A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia

• Published in: Pediatric blood & cancer 2011-08, Vol.57 (2), p.231-239
• Main Authors: Donnan, Jennifer R., Ungar, Wendy J., Mathews, Maria, Hancock-Howard, Rebecca L., Rahman, Proton
• Format: Article
• Language: English
• Subjects: 6-Mercaptopurine; Acute lymphatic leukemia; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Blood; Bone Marrow Diseases - chemically induced; Bone Marrow Diseases - prevention & control; Cancer; Child, Preschool; Children; Clinical Enzyme Tests - economics; Cost-Benefit Analysis; cost-effectiveness analysis; costs and cost analysis; Decision Trees; Drug Dosage Calculations; Genetic screening; Genetic Testing - economics; Genotype; Genotypes; Genotyping; Humans; lymphoid leukemia; Mercaptopurine - administration & dosage; Mercaptopurine - adverse effects; Methyltransferases - deficiency; Methyltransferases - genetics; Models, Econometric; Mutation; Myelosuppression; Ontario; Pediatrics; pharmacogenetics; Phenotyping; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - enzymology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Sensitivity and Specificity; Survival; Survival Analysis; thiopurine methyltransferase; Thiopurine S-methyltransferase
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.22936

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. Procedure 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. Pediatr Blood Cancer 2011; 57: 231–239. © 2011 Wiley‐Liss, Inc.