Lilla M Roy1, Richard M Zur1, Elizabeth Uleryk2, Chris Carew3, Shinya Ito4,5, Wendy J Ungar1,6. 1. Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada. 2. Library Services, The Hospital for Sick Children, Toronto, Canada. 3. Institute for Health Policy, Management & Evaluation, University of Toronto, Canada. 4. Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Canada. 5. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, Toronto, Canada. 6. Departments of Pharmacology & Pharmacy, Faculty of Medicine Department of Paediatrics, University of Toronto, Canada.
Abstract
AIM: Thiopurine S-methyltransferase (TPMT) testing is used in patients receiving thiopurines to identify enzyme deficiencies and risk for adverse drug reactions. It is uncertain whether genotyping is superior to phenotyping. The objectives were to conduct a systematic review of TPMT-test performance studies. MATERIALS & METHODS: Electronic and grey literature sources were searched for studies reporting test performance compared with a reference standard. Sixty-six eligible studies were appraised for quality. RESULTS: Thirty phenotype-genotype and six phenotype-phenotype comparisons were of high quality. The calculated sensitivity and specificity for genotyping to identify a homozygous mutation ranged from 0.0-100.0% and from 97.8-100.0%, respectively. CONCLUSION: Clinical decision-makers require high-quality evidence of clinical validity and clinical utility of TPMT genotyping to ensure appropriate use in patients.
AIM: Thiopurine S-methyltransferase (TPMT) testing is used in patients receiving thiopurines to identify enzyme deficiencies and risk for adverse drug reactions. It is uncertain whether genotyping is superior to phenotyping. The objectives were to conduct a systematic review of TPMT-test performance studies. MATERIALS & METHODS: Electronic and grey literature sources were searched for studies reporting test performance compared with a reference standard. Sixty-six eligible studies were appraised for quality. RESULTS: Thirty phenotype-genotype and six phenotype-phenotype comparisons were of high quality. The calculated sensitivity and specificity for genotyping to identify a homozygous mutation ranged from 0.0-100.0% and from 97.8-100.0%, respectively. CONCLUSION: Clinical decision-makers require high-quality evidence of clinical validity and clinical utility of TPMT genotyping to ensure appropriate use in patients.
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