title: Avoiding adverse drug reactions by pharmacogenetic testing: a systematic review of the economic evidence in the case of TPMT and AZA-induced side effects.
abstract: OBJECTIVE
  The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.
  
  
  METHODS
  A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.
  
  
  RESULTS
  Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered 2,116 euros as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (68 euros) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to 5,300 euros.
  
  
  CONCLUSIONS
  Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.
authors.affiliation: Center for Research in Health and Social Care Management, Department of Institutional Analysis and Public Management, Università Bocconi, Milan, Italy. amelia.compagni@unibocconi.it
authors.forename: Amelia
authors.initials: A
authors.lastname: Compagni
authors.forename: Simona
authors.initials: S
authors.lastname: Bartoli
authors.forename: Bernhard
authors.initials: B
authors.lastname: Buehrlen
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fattore
authors.forename: Dolores
authors.initials: D
authors.lastname: Ibarreta
authors.forename: Emma Gutierrez
authors.initials: EG
authors.lastname: de Mesa
mesh_terms: D001379:Azathioprine / Q000009:adverse effects* / Q000493:pharmacokinetics; D001711:Biotransformation; D003362:Cost-Benefit Analysis; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008780:Methyltransferases / Q000172:deficiency*; D009503:Neutropenia / Q000191:economics; D010597:Pharmacogenetics / Q000191:economics*
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine