Pharmacogenomics Implementation at the National Institutes of Health Clinical Center

Abstract

The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality is a major goal of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in two phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol. In the second phase, we implemented genotyping for drug metabolizing enzymes and transporters (DMET): SLCO1B1 for CDS of simvastatin and TPMT for CDS of mercaptopurine, azathioprine, and thioguanine. The purpose of this review is to describe the implementation process, which involves clinical, laboratory, informatics, and policy decisions pertinent to the NIH CC.

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

“…These guidelines align well with implementation of TPMT genotyping in cancer treatment settings, in which the genotype test is used nearly exclusively in the inpatient setting due to the presence of disease and treatment factors in this population that decrease the accuracy of phenotyping . Published descriptions of TPMT genotyping implementations in specialized cancer and/or pediatric practice settings also exist . However, the current practice‐based guidance and/or published experience descriptions provide little guidance for clinicians implementing TPMT genotype and/or phenotype testing in diverse, multispecialty (primarily noncancer) populations .…”

“…16 Published descriptions of TPMT genotyping implementations in specialized cancer and/or pediatric practice settings also exist. [17][18][19][20][21] However, the current practicebased guidance and/or published experience descriptions provide little guidance for clinicians implementing TPMT genotype and/or phenotype testing in diverse, multispecialty (primarily noncancer) populations. 22 Practical guidance for implementation of TPMT testing is especially important for a variety of reasons.…”

Impact of SLCO1B1 Pharmacogenetic Testing on Patient and Healthcare Outcomes: A Systematic Review

“…With the previously described recommendations, ongoing projects using SLCO1B1 genotyping in research or clinical care in the United States and internationally have a tremendous opportunity to contribute to the lack of evidence for its clinical utility. We identified 10 institutions with ongoing studies whose designs and planned outcomes would have been eligible for this review . Most of these represent multi‐institutional efforts, such as the Electronic Medical Records and Genomics (eMERGE)–PGx Consortium, the Pharmacogenomics Research Network Translational Pharmacogenetics Program (TPP), the Implementing Genomics in Practice (IGNITE) Consortium, and the seven‐country Ubiquitous Pharmacogenomics (U‐PGx) Consortium .…”

“…We identified 10 institutions with ongoing studies whose designs and planned outcomes would have been eligible for this review. 11,12,14,[78][79][80][81] Most of these represent multi-institutional efforts, such as the Electronic Medical Records and Genomics (eMERGE)-PGx Consortium, 12 the Pharmacogenomics Research Network Translational Pharmacogenetics Program (TPP), 11 the Implementing Genomics in Practice (IGNITE) Consortium, 13 and the seven-country Ubiquitous Pharmacogenomics (U-PGx) Consortium. 14 These projects are collecting a range of prescription, clinical, and economic outcomes, and their large scale will enable more precise estimates of the clinical utility of pharmacogenetic testing.…”

Assessment of Patient Knowledge and Perceptions of Pharmacogenomics Before and After Using a Mock Results Patient Web Portal

“…Pharmacogenomics (PGx) is the study of how genetic variations affect individual responses to medications. Within the past decade, PGx approaches have been successfully implemented in several clinical trials, including The University of Chicago “The 1200 Patients Project,” which has demonstrated utility and positive outcomes in the outpatient care setting . In our previous institutional PGx implementation studies, PGx results have been primarily disseminated to providers who may or may not share the results with their patients; however, patients are often not provided direct access to their PGx results.…”