title: Model-based approaches to increase efficiency of drug development in schizophrenia: a can't miss opportunity.
abstract: BACKGROUND
  Schizophrenia is a severe mental disorder characterized by definite specificities and complexities (heterogeneity of the disease symptoms, large between-subject variability in disease progression and response to therapeutic agents, placebo response, dropout, questionable preclinical models, importance of market differentiation, etc.) that make drug development in this field particularly difficult when compared to the other therapeutic areas. However, drug receptor binding (especially to D2, 5-HT2 and H1 receptors) can provide a useful quantitative framework that can be related to the downstream clinical (amelioration of disease-related scores) and unwanted (neurological effects and metabolic disregulation) effects.
  
  
  OBJECTIVE
  This paper reviews the pharmacokinetic, pharmacodynamic and disease progression approaches applied to the development of new drugs for the treatment of schizophrenia.
  
  
  CONCLUSIONS
  Only model-based methodologies, able to integrate the diverse characteristics of a compound, can provide a rational approach to increase efficiency in drug development in this area, through the development of pharmacokinetic-pharmacodynamics models able to integrate quantitative descriptions of pharmacokinetics, desired and unwanted effects. These holistic approaches can be used in clinical trial simulations for reliably predicting the outcome of future trials. Meta-analyses of the competitor environment are also essential to position the new drug into a crowded competitive landscape.
authors.affiliation: Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, CT 06320, New London, USA.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Nucci
authors.forename: Roberto
authors.initials: R
authors.lastname: Gomeni
authors.forename: Italo
authors.initials: I
authors.lastname: Poggesi