEs."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Cannon 2008","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Arch Drug Info 2008;1:4–13","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Etorcoxib, celecoxib, ibuprofen","Comparator","Placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","After clinical exams were complete, all eligible patients were randomized according to a computer\u0002generated, sponsor-supplied random allocation\r\nschedule in a 1:1:1:1 ratio to one of the following four treatments: etoricoxib 90 mg once daily, cele\u0002coxib 200 mg twice daily, ibuprofen 800 mg three times daily, or placebo. \r\nBlinding was maintained using bottles labeled with the patients’ allocation number."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Baseline demographics and vital signs were similar across the four treatment groups."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Blinding was maintained using bottles labeled with the patients’ allocation number."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Analyses of clinical and laboratory adverse experiences used data from all randomized patients."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Analyses of clinical and laboratory adverse experiences used data from all randomized patients."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","The three nonfatal potential investigator\u0002reported thrombotic CV events that were reported in this trial were adjudicated by an external committee as part of an established adjudicationprocess for all randomized clinical trials."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Blinding was maintained using bottles labeled with the patients’ allocation number."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Clegg 2006","Study ID","NCT00032890","Assessor","Cheng"]
["Ref or Label","N Engl J Med 2006;354:795-808.","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Glucosamine, chondroitin sulfate, and the two in combination ","Comparator","Celecoxib, placebo","Source"," Journal article(s) with results of the trial; Trial protocol"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization code list was developed by the Veterans Affairs Cooperative Studies Program Data Coordi\u0002nating Center in Hines, Illinois.  During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The groups were well balanced at baseline (Table 1)."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","The randomization code list was developed by the Veterans Affairs Cooperative Studies Program Data Coordi\u0002nating Center in Hines, Illinois. During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Analysis of the primary outcome mea\u0002sure was conducted according to the intention to treat."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution. Seventy-seven serious adverse events were reported in 61 patients. Three serious adverse events were judged by the investigator to be related to study treatment."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN","Of the patients withdrw, 59 had an adverse event."]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN","The withdraw rate of 20.5 percent did not differ significantly among the \r\ngroups and was similar to the predicted rate of 20 percent. "]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Adverse events and serious adverse events were as\u0002sessed by the investigator at each study visit and followed until resolution."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Conaghan 2012","Study ID","NCT007165","Assessor","Cheng"]
["Ref or Label","Rheumatology 2013;52:1303\u00021312","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","topical ketoprofen in transfersome gel with ketoprofen-free vehicle","Comparator","Celecoxib, placebo","Source"," Journal article(s) with results of the trial; Trial protocol"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Eligible patients were randomized at B2 (according to a centre-specific assignment list generated by a random permuted block scheme) to receive treatment. Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Demographics and baseline characteristics were similar across treatment groups."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"PY","AEs were assessed at study visits and up to 30 days after discontinuation of study drug. "]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","The total number of patients in the adverse events table was in accordance with patients randomized."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","AEs were assessed at study visits and up to 30 days after discontinuation of study drug."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","AEs were assessed at study visits and up to 30 days after discontinuation of study drug."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Investigators and patients were blinded to whether they were allocated to active or placebo treatment, but not to whether they were allocated topical or oral medication."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Cryer 2012","Study ID",null,"Assessor","Cheng"]
["Ref or Label",null,"Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","nsNSAIDs","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Eligible patients were randomized via an interactive voice response system (1:1) in block sizes of 4 to either open-label celecoxib or an nsNSAID for 6 months.\r\nThis trial was open-label."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"N"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Baseline demographics were similar between treatment arms."]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This trial was open-label."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[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,null,"PN","Our primary outcome were objective."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Safety data, physical examination, vital signs, laboratory data, and treatment-emergent adverse events were summarized."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","99.6% and 99.8%"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Safety data, physical examination, vital signs, laboratory data, and treatment-emergent adverse events were summarized."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PY"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PN"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Dahlberg 2009","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Scand J Rheumatol 2009;38:133–14","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Diclofenac, celecoxib","Comparator",null,"Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were randomized in a 1:1 ratio to one of the two treatment groups (celecoxib 200 mg once daily or diclofenac 50 mg twice daily) according to a computer-generated list prepared by the Biostat AS unit in Oslo, Norway. Randomization was stratified by centre with a block size of six.\r\nTo conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant differences were observed between treatment groups in any demographic category."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Patients were randomized in a 1:1 ratio to one of the two treatment groups (celecoxib 200 mg once daily or diclofenac 50 mg twice daily) according to a computer-generated list prepared by the Biostat AS unit in Oslo, Norway. Randomization was stratified by centre with a block size of six.\r\nTo conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","All randomized patients who had taken at least one dose of study medication were included in the modified intent-to-treat (m-ITT) and the safety populations."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","All randomized patients who had taken at least one dose of study medication were included in the modified intent-to-treat (m-ITT) and the safety populations."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Safety analyses were performed on the safety population (which was\r\nidentical to the m-ITT population)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","To conceal allocation, the double-blind supplies were identical in physical appearance and were provided to the investigator in bottles marked with randomization number and visit number."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Essex 2014","Study ID",null,"Assessor","Cheng"]
["Ref or Label","International Journal of General Medicine 2014:7 227–235","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","Naproxen, placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were randomized in a 2:2:1 ratio to one of three treatments, ie, celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo, according to a predetermined computer randomization schedule. Patients were assigned their randomization number based on the order in which \r\nthey enrolled in the study. \r\nBoth the investigator and patient were blinded to the study medications and to placebo, and all assessments were made by individuals who had been blinded. Each study medication had a matching placebo that was of \r\nsimilar appearance (capsule size, color, smell, and taste)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Baseline characteristics of the patients were similar among the treatment groups."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Both the investigator and patient were blinded to the study medications and to placebo, and all assessments were made by individuals who had been blinded. Each study medication had a matching placebo that was of \r\nsimilar appearance (capsule size, color, smell, and taste)."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Safety analyses were carried out in the safety population, which included all randomized patients who received at least one dose of study medication."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Safety analyses were carried out in the safety population, which included all randomized patients who received at least one dose of study medication."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","General clinical safety was assessed by monitoring treatment\u0002emergent adverse events and serious adverse events and by physical examination."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Gibofsky 2003","Study ID",null,"Assessor","Cheng"]
["Ref or Label","ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3102–3111","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib,rofecoxib","Comparator","Placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Upon enrollment, patients were randomly assigned to receive either celecoxib 200 mg/day, rofecoxib 25 mg/day, or placebo. Patients were instructed to take the study drug with the evening meal. Regimens were masked (double-dummied) so as to be unidentifiable to both patients and study personnel. Treatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the\r\nstudy. No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The statistical analyses showed no differences across treatment groups with respect to demographic and medical history factors."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","Upon enrollment, patients were randomly assigned to receive either celecoxib 200 mg/day, rofecoxib 25 mg/day, or placebo. Patients were instructed to take the study drug with the evening meal. Regimens were masked (double-dummied) so as to be unidentifiable to both patients and study personnel. Treatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the\r\nstudy. No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Comparisons of safety results across treatment groups included all patients who received at least 1 dose of study medication and consisted primarily of laboratory findings and the incidences of adverse events."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Comparisons of safety results across treatment groups included all patients who received at least 1 dose of study medication and consisted primarily of laboratory findings and the incidences of adverse events."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"N","No patient’s treatment was unblinded until after com\u0002pletion of the clinical conduct of the study and verification of all patient data."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Hawel 2003","Study ID",null,"Assessor","Cheng"]
["Ref or Label","International Journal of Clinical Pharmacology and Therapeutics, Vol. 41 – No. 4/2003 (153-16)","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Dexibuprofen, celecoxib","Comparator",null,"Source","  Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"NI","only mentioned RANDOM"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"Y","Treatment groups were comparable in age, gender, weight, height, affected body site, rea\u0002son for OA, global dimension of pain and base\u0002line WOMAC OA index scores."]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Exact matching placebo tablets (double dummy technique) were\r\nused to double-blind the clinical trial.\r\n"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The occurrence of adverse events and clinically relevant changes in laboratory char\u0002acteristics were analyzed descriptively."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The occurrence of adverse events and clinically relevant changes in laboratory char\u0002acteristics were analyzed descriptively."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID","MacDonald 2017","Study ID",null,"Assessor","Cheng"]
["Ref or Label","European Heart Journal (2016) 0, 1–9","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","nsNSAIDs","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","(Eligible patients) were randomly assigned to switch to prescribed celecoxib (the celecoxib group) or to continue their usual prescribed nsNSAID (the nsNSAID group) using a central randomization system. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This trial was open-label."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[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,null,"N"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","These analyses were supported by a modified intention\u0002to-treat (ITT) analysis censoring on the first of death, withdrawal of consent for follow-up, or end-of-study date."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","In the prescribed celecoxib group, 50.9% withdrew from the\r\nrandomized therapy compared with 30.2% not continuing with any\r\nprescribed nsNSAID therapy."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The principal method of follow-up in the SCOT was by record-link\u0002age10 (see Supplementary material online, Supplementary methods). Treatment-related adverse events and all serious adverse events reported by study sites were recorded and reconciled with the record-linkage data. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PY"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PN"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID","McKenna 2001","Study ID",null,"Assessor","Cheng"]
["Ref or Label","J Clin Rheumatol 2001;7:151-159","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib, rofecoxib","Comparator","placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y"]
[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,null,"N","There were no stastically significant differences between the three treatment groups. "]
[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,null,"PN"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Adverse events were reported at each visit as individual events."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[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,null,"NA"]
[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,null,"NA"]
[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"]
[]
[]
["Unique ID","Nissen 2016","Study ID","NCT00346216","Assessor","Cheng"]
["Ref or Label","N Engl J Med 2016;375:2519-29.","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","Ibuprofen, naproxen","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Patients were randomly assigned, in a 1:1:1 ratio, to receive celecoxib (100 mg twice a day), ibuprofen (600 mg three times a day), or naproxen (375 mg twice a day) with matching placebo."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The investigator did both ITT and on-treatment analysis."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"N","An independent committee of multidisciplinary specialists at C5Research who were unaware of the treatment assignments re\u0002viewed and adjudicated events."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Sampalis 2012","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Nutrition Journal 2012, 11:21","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","UP446","Comparator","Placebo, celecoxib","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",{"$nulls":3},"Subjects that met the inclusion/exclusion criteria were randomly assigned to 1 of the 4 study groups (Table 1)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There were no statistically significant differences between the four groups with respect to demographic characteristics and baseline disease activity."]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",{"$nulls":3},"This was a randomized, double blind, placebo and active comparator controlled study."]
[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,null,"PY","Of the 60 subjects who enrolled, 52 (87%) completed the study (Table 3)."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Safety was measured by physical examinations."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement"]
[]
[]
["Unique ID","Sawitzke 2010","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Ann Rheum Dis 2010;69:1459–1464","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","GS, CS, GS+CS","Comparator","Placebo, celecoxib","Source"," Journal article(s) with results of the trial"]
["Outcome",null,"Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Participants in the structural study contin\u0002ued to receive their originally assigned blinded treatment for up  to 2 years and continued to have safety monitoring and efficacy assessments as prescribed by the protocol (approximately quarterly) throughout the 2-year follow-up period. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The baseline data were similar among all groups with no statis\u0002tically significant differences between them."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","Participants in the structural study contin\u0002ued to receive their originally assigned blinded treatment for up  to 2 years and continued to have safety monitoring and efficacy assessments as prescribed by the protocol (approximately quarterly) throughout the 2-year follow-up period. "]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","All analyses compared placebo with each of the four treatments on a modified intention-to-treat basis."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Information on AEs was collected for each patient at each visit in response to an open-ended query. The reported events were assessed by the investigator at each study visit and followed up until resolution or the end of follow-up. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Schnitzer 2011","Study ID","NCT00154219","Assessor","Cheng"]
["Ref or Label","Clin Rheumatol (2011) 30:1433–1446","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Lumiracoxib","Comparator","Celecoxib, placebo","Source"," Journal article(s) with results of the trial; Trial protocol"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were randomized according to a randomization list, which was computer generated by Novartis Drug Supply Management (Basel, Switzerland) using a validated system (Almedica Drug Label System). A treatment assignment was stratified by block within a center. The patient randomization numbers were generated using a block size of six."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Baseline demographic and background character\u0002istics were summarized in Table 1 and were comparable among the treatment groups."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","Patients were randomized according to a randomization list, which was computer generated by Novartis Drug Supply Management (Basel, Switzerland) using a validated system (Almedica Drug Label System). A treatment assignment was stratified by block within a center. The patient randomization numbers were generated using a block size of six."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The safety and intention-to-treat (ITT) populations were identical and included all patients randomized to treatment who were exposed to the study medication."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","The completion rate was 69%,78% and 78.9%."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Safety and tolerability were evaluated by recording adverse events (AEs) and serious adverse events (SAEs) throughout the study."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Simon 1999","Study ID",null,"Assessor","Cheng"]
["Ref or Label","JAMA November 24, 1999-- Vol 282, No.20","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","Naproxen, Placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were assigned by a computer generated randomization schedual.  "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant differences were detected among treatment groups with respect to baseline characteristics."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","All treatment regimens were fully masked."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Efficacy analyses were based on the ITT population."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","The study was completed by 69% of total patients."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Smugar 2006","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Current Medical Research and Opinion®","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Rofecoxib","Comparator","Celecoxib, placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",{"$nulls":3},"Patients who met baseline eligibility criteria were randomly assigned in a 3:3:3:1 ratio to QD treatment with either rofecoxib 12.5 mg, rofecoxib 25 mg, celecoxib 200 mg, or matching placebos in Study 1, and in a 3:3:1 ratio to treatment with QD rofecoxib 25 mg, celecoxib 200 mg, or matching placebos in Study 2, with all treatments administered for 6 weeks."]
[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,null,"N","Baseline demographics, patient characteristics, and pain scores were similar\r\nacross treatment groups in both studies (Tables 1 and 2)."]
[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,null,"PN"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","A modified intent to treat analysis was employed for the analysis of efficacy and safety data."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","In both studies, approximately 85% of patients in the active treatment groups completed the 6-week study."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement"]
[]
[]
["Unique ID","White 2002","Study ID",null,"Assessor","Cheng"]
["Ref or Label","Am J Cardiol 2002;89:425–430","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","Diclofenac, Ibuprofen","Source","  Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were randomly assigned to treatments (celecoxib 400 mg twice daily [two- to fourfold greater than the maximally effective doses for rheumatoid arthritis or osteoarthritis] or a comparator NSAID, ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily) on a 2:1:1 basis by a computer\u0002generated randomization schedule. All treatment regimens were blinded and double-dummy."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"Y"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"N","Patients were randomly assigned to treatments (celecoxib 400 mg twice daily [two- to fourfold greater than the maximally effective doses for rheumatoid arthritis or osteoarthritis] or a comparator NSAID, ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily) on a 2:1:1 basis by a computer\u0002generated randomization schedule. All treatment regimens were blinded and double-dummy."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"N"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Statistical analyses were con\u0002ducted on the intent-to-treat population defined in the protocol as consisting of all patients who received at\r\nleast 1 dose of assigned study medication."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","The discontinuation number was higher than CV events."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","In addition to potential upper gastrointestinal ulcer complications, adverse event data were collected at each visit (and as reported spontaneously) using the following question: “Since your last visit, have you experienced or do you cur\u0002rently have any symptoms that are not associated with\r\nyour arthritis?” All positive responses were recorded\r\nregardless of severity or putative relation to study drug."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Williams 2001","Study ID",null,"Assessor","Cheng"]
["Ref or Label","CLINICAL THERAPEUTICS VOL. 23, NO. 2,200l ","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Celecoxib","Comparator","Placebo","Source"," Journal article(s) with results of the trial"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There were no signili\u0002cant differences in baseline demographic characteristics between the treatment groups (P 2 0.300) (Table I). "]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","All randomized patients were included in the baseline analyses."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","74% completed the study."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PN"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]
[]
[]
["Unique ID","Wittenberg 2006","Study ID","NCT00267215","Assessor","Cheng"]
["Ref or Label","Arthritis Research & Therapy 2006, 8:R35","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Lumiracoxib","Comparator","Celecoxib, placebo","Source","   Journal article(s) with results of the trial;   Trial protocol"]
["Outcome","APTC","Results",null,"Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Overall, the treatment groups were balanced for baseline demographics and clinical characteristics (Table 1)."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"PN","Blinding was maintained by the double-dummy technique."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"PN"]
[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,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","All adverse events reported by the patient or discovered by the\r\ninvestigator during the study period were recorded and evalu\u0002ated in terms of seriousness, severity and potential relation\u0002ship to study medication."]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","The withdrawn rate was 1.7%"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","All adverse events reported by the patient or discovered by the\r\ninvestigator during the study period were recorded and evalu\u0002ated in terms of seriousness, severity and potential relation\u0002ship to study medication. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[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,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["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,null,"Y"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Low"]

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["2020/12/29 14.08","Bingham 2007","Gao","NCT00092768; NCT00092791","Rheumatology 2007;46:496–507","etoricoxib","celecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"    Journal article(s) with results of the trial","Y","PY","There were 599 patients in study 1 and 608 patients in study 2 randomized 4:4:1:1 to etoricoxib 30mg qd, celecoxib 200mgqd or one of two placebo groups for 12 weeks. ","N","The treatment groups in both studies were similar with respect to gender, age, race, prior medication use, pain severity and primary OA joint (Table 1). The distribution of pain scores based on medians and percentiles was also similar for all groups in both studies indicating that there were comparable proportions of subjects across pain strata (e.g. minimal, moderate, severe).","Low","Low",{"$nulls":3},"PN","PN","Two 26-week, multi-centre, randomized, double-blind, doubledummy, placebo-controlled, two-part studies were conducted [Protocols 076 (study 1) and 077 (study 2)] at 74 centres each.","NA",null,"NA",null,"NA",null,"Y","The primary efficacy analysis was a modified intention-to-treat (mITT) approach on TWA response.","NA",null,"Low","Low",{"$nulls":3},"N","Between March 2004 and February 2005, 599 patients were randomized in study 1 and 608 in study 2 (Fig. 2a and b), of which 468 (78.1%) patients in study 1 and 474 (78.0%) patients in study 2 completed the studies through 12 weeks (part I).","N","The most common cause of discontinuation was lack of efficacy.","Y","The difference in withdrawals between etoricoxib and celecoxib was not significant in either study.","N",null,"Some concerns","Some concerns",{"$nulls":3},"N","WOMAC) Universities' OA Index Pain and\r\n\r\nWOMAC Physical Function Subscales, and the PGADS","PN",null,"PN","Two multi-centre, 26-week, double-blind, placebo-controlled, non-inferiority studies were conducted, enrolling patients who were prior non-steroidal anti-inflammatory drug (NSAID) or acetaminophen users.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"N",null,"N",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 14.10","Birbara 2006","Gao",null,"Current Medical Research and Opinion® Vol. 22, No.1, 2006, 199–210","rofecoxib","celecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,"      Journal article(s) with results of the trial","Y","PY","Two randomized, double-blind parallel-group, placebocontrolled studies were conducted at investigative sites in the United States from February to November 2003.\r\nPatients who met baseline eligibility criteria were randomly assigned, using a computer-generated allocation schedule, in a 2:2:1 ratio to rofecoxib 12.5mg qd, celecoxib 200mg qd, or placebo, respectively, for 6 weeks. ","N","The baseline characteristics of the patients within\r\nthe rofecoxib, celecoxib, and placebo treatment groups\r\nin each study were similar (Table 2)","Low","Low",{"$nulls":3},"N","N","A double-dummy design was used to maintain\r\npatient and investigator blinding: one tablet of rofecoxib\r\n12.5mg and one capsule of celecoxib-matching placebo; one capsule of celecoxib 200 mg and one tablet of rofecoxib-matching placebo; or one tablet of rofecoxibmatching and one capsule of celecoxib-matching placebo. ","NA",null,"NA",null,"NA",null,"Y","All patients randomized who took at least one dose of\r\nstudy medication, and had at least one on-treatment\r\nassessment, were included in a modified Intentionto-Treat (mITT) analysis","NA",null,"Low","Low",{"$nulls":3},"PY","The majority of patients who discontinued in all treatment groups did so because of a lack of efficacy, which occurred less often with the active treatments (approximately 5%) than with placebo (approximately 18%).","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"N","Efficacy was assessed at each visit using the Patient\r\nGlobal Assessment of Response to Therapy (PGART)\r\nquestion­naire (a five-point categorical scale where\r\n0 = none, 1 = poor, 2 = fair, 3 = good, and\r\n4 = excellent) as the primary endpoint. Safety was assessed by complete physical examination during the screening visit and at 6 weeks. At baseline and at each scheduled clinic visit, vital signs (blood pressure, heart rate, and respiratory rate) were obtained with the patient in a sitting position after a 10-minute rest. Complete blood count, serum chemistry panel, and urinalysis were obtained at screening and the final study visit.","N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2020/12/29 14.12","Cannon 2008","Gao","10.1111/j.1753-5174.2007.00002.x","Arch Drug Info 2008;1:4–13","etoricoxib","celecoxib and ibuprofen,placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,null,"Y","Y","Etoricoxib protocol 065 was a 12-week, randomized, parallel-group, double-blind, placebocontrolled trial performed at 60 centers in the United States","N","Baseline demographics and vital signs were similar across the four treatment groups (Table 1). ","Low","Low",{"$nulls":3},"N","N","Etoricoxib protocol 065 was a 12-week, randomized, parallel-group, double-blind, placebocontrolled trial performed at 60 centers in the United States.","NA",null,"NA",null,"NA",null,"Y","Analyses of clinical and laboratory adverse experiences used data from all randomized patients.","NA",null,"Low","Low",{"$nulls":3},"N","discontinued people of Placebo, etorocoxib,celecoxib, ibuprofen were 32, 25, 23, 24, those of them because of APTC were 8, 12, 11, 11.","PN",null,"PY","less than half of discontinued people discontinued because of APTC","PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"N",null,"PN","Etoricoxib protocol 065 was a 12-week, randomized, parallel-group, double-blind, placebocontrolled trial performed at 60 centers in the United States","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/28 19.03","Clegg 2006","Gao","NCT00032890","N Engl J Med 2006;354:795-808.","Glucosamine, Chondroitin Sulfate and the Two","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Eligible patients were randomly assigned with the use of a double-dummy scheme to one of five orally administered treatments.During data collection, neither the clinical centers nor the coordinating center at the University of Utah had access to the randomization codes or statistical summaries of follow-up data.","PN","The groups were well balanced at baseline (Table 1).","Low","Low",{"$nulls":3},"N","N","Eligible patients were randomly assigned with the use of a double-dummy scheme to one of five orally administered treatments.","NA",null,"NA",null,"NA",null,"Y","We used the last-observation-carriedforward method in the analysis of all outcomes among patients who made at least one follow-up visit but who did not complete follow-up.","NA",null,"Low","Low",{"$nulls":3},"PN","The withdrawal rate of 20.5 percent did not differ significantly among the groups and was similar to the predicted rate of 20 percent.","PN",null,"PN","The withdrawal rate of 20.5 percent did not differ significantly among the groups and was similar to the predicted rate of 20 percent.","NA",null,"Low","Low",{"$nulls":3},"N",null,"N",null,"PN","Eligible patients were randomly assigned with the use of a double-dummy scheme to one of five orally administered treatments.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2020/12/28 19.20","Conaghan 2012","Gao","NCT00716547","Rheumatology 2013;52:13031312","IDEA-033,TDT 064","celecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Eligible patients were randomized at B2 (according to a\r\ncentre-specific assignment list generated by a random\r\npermuted block scheme) to receive treatment","N","Demographics and baseline characteristics were similar across treatment\r\ngroups (Table 1).","Low","Low",{"$nulls":3},"PN","PN","A multicentre, double-blind controlled study","NA",null,"NA",null,"NA",null,"Y","The primary efficacy analysis was performed on patients who received at least one dose of study medication, the intent-to-treat (ITT) population","NA",null,"Low","Low",{"$nulls":3},"Y","Between May 2008 and April 2009, 1591 patients were screened, 1399 patients were randomized and 1395 patients went on to receive treatment (Fig. 1)","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PN","A multicentre, double-blind controlled study","NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2020/12/28 19.58","Cryer 2012","Gao",null,"Am J Gastroenterol 2013; 108:392–400","celecoxib","nsNSAIDs","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Eligible patients were randomized via an interactive voice response system (1:1) in block sizes of 4 to either open-label celecoxib or an nsNSAID for 6 months.","PN","Baseline demographics were similar between treatment arms. ","Low","Low",{"$nulls":3},"NI","Y",null,"PN",null,"NA",null,"NA",null,"Y","Th e primary and secondary endpoint analyses were based on the\r\nintent-to-treat population, defi ned as all randomized subjects.","NA",null,"Low","Low",{"$nulls":3},"PN","Overall, 1,376 (34.5 % ) and 1,340 (33.9 % ) patients discontinued treatment in the celecoxib and nsNSAID treatment groups, respectively","PN",null,"PN","Reasons for discontinuations were similar between the two treatment arms, and patients discontinued because of adverse events were 7.0 % and 6.4 % of the celecoxib- and nsNSAIDtreated patients, respectively.","NA",null,"Low","Low",{"$nulls":3},"N",null,"N",null,"PN","Cardiovascular events were also assessed and adjudicated by an independent, blinded, expert cardiovascular adjudication committee.","NA",null,"NA",null,"Low","Low",{"$nulls":3},"N",null,"PN",null,"PN",null,"Some concerns","Low",{"$nulls":3},"Low","Low"]
["2020/12/28 20.20","Dahlberg 2009","Gao",null,"Scand J Rheumatol 2009;38:133–143","celecoxib","diclofenac","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","This was a double-blind, randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg once daily and diclofenac 50 mg twice daily in 925 patients with OA aged > 60 years. \r\nPatients were randomized in a 1:1 ratio to one of the two treatment groups (celecoxib 200 mg once daily or diclofenac 50 mg twice daily) according to a\r\ncomputer-generated list prepared by the Biostat AS unit in Oslo, Norway.","N","No significant differences were observed between treatment groups in any demographic category (Table 1).","Low","Low",{"$nulls":3},"PN","PN","This was a double-blind, randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg once daily and diclofenac 50 mg twice daily in 925 patients with OA aged > 60 years. ","NA",null,"NA",null,"NA",null,"Y","All randomized patients who had taken at least one dose of study medication were included in the modified intent-to-treat (m-ITT) and the safety populations. ","NA",null,"Low","Low",{"$nulls":3},"PN","The rate of study discontinuation due to AEs, laboratory abnormalities, and deaths was 27% for celecoxib and 31% for diclofenac (p50.22)","PN",null,"PY","A total of 62/458 patients (14%) in the celecoxib group and 68/458 patients (15%) in the diclofenac group experienced at least one serious AE or death. There were 187 serious AEs (including deaths) in total (90 in the celecoxib group and 97 in the diclofenac group).Of the 187 serious AEs, 16 were considered to be related to the study treatment. ","PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/28 21.20","Essex 2014","Gao",null,"International Journal of General Medicine 2014:7 227–235","celecoxib and naproxen","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","PY","PY","This was a 6-week, randomized, double-blind, placebocontrolled, active-comparator, parallel-group trial carried out in 31 US centers in compliance with the principles of Good Clinical Practice and the Declaration of Helsinki.\r\nPatients were assigned their randomization number based on the order in which they enrolled in the study.","PN","Baseline characteristics of the patients were similar among the treatment groups.","Low","Low",{"$nulls":3},"N","N","Both the investigator and patient were blinded to the study medications and to placebo, and all assessments were made by individuals who had been blinded.","NA",null,"NA",null,"NA",null,"Y","Safety analyses were carried out in the safety population, which included all randomized patients who received at least one dose of study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","82/318","PN",null,"Y","Thirteen patients in total discontinued the study as a result of adverse events, while ten were withdrawn because of adverse events that were deemed to be treatment-related (two, seven, and one patients in the celecoxib, naproxen, and placebo groups, respectively).","PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/28 22.06","Gibofsky 2003","Gao",null,"ARTHRITIS & RHEUMATISM Vol. 48, No. 11, November 2003, pp 3102–3111","celecoxib","rofecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","Y","In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189),\r\nrofecoxib 25 mg/day (n = 190), or placebo (n =96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).\r\nTreatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the study. No patient's treatment was unblinded until after completion of the clinical conduct of the study and verification of all patient data.","PN","This similarity was confirmed by the statistical analyses: none of the minor differences among treatment groups was statistically significant.","Low","Low",{"$nulls":3},"PN","PN","Treatment assignment was based on a computer-generated randomization schedule prepared prior to the beginning of the study. No patient's treatment was unblinded until after completion of the clinical conduct of the study and verification of all patient data.","NA",null,"NA",null,"NA",null,"PY","Comparisons of safety results across treatment groups included all patients who received at least 1 dose of study medication","NA",null,"Low","Low",{"$nulls":3},"PY","Approximately 95% of patients in the intent-to-treat cohort qualified for inclusion in the evaluable cohort, which included 178 patients in the celecoxib group, 181 patients in the rofecoxib group, and 91 in the placebo group. ","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2020/12/29 08.59","Hawel 2003","Gao",null,"International Journal of Clinical Pharmacology and Therapeutics, Vol. 41 – No. 4/2003 (153-164)","dexibuprofen","celecoxib","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Methods: The investigation was a randomized, parallel-group, double-blind, active controlled clinical trial, conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria.","Y","Treatment groups were comparable in age,gender, weight, height, affected body site, reason for OA, global dimension of pain and baseline WOMAC OA index scores (Table 1).","Some concerns","Some concerns",{"$nulls":3},"PN","PN","This double-blind, randomized, multicenter, mononational, active comparator controlled clinical trial was designated to prove equivalent efficacy of dexibuprofen (S(+)ibuprofen) 800 mg vs. celecoxib 200 mg per day. ","NA",null,"NA",null,"NA",null,"PY","The occurrence of adverse events and clinically relevant changes in laboratory characteristics were analyzed descriptively.","NA",null,"Low","Low",{"$nulls":3},"NI",null,"PN",null,"PY",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 10.30","MacDonald 2017","Gao",null,"European Heart Journal (2016) 0, 1–9","celecoxib","nsNSAID","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","PY","PY","In total, 7297 participants were randomized. \r\nWe conducted the Standard care vs. Celecoxib Outcome Trial (SCOT), which randomized patients free from established CV disease to switch to celecoxib or to remain on their prescribed nsNSAID, to clarify the risk–benefit balance of switching to celecoxib.","PY","There were no statistically significant differences between the two groups except for age (P ¼ 0.006) and sex (P ¼ 0.02), with values not adjusted for multiple testing.","Some concerns","Low",{"$nulls":3},"Y","Y","The SCOT trial used a Prospective, Randomized, Open label, Blinded Endpoint evaluation (PROBE) design8 to compare the CV and GI safety of continuing prescribed nsNSAID therapy vs","PN",null,"NA",null,"NA",null,"PY","On-treatment analyses censored subjects after the first of, discontinuation from the randomized treatment group (for the nsNSAID group this involved withdrawal from any nsNSAID; see Supplementary material online, Supplementary methods), death, withdrawal of consent, or end-ofstudy date. These analyses were supported by a modified intentionto-treat (ITT) analysis censoring on the first of death, withdrawal of consent for follow-up, or end-of-study date.","NA",null,"Low","Low",{"$nulls":3},"PN","In the prescribed celecoxib group, 50.9% withdrew from the\r\nrandomized therapy compared with 30.2% not continuing with any prescribed nsNSAID therapy","PN",null,"PY",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PY",null,"PN",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 10.52","McKenna 2001","Gao",null,"J Clin Rheumatol 2001;7:151-159","celecoxib","rofecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","PY","PY","In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (240 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n 59), or placebo (n = 60) for 6 weeks.","PN","There were no statistically significant differences between the three treatment groups for any of the baseline characteristics, including demographics, disease history, or previous NSAID analgesic use (Table 1).","Low","Low",{"$nulls":3},"PN","PN","In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (240 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n 59), or placebo (n = 60) for 6 weeks.","NA",null,"NA",null,"NA",null,"PY","\r\nAll efficacy analyses were conducted using the intent-to-treat cohort, which included any patient who received at least one dose of study medication. ","NA",null,"Low","Low",{"$nulls":3},"PN","Of the 182 patients who entered the doubleblind treatment phase, 142 (78%) completed the entire study.","PN",null,"PY","There was no difference in withdrawal resulting from treatment failure between the active treatment groups (p = 0.44).","PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 11.16","Nissen 2016","Gao","NCT00346216","N Engl J Med 2016;375:2519-29.","Celecoxib","Naproxen, Ibuprofen","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","PRECISION was a randomized, multicenter, double-blind, noninferiority trial involving patients who were at increased cardiovascular risk and had rheumatoid arthritis or osteoarthritis","PN","The characteristics of the patients at baseline were similar among the\r\ntreatment groups (Table 1).","Low","Low",{"$nulls":3},"PN","PN","PRECISION was a randomized, multicenter, double-blind, noninferiority trial involving patients who were at increased cardiovascular risk and had rheumatoid arthritis or osteoarthritis","NA",null,"NA",null,"NA",null,"PY","In the intention-to-treat population (Table 2 and Fig. 1)","NA",null,"Low","Low",{"$nulls":3},"N","During this 10-year trial, 68.8% of patients stopped taking the study drug, and 27.4% of patients discontinued follow-up; 2.5% of patients died, 8.3% withdrew consent in writing, 7.4% verbally expressed unwillingness to continue participation, and 7.2% were lost to follow-up before a final follow-up\r\nvisit.","PN",null,"PY",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 11.29","Sampalis 2012","Gao",null,"Sampalis and Brownell Nutrition Journal 2012, 11:21","UP446","Celecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1,null,"Y","PY","A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. ","N","There were no statistically significant differences between the four groups with respect to demographic characteristics and baseline disease activity.","Low","Low",{"$nulls":3},"PN","PN","A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. ","NA",null,"NA",null,"NA",null,"NI",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"Y","Of the 60 subjects who enrolled, 52 (87%) completed the study (Table 3).","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 12.35","Sawitzke 2010","Gao",null,"Ann Rheum Dis 2010;69:1459–1464","glucosamine,chondroitin sulphate and their combination","celecoxib and placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfi ed radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm).","N","Table 1 shows that the baseline data were similar among all groups with no statistically signifi cant differences between them. ","Low","Low",{"$nulls":3},"PN","PN","A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfi ed radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm).","NA",null,"NA",null,"NA",null,"Y","All analyses compared placebo with each of the four treatments on a modifi ed intention-to-treat basis.","NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"Y",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"N",null,"N",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 12.46","Schnitzer 2011","Gao","NCT00154219","Clin Rheumatol (2011) 30:1433–1446","lumiracoxib","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Patients were randomized according to a randomization list, which was computer generated by Novartis Drug Supply Management (Basel, Switzerland) using a validated system (Almedica Drug Label System). ","Y","Baseline demographic and background characteristics were summarized in Table 1 and were comparable among the treatment groups.","Some concerns","Some concerns",{"$nulls":3},"PN","PN","This 13-week, multicenter (Canada [42 centers], USA [71 centers], Germany [30 centers], Italy [12 centers], and UK [7 centers]), randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was conducted at 162 centers in five countries.","NA",null,"NA",null,"NA",null,"Y","The safety and intention-to-treat (ITT) populations were identical and included all patients randomized to treatment who were exposed to the study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","Of the 1,262 patients randomized, 951(75.4%) completed the study and 311(24.6%) discontinued (Fig. 1)","PN",null,"Y",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 13.15","Simon 1999","Gao",null,"JAMA, November 24, 1999-Vol 282, No.20","celecoxib","naproxen, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Randomized, multicenter, placebo-controlled, double-blind trial lasting 12 weeks,\r\nwith follow-up at weeks 2, 6, and 12, from September 1996 thorugh February 1998.","PN","No significant differences among the treatment groups at entry were detected\r\nwith respect to baseline characteristics (Table 1).","Low","Low",{"$nulls":3},"PN","PN","Randomized, multicenter, placebo-controlled, double-blind trial lasting 12 weeks,\r\nwith follow-up at weeks 2, 6, and 12, from September 1996 thorugh February 1998.","NA",null,"NA",null,"NA",null,"PY","Efficacy analyses were based on the intent-to-treat cohort, defined as all patients who took at least 1 dose of study medication. ","NA",null,"Low","Low",{"$nulls":3},"PN","The study was completed by 688 patients (60%).","PN",null,"Y",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 13.23","Smugar 2006","Gao",null,"Current Medical Research and Opinion®Vol. 22, No. 7, 2006, 1353–1367","rofecoxib","celecoxib, placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Patients who met baseline eligibility criteria were randomly assigned in a 3:3:3:1 ratio to QD treatment with either rofecoxib 12.5mg, rofecoxib 25mg, celecoxib 200mg, or matching placebos in Study 1, and in a 3:3:1 ratio to treatment with QD rofecoxib 25mg, celecoxib 200mg, or matching placebos in Study 2, with all treatments administered for 6 weeks.","PN","Baseline demographics, patient characteristics, and pain scores were similar across treatment groups in both studies (Tables 1 and 2). ","Low","Low",{"$nulls":3},"PN","PN","These were multicenter, randomized, double-blind, parallel-group, placebo-controlled studies, conducted in the United States between October 1999 and September 2000.","NA",null,"NA",null,"NA",null,"PY","A modified intent to treat analysis was employed for the analysis of efficacy and safety data.","NA",null,"Low","Low",{"$nulls":3},"PY","In both studies, approximately 85% of patients in the active treatment groups completed the 6-week study.","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]
["2020/12/29 13.40","White 2002","Gao",null,"Am J Cardiol 2002;89:425–430","celecoxib","ibuprofen,diclofenac","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Patients were randomly assigned to treatments(celecoxib 400 mg twice daily [two- to fourfold greater than the maximally effective doses for rheumatoid arthritis or osteoarthritis] or a comparator NSAID, ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily) on a 2:1:1 basis by a computergenerated randomization schedule. ","PY","No significant differences in baseline factors were evident except for small differences in average age and the incidence of coronary artery disease among treatment groups. ","Some concerns","Some concerns",{"$nulls":3},"PN","PN","The trial was conducted in a prospective, randomized, doubleblind fashion at 386 centers in the United States and Canada from December 1998 to January 2000. All treatment regimens were blinded and double-dummy. ","NA",null,"NA",null,"NA",null,"Y","Statistical analyses were conducted on the intent-to-treat population defined in the protocol as consisting of all patients who received at least 1 dose of assigned study medication.","NA",null,"Low","Low",{"$nulls":3},"PN","There were 3,987 persons randomized to celecoxib (2,320 person-years of exposure) and 3,981 exposed to either ibuprofen or diclofenac (2,203 person-years). ","PN",null,"PY",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 13.50","Williams 2001","Gao",null,"CLINICAL THERAPEUTICSVVOL. 23, NO. 2,2001","celecoxib","placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","This prospective, randomized, doubleblind, placebo-controlled, parallel-group study was conducted at 98 clinical sites in the United States, in accordance with good clinical practice and the Declaration of Helsinki.","PN","There were no significant differences in baseline demographic characteristics between the treatment groups (P 0.300) (Table 1).","Low","Low",{"$nulls":3},"PN","PN","This prospective, randomized, doubleblind, placebo-controlled, parallel-group study was conducted at 98 clinical sites in the United States, in accordance with good clinical practice and the Declaration of Helsinki.","NA",null,"NA",null,"NA",null,"PN","Every randomized patient receiving 21 dose of study drug was included in the safety assessment, which included a summary of incidences of patient-reported adverse events as well as laboratory and physical examination findings.","PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN","Of the 718 patients randomized, 549 (76%) completed the study.","PN",null,"PY",null,"PN",null,"Some concerns","Some concerns",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Some concerns","Some concerns"]
["2020/12/29 14.04","Wittenberg 2006","Gao",null,"Arthritis Research & Therapy Vol 8 No 2 Wittenberg et al.","Prexige","lumiracoxib,placebo","APTC",null,"assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s) with results of the trial","Y","PY","Patients were subsequently randomly assigned (in the ratio 2:2:1) to oral treatment with lumiracoxib 400 mg once daily, celecoxib 200 mg twice daily, or placebo.","PN","Overall, the treatment groups were balanced for baseline demographics and clinical characteristics (Table 1). ","Low","Low",{"$nulls":3},"PN","PN","Blinding was maintained by the double-dummy technique.","NA",null,"NA",null,"NA",null,"PY","Analysis of efficacy was performed for all randomized patients who had been exposed to study medication (intent-to-treat population)","NA",null,"Low","Low",{"$nulls":3},"Y","After screening 418 patients, a total of 364 were enrolled into the study and received at least one dose of study medication (lumiracoxib 400 mg once daily [n = 144], celecoxib 200 mg twice daily [n = 145] and placebo [n = 75]). Five patients (1.4%) withdrew from the study, four from the lumiracoxib group (three due to adverse events and one for unsatisfactory therapeutic effect) and one from the celecoxib group (due to protocol violation).","NA",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"PN",null,"PN",null,"PN",null,"NA",null,"NA",null,"Low","Low",{"$nulls":3},"Y",null,"PN",null,"PN",null,"Low","Low",{"$nulls":3},"Low","Low"]

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["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"]

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[null,"Journal article(s) with results of the trial","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?",{"$nulls":3},"occurance of non-protocol interventions"]
["NA","Trial protocol","Favours experimental ","No (Please include reasons in the note)","Y","1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?","Low","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,"3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data?",null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?","adhering to intervention (the 'per-protocol' effect)","5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",{"$nulls":3},"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 non- protocol 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 experimental 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?",{"$nulls":3},"non-adherence to their assigned intervention by trial participants"]
["PY","Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Towards null ",null,"PN",null,"Some concerns","2.4 [if applicable:] Were there failures in implementing the intervention that could have affected the outcome?","2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
["PN","Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Away from null ",null,"N",null,null,"2.5 [if applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?","2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",{"$nulls":3},"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",{"$nulls":6},"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, UKRI Gateway to Research)"]
[null,"Personal communication with trialist"]
[null,"Personal communication with the sponsor"]