title: Safe and effective variability-a criterion for dose individualization.
abstract: BACKGROUND
  A primary goal of clinical pharmacology is to understand the factors that determine the dose-effect relationship and to use this knowledge to individualize drug dose.
  
  
  METHODS
  A principle-based criterion is proposed for deciding among alternative individualization methods.
  
  
  RESULTS
  Safe and effective variability defines the maximum acceptable population variability in drug concentration around the population average.
  
  
  CONCLUSIONS
  A decision on whether patient covariates alone are sufficient, or whether therapeutic drug monitoring in combination with target concentration intervention is needed, can be made by comparing the remaining population variability after a particular dosing method with the safe and effective variability.
authors.affiliation: Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand. n.holford@auckland.ac.nz
authors.forename: Nicholas H G
authors.initials: NH
authors.lastname: Holford
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
mesh_terms: D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D057285:Precision Medicine / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations