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Master Thesis

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

Abstract : Abstract: 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.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03470905
Contributor : Université Paris Descartes - Scd Connect in order to contact the contributor
Submitted on : Wednesday, December 8, 2021 - 3:38:10 PM
Last modification on : Thursday, April 21, 2022 - 5:17:38 PM
Long-term archiving on: : Wednesday, March 9, 2022 - 6:55:24 PM

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  • HAL Id : dumas-03470905, version 1

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Gillian Divard. 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. Médecine humaine et pathologie. 2019. ⟨dumas-03470905⟩

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