PGx ECHO Program

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The University of Minnesota College of Pharmacy invites all actively practicing clinicians to join their Pharmacogenomics (PGx) ECHO project. PGx ECHO aims to improve health professionals’ confidence in using PGx in patient care by providing case-based education and consultation through telementoring. Every month, clinicians from across the nation seek PGx advice regarding real clinical cases. PGx ECHO is modeled on the all-teach-all-learn principle and encourages interactive and engaging discussion between attendees and facilitators.

The University of Minnesota works with colleagues at Children’s MN, Ferris State University, M Health Fairview, Manchester University, North Dakota State University, South Dakota State University, and Sanford Health to coordinate and facilitate the monthly sessions. PGx ECHO meets the third Friday of every month over the lunch hour. For past ECHO cases and topics, and a schedule of upcoming cases, please visit the PGx ECHO website.

If you are interested in joining, please use this link to register.

PGx ECHO is for practicing clinicians with direct patient care responsibilities. Student learners are welcome to join.

If you would like to present a case or have any questions, please contact pgxecho@umn.edu.

The clinical utility of polygenic risk scores in genomic medicine practices: a systematic review

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Judit Kumuthini, Brittany Zick, Angeliki Balasopoulou, Constantina Chalikiopoulou, Collet Dandara, Ghada El-Kamah, Laura Findley, Theodora Katsila, Rongling Li, Ebner Bon Maceda, Henrietta Monye, Gabriel Rada, Meow-Keong Thong, Thilina Wanigasekera, Hannah Kennel, Veeramani Marimuthu, G2MC Evidence investigators; Marc S Williams, Fahd Al-Mulla, Marc Abramowicz

Abstract
Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translational research is still needed before they should enter mainstream clinical practice.

Development and Validation of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL)

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Josiah D Allen, Lusi Zhang, Alyssa N K Johnson, Pamala A Jacobson, Catherine A McCarty, Amy L Pittenger, Jeffrey R Bishop

Abstract
Ensuring that patients have an adequate understanding of pharmacogenomic (PGx) test results is a critical component of implementing precision medicine into clinical care. However, no PGx-specific validated literacy assessment has yet been developed. To address this need, we developed and validated the Minnesota Assessment of Pharmacogenomic Literacy (MAPLTM). Foundational work included a scoping review of patient and general public attitudes and experiences with pharmacogenomic testing, three focus groups, readability assessments, and review by experts and members of the general public. This resulted in a 15-item assessment designed to assess knowledge in four domains: underlying concepts, limitations, benefits, and privacy. For validation, 646 participants completed the MAPL as a part of a larger survey about pharmacogenomic research and statewide PGx implementation. Two items were deemed to be “too easy” and dropped. The remaining 13 items were retained in the final MAPL with good internal reliability (Cronbach’s alpha = 0.75). Confirmatory factor analysis validated the four-domain construct of MAPL and suggested good model performance and high internal validity. The estimated coefficient loadings across 13 questions on the corresponding domains are all positive and statistically significant (p < 0.05). The MAPL covers multiple knowledge domains of specific relevance to PGx and is a useful tool for clinical and research settings where quantitative assessment of PGx literacy is of value.

Keywords: genetic counseling; genomic literacy; literacy assessment; pharmacogenomics; psychometric validation.

Health equity in the implementation of genomics and precision medicine: A public health imperative

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Muin J Khoury, Scott Bowen, W David Dotson, Emily Drzymalla, Ridgely F Green, Robert Goldstein, Katherine Kolor, Leandris C Liburd, Laurence S Sperling, Rebecca Bunnell

Abstract

Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade.

Keywords: Genomics; Health equity; Precision medicine; Public health genomics.

Pharmacogenomics in treatment of depression and psychosis: an update

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Marin Jukic, Filip Milosavljević, Espen Molden, Magnus Ingelman-Sundberg

Abstract

Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent large studies indicate a true benefit and cost-effectiveness of pre-emptive genotyping for more successful psychotherapy. However, it is apparent that we still lack knowledge of many additional heritable genetic factors of importance for explanation of the interindividual differences in response to psychiatric drugs. Thus, more effort to further develop pharmacogenomic psychiatry should be invested to achieve a broader clinical implementation.

Keywords: ADME genes; drug metabolism; personalized medicine; pharmacogenomics; psychiatric genetics

Implementing comprehensive pharmacogenomics in a community hospital–associated primary care setting

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Jennifer A. Wick, Tara Schmidlen, Kendra Grande, Chad Moretz, Kristine Ashcraft, Julia Green, Nicolas Moyer, Burns C. Blaxall

Background
Pharmacogenomics (PGx) is an emerging field. Many drug-gene interactions are known but not yet routinely addressed in clinical practice. Therefore, there is a significant gap in care, necessitating development of implementation strategies.

Objective
The objective of the study was to assess the impact of implementing a PGx practice model which incorporates comprehensive pharmacogenomic risk evaluation, testing and medication optimization administered by 7 PGx-certified ambulatory care pharmacists embedded across 30 primary care clinic sites.

Assessment of the Clinical Utility of Pretreatment DPYD Testing for Patients Receiving Fluoropyrimidine Chemotherapy

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Daniel L. Hertz

Abstract

Purpose: Patients who carry pathogenic variants in DPYD have higher systemic fluoropyrimidine (FP) concentrations and greater risk of severe and fatal FP toxicity. Pretreatment DPYD testing and DPYD-guided FP dosing to reduce toxicity and health care costs is recommended by European clinical oncology guidelines and has been adopted across Europe, but has not been recommended or adopted in the United States. The cochairs of the National Comprehensive Cancer Network Guidelines for colon cancer treatment explained their concerns with recommending pretreatment DPYD testing, particularly the risk that reduced FP doses in DPYD carriers may reduce treatment efficacy.

A Mixed-Methods Protocol to Identify Best Practices for Implementing Pharmacogenetic Testing in Clinical Settings

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Nina R. Sperber, Deborah Cragun, Megan C. Roberts, Lisa M. Bendz, Parker Ince, Sarah Gonzales,
Susanne B. Haga, R. Ryanne Wu, Natasha J. Petry, Laura Ramsey, and Ryley Uber

Abstract

Using a patient’s genetic information to inform medication prescriptions can be clinically effective; however, the practice has not been widely implemented. Health systems need guidance on how to engage with providers to improve pharmacogenetic test utilization. Approaches from the field of implementation science may shed light on the complex factors affecting pharmacogenetic test use in real-world settings and areas to target to improve utilization. This paper presents an approach to studying the application of precision medicine that utilizes mixed qualitative and quantitative methods and implementation science frameworks to understand which factors or combinations consistently account for high versus low utilization of pharmocogenetic testing. This approach involves two phases: (1) collection of qualitative and quantitative data from providers-the cases-at four clinical institutions about their experiences with, and utilization of, pharmacogenetic testing to identify salient factors; and (2) analysis using a Configurational Comparative Method (CCM), using a mathematical algorithm to identify the minimally necessary and sufficient factors that distinguish providers who have higher utilization from those with low utilization. Advantages of this approach are that it can be used for small to moderate sample sizes, and it accounts for conditions found in real-world settings by demonstrating how they coincide to affect utilization.

Keywords: coincidence analysis; configurational comparative methods; health services research; implementation science; mixed methods; pharmacogenomics