title: Prioritizing pharmacogenetic research: a value of information analysis of CYP2D6 testing to guide breast cancer treatment.
abstract: OBJECTIVE
  To demonstrate how value of information (VOI) analysis can be used to establish research priorities regarding the use of pharmacogenetic tests using CYP2D6 testing to select adjuvant hormonal therapy in early stage breast cancer as a case study.
  
  
  METHODS
  The following four treatment pathways are compared in a Markov model: tamoxifen treatment; CYP2D6 test and treat homozygous and heterozygous wild type patients (wt/wt; wt/*4) with tamoxifen and *4/*4 patients with anastrozole (HetTam); CYP2D6 test and treat homozygous wild type patients with tamoxifen and others with anastrozole (HomTam); and anastrozole treatment. Pharmacogenetic testing efficacy is estimated by synthesizing randomized controlled trial data comparing tamoxifen to anastrozole with observational data linking CYP2D6 genotype to tamoxifen outcomes.
  
  
  RESULTS
  In order of increasing effectiveness the comparators are tamoxifen, HetTam, HomTam, anastrozole. Health outcomes for test and treatment strategies are highly uncertain. Differences in comparator costs depend on assumptions made regarding anastrozole patent expiry. The expected value of a decision taken with perfect information is £69 to £106 million (pound sterling) for the United Kingdom depending on patent expiry assumptions and the acceptable cost-effectiveness threshold. The most valuable research (VOI £53-£82 million) elucidates the relationship between CYP2D6 genotype and tamoxifen effectiveness. It is uncertain whether values of other research designs would exceed their costs.
  
  
  CONCLUSIONS
  Retrospective analysis of one of the large adjuvant aromatase inhibitor trials is warranted to better understand any association between CYP2D6 genotype and tamoxifen outcomes. VOI approaches may be helpful for prioritising evidence needs and structuring coverage with evidence development agreements for pharmacogenetics.
authors.affiliation: Oxford Outcomes Ltd, Oxford, United Kingdom. beth.woods@oxfordoutcomes.com
authors.forename: Beth
authors.initials: B
authors.lastname: Woods
authors.forename: David
authors.initials: D
authors.lastname: Veenstra
authors.forename: Neil
authors.initials: N
authors.lastname: Hawkins
mesh_terms: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000191:economics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003661:Decision Support Techniques; D017850:Economics, Pharmaceutical; D005260:Female; D005838:Genotype; D006801:Humans; D008390:Markov Chains; D009570:Nitriles / Q000191:economics / Q000627:therapeutic use*; D010597:Pharmacogenetics; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013629:Tamoxifen / Q000191:economics / Q000627:therapeutic use*; D014230:Triazoles / Q000191:economics / Q000627:therapeutic use*; D006113:United Kingdom
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D019389:Cytochrome P-450 CYP2D6