S Gourgou-Bourgade1, D Cameron2, P Poortmans3, B Asselain4, D Azria5, F Cardoso6, R A'Hern7, J Bliss7, J Bogaerts8, H Bonnefoi9, E Brain10, M J Cardoso6, B Chibaudel11, R Coleman12, T Cufer13, L Dal Lago14, F Dalenc15, E De Azambuja14, M Debled9, S Delaloge16, T Filleron15, J Gligorov17, M Gutowski18, W Jacot19, C Kirkove20, G MacGrogan9, S Michiels21, I Negreiros22, B V Offersen23, F Penault Llorca24, G Pruneri25, H Roche15, N S Russell26, F Schmitt27, V Servent28, B Thürlimann29, M Untch30, J A van der Hage31, G van Tienhoven32, H Wildiers33, J Yarnold34, F Bonnetain35, S Mathoulin-Pélissier36, C Bellera36, T S Dabakuyo-Yonli37. 1. Biostatistic Unit, Montpellier Cancer Institute, Montpellier Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France sophie.gourgou@icm.unicancer.fr. 2. Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK. 3. Department of Radiation Oncology, Institute Verbeeten, Tilburg, The Netherlands. 4. Department of Biostatistics, Institut Curie, Paris. 5. Department of Radiation Oncology, Montpellier Cancer Institute, Montpellier, France. 6. Breast Cancer Unit, Champalimaud Cancer Center, Lisbon, Portugal. 7. Institute of Cancer Research, London, UK. 8. EORTC Data Center (European Organization of Research and Treatment of Cancer - Statistics Department), Brussels, Belgium. 9. Institut Bergonié, Comprehensive Cancer Centre, Bordeaux. 10. Departments of Clinical Research and Medical Oncology, Institut Curie - Hôpital René Huguenin, Saint-Cloud. 11. Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France. 12. FRCP, FRCPE YCR National Institute for Health Research Cancer Research Network (NCRN), Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield Cancer Research Centre, Sheffield, UK. 13. University Clinic Golnik, Golnik, Slovenia. 14. Institut Jules Bordet, University 'Libre' of Brussels, Brussels, Belgium. 15. Institut Claudius Régaud, Toulouse. 16. Breast Cancer Group, Gustave Roussy Institute, Villejuif. 17. APHP Tenon - University Cancer Institute - Pierre & Marie Curie, Sorbonne University, Paris. 18. Department of Surgery. 19. Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France. 20. Université catholique Louvain, Louvain-la-Neuve, Belgium. 21. Biostatistic and Epidemiology Unit, Gustave Roussy, Villejuif University of Paris-Sud, Villejuif, France. 22. Breast Unit, Hospital CUF Descobertas, Lisbon, Portugal. 23. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 24. Centre Jean Perrin, Clermont-Ferrand ERTICA EA4677, UFR Medicine, University of Clermont-Ferrand 1, Clermont-Ferrand, France. 25. European Institute of Oncology, Milan University of Milan, School of Medicine, Milan, Italy. 26. Department of Radiotherapy, The Netherlands Cancer Institute - Antoni van Leeuwnhoek Hospital, Amsterdam, The Netherlands. 27. IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Porto Medical Faculty of Porto University, Porto, Portugal. 28. Oscar Lambret Comprehensive Cancer Center, Lille, France. 29. Kantonsspital St Gallen, Breast Center, St Gallen, Switzerland. 30. Clinic for Gynecology, Gynecologic Oncology and Obstetrics-Interdisciplinary Breast Cancer Center, HELIOS Klinikum Berlin-Buch, Berlin, Germany. 31. Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam. 32. Academic Medical Center Amsterdam, Amsterdam, The Netherlands. 33. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium. 34. The Institute of Cancer Research, Royal Cancer Hospital, London, UK. 35. Methodological and Quality of Life Unit in Oncology (EA3181), CHU Besançon, Besançon. 36. Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux. 37. Biostatistics and Quality of Life Unit (EA4184), Centre Georges François Leclerc Comprehensive Cancer Centre, Dijon, France.
Abstract
BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.
BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.
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Authors: Fangfang Liu; Thomas Hardiman; Kailiang Wu; Jelmar Quist; Patrycja Gazinska; Tony Ng; Arnie Purushotham; Roberto Salgado; Xiaojing Guo; Sarah E Pinder; Anita Grigoriadis Journal: NPJ Breast Cancer Date: 2021-07-05