رسالة جامعية
Validation and first application of a multidimensional system to predict long term allograft survival as a surrogate endpoint in kidney transplant randomized controlled trials ; Validation et application d’un système de scores pronostiques multidimensionnels de la survie du greffon comme critère de jugement principal des essais thérapeutiques en transplantation rénale
| العنوان: | Validation and first application of a multidimensional system to predict long term allograft survival as a surrogate endpoint in kidney transplant randomized controlled trials ; Validation et application d’un système de scores pronostiques multidimensionnels de la survie du greffon comme critère de jugement principal des essais thérapeutiques en transplantation rénale |
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| المؤلفون: | Divard, Gillian |
| المساهمون: | Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Alexandre Loupy |
| المصدر: | https://dumas.ccsd.cnrs.fr/dumas-03470905Test ; Médecine humaine et pathologie. 2019. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2019 |
| المجموعة: | DUMAS (Dépôt Universitaire de Mémoires Après Soutenance) |
| مصطلحات موضوعية: | Surrogate Endpoint, Allograft Survival, Marqueurs biologiques, Transplantation rénale, Survie du greffon, Essais contrôlés randomisés, Pronostique, MESH: Biomarkers, MESH: Kidney Transplantation, MESH: Graft Survival, MESH: Randomized Controlled Trials as Topic, MESH: Prognosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | the development of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We sought to validate and use a risk stratification system as a surrogate endpoint in randomized controlled trial in kidney transplantation. Methods: a post-hoc analysis of three randomized controlled trials was performed to validate an integrative risk score system named iBox as a surrogate endpoint in randomized controlled trials. Allograft survival predicted by the iBox system was compared with the observed allograft survival. We also applied the iBox system as a surrogate endpoint using the validated data from the TRANSFORM trial measured at 12 months after randomization (primary end point timeline) and projected patient's individual long-term allograft survival. Results: The immunological, functional and histological parameters were entered into the iBox risk prediction system, which translated to an overall patient graft survival at 4, 6, 8 and 11 years after randomization of 90.92 % vs 92.12 %, of 87.9% vs 86.24%, of 87.6 % vs 88.7 %, and 79.98% vs 82.45% in the everolimus and MPA arms respectively (below the non-inferiority margin of 10%). These results were confirmed in the subset of patient with immunological and histological data available. Conclusion: the iBox system confirms the non-inferiority of everolimus vs mycophenolic acid 11 years after patient’s randomization in the RCT. Given the unmet need for surrogate end point for clinical trials, this study shows the potential of a clinical trial simulation tool to fast track the development and approval of pharmaceutical agents. ; Résumé : l'arrivée de nouvelles molécules en transplantation rénale est actuellement limitée par la difficulté de construire des essais thérapeutiques avec un critère de jugement de substitution permettant de prédire précocement la survie à long terme du greffon. Un outil de stratification du risque de perte du greffon a été validé puis utilisé comme critère de jugement dans quatre essais ... |
| نوع الوثيقة: | master thesis |
| اللغة: | French |
| العلاقة: | dumas-03470905; https://dumas.ccsd.cnrs.fr/dumas-03470905Test; https://dumas.ccsd.cnrs.fr/dumas-03470905/documentTest; https://dumas.ccsd.cnrs.fr/dumas-03470905/file/ThExe_Divard_Gillian_DUMAS.pdfTest |
| الإتاحة: | https://dumas.ccsd.cnrs.fr/dumas-03470905Test https://dumas.ccsd.cnrs.fr/dumas-03470905/documentTest https://dumas.ccsd.cnrs.fr/dumas-03470905/file/ThExe_Divard_Gillian_DUMAS.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc-ndTest/ |
| رقم الانضمام: | edsbas.88C3C0E7 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |