The increasing body of data available in biomedicine makes it crucial to develop and to use adequate biological and statistical models for their analysis. This is particularly true in clinical investigation on infectious diseases, where several biomarkers often need to be simultaneously analyzed, and explains the success of pharmacometrics, the ‘science of quantitative clinical pharmacology’, in this field. Pharmacometrics is based on the development of semi-physiological models of drug response(s) in order to improve drug development and drug personalisation. In the last decade, the industry has largely invested this new discipline, as shown by the rapid development of Modelling & Simulation groups in all major pharmaceutical companies. Academia in parallel has played a crucial role both in answering methodological needs raised by these models and in investigating medical fields for which there is less commercial interest. Our group attempts to meet these needs with an internationally recognized experience, due to our broad expertise from theoretical mathematical modelling to clinical investigation. Our methodological developments support our involvement in clinical researches. We design, perform and analyse clinical trials and cohorts in order to better understand variability in response to antimicrobial agents and for epidemiological description and prognosis assessment of infectious diseases. By making our methodological developments available as free software tools, we reach out to the community involved in the design and the analysis of clinical trials, namely biostatisticians, pharmacologists, physicians, drug companies and regulatory agencies.
To adress these broad objectives, four research axes have been defined as follows
- Axis 1. Methods in pharmacometrics (lead Emmanuelle Comets): encompasses methodological developments in nonlinear mixed effect models, with an expertise in optimising study design, developing inference methods and evaluating models with pharmacometric applications.
- Axis 2. Mathematical modelling of pathogen dynamics (lead Jérémie Guedj): develops conceptual mathematical model to characterize the interactions between the host organisms (human or animal), the pathogen and the drug. The main medical areas studied are antivirals in the context of HIV/SIV, HBV/HDV, HCV, Ebola virus.
- Axis 3. Clinical trial methodology and investigations in severe or emerging infectious diseases (lead Xavier Duval and Cédric Laouénan): provides methodological and logistical support for the conception, the analyses and the modelling of clinical trials but also to implement our own clinical trials. The main fields studied are pathophysiology, diagnosis and therapeutics (efficacy, safety) of severe and/or emerging infectious diseases.
- Axis 4. Infections and anti-infectious agents during pregnancy and childhood (lead Laurent Mandelbrot): designs and performs clinical studies in the context of materno-fetal and children infections, with a focus on antiretroviral therapy in pregnancy, prevention of perinatal Cytomegalovirus infection, maternal-fetal bacterial infections, antibiotic use and prescription in childhood.