Improved provider preparedness through an 8-part genetics and genomic education program.

PURPOSE: Large-scale genetics education appropriate for general practice providers is a growing priority. We describe the content and impact of a mandatory system-wide program implemented at Sanford Health. METHODS: The Imagenetics Initiative at Sanford Health developed a 2-year genetics education program with quarterly web-based modules that were mandatory for all physicians and advanced practice providers. Scores of 0 to 5 were calculated for each module on the basis of the number of objectives that the participants reported as fulfilled. In addition, the participants completed surveys before starting and after finishing the education program, which included a 7-item measure scored 7 to 28 on the perceived preparedness to practice genetics. RESULTS: Between 2252 and 2822 Sanford Health employees completed each of the 8 quarterly education modules. The ratings were highest for the module about using genomics to improve patient management (mean score = 4.3) and lowest for the module about different types of genetic tests and specialists. The mean perceived preparedness scores increased from 15.7 at pre-education to 19.1 at post-education (P < .001). CONCLUSION: Web-based genetics education was highly effective in increasing health care providers' confidence about using genetics. Both comfort with personal knowledge and confidence regarding access to the system's genomic medicine experts increased significantly. The results demonstrate how scalable approaches can improve provider preparedness.

Multisite investigation of strategies for the clinical implementation of pre-emptive pharmacogenetic testing.

PURPOSE: The increased availability of clinical pharmacogenetic (PGx) guidelines and decreasing costs for genetic testing have slowly led to increased utilization of PGx testing in clinical practice. Pre-emptive PGx testing, where testing is performed in advance of drug prescribing, is one means to ensure results are available at the time of prescribing decisions. However, the most efficient and effective methods to clinically implement this strategy remain unclear. METHODS: In this report, we compare and contrast implementation strategies for pre-emptive PGx testing by 15 early-adopter institutions. We surveyed these groups, collecting data on testing approaches, team composition, and workflow dynamics, in addition to estimated third-party reimbursement rates. RESULTS: We found that while pre-emptive PGx testing models varied across sites, institutions shared several commonalities, including methods to identify patients eligible for testing, involvement of a precision medicine clinical team in program leadership, and the implementation of pharmacogenes with Clinical Pharmacogenetics Implementation Consortium guidelines available. Finally, while reimbursement rate data were difficult to obtain, the data available suggested that reimbursement rates for pre-emptive PGx testing remain low. CONCLUSION: These findings should inform the establishment of future implementation efforts at institutions considering a pre-emptive PGx testing program.

Use of the 9-Item Patient Health Questionnaire for Depression Assessment in Primary Care Patients With Type 2 Diabetes.

The purpose of the current study was to assess the frequency and distribution of the 9-Item Patient Health Questionnaire (PHQ-9) among individuals with type 2 diabetes with and without depression. The current case-control study used electronic medical record data from two primary care institutions. The sample was divided into cases with coexisting depression and type 2 diabetes and controls without depression. Data included demographics, biomarkers, number of services delivered, and clinic visits in 2013. Similar PHQ-9 use was seen between unique primary care practices. However, less than one third of patients at either site received depression screening with the PHQ-9 in 2013. Male and older adult patients were less likely to receive assessment. Guideline ambiguity and lack of accountability in primary care practice has made the use of depression metrics arbitrary in diabetic populations at risk for depression. To assure adequate care provision, it is imperative that proven tools for assessing depressive symptoms are used.

The expanding role of HLA gene tests for predicting drug side effects.

Adverse drug reactions can be either dose-dependent (Type A) or idiosyncratic (Type B). Type B adverse drug reactions tend to be extremely rare and difficult to predict. They are usually immune-mediated. Examples include severe skin reactions and drug-induced liver injury. For many commonly prescribed drugs (such as antibiotics), the risk of developing an idiosyncratic adverse drug reaction is influenced by variability in the human leukocyte antigen (HLA) genes. Because these HLA-mediated adverse drug reactions can be lethal, there is growing interest in defining which specific drug-gene relationships might benefit from pre-emptive HLA genotyping and automated clinical decision support. This review summarizes the literature for HLA-mediated adverse reactions linked to common drugs.

Incidence of statin-associated muscle symptoms in patients taking statins with RYR1 or CACNA1S variants.

Background: Statins are commonly used medications. Variants in SLCO1B1, CYP2C9, and ABCG2 are known predictors of muscle effects when taking statins. More exploratory genes include RYR1 and CACNA1S, which can also be associated with disease conditions. Methods: Patients with pathogenic/likely pathogenic variants in RYR1 or CACNA1S were identified through an elective genomic testing program. Through chart review, patients with a history of statin use were assessed for statin-associated muscle symptoms (SAMS) along with collection of demographics and other known risk factors for SAMS. Results: Of the 23 patients who had a pathogenic or likely pathogenic RYR1 or CACNA1S variant found, 12 had previous statin use; of these, SAMS were identified in four patients. Conclusion: These data contribute to previous literature suggesting patients with RYR1 variants may have an increased SAMS risk. Additional research will be helpful in further investigating this relationship and providing recommendations.

Implementation of CYP2C19 and CYP2D6 genotyping to guide antidepressant use in a large rural health system.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: We describe the implementation and ongoing maintenance of CYP2C19 and CYP2D6 focused pharmacogenetic (PGx) testing to guide antidepressant and antianxiety medication prescriptions in a large rural, nonprofit health system. SUMMARY: Depression and anxiety are common psychiatric conditions. Sanford Health implemented PGx testing for metabolism of cytochrome P450 (CYP) isozymes 2C19 and 2D6 in 2014 to inform prescribing for multiple medications, including antidepressant and antianxiety therapies. As guidelines, genotype to phenotype translation, panel offerings, and other resources are updated, we adapt our approach. We make educational and informational materials available to providers and patients. Pharmacogenomic clinical pharmacists review PGx results with discrete values and provide guidance documentation in the electronic medical record. A robust clinical decision support system is in place to provide interruptive alerts, noninterruptive alerts, and genomic indicators. A referral-based interdisciplinary clinic is also available to provide in-depth education to patients regarding PGx results and implications. Additionally, partnering with our health plan has expanded access to PGx testing for patients with anxiety or depression. CONCLUSION: The implementation and maintenance of Sanford Health's PGx program to guide antidepressant and antianxiety medication use continues to evolve and requires a multipronged approach relying on both human and informatics-based resources.

Pharmacogenetic testing in primary care could bolster depression treatment: A value proposition.

Pharmacogenetic testing could reduce the time to identify a safe and effective medication for depression; however, it is underutilized in practice. Major depression constitutes the most common mental disorder in the US, and while antidepressant therapy can help, the current trial -and error approach can require patients to endure multiple medication trials before finding one that is effective. Tailoring the fit of pharmacogenetic testing with prescribers' needs across a variety of settings could help to establish a generalizable value proposition to improve likelihood of adoption. We conducted a study to explore the value proposition for health systems using pharmacogenetic testing for mental health medications through prescribers' real-world experiences using implementation science concepts and systematic interviews with prescribers and administrators from four health care systems. To identify a value proposition, we organized the themes according to the Triple Aim framework, a leading framework for health care policy which asserts that high-value care should focus on three key metrics: (1) better health care quality and (2) population-level outcomes with (3) reduced per capita costs. Primary care providers whom we interviewed said that they value pharmacogenetic testing because it would provide more information about medications that they can prescribe, expanding their ability to identify medications that best-fit patients and reducing their reliance on referrals to specialists; they said that this capacity would help meet patients' needs for access to mental health care through primary care. At the same time, prescribers expressed differing views about how pharmacogenetic testing can help with quality of care and whether their views about out-of-pocket cost would prevent them from offering it. Thus, implementation should focus on integrating pharmacogenetic testing into primary care and using strategies to support prescribers' interactions with patients.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

Impact of transitioning to an active, noninterruptive CYP2C19/proton pump inhibitor alert on prescribing patterns.

PURPOSE: To compare rates of prescriber acceptance of interruptive and noninterruptive clinical decision support (CDS) alerts regarding potential diminished therapeutic effectiveness and safety risks associated with proton pump inhibitor (PPI) use in carriers of gene variants affecting cytochrome P450 (CYP) isozyme 2C19 metabolism. METHODS: A retrospective study was conducted at a large rural health system to examine different approaches to improving CDS alert acceptance while minimizing alert fatigue. Manual reviews were conducted to identify alerts regarding CYP2C19 metabolizer status displayed at the time of PPI ordering over 30-day periods before and after the transition from interruptive to noninterruptive CDS alert functionality. A chi-square test was conducted to analyze prescriber acceptance of CDS recommendations by alert modality and type of treatment modification. RESULTS: Overall, interruptive alerts had an acceptance rate of 18.6% (64/344), compared to 8.4% acceptance (30/357 alerts) for noninterruptive alerts (P ≤ 0.0001). Analysis of acceptance criteria -revealed the noninterruptive alert cohort had higher acceptance, as determined by documented medication dose adjustments, than the interruptive alert cohort (53.3% [16/30] and 4.7% [3/64], respectively). The difference in acceptance rates by CDS modality and treatment modification was statistically significant (P ≤ 0.00001). The predominant indication for PPI use was gastroesophageal reflux disease (GERD) in both cohorts. CONCLUSION: Interruptive alerts that actively influenced workflow had higher acceptance rates than noninterruptive alerts that served an informational purpose without a direct disruption of workflow. The study results suggest the utilization of noninterruptive alerts may be a beneficial tool for prompting clinicians to alter dosing regimens rather than transition to an alternative agent.

Patient satisfaction with return of pharmacogenomic results utilizing a patient portal message.

Background: Returning pharmacogenomics (PGx) results to patients is complex and challenging. Patients prefer provider education; however, a gap in provider comfort in PGx results has been documented. Objectives: This study's purpose was to evaluate satisfaction with the return of PGx test results using a patient portal message. Methods: A survey was sent to two cohorts with PGx results, one that received a PGx result message and one that did not. Results: Following implementation of the PGx result message, there was a decrease in patients reporting negative responses surrounding satisfaction in the return of their PGx results, with 39% responding negatively pre-implementation and 21% post-implementation. Conclusion: Satisfaction with the return of results improved following the implementation of a patient portal message.

Impact of Automated Best Practice Advisories on Provider Response to CYP2C19 Genotyping Results for Patients on Clopidogrel.

ObjectiveThe study objective was to examine provider acceptance and genotyping responses to a best practice advisory (BPA) concerning clopidogrel and CYP2C19 intermediate and poor metabolizers within the context of a new pharmacogenomics program at a Midwestern health system. Other secondary objectives analyzed included appropriate BPA firing, the distribution of alleles in study population, indications for clopidogrel use, and impact of indication on therapy change. Methods: In this study, the progress of this program was assessed by quantifying how providers respond to BPAs generated in the electronic medical record (EMR), in the context of a single representative gene-drug-outcome relationship. Patient data was pulled via reports yielding patients with genotyped information in the EMR and cross-referenced with a report evaluating BPA firing occurrences. Results: By capturing antiplatelet therapy changes in response to CYP2C19 genotyping results, 37 patients were found that had 73 BPAs fire. Nine of those patients had alternative antiplatelet therapy ordered. Of these, 6 alternative antiplatelet therapies were ordered from the BPA. Conclusion: Providers utilized BPAs, but responded differently based on individual knowledge of genotypes and indications. Information obtained from this study can be used for provider education and as reference for future design and wording of BPAs.

Advancing Pharmacogenomics-Based Care Through Interprofessional Education.

As genomic medicine becomes increasingly complex, pharmacists need to work collaboratively with other healthcare professionals to provide genomics-based care. The core pharmacist competencies in genomics were recently updated and mapped to the entrustable professional activities (EPAs). The new competency that is mapped to the "Interprofessional Team Member" EPA domain emphasizes the role of pharmacists as the pharmacogenomics experts in an interprofessional healthcare team. Interprofessional education (IPE) activities involving student pharmacists and students from other healthcare disciplines are crucial to prepare student pharmacists for a team-based approach to patient-centered care. This commentary discusses the pharmacogenomics-focused IPE activities implemented by 3 programs, the challenges faced, and the lessons learned. It also discusses strategies to develop pharmacogenomics-focused IPE activities based on existing resources. Developing pharmacogenomics-focused IPE activities will help prepare pharmacy graduates with the knowledge, skills, and attitudes to lead collaborative, interprofessional teams in the provision of pharmacogenomics-based care, consistent with the standards described in the genomics competencies for pharmacists.

Metoprolol and CYP2D6: A Retrospective Cohort Study Evaluating Genotype-Based Outcomes.

Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via CYP2D6. Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol. Current pharmacogenomics guidelines by the Dutch Pharmacogenomics Working Group recommend slower titrations and dose decreases to minimize adverse effects from poor metabolizers or normal metabolizers taking concomitant medications that are strong inhibitors of CYP2D6 (phenoconverters). This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug-drug or drug-gene interactions. The secondary aims of this study were to evaluate heart rate measurements for the included participants. Retrospective data were collected for individuals with CYP2D6 genotyping results obtained for clinical purposes. Three categories (CYP2D6 normal metabolizers, poor metabolizers, and phenoconverters) were assigned. A total of 325 participants were included. There was no statistically significant difference found in the primary composite outcome between the three metabolizer groups (p = 0.054). However, a statistically significant difference was identified in the incidences of bradycardia between the poor metabolizers and the normal metabolizers or phenoconverters (p < 0.0001). The average heart rates were 2.8 beats per minute (bpm) and 2.6 bpm lower for the poor metabolizer and phenoconverter groups, respectively, compared to the normal metabolizers (p < 0.0001 for both comparisons). This study further supports the role of genetic testing in precision medicine to help individualize patient care as CYP2D6 poor metabolizers taking metoprolol were found to have an increase in bradycardia. Additional research is needed to clarify the dose relationship in this drug-gene interaction.

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system.

Introduction: Pharmacogenomics (PGx) aims to maximize drug benefits while minimizing risk of toxicity. Although PGx has proven beneficial in many settings, clinical uptake lags. Lack of clinician confidence and limited availability of PGx testing can deter patients from completing PGx testing. A few novel PGx clinic models have been described as a way to incorporate PGx testing into the standard of care. Background: A PGx clinic was implemented to fill an identified gap in provider availability, confidence, and utilization of PGx across our health system. Through a joint pharmacist and Advanced Practice Provider (APP) collaborative clinic, patients received counseling and PGx medication recommendations both before and after PGx testing. The clinic serves patients both in-person and virtually across four states in the upper Midwest. Results: The majority of patients seen in the PGx clinic during the early months were clinician referred (77%, n = 102) with the remainder being self-referred. Patients were, on average, taking two medications with Clinical Pharmacogenetics Implementation Consortium guidelines. Visits were split almost equally between in-person and virtual visits. Conclusion: Herein, we describe the successful implementation of an interdisciplinary PGx clinic to further enhance our PGx program. Throughout the implementation of the PGx clinic we have learned valuable lessons that may be of interest to other implementors. Clinicians were actively engaged in clinic referrals and early adoption of telemedicine was key to the clinic's early successes.

Well-being Content Inclusion in Pharmacy Education Across the United States and Canada.

Objective. To describe the landscape of well-being content inclusion across schools and colleges of pharmacy in the United States and Canada through identification of content implementation, incorporation, and assessment.Methods. A cross-sectional survey was distributed to all accredited schools and colleges of pharmacy in the United States (n=143) and Canada (n=10). Survey questions included curricular and cocurricular timing, frequency, assessment strategies, and support for well-being initiatives, using a framework of eight dimensions (pillars) of wellness to categorize content.Results. Descriptive data analyses were applied to 99 completed surveys (65%), 89 (62%) in the United States and 10 (100%) in Canada. Well-being content was most prevalent within the cocurricular realm and incorporated into didactic and elective more than experiential curricula. The most content came from intellectual, emotional, and physical pillars, and the least content came from financial, spiritual, and environmental pillars. Less than 50% of schools and colleges of pharmacy include well-being within their strategic plans or core values. Funding is primarily at the level of the university (59%) or the school or college of pharmacy (59%). Almost half of respondents reported inclusion of some assessment, with a need for more training, expertise, and standardization.Conclusion. Survey results revealed a wide range of implementation and assessment of well-being programs across the United States and Canada. These results provide a reference point for the state of well-being programs that can serve as a call to action and research across the Academy.

Pharmacogenetic Review: Germline Genetic Variants Possessing Increased Cancer Risk With Clinically Actionable Therapeutic Relationships.

As our understanding of genomics and genetic testing continues to advance, the personalization of medical decision making is progressing simultaneously. By carefully crafting medical care to fit the specific needs of the individual, patients can experience better long-term outcomes, reduced toxicities, and improved healthcare experiences. Genetic tests are frequently ordered to help diagnose a clinical presentation and even to guide surveillance. Through persistent investigation, studies have begun to delineate further therapeutic implications based upon unique relationships with genetic variants. In this review, a pre-emptive approach is taken to understand the existing evidence of relationships between specific genetic variants and available therapies. The review revealed an array of diverse relationships, ranging from well-documented clinical approaches to investigative findings with potential for future application. Therapeutic agents identified in the study ranged from highly specific targeted therapies to agents possessing similar risk factors as a genetic variant. Working in conjunction with national standardized treatment approaches, it is critical that physicians appropriately consider these relationships when developing personalized treatment plans for their patients.

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice.

Background: Medication reconciliation is recognized as a critically important medication safety element and a key initiative by multiple organizations. Within our precision medicine program, accurate medication lists are essential to our ability to make specific medication recommendations based on pharmacogenetic results. Our study aimed to identify discrepancies within the patient's medication list to improve medication management via genetic factors through a pharmacy team-based approach. Methods: A dedicated team of pharmacists and trained student pharmacists conducted telephone interviews to complete medication reconciliation for individuals enrolled in our precision medicine preemptive screening program. Medication list discrepancies were tracked as well as if pharmacogenetic consults were altered by findings during the telephone interviews. Results: Medication reconciliation was completed on 465 participants who had recently received or were awaiting pharmacogenetic testing. We found similar results to previously described rates of medication list discrepancies with an average of 4.9 medication discrepancies per patient as well as greater than 90% of individuals having at least one medication discrepancy. Pharmacogenetic recommendations for 20 individuals (4.3%) required adjustment following medication reconciliation. Conclusions: This pilot program supports the value of a dedicated team for medication reconciliation and the importance of accurate medication lists to optimize precision medicine programs.

Implementation and evaluation of a student scholarship program to increase care initiatives in rural pharmacies.

INTRODUCTION: Availability of patient care services in rural areas is often lacking, which can reduce access to care for patients living in these areas. Patient care within community pharmacies is vital to care access in rural areas, but expanding pharmacy services can often be challenging. Pharmacy students, especially those on advanced pharmacy practice experiences, are positioned to make an impact on sites. METHODS: The objective of this study was to describe the implementation, evaluation, and impact of a student scholarship program designed to increase patient care initiatives in rural community pharmacies. Scholarships were provided to students to expand patient care initiatives targeting chronic disease in select rural community pharmacies. Before and after participating in the scholarship program, students completed a survey assessing their perceived ability and confidence to initiate new patient care activities. In addition, patient care services provided by students were tracked and reported cumulatively. RESULTS: During the first year of implementation, 24 student scholarship rotations were completed. Throughout the 24 rotations, 369 patients were screened for prediabetes, 391 were screened for hypertension, and 552 patients were screened for immunizations. Of the 27 items presented in the survey, 20 items showed a mean statistically significant change indicating an increase in student confidence in leading, developing, and performing patient care activities. CONCLUSIONS: A student scholarship program designed to increase patient care initiatives in rural community pharmacies led to new patient care services in rural areas and increased student confidence in leading, developing, and expanding upon patient care activities.