title: Changes and determination of dosing recommendations for medicinal products recently authorised in the European Union.
abstract: BACKGROUND
  The quantity and quality of data for determining the dose and treatment schedule of medicinal products is directly related to how safe and efficacious these medicines are and how successful they can be used to treat patients.
  
  
  METHODS
  This review provides an analysis of dose-related label modifications of recently approved drugs. It shows which areas could benefit from a better dose-exposure-response understanding, both during initial assessment and after marketing authorisation. This analysis highlights regulators' considerations in dosage evaluations and provides reflections for drug developers on how to ensure best possible dose selection in the interest of the patients.
  
  
  CONCLUSIONS
  Using modelling and simulation, pharmacogenomics, population pharmacokinetics, physiologically based pharmacokinetic models and drug-drug interaction studies in conjunction with well-designed clinical trials will improve the understanding of the pharmacology of medicines, of the physiology of the disease and of the dose-exposure-response relationship during drug development. More focus should be given to the investigation of dose and regimens for special populations before applying for marketing authorisation. Consequently, regulators could review dose-exposure-response data with more certainty and better define dose recommendations in the label.
authors.affiliation: 1European Medicines Agency, Clinical Pharmacology - Science and Innovation , 30 Churchill Place, Canary Wharf, London E14 5EU , UK Falk.Ehmann@ema.europa.eu.
authors.forename: Falk
authors.initials: F
authors.lastname: Ehmann
authors.forename: Marisa
authors.initials: M
authors.lastname: Papaluca
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Giuseppe
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.forename: Andrea
authors.initials: A
authors.lastname: Eskova
authors.forename: Efthymios
authors.initials: E
authors.lastname: Manolis
authors.forename: Ralf
authors.initials: R
authors.lastname: Herold
mesh_terms: D004334:Drug Administration Schedule; D017277:Drug Approval; D004345:Drug Industry; D004347:Drug Interactions; D004348:Drug Labeling; D005062:European Union; D006801:Humans
keywords: dose; dose–concentration relationships; dose–response; marketing authorisation application; pharmaceuticals; product label