title: Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling.
abstract: BACKGROUND
  In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes.
  
  
  METHODS
  A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles.
  
  
  RESULTS
  The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes.
  
  
  CONCLUSIONS
  The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications.
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France. claireburny1@gmail.com.|Université de Lyon, F-69000, Lyon, France. claireburny1@gmail.com.|Université Lyon 1, F-69100, Villeurbanne, France. claireburny1@gmail.com.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France. claireburny1@gmail.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Burny
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France. muriel.rabilloud@chu-lyon.fr.|Université de Lyon, F-69000, Lyon, France. muriel.rabilloud@chu-lyon.fr.|Université Lyon 1, F-69100, Villeurbanne, France. muriel.rabilloud@chu-lyon.fr.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France. muriel.rabilloud@chu-lyon.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rabilloud
authors.affiliation: Université de Lyon, F-69000, Lyon, France. francois.golfier@chu-lyon.fr.|Université Lyon 1, F-69100, Villeurbanne, France. francois.golfier@chu-lyon.fr.|Department of Gynaecological and Oncological Surgery-Obstetrics, Lyon Sud University Hospital, Lyon, France. francois.golfier@chu-lyon.fr.|French Trophoblastic Disease Reference Centre, Lyon Sud University Hospital, Lyon, France. francois.golfier@chu-lyon.fr.
authors.forename: François
authors.initials: F
authors.lastname: Golfier
authors.affiliation: French Trophoblastic Disease Reference Centre, Lyon Sud University Hospital, Lyon, France. jerome.massardier@chu-lyon.fr.|Department of Obstetrics, University Hospital Femme-Mère-Enfant, Lyon, France. jerome.massardier@chu-lyon.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Massardier
authors.affiliation: Université de Lyon, F-69000, Lyon, France. touria.hajri@chu-lyon.fr.|Université Lyon 1, F-69100, Villeurbanne, France. touria.hajri@chu-lyon.fr.|French Trophoblastic Disease Reference Centre, Lyon Sud University Hospital, Lyon, France. touria.hajri@chu-lyon.fr.|Pôle Information Médicale Evaluation Recherche, Equipe d'Accueil 4129, Hospices Civils de Lyon, Lyon, France. touria.hajri@chu-lyon.fr.
authors.forename: Touria
authors.initials: T
authors.lastname: Hajri
authors.affiliation: Université de Lyon, F-69000, Lyon, France. anne-marie.schott-pethelaz@chu-lyon.fr.|Université Lyon 1, F-69100, Villeurbanne, France. anne-marie.schott-pethelaz@chu-lyon.fr.|Pôle Information Médicale Evaluation Recherche, Equipe d'Accueil 4129, Hospices Civils de Lyon, Lyon, France. anne-marie.schott-pethelaz@chu-lyon.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schott
authors.affiliation: Service de Biostatistique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France. fabien.subtil@chu-lyon.fr.|Université de Lyon, F-69000, Lyon, France. fabien.subtil@chu-lyon.fr.|Université Lyon 1, F-69100, Villeurbanne, France. fabien.subtil@chu-lyon.fr.|CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100, Villeurbanne, France. fabien.subtil@chu-lyon.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Subtil
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D006063:Chorionic Gonadotropin / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D006828:Hydatidiform Mole / Q000097:blood / Q000601:surgery*; D007700:Kinetics; D008954:Models, Biological; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D014594:Uterine Neoplasms / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin