ENBIS-18 in Nancy

2 – 25 September 2018; Ecoles des Mines, Nancy (France) Abstract submission: 20 December 2017 – 4 June 2018

Use of Mechanistic Models for in Silico Trials

3 September 2018, 14:40 – 15:00

Abstract

Submitted by
Mélanie PRAGUE
Authors
Mélanie Prague (Univ Bordeaux, Inria/Inserm, Vaccine Research institute), Chloé Pasin (Univ Bordeaux Inria/Inserm), Rodolphe Thiébaut (Univ Bordeaux, Inria/Inserm, Vaccine Research institute)
Abstract
An in silico clinical trial is an individualized computer simulation used in the development of a medicinal product, device, or intervention. Expected benefits are to provide a mechanistic understanding, to optimize the strategies of delivery and to improve the clinical trials designs. We propose to present how in silico trials could be used to investigate simplified antiretroviral therapies (HAART) such as therapies based on two antiretroviral treatments (ANRS 163 ETRAL, ANRS 167 LAMIDOL), dose reduction (ANRS 165 DARULIGHT) or short cycle treatment interruption (ANRS 162 4D, BREATHER Study, ANRS 170 QUATUOR). We propose to model dynamics of viral load and CD4 with a dynamical model based on ordinary differential equations (ODE) with mixed effects models on parameters (NLME). We account for pharmacokinetics and pharmacodynamics properties of HAART by using in vitro indicators and in vivo pre-established properties from phase I trials. Model for in silico trials has been defined and parameters estimated using data from previous clinical trials and observational cohort (the Aquitaine cohort). By simulating a phase III in silico trial, we investigate the expected results of on-going studies. We discuss how to simulate an in-silico population which is heterogeneous enough to build reliable confidence bounds. Altogether, we show that such pipeline for in silico trials is a promising tool for investigating novel strategies of treatment and opens the perspective for personalized medicine for HIV.

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