title: A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) compared to enzymatic testing and standard weight-based dosing.
  
  
  METHODS
  A cost-effectiveness analysis was conducted from a health care system perspective comparing costs and consequences over 3 months. Decision analysis was used to evaluate the impact of TPMT tests on preventing myelosuppression and improving survival in ALL patients receiving 6-MP. Direct medical costs included laboratory tests, medications, physician services, pharmacy and inpatient care. Probabilities were derived from published evidence. Survival was measured in life-months. The robustness of the results to variable uncertainty was tested in one-way sensitivity analyses. Probabilistic sensitivity analysis examined the impact of parameter uncertainty and generated confidence intervals around point estimates.
  
  
  RESULTS
  Neither of the testing interventions showed a benefit in survival compared to weight-based dosing. Both test strategies were more costly compared to weight-based dosing. Incremental costs per child (95% confidence interval) were $277 ($112, $442) and $298 ($392, $421) for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing.
  
  
  CONCLUSIONS
  The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective.
authors.affiliation: Department of Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Donnan
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Ungar
authors.forename: Maria
authors.initials: M
authors.lastname: Mathews
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hancock-Howard
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control; D002675:Child, Preschool; D004796:Clinical Enzyme Tests / Q000191:economics*; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D054796:Drug Dosage Calculations; D005820:Genetic Testing / Q000191:economics*; D005838:Genotype; D006801:Humans; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000009:adverse effects; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics; D017059:Models, Econometric; D009864:Ontario; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase