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 are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 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: 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.

Keywords: implementation; pharmacogenomics; precision medicine; translation.

FIGURE 1

Diagram of the NIH CC institutional process.

FIGURE 2

(A) The design for the order set form for drugs included in the pharmacogenomics DMET program is shown. In this case, the information displayed to the prescriber is based on the case where the Pharmacogenomics Multigene Test has not yet been ordered. The displayed messages and order actions are determined by the control table. The standard design for the order set form includes (1) a message box where the clinical information message is displayed, and (2) a message box where over-ride reasons are displayed (the ‘over-ride reason number’ field becomes a required entry if an over-ride reason is allowed), (3) a link to the Education Document to provide to the patient, (4) a message box where pharmacogenomics test information and when appropriate result information is displayed, (5) a grid where the Pharmacogenomics Multigene Test can be ordered or are automatically preselected depending on the case, and (6) a grid where medications can be ordered through the Clinical Research Information System. (B) The top image shows the modal window showing the override options. The bottom image shows how override reason 2 will display when selected. (C) The image shows information related to the actual result of the Pharmacogenomics Multigene Test. The MLMs uses a control table to process clinical rules for medication orders. The control table allows the management of the process through logic defined in the MLM and also allows the user to add new medications or add or modify rules for test results as needed to refine the logic. Each medication within the pharmacogenomics DMET program will have entries in the control table as seen in Table 1. This report is a sample and does not refer to an actual patient.

FIGURE 2

(A) The design for the order set form for drugs included in the pharmacogenomics DMET program is shown. In this case, the information displayed to the prescriber is based on the case where the Pharmacogenomics Multigene Test has not yet been ordered. The displayed messages and order actions are determined by the control table. The standard design for the order set form includes (1) a message box where the clinical information message is displayed, and (2) a message box where over-ride reasons are displayed (the ‘over-ride reason number’ field becomes a required entry if an over-ride reason is allowed), (3) a link to the Education Document to provide to the patient, (4) a message box where pharmacogenomics test information and when appropriate result information is displayed, (5) a grid where the Pharmacogenomics Multigene Test can be ordered or are automatically preselected depending on the case, and (6) a grid where medications can be ordered through the Clinical Research Information System. (B) The top image shows the modal window showing the override options. The bottom image shows how override reason 2 will display when selected. (C) The image shows information related to the actual result of the Pharmacogenomics Multigene Test. The MLMs uses a control table to process clinical rules for medication orders. The control table allows the management of the process through logic defined in the MLM and also allows the user to add new medications or add or modify rules for test results as needed to refine the logic. Each medication within the pharmacogenomics DMET program will have entries in the control table as seen in Table 1. This report is a sample and does not refer to an actual patient.

FIGURE 3

Example PDF Report containing (1) dates (laboratory test requested date, results received date, and date added to table), (2) identification numbers for the patient, (3) table logic parameters (medication name, laboratory test name, allele information), (4) a textual description of the results value, (5) the result for the variant. Fields with example data stored with in the DMET Results table are shown in Table 2. This report is a sample and does not refer to an actual patient.