Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: A meta-analysis of diagnostic test accuracy

Zur RM, Roy LM, Ungar WJ
Record ID 32015001122
Authors' objectives: The aim of this study was to meta-analyze the sensitivity and specificity of phenotype and genotype Thiopurine S-methyltransferase (TPMT) testing reported in the literature. The specific objectives were: 1. To perform meta-analyses of two methods of evaluating TMPT enzyme activity: a) identifying patients with deficient or absent TPMT enzyme activity (patients that are homozygous for TPMT mutations) versus the rest of the population and b) identifying patients that have either low or intermediate TPMT enzyme activity (patients that are homozygous or heterozygous for TPMT mutations) versus the rest of the population. 2. To perform a DTA meta-analysis that accounts for the imperfect reference standard provided by genotype testing.
Authors' recommendations: The pooled estimates of sensitivity suggest that genotype testing has higher sensitivity than phenotype testing as long as both TPMT*2 and TPMT*3 polymorphisms are tested. However, due to the large 95% CrIs around sensitivity estimates the results are not statistically significant. Both tests have been shown to have high specificity, valuable for ruling in the presence of TPMT deficiency. This meta-analysis cannot conclude that one test is superior to the other. Although more complex than standard meta-analysis techniques, the latent class HSROC approach is straight-forward to implement and interpret. Therefore, this report supports existing recommendations to perform HSROC or bivariate methods for DTA meta-analyses.
Project Status: Completed
Year Published: 2015
English language abstract: An English language summary is available
Publication Type: Not Assigned
Country: Canada
MeSH Terms
  • Drug-Related Side Effects and Adverse Reactions
  • Methyltransferases
  • Purine Nucleosides
Organisation Name: Technology Assessment at SickKids
Contact Address: Program of Child Health Evaluative Sciences, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8 tel: (416) 813-8519 fax: (416) 813-5979
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Copyright: The Hospital for Sick Children Research Institute
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.