Implementation of Standardized Clinical Processes for TPMT Testing in a Diverse Multidisciplinary Population: Challenges and Lessons Learned

Abstract

Although thiopurine S‐methyltransferase (TPMT) genotyping to guide thiopurine dosing is common in the pediatric cancer population, limited data exist on TPMT testing implementation in diverse, multidisciplinary settings. We established TPMT testing (genotype and enzyme) with clinical decision support, provider/patient education, and pharmacist consultations in a tertiary medical center and collected data over 3 years. During this time, 834 patients underwent 873 TPMT tests (147 (17%) genotype, 726 (83%) enzyme). TPMT tests were most commonly ordered for gastroenterology, rheumatology, dermatology, and hematology/oncology patients (661 of 834 patients (79.2%); 580 outpatient vs. 293 inpatient; P < 0.0001). Thirty‐nine patients had both genotype and enzyme tests (n = 2 discordant results). We observed significant differences between TPMT test use and characteristics in a diverse, multispecialty environment vs. a pediatric cancer setting, which led to unique implementation needs. As pharmacogenetic implementations expand, disseminating lessons learned in diverse, real‐world environments will be important to support routine adoption.

Pediatric pharmacogenomics: challenges and opportunities: on behalf of the Sanford Children’s Genomic Medicine Consortium

“…The University of Florida implemented a custom array with 256 clinically actionable genetic polymorphisms [18]. Pediatric focused gene implementations by the University of Florida include TPMT/thiopurines [19] and CYP2C19/ proton pump inhibitors (in partnership with Nemours Children's Specialty Care, Jacksonville, FL and Nemours Children's Hospital, Orlando, FL [20]. Boston Children's Hospital has focused on children with significant adverse drug reactions or failed treatment using either single gene sequencing tests for TPMT and CYP2C9/VKORC1 or microarray panels testing up to 225 SNPs [13].…”

Advances in Genomic Discovery and Implications for Personalized Prevention and Medicine: Estonia as Example

“…For example, lead drug developer Astra Zeneca showed that genetically informed decisions not only led to an increase in number of successful drug development projects, but also a reduced time to market [ 102 ]. Similarly, for personalized medicine, genetic profiling already helps optimizing drug dosage and avoiding adverse effects, such as done for S-methyltransferase (TPMT) genotype testing prior to administration of a class of drugs named thiopurines [ 103 ]. Additional genetic testing helps to select medication for individuals with specific genetic mutations, an example being melanoma patients with particular mutations in the BRAF gene developing resistance against the normally used single agent BRAF inhibitors, who display a better response with combined use of MEK inhibitors [ 104 ].…”

Establishment of a Pharmacogenetics Service Focused on Optimizing Existing Pharmacogenetic Testing at a Large Academic Health Center

“…Therefore, our service focused on developing standardized strategies for incorporating existing PGx results into the EMR, for all relevant patient care decisions for gene-drug pairs, with established recommendations for dosing or use, based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines or Food and Drug Administration (FDA) package insert information. The description of these implementation efforts are unique because the strategies for evaluating and integrating existing PGx results are less well described than implementation of a new PGx-service that sets the testing criteria [ 16 ]. We believe that describing our PGx implementation strategy will be informative for clinicians at institutions that are encountering external PGx testing.…”