A Tutorial for Pharmacogenomics Implementation Through End‐to‐End Clinical Decision Support Based on Ten Years of Experience from PREDICT

Abstract

Center implemented pharmacogenomics (PGx) testing with the Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment (PREDICT) initiative in 2010. This tutorial reviews the laboratory considerations, technical infrastructure, and programmatic support required to deliver panel-based PGx testing across a large health system with examples and experiences from the first decade of the PREDICT initiative. From the time of inception, automated clinical decision support (CDS) has been a critical capability for delivering PGx results to the point-of-care. Key features of the CDS include human-readable interpretations and clinical guidance that is anticipatory, actionable, and adaptable to changes in the scientific literature. Implementing CDS requires that structured results from the laboratory be encoded in standards-based messages that are securely ingested by electronic health records. Translating results to guidance also requires an informatics infrastructure with multiple components: (1) to manage the interpretation of raw genomic data to "star allele" results to expected phenotype, (2) to define the rules that associate a phenotype with recommended changes to clinical care, and (3) to manage and update the knowledge base. Knowledge base management is key to processing new results with the latest guidelines, and to ensure that historical genomic results can be reinterpreted with revised CDS. We recommend that these components be deployed with institutional authorization, programmatic support, and clinician education to govern the CDS content and policies around delivery.

Revisiting Secondary Information Related to Pharmacogenetic Testing

“…Educational support is needed for not only authorized prescribers, but other health professionals such as nurses and pharmacists. While clinical decision supports provide an important component in the appropriate use of PGx testing (Nishimura et al, 2015;Liu et al, 2021), they may not be widely accessible or as helpful with respect to secondary findings. In some cases, the PGx testordering provider may not be the appropriate person to communicate secondary findings and referral to a pharmacist or a genetic counselor for secondary information related to other medications or disease risk, respectively, may be warranted (Callard et al, 2012;Zierhut et al, 2017;Chart et al, 2021).…”

Precision Dosing: The Clinical Pharmacology of Goldilocks

“…The induction of transporters is also an essential consideration for the pharmacokinetics and dosing of some drugs 4 . Identification and implementation of dosing changes based on patient genotype can be challenging to implement; however, it is hoped the decade of experience at Vanderbilt University Medical Center will be helpful in overcoming challenges that hinder the smooth implementation of genetics in guiding pharmacotherapeutic dosing recommendation 5 . Likewise, consortia’s combined expertise, such as PharmGKB, 6 serves as a freely available comprehensive resource that facilitates the implementation of pharmacogenetics in clinical practice, including through CPIC guidelines, 7 which can be hugely influential in guiding dosing recommendations across different patients.…”

Pharmacogenomics in the United States Community Pharmacy Setting: The Clopidogrel-CYP2C19 Example

“…7 While multiple barriers exist to implementing PGx, there are many examples of successful clinical implementation. 2,[8][9][10][11][12][13][14][15] The implementation of a full scale PGx program is a large undertaking and some programs start with implementation of a single gene, such as CYP2C19, for use as reactive testing in guiding clopidogrel dosing; 2,16 or a single specialty area such as cardiology. 17 Many programs have documented success implementing pre-emptive panel-based PGx programs.…”

“…In-house laboratories often offer benefits such as the ability for increased interoperability within electronic health records (EHR) for use of storage and automated clinical decision support, control over test content and results reporting, in addition to turn around time. 8 , 22 External labs allow for health systems and community pharmacies to focus on clinical care while leaving the complexities of genetic laboratory maintenance to lab experts. While most clinical use of PGx is through provider-ordered testing, direct-to-consumer (DTC) PGx testing is also an option for patients to obtain some PGx information directly without requiring the involvement of a health-care professional.…”