Prevalence and types of inconsistencies in clinical pharmacogenetic recommendations among major U.S. sources

Shugg, Tyler; Pasternak, Amy L; London, Bianca

doi:10.1038/s41525-020-00156-7

Cited by 27 publications

(28 citation statements)

References 31 publications

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“…Clinical investigation on PGx testing continues to address questions about clinical utility and limited evidence basis, 28 the role of other factors that may contribute to development of adverse responses or limited efficacy, or pharmacoresistance, [29][30][31][32] and inconsistencies between clinical laboratory testing platforms, variant interpretation, and clinical guidelines. [33][34][35][36][37][38] However, much attention has focused on provider preparedness to deliver and integrate single-gene PGx testing into clinical care, including pharmacist preparedness. 39,40 Pharmacists in particular have played a leading role in the development and implementation of PGx testing at academic medical centers and large health systems.…”

Section: Discussionmentioning

confidence: 99%

Independent Community Pharmacists’ Experience in Offering Pharmacogenetic Testing

Haga¹,

Mills²,

Moaddeb³

et al. 2021

PGPM

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This study assessed pharmacist experiences with delivering pharmacogenetic (PGx) testing in independent community pharmacies. Methods: We conducted a cluster randomized trial of independent community pharmacies in North Carolina randomized to provide either PGx testing as a standalone service or integrated into medication therapy management (MTM) services. Surveys and pharmacist data about the delivery of PGx testing were collected. Semi-structured interviews were also conducted. Results: A total of 36 pharmacists participated in the study from 22 pharmacies. Sixteen pharmacists completed the pre-study and post-study surveys, and four pharmacists completed the semi-structured interviews. Thirty-one percent (11/36) of pharmacists had had some education in personalized medicine or PGx prior to the study. The only outcome that differed by study arm was the use of educational resources, with significantly higher utilization in the PGx testing only arm (p=0.007). Overall, compared to the pre-study assessment, pharmacists' knowledge about PGx significantly improved post-study (p=0.018). In the post-study survey, almost all pharmacists indicated that they felt qualified/able to provide PGx testing at their pharmacy. While 75% of pharmacists indicated that they may continue to provide PGx testing at their pharmacy after the study, the major concerns were lack of reimbursement for PGx counseling and consultation given the necessary time required. Conclusion:Our findings demonstrated a positive experience with delivering PGx testing in the community pharmacy setting with little difference in pharmacists' experiences in providing PGx testing with or without MTM. Pharmacists were confident in their ability to provide PGx testing and were interested in continuing to offer testing, though sustained delivery may be challenged by lack of prescribing provider engagement and reimbursement.

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Section: Discussionmentioning

confidence: 99%

Independent Community Pharmacists’ Experience in Offering Pharmacogenetic Testing

Haga¹,

Mills²,

Moaddeb³

et al. 2021

PGPM

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“…Regardless, the American College of Gastroenterology clinical guideline for the management of Crohn’s disease in adults states “Thiopurine methyltransferase (TPMT) testing should be considered before initial use of azathioprine or 6‐mercaptopurine to treat patients with Crohn’s disease (strong recommendation, low level of evidence).” 78 Another example is in the 2017 AHA/ACC/HRS guideline for the management of patients with syncope, which states “The response to beta‐blockers depends on the genotype…” 79 The data supporting that statement comes solely from two observational registries 80 . Nearly half of drug‐gene pairs have differences in their guideline recommendations, 81 which demonstrates variable interpretations of the available evidence in practice guidelines.…”

Section: Different Perspectives On Pharmacogenetic Evidencementioning

confidence: 99%

“…78 Another example is in the 2017 AHA/ACC/HRS guideline for the management of patients with syncope, which states "The response to beta-blockers depends on the genotype…" 79 The data supporting that statement comes solely from two observational registries. 80 Nearly half of drug-gene pairs have differences in their guideline recommendations, 81 which demonstrates variable interpretations of the available evidence in practice guidelines.…”

Section: Practice Guideline Perspectivementioning

confidence: 99%

“…107 The goal of the PGx Dissemination Working Group is to raise awareness and educate about resources available for pharmacogenetic implementation, such as CPIC guidelines, PharmGKB, the Pharmacogenomics Research Network (PGRN), and PharmVar, including also commentaries in journals, outreach to medical societies, letters to insurance companies, and through social media. Alignment of medical society practice guideline pharmacogenetic recommendations with these other resources is a critical step to enhance provider acceptance of the value of pharmacogenetic testing, 81 and to enhance the adoption into standard practice and availability for patients.…”

Section: Reviewmentioning

confidence: 99%

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Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

Luzum

Petry

Taylor

et al. 2021

Clin Pharma and Therapeutics

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The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics. First, we present two patient cases that demonstrate how knowledge of pharmacogenetic evidence affected their care. Then we summarize resources that curate pharmacogenetic evidence, types of evidence (with an emphasis on randomized controlled trials [RCT]) and their limitations, and different perspectives from implementers, clinicians, and patients. We compare pharmacogenetics to a historical example (i.e., the evidence required for the clinical implementation of pharmacokinetics/therapeutic drug monitoring), and we provide future perspectives on the evidence for pharmacogenetic panels and the need for more education in addition to evidence. Although there are differences in the interpretation of pharmacogenetic evidence across resources, efforts for standardization are underway. Survey data illustrate the value of pharmacogenetic testing from the patient perspective, with their providers seen as key to ensuring maximum benefit from test results. However, clinicians and practice guidelines from medical societies often rely on RCT data to guide treatment decisions, which are not always feasible or ethical in pharmacogenetics. Thus, recognition of other types of evidence to support pharmacogenetic implementation is needed. Among pharmacogenetic implementers, consistent evidence of pharmacogenetic associations is deemed most critical. Ultimately, moving pharmacogenetics into practice will require consideration of multiple stakeholder perspectives, keeping particularly attuned to the voice of the ultimate stakeholder—the patient.

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“…6 Moreover, clinical practice guidelines that include PGx-guided recommendations have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and prominent discipline-specific professional organizations (eg, the National Comprehensive Cancer Network) for over 100 medications. 7,8 Similarly, DDIs are known to contribute to adverse drug events, 9,10 and strategies to manage DDIs have been shown to improve patient outcomes. 11 Given their important clinical implications, recommendations to manage DDIs are included both in FDA drug development guidance to industry 12 and in numerous clinical practice guidelines.…”

Section: Introductionmentioning

confidence: 99%

Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers

Shugg

Rowe

et al. 2022

JCO Precision Oncology

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PURPOSE Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PGx and DDI management within a cohort of adults with advanced cancer. METHODS Medication data were collected from the electronic health records for 481 subjects since their first cancer diagnosis. All subjects were genotyped for variants with clinically actionable recommendations in Clinical Pharmacogenetics Implementation Consortium guidelines for 13 pharmacogenes. DDIs were defined as concomitant prescription of strong inhibitors or inducers with sensitive substrates of the same drug-metabolizing enzyme and were assessed for six major cytochrome P450 (CYP) enzymes. RESULTS Approximately 60% of subjects were prescribed at least one medication with Clinical Pharmacogenetics Implementation Consortium recommendations, and approximately 14% of subjects had an instance for actionable PGx, defined as a prescription for a drug in a subject with an actionable genotype. The overall subject-level prevalence of DDIs and serious DDIs were 50.3% and 34.8%, respectively. Serious DDIs were most common for CYP3A, CYP2D6, and CYP2C19, occurring in 24.9%, 16.8%, and 11.7% of subjects, respectively. When assessing PGx and DDIs together, approximately 40% of subjects had at least one opportunity for a precision medicine–based intervention and approximately 98% of subjects had an actionable phenotype for at least one CYP enzyme. CONCLUSION Our findings demonstrate numerous clinical opportunities for germline PGx and DDI management in adults with advanced cancer.

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Prevalence and types of inconsistencies in clinical pharmacogenetic recommendations among major U.S. sources

Cited by 27 publications

References 31 publications

Independent Community Pharmacists’ Experience in Offering Pharmacogenetic Testing

Independent Community Pharmacists’ Experience in Offering Pharmacogenetic Testing

Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers

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