Members

  First name: Emmanuelle
  Last name: Comets
  Function: Chercheuse
  Position: Researcher
  Email: emmanuelle.comets
._
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inserm.fr

Research interest


Nonlinear mixed effect models, with an emphasis on: - Pharmacogenetics - Model evaluation - Design optimisation - Parameter estimation

Education

Degree

1994: Ingénieur de l’Ecole Polytechnique
1996: Ingénieur de l’Institut National Agronomique
2000: Thèse de biomathématiques
2010: Habilitation à diriger les recherches

Academic positions

2002-present: CR1 INSERM

List of the main publications

Tessier A, Bertrand J, Chenel M, Comets E
Combined Analysis of Phase I and Phase II Data to Enhance the Power of Pharmacogenetic Tests.
CPT: pharmacometrics & systems pharmacology 2016, 5, 123–131.

Petit C, Jullien V, Samson A, Guedj J, Kiechel JR, Zohar S, Comets E
Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults.
Antimicrobial Agents and Chemotherapy 2015, 60, 1481-1491.

Thai HT, Mentré F, Holford NHG, Veyrat-Follet C, Comets E
A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed-effects models.
Pharmaceutical Statistics 2013, 12, 129–140.

Nguyen THT, Comets E, Mentré F
Extension of NPDE for evaluation of nonlinear mixed effect models in presence of data below the quantification limit with applications to HIV dynamic model.
Journal of Pharmacokinetics and Pharmacodynamics 2012, 39, 499–518.

Comets E, Diquet B, Legrain S, Huisse MG, Godon A, Bruhat C, Chauveheid MP, Delpierre S, Duval X, Berrut G, Verstuyft C, Aumont MC, Mentré F
Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians.
Clinical Pharmacology and Therapeutics 2012, 91, 777–786.

Bertrand J, Comets E, Chenel M, Mentré F
Some alternatives to asymptotic tests for the analysis of pharmacogenetic data using nonlinear mixed effects models.
Biometrics 2012, 68, 146–155.


Exhaustive list of publications

2020


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 & systems pharmacology 2020, 9, 509-514.

2019


Ursino M, Yuan Y, Alberti C, Comets E, Favrais G, Friede T, Lentz F, Stallard N, Zohar S
A dose finding design for seizure reduction in neonates.
Journal of the Royal Statistical Society: Series C (Applied Statistics) 2019, 68, 427-444.

Cerou M, Peigné S, Comets E, Chenel M
Application of Item Response Theory to Model Disease Progression and Agomelatine Effect in Patients with Major Depressive Disorder.
The AAPS journal 2019, 22, 4.

2018


Terranova N, Smith MK, Nordgren R, Comets E, Lavielle M, Harling K, Hooker AC, Sarr C, Mentré F, Yvon F, Swat MJ
The Standard Output: A Tool-Agnostic Modeling Storage Format.
CPT: pharmacometrics & systems pharmacology 2018, 7, 543-546.

Cerou M, Lavielle M, Brendel K, Chenel M, Comets E
Development and performance of npde for the evaluation of time-to-event models.
Pharmaceutical Research 2018, 35, 30.

Dumont C, Lestini G, Le Nagard H, Mentré F, Comets E, Nguyen TT, PG
PFIM 4.0, an extended R program for design evaluation and optimization in nonlinear mixed-effect models.
Computer Methods and Programs in Biomedicine 2018, 156, 217-229.

Toumazi A, Comets E, Alberti C, Friede T, Lentz F, Stallard N, Zohar S, Ursino M
dfpk: An R-package for Bayesian dose-finding designs using pharmacokinetics (PK) for phase I clinical trials.
Computer Methods and Programs in Biomedicine 2018, 157, 163-177.

Petit C, Samson A, Morita S, Ursino M, Guedj J, Jullien V, Comets E, Zohar S
Unified approach for extrapolation and bridging of adult information in early-phase dose-finding paediatric studies.
Statistical Methods in Medical Research 2018, 27, 1860-1877.

Friede T, Posch M, Zohar S, Alberti C, Benda N, Comets E, Day S, Dmitrienko A, Graf A, Günhan BK, Hee SW, Lentz F, Madan J, Miller F, Ondra T, Pearce M, Röver C, Toumazi A, Unkel S, Ursino M, Wassmer G, Stallard N
Recent advances in methodology for clinical trials in small populations: the InSPiRe project.
Orphanet Journal of Rare Diseases 2018, 13, 186.

2017


Ursino M, Zohar S, Lentz F, Alberti C, Friede T, Stallard N, Comets E
Dose-finding methods for Phase I clinical trials using pharmacokinetics in small populations.
Biometrical Journal. Biometrische Zeitschrift 2017, 59, 804-825.

Nguyen THT, Mouksassi MS, Holford N, Al-Huniti N, Freedman I, Hooker AC, John J, Karlsson MO, Mould DR, Pérez Ruixo JJ, Plan EL, Savic R, van Hasselt JGC, Weber B, Zhou C, Comets E, Mentré F, MEGotISoP(BPC
Model Evaluation of Continuous Data Pharmacometric Models: Metrics and Graphics.
CPT: pharmacometrics & systems pharmacology 2017, 6, 87-109.

Bizzotto R, Comets E, Smith G, Yvon F, Kristensen NR, Swat MJ
PharmML in Action: an Interoperable Language for Modeling and Simulation.
CPT: pharmacometrics & systems pharmacology 2017, 6, 651-665.

Smith MK, Moodie SL, Bizzotto R, Blaudez E, Borella E, Carrara L, Chan P, Chenel M, Comets E, Gieschke R, Harling K, Harnisch L, Hartung N, Hooker AC, Karlsson MO, Kaye R, Kloft C, Kokash N, Lavielle M, Lestini G, Magni P, Mari A, Mentré F, Muselle C, Nordgren R, Nyberg HB, Parra-Guillén ZP, Pasotti L, Rode-Kristensen N, Sardu ML, Smith GR, Swat MJ, Terranova N, Yngman G, Yvon F, Holford N, Dc
Model Description Language (MDL): A Standard for Modeling and Simulation.
CPT: pharmacometrics & systems pharmacology 2017, 6, 647-650.

Mahe G, Comets E, Nouni A, Paillard F, Dourmap C, Le Faucheur A, Jaquinandi V
A minimal resting time of 25 min is needed before measuring stabilized blood pressure in subjects addressed for vascular investigations.
Scientific Reports 2017, 7, 12893.

Rodrigues C, Chiron C, Rey E, Dulac O, Comets E, Pons G, Jullien V
Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children.
British Journal of Clinical Pharmacology 2017, 83, 2695-2708.

Hamitouche N, Comets E, Ribot M, Alvarez JC, Bellissant E, Laviolle B
Population Pharmacokinetic-Pharmacodynamic Model of Oral Fludrocortisone and Intravenous Hydrocortisone in Healthy Volunteers.
The AAPS journal 2017, 19, 727-735.

Comets E, Lavenu A, Lavielle M
Parameter estimation in nonlinear mixed effect models using saemix, an R implementation of the SAEM algorithm.
Journal of Statistical Software 2017

2016


Tessier A, Bertrand J, Chenel M, Comets E
Combined Analysis of Phase I and Phase II Data to Enhance the Power of Pharmacogenetic Tests.
CPT: pharmacometrics & systems pharmacology 2016, 5, 123–131.

Lainé F, Angeli A, Ropert M, Jezequel C, Bardou-Jacquet E, Deugnier Y, Gissot V, Lacut K, Sacher-Huvelin S, Lavenu A, Laviolle B, Comets E
Variations of hepcidin and iron-status parameters during the menstrual cycle in healthy women.
British Journal of Haematology 2016, 175, 980–982.

Angeli A, Lainé F, Lavenu A, Ropert M, Lacut K, Gissot V, Sacher-Huvelin S, Jezequel C, Moignet A, Laviolle B, Comets E
Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women.
The AAPS journal 2016, 18, 490–504.

2015


Swat MJ, Moodie S, Wimalaratne SM, Kristensen NR, Lavielle M, Mari A, Magni P, Smith MK, Bizzotto R, Pasotti L, Mezzalana E, Comets E, Sarr C, Terranova N, Blaudez E, Chan P, Chard J, Chatel K, Chenel M, Edwards D, Franklin C, Giorgino T, Glont M, Girard P, Grenon P, Harling K, Hooker AC, Kaye R, Keizer R, Kloft C, Kok JN, Kokash N, Laibe C, Laveille C, Lestini G, Mentré F, Munafo A, Nordgren R, Nyberg HB, Parra-Guillen ZP, Plan E, Ribba B, Smith G, Trocóniz IF, Yvon F, Milligan PA, Harnisch L, Karlsson M, Hermjakob H, Le Novère N
Pharmacometrics Markup Language (PharmML): Opening New Perspectives for Model Exchange in Drug Development.
CPT: pharmacometrics & systems pharmacology 2015, 4, 316–319.

Costet N, Pelé F, Comets E, Rouget F, Monfort C, Bodeau-Livinec F, Linganiza EM, Bataille H, Kadhel P, Multigner L, Cordier S
Perinatal exposure to chlordecone and infant growth.
Environmental Research 2015, 142, 123–134.

Petit C, Jullien V, Samson A, Guedj J, Kiechel JR, Zohar S, Comets E
Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults.
Antimicrobial Agents and Chemotherapy 2015, 60, 1481-1491.

Tessier A, Bertrand J, Chenel M, Comets E
Comparison of Nonlinear Mixed Effects Models and Noncompartmental Approaches in Detecting Pharmacogenetic Covariates.
The AAPS journal 2015, 17, 597–608.

2014


Thai HT, Mentré F, Holford NHG, Veyrat-Follet C, Comets E
Evaluation of bootstrap methods for estimating uncertainty of parameters in nonlinear mixed-effects models: a simulation study in population pharmacokinetics.
Journal of Pharmacokinetics and Pharmacodynamics 2014, 41, 15–33.

Grégoire N, Mimoz O, Mégarbane B, Comets E, Chatelier D, Lasocki S, Gauzit R, Balayn D, Gobin P, Marchand S, Couet W
New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale.
Antimicrobial Agents and Chemotherapy 2014, 58, 7324–7330.

2013


Thai HT, Mentré F, Holford NHG, Veyrat-Follet C, Comets E
A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed-effects models.
Pharmaceutical Statistics 2013, 12, 129–140.

Thai HT, Veyrat-Follet C, Mentré F, Comets E
Population pharmacokinetic analysis of free and bound aflibercept in patients with advanced solid tumors.
Cancer Chemotherapy and Pharmacology 2013, 72, 167–180.

Vlasakakis G, Comets E, Keunecke A, Gueorguieva I, Magni P, Terranova N, Della Pasqua O, de Lange EC, Kloft C
White paper: landscape on technical and conceptual requirements and competence framework in drug/disease modeling and simulation.
CPT: pharmacometrics & systems pharmacology 2013, 2, e40.

Mentré F, Chenel M, Comets E, Grevel J, Hooker A, Karlsson MO, Lavielle M, Gueorguieva I
Current Use and Developments Needed for Optimal Design in Pharmacometrics: A Study Performed Among DDMoRe's European Federation of Pharmaceutical Industries and Associations Members.
CPT: pharmacometrics & systems pharmacology 2013, 2, e46.

2012


Nguyen THT, Comets E, Mentré F
Extension of NPDE for evaluation of nonlinear mixed effect models in presence of data below the quantification limit with applications to HIV dynamic model.
Journal of Pharmacokinetics and Pharmacodynamics 2012, 39, 499–518.

Comets E, Diquet B, Legrain S, Huisse MG, Godon A, Bruhat C, Chauveheid MP, Delpierre S, Duval X, Berrut G, Verstuyft C, Aumont MC, Mentré F
Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians.
Clinical Pharmacology and Therapeutics 2012, 91, 777–786.

Bertrand J, Comets E, Chenel M, Mentré F
Some alternatives to asymptotic tests for the analysis of pharmacogenetic data using nonlinear mixed effects models.
Biometrics 2012, 68, 146–155.

2011


Thai HT, Veyrat-Follet C, Vivier N, Dubruc C, Sanderink G, Mentré F, Comets E
A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects.
British Journal of Clinical Pharmacology 2011, 72, 402-414.

Bonnet-Zamponi D, Aumont MC, Comets E, Bruhat C, Chauveheid MP, Duval X, Huisse MG, Diquet B, Berrut G, Mentre F, Delpierre S, Legrain S
Heparin bridging therapy and bleeding events in octogenarian inpatients with atrial fibrillation starting anticoagulation: results of an ancillary study.
Journal of the American Geriatrics Society 2011, 59, 2174-2178.

Bertrand J, Laffont CM, Mentré F, Chenel M, Comets E
Development of a complex parent-metabolite joint population pharmacokinetic model.
The AAPS journal 2011, 13, 390-404.

2010


Brendel K, Comets E, Laffont C, Mentré F
Evaluation of different tests based on observations for external model evaluation of population analyses.
Journal of Pharmacokinetics and Pharmacodynamics 2010, 37, 49-65.

Gestermann N, Mekinian A, Comets E, Loiseau P, Puechal X, Hachulla E, Gottenberg JE, Mariette X, Miceli-Richard C
STAT4 is a confirmed genetic risk factor for Sjögren's syndrome and could be involved in type 1 interferon pathway signaling.
Genes and Immunity 2010, 11, 432-438.

Chou M, Bertrand J, Segeral O, Verstuyft C, Borand L, Comets E, Le Tiec C, Becquemont L, Ouk V, Mentre F, Taburet AM
Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients.
Antimicrobial Agents and Chemotherapy 2010, 54, 4432-4439.

Grégoire N, Raherison S, Grignon C, Comets E, Marliat M, Ploy MC, Couet W
Semimechanistic pharmacokinetic-pharmacodynamic model with adaptation development for time-kill experiments of ciprofloxacin against Pseudomonas aeruginosa.
Antimicrobial Agents and Chemotherapy 2010, 54, 2379-2384.

Comets E, Brendel K, Mentré F
Model evaluation in nonlinear mixed effect models, with applications to pharmacokinetics.
Journal de la Société Française de Statistique 2010, 151, 106-128.

2009


Miceli-Richard C, Gestermann N, Ittah M, Comets E, Loiseau P, Puechal X, Hachulla E, Gottenberg JE, Lebon P, Becquemont L, Mariette X
The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome.
Arthritis and Rheumatism 2009, 60, 1991-1997.

Bertrand J, Comets E, Laffont CM, Chenel M, Mentré F
Pharmacogenetics and population pharmacokinetics: impact of the design on three tests using the SAEM algorithm.
Journal of Pharmacokinetics and Pharmacodynamics 2009, 36, 317-339.

Retout S, Comets E, Bazzoli C, Mentré F
Design Optimization in Nonlinear Mixed Effects Models Using Cost Functions: Application to a Joint Model of Infliximab and Methotrexate Pharmacokinetics.
Communications in Statistics - Theory and Methods 2009, 38, 3351-3368.

Abbara C, Rousseau JM, Turcant A, Lallement G, Comets E, Bardot I, Clair P, Diquet B
Bioavailability of diazepam after intramuscular injection of its water-soluble prodrug alone or with atropine-pralidoxime in healthy volunteers.
British Journal of Pharmacology 2009, 157, 1390-1397.

Comets E, Zohar S
A survey of the way pharmacokinetics are reported in published phase I clinical trials, with an emphasis on oncology.
Clinical Pharmacokinetics 2009, 48, 387-395.

2008


Comets E, Brendel K, Mentré F
Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R.
Computer Methods and Programs in Biomedicine 2008, 90, 154-166.

Bertrand J, Comets E, Mentre F
Comparison of model-based tests and selection strategies to detect genetic polymorphisms influencing pharmacokinetic parameters.
Journal of Biopharmaceutical Statistics 2008, 18, 1084-1102.

Miceli-Richard C, Comets E, Verstuyft C, Tamouza R, Loiseau P, Ravaud P, Kupper H, Becquemont L, Charron D, Mariette X
A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis.
Annals of the Rheumatic Diseases 2008, 67, 478-484.

2007


Miceli-Richard C, Comets E, Loiseau P, Puechal X, Hachulla E, Mariette X
Association of an IRF5 gene functional polymorphism with Sjögren's syndrome.
Arthritis and Rheumatism 2007, 56, 3989-3994.

Retout S, Comets E, Samson A, Mentré F
Design in nonlinear mixed effects models: optimization using the Fedorov-Wynn algorithm and power of the Wald test for binary covariates.
Statistics in Medicine 2007, 26, 5162-5179.

Comets E, Verstuyft C, Lavielle M, Jaillon P, Becquemont L, Mentré F
Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters.
European Journal of Clinical Pharmacology 2007, 63, 437-449.

Dartois C, Brendel K, Comets E, Laffont CM, Laveille C, Tranchand B, Mentre F, Lemenuel-Diot A, Girard P
Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey.
British Journal of Clinical Pharmacology 2007, 64, 603-612.

Brendel K, Dartois C, Comets E, Lemenuel-Diot A, Laveille C, Tranchand B, Girard P, Laffont CM, Mentré F
Are population pharmacokinetic and/or pharmacodynamic models adequately evaluated? A survey of the literature from 2002 to 2004.
Clinical Pharmacokinetics 2007, 46, 221-234.

2006


Brendel K, Comets E, Laffont C, Laveille C, Mentré F
Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide.
Pharmaceutical Research 2006, 23, 2036-2049.

Marchand S, Forsell A, Chenel M, Comets E, Lamarche I, Couet W
Norfloxacin blood-brain barrier transport in rats is not affected by probenecid coadministration.
Antimicrobial Agents and Chemotherapy 2006, 50, 371-373.

2005


Jamois C, Comets E, Mentré F, Marion S, Farinotti R, Bonhomme-Faivre L
Pharmacokinetics and neutrophil toxicity of paclitaxel orally administered in mice with recombinant interleukin-2.
Cancer Chemotherapy and Pharmacology 2005, 55, 61-71.

2004


Barraud de Lagerie S, Comets E, Gautrand C, Fernandez C, Auchere D, Singlas E, Mentre F, Gimenez F
Cerebral uptake of mefloquine enantiomers with and without the P-gp inhibitor elacridar (GF1210918) in mice.
British Journal of Pharmacology 2004, 141, 1214-1222.

2003


Comets E, Mentré F, Grass P, Kawai R, Marbach P, Vonderscher J
Population pharmacodynamic analysis of octreotide in acromegalic patients.
Clinical Pharmacology and Therapeutics 2003, 73, 95-106.

Legrand M, Comets E, Aymard G, Tubiana R, Katlama C, Diquet B
An in vivo pharmacokinetic/pharmacodynamic model for antiretroviral combination.
HIV clinical trials 2003, 4, 170-183.

Comets E, Ikeda K, Hoff P, Fumoleau P, Wanders J, Tanigawara Y
Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western and Japanese patients.
Journal of Pharmacokinetics and Pharmacodynamics 2003, 30, 257-283.

2001


Comets E, Mentre F
Evaluation of tests based on individual versus population modeling to compare dissolution curves..
Journal of biopharmaceutical statistics 2001, 11, 107-23.

2000


Comets E, Mentre F, Kawai R, Nimmerfall F, Marbach P, Vonderscher J
Modeling the kinetics of release of octreotide from long-acting formulations injected intramuscularly in rabbits.
Journal of Pharmaceutical Sciences 2000, 89, 1123-1133.

Comets E, Pousset F, Mentre F, Diquet B, Ankri A, Mallet A, Lechat P
Prediction of fluindione maintenance dosage hampered by large intraindividual variability.
Therapeutic Drug Monitoring 2000, 22, 668-675.

1999


Comets E, Mentre F, Nimmerfall F, Kawai R, Mueller I, Marbach P, Vonderscher J
Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR.
Journal of Controlled Release 1999, 59, 197-205.

1998


Mentre F, Pousset F, Comets E, Plaud B, Diquet B, Montalescot G, Ankri A, Mallet A, Lechat P
Population pharmacokinetic-pharmacodynamic analysis of fluindione in patients.
Clinical Pharmacology & Therapeutics 1998, 63, 64-78.

Aymard G, Legrand M, Comets E, Mentre F, Diquet B
Rapid and simple micromethod for the quantification of fluindione in human plasma using high-performance liquid chromatography.
Journal of Chromatography B 1998, 707, 169-173.

Comets E, Mentre F, Pousset F, Diquet B, Montalescot G, Ankri A, Mallet A, Lechat P
Modeling INR data to predict maintenance fluindione dosage.
Therapeutic Drug Monitoring 1998, 20, 631-639.