title: Monitoring white blood cell count in adult patients with schizophrenia who are taking clozapine: a cost-effectiveness analysis.
abstract: BACKGROUND
  Long-term monitoring of white blood cell count is compulsory in patients taking clozapine, although the incidence of drug-induced agranulocytosis is lower than previously expected. The cost-effectiveness of this monitoring is unknown. We aimed to assess the cost-effectiveness of various strategies to monitor white blood cell count in adult patients with schizophrenia taking clozapine.
  
  
  METHODS
  We assessed the cost-effectiveness of four strategies for monitoring white blood cell count (national strategies used in the UK, USA, and European countries, and a hypothetical 8-week strategy) compared with that of no monitoring. We used a semi-Markov model to do the cost-utility analysis from a health-care perspective with a 3-year time horizon, assuming a probability of 0·7% that a patient would develop agranulocytosis. Clinical and resource parameters were based on data from national registries of patients treated with clozapine, study cohorts, and a pharmacovigilance database; we derived estimates of health-related quality of life and mortality from the scientific literature. We assessed model uncertainty, including time horizon, with one-way and probabilistic sensitivity analyses.
  
  
  RESULTS
  Compared with no monitoring, all four monitoring strategies increased quality-adjusted survival by less than 1 day per patient; more than 5000 patients would need to be monitored to avoid one death. The incremental cost-effectiveness ratios (ICERs) were at least US$970 000 per quality-adjusted life-year gained for all four strategies compared with no monitoring. The ICERs were highest in the strategies with highest frequencies and longest durations of monitoring. The results remained robust in the one-way and probabilistic sensitivity analyses, suggesting that no monitoring had the highest probability of being cost effective.
  
  
  CONCLUSIONS
  Existing strategies for monitoring white blood cell count in patients taking clozapine, based on divergent national requirements, do not seem to be cost effective. This finding should be taken into account by public health authorities and policy makers in the revision of guidance for clozapine prescription.
  
  
  BACKGROUND
  University Hospitals of Geneva.
authors.affiliation: Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals and University of Geneva, Geneva, Switzerland; Centre for Health Economics, University of York, York, UK. Electronic address: francois.girardin@hcuge.ch.
authors.forename: François R
authors.initials: FR
authors.lastname: Girardin
authors.affiliation: Department of Health and Community Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Poncet
authors.affiliation: Department of Medical Specialties, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Blondon
authors.affiliation: Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Rollason
authors.affiliation: Department of Pharmacy, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vernaz
authors.affiliation: Department of Medical Specialties, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.affiliation: Department of Health and Community Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure