title: Testing for thiopurine methyltransferase status for safe and effective thiopurine administration: a systematic review of clinical guidance documents.
abstract: A common pharmacogenomic test is for thiopurine S-methyltransferase (TPMT) status prior to treatment with thiopurine drugs, used to treat auto-immune conditions and pediatric cancer. Guidelines assist practitioners with decisions regarding testing and treatment. The objectives were to conduct a systematic review and critical appraisal of guidance documents with statements regarding TPMT testing and thiopurine dosing. Guidelines, clinical protocols and care pathways from all disciplines were eligible. A quality appraisal was carried out by three appraisers using the Appraisal of Guidelines for Research and Evaluation II. Of the 20 documents found, 5 recommended genotyping while 4 recommended phenotyping. Thirteen documents provided dosing recommendations based on TPMT status. The quality appraisal revealed wide variation across documents. The National Institute for Health and Clinical Excellence and Cincinnati Children's Hospital guidelines demonstrated the highest overall quality with scores of 79 and 76, respectively. Low-scoring documents failed to use systematic methods to develop recommendations or to provide evidence to support recommendations. Guidance documents that included dosing recommendations demonstrated higher quality.
authors.affiliation: Program of Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: H F
authors.initials: HF
authors.lastname: Burnett
authors.affiliation: Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Tanoshima
authors.affiliation: Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Chandranipapongse
authors.affiliation: Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Madadi
authors.affiliation: 1] Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada [2] Departments of Medicine, Pharmacology and Pharmacy, and Paediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.affiliation: 1] Program of Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada [2] Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
authors.forename: W J
authors.initials: WJ
authors.lastname: Ungar
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase