Sergio Leonardi1,2, Mattia Branca3, Anna Franzone4, Eugene McFadden5,6, Raffaele Piccolo4, Peter Jüni7, Pascal Vranckx8, Philippe Gabriel Steg9, Patrick W Serruys10, Edouard Benit11, Christoph Liebetrau12, Luc Janssens13, Maurizio Ferrario14, Aleksander Zurakowski15, Roberto Diletti16, Marcello Dominici17, Kurt Huber18, Ton Slagboom19, Pawel Buszman20,21, Leonardo Bolognese22, Carlo Tumscitz23, Krzysztof Bryniarski24, Adel Aminian25, Mathias Vrolix26, Ivo Petrov27, Scot Garg28, Cristoph Naber29, Janusz Prokopczuk30, Christian Hamm12,13, Dik Heg31, Stephan Windecker32, Marco Valgimigli33. 1. Department of Molecular Medicine, Cardiology Unit, University of Pavia, Italy (S.L.). 2. Coronary Care Unit (S.L.), Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. 3. Clinical Trials Unit Bern (M.B.), University of Bern, Switzerland. 4. Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy (A.F., R.P.). 5. Cardialysis Core Laboratories and Clinical Trial Management, Rotterdam, the Netherlands (E.M.). 6. Department of Cardiology, Cork University Hospital, Ireland (E.M.). 7. Department of Medicine, Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Ontario, Canada (P.J.). 8. Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Belgium (P.V.). 9. Hôpital Bichat, AP-HP, Université Paris-Diderot, France (P.G.S.). 10. Department of Cardiology, Imperial College of London, United Kingdom (P.W.S.). 11. Department of Cardiology, Jessa Hospital, Hasselt, Belgium (E.B.). 12. Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.L., C.H.). 13. German Center for Cardiovascular Research, Partner Site RheinMain, Frankfurt am Main, Germany (C.L., C.H.). 14. Division of Cardiology (M.F.), Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. 15. Department of Interventional Cardiology, American Heart of Poland SA, Chrzanów (A.Z.). 16. Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands (R.D.). 17. Santa Maria University Hospital, Terni, Italy (M.D.). 18. 3rd Medical Department, Cardiology, Wilhelminen Hospital, Vienna, Austria (K.H.). 19. Sigmund Freud University Medical School, Vienna, Austria (K.H.). 20. Center for Cardiovascular Research and Development, American Heart of Poland, Ustroń (P.B.). 21. Department of Epidemiology and Statistics, Medical University of Silesia, Katowice, Poland (P.B.). 22. Azienda Toscana Usl Sudest, Arezzo, Italy (L.B.). 23. Cardiology Unit Sant'Anna Hospital, Ferrara, Italy (C.T.). 24. Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland (K.B.). 25. Department of Cardiology, Centre Hospitalier Universitaire de Charleroi, Belgium (A.A.). 26. Ziekenhuis Oost Limburg, Genk, Belgium (M. Vrolix). 27. Acibadem City Clinic Cardiovascular Center, Sofia, Bulgaria (I.P.). 28. East Lancashire Hospitals NHS Trust, Blackburn, United Kingdom (S.G.). 29. Contilia Heart and Vascular Centre, Stadtspital Triemli, Zürich, Switzerland (C.N.). 30. Polsko-Amerykańskie Kliniki Serca Kozle, Poland (J.P.). 31. Institute of Social and Preventive Medicine and Clinical Trials Unit (D.H.), University of Bern, Switzerland. 32. Department of Cardiology, Inselspital (S.W.), University of Bern, Switzerland. 33. Department of Cardiology, Cardiocentro Ticino, Lugano, Switzerland (M. Valgimigli).
Abstract
BACKGROUND: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. METHODS: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. RESULTS: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. CONCLUSIONS: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.
BACKGROUND: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. METHODS: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. RESULTS: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. CONCLUSIONS: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.
Authors: Yue Ma; Tao Tian; Tianjie Wang; Juan Wang; Hao Guan; Jiansong Yuan; Lei Song; Weixian Yang; Shubin Qiao Journal: Front Cardiovasc Med Date: 2022-05-26
Authors: Marco Valgimigli; Felice Gragnano; Mattia Branca; Anna Franzone; Usman Baber; Yangsoo Jang; Takeshi Kimura; Joo-Yong Hahn; Qiang Zhao; Stephan Windecker; Charles M Gibson; Byeong-Keuk Kim; Hirotoshi Watanabe; Young Bin Song; Yunpeng Zhu; Pascal Vranckx; Shamir Mehta; Sung-Jin Hong; Kenji Ando; Hyeon-Cheol Gwon; Patrick W Serruys; George D Dangas; Eùgene P McFadden; Dominick J Angiolillo; Dik Heg; Peter Jüni; Roxana Mehran Journal: BMJ Date: 2021-06-16