Pharmacometrics to support clinical investigation during COVID-19 pandemics
France Mentré & Jérémie Guedj
Objectives: We will present our involvement into the design and the analysis of clinical trials, and how we used pharmacometrics and modelling to support the development of antiviral strategies against SARS-CoV-2.
Overview/Description of presentation: We will discuss the use of modelling to support clinical investigation during COVID-19 pandemics. Our presentation will browse into different insights of models, from basic pharmacological and preclinical predictions [1,2] to support clinical evaluation of repurposed drugs early on in the epidemics, to the use of host/pathogen models to predict the efficacy of new specific therapeutics , such as monoclonal antibodies. We will also show how such models can be used to understand specific aspects of infectious diseases, such as transmission and infectiousness. We will discuss our experience as methodologists of large clinical trials and cohorts of patients ,
and how our background in pharmacometrics in infectious diseases has served clinical investigation. We will conclude on a more general view on the use of pharmacometrics by academic groups and industry during this pandemic.
Conclusions/Take home message: Bringing together pharmacometrics and clinical investigation is key during a pandemic to avoid unnecessary trials and accelerate drug development.
 Gonçalves A, Bertrand J, Ke R, Comets E, de Lamballerie X, Malvy D, Pizzorno A, Terrier O, Rosa Calatrava M, Mentré F, Smith P, Perelson AS, Guedj J. Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load. CPT Pharmacometrics Syst Pharmacol 2020; 9(9):509-14. https://doi.org/10.1002/psp4.12543
 Maisonnasse P, Guedj J, Contreras V, Behillil S, Solas C, Marlin R, Naninck T, Pizzorno A, Lemaitre J, Gonçalves A, Kahlaoui N, Terrier O, Fang RHT, Enouf V, Dereuddre-Bosquet N, Brisebarre A, Touret F, Chapon C, Hoen B, Lina B, Calatrava MR, van der Werf S, de Lamballerie X, Le Grand R. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates. Nature. 22 juill 2020; 585(7826):584-7
 Néant N, Lingas G, Le Hingrat Q, Ghosn J, Engelmann I, Lepiller Q, Gaymard A, Ferré V, Hartard C, Plantier J-C, Thibault V, Marlet J, Montes B, Bouiller K, Lescure F-X, Timsit J-F, Faure E, Poissy J, Chidiac C, Raffi F, Kimmoun A, Etienne M, Richard J-C, Tattevin P, Garot D, Le Moing V, Bachelet D, Tardivon C, Duval X, Yazdanpanah Y, Mentré F, Laouénan C, the French COVID cohort. Proc Natl Acad Sci U S A. 23 févr 2021;118(8). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929555/
 Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D, Diallo A, Delmas C, Saillard J, Dechanet A, Mercier N, Dupont A, Alfaiate T, Lescure FX, Raffi F, Goehringer F, Kimmoun A, Jaureguiberry S, Reignier J, Nseir S, Danion F, Clere-Jehl R, Bouiller K, Navellou JC, Tolsma V, Cabié A, Dubost C, Courjon J, Leroy S, Mootien J, Gaci R, Mourvillier B, Faure E, Pourcher V, Gallien S, Launay O, Lacombe K, Lanoix JP, Makinson A, Martin-Blondel G, Bouadma L, Botelho-Nevers E, Gagneux-Brunon A, Epaulard O, Piroth L, Wallet F, Richard JC, Reuter J, Staub T, Lina B, Noret M, Andrejak C, Lê MP, Peytavin G, Hites M, Costagliola D, Yazdanpanah Y, Burdet C, Mentré F; DisCoVeRy study group. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin Microbiol Infect. 2021 May 26:S1198-743X(21)00259-7. doi: 10.1016/j.cmi.2021.05.020. Epub ahead of print. PMID: 34048876; PMCID: PMC8149166.