Assessment of the current status of real-world pharmacogenomic testing: informed consent, patient education, and related practices.

Introduction: The practice of informed consent (IC) for pharmacogenomic testing in clinical settings varies, and there is currently no consensus on which elements of IC to provide to patients. This study aims to assess current IC practices for pharmacogenomic testing. Methods: An online survey was developed and sent to health providers at institutions that offer clinical germline pharmacogenomic testing to assess current IC practices. Results: Forty-six completed surveys representing 43 clinical institutions offering pharmacogenomic testing were received. Thirty-two (74%) respondents obtain IC from patients with variability in elements incorporated. Results revealed that twenty-nine (67%) institutions discuss the benefits, description, and purpose of pharmacogenomic testing with patients. Less commonly discussed elements included methodology and accuracy of testing, and laboratory storage of samples. Discussion: IC practices varied widely among survey respondents. Most respondents desire the establishment of consensus IC recommendations from a trusted pharmacogenomics organization to help address these disparities.

The Critical Role of Pharmacists in the Clinical Delivery of Pharmacogenetics in the U.S.

Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice.

Expanding Family Health History to Include Family Medication History.

The collection of family health history (FHH) is an essential component of clinical practice and an important piece of data for patient risk assessment. However, family history data have generally been limited to diseases and have not included medication history. Family history was a key component of early pharmacogenetic research, confirming the role of genes in drug response. With the substantial number of known pharmacogenes, many affecting response to commonly prescribed medications, and the availability of clinical pharmacogenetic (PGx) tests and guidelines for interpretation, the collection of family medication history can inform testing decisions. This paper explores the roots of family-based pharmacogenetic studies to confirm the role of genes in these complex phenotypes and the benefits and challenges of collecting family medication history as part of family health history intake.

Development of Competency-based Online Genomic Medicine Training (COGENT).

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training modules that are broadly available for busy clinicians.

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

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.

A Systematic Review of the Scope of Study of mHealth Interventions for Wellness and Related Challenges in Pediatric and Young Adult Populations.

BACKGROUND: Despite the purported advantages and potential efficacy of mHealth interventions to promote wellness in children, adolescents, and young adults, it is not clear what areas have been explored and the challenges reported in the biomedical literature. METHODS: We conducted a scoping review of publications between 2015 and 2019. RESULTS: We identified 54 papers that met our inclusion criteria. Studies were conducted in 21 countries and ranged in size from six to 9851 participants (median: 184). A total of 41% of studies enrolled adolescents only (n = 19). Of the seven types of mHealth interventions identified, apps were the most common intervention (59%; n = 32) evaluated and 44% of the studies evaluated two or more interventions. The most common topic of the studies reviewed was sexual and reproductive health (24%; n = 13). CONCLUSION: Most pediatric mHealth intervention studies are conducted in adolescents in large part, and sexual and reproductive health is the most commonly studied topic. With the easy and widespread accessibility to smartphone technology, the use of mobile apps for wellness interventions will likely continue to expand to other wellness topics.

Revisiting Secondary Information Related to Pharmacogenetic Testing.

Incidental or secondary findings have been a major part of the discussion of genomic medicine research and clinical applications. For pharmacogenetic (PGx) testing, secondary findings arise due to the pleiotropic effects of pharmacogenes, often related to their endogenous functions. Unlike the guidelines that have been developed for whole exome or genome sequencing applications for management of secondary findings (though slightly different from PGx testing in that these refer to detection of variants in multiple genes, some with clinical significance and actionability), no corresponding guidelines have been developed for PGx clinical laboratories. Nonetheless, patient and provider education will remain key components of any PGx testing program to minimize adverse responses related to secondary findings.

Evaluating Primary Care Providers' Readiness for Delivering Genetic and Genomic Services to Underserved Populations.

INTRODUCTION: Increased genomics knowledge and access are advancing precision medicine and care delivery. With the translation of precision medicine across health care, genetics and genomics will play a greater role in primary care services. Health disparities and inadequate representation of racial and ethnically diverse groups threaten equitable access for those historically underserved. Health provider awareness, knowledge, and perceived importance are important determinants of the utilization of genomic applications. METHODS: We evaluated the readiness of primary care providers at a Federally Qualified Health Center, the Community Health Center, Inc. (CHCI) for delivering genetic and genomic testing to underserved populations. Online survey questions focused on providers' education and training in basic and clinical genetics, familiarity with current genetic tests, and needs for incorporating genetics and genomics into their current practice. RESULTS: Fifty of 77 (65%) primary care providers responded to the survey. Less than half received any training in basic or clinical genetics (40%), were familiar with specific genetic tests (36%), or felt confident with collecting family health history (44%), and 70% believed patients would benefit from genetic testing. CONCLUSION: Despite knowledge gaps, respondents recognized the value and need to bring these services to their patients, though would like more education on applying genetics and genomics into their practice, and more training about discussing risk factors associated with race or ethnicity. We provide further evidence of the need for educational resources and standardized guidelines for providers caring for underserved populations to optimize appropriate use and referral of genetic and genomic services and to reduce disparities in care.

Delivery of Pharmacogenetic Testing with or without Medication Therapy Management in a Community Pharmacy Setting.

OBJECTIVE: The delivery of pharmacogenetic (PGx) testing has primarily been through clinical and hospital settings. We conducted a study to explore the feasibility of delivering PGx testing through community pharmacies, a less-studied setting. METHODS: We conducted a cluster randomized trial of community pharmacies in North Carolina through two approaches: the provision of PGx testing alone or PGx testing with medication therapy management (MTM). RESULTS: A total of 150 patient participants were enrolled at 17 pharmacies and reported high satisfaction with their testing experience. Participants in the PGx plus MTM arm were more likely to recall a higher number of results (p=0.04) and more likely to clearly understand their choices for prevention or early detection of side effects (p=0.01). A medication or dose change based on the PGx results was made for 8.7% of participants. CONCLUSION: Limited differences were observed in the provision of PGx testing as a standalone test or combined with MTM. A limited number of treatment changes were made based on PGx test results. Patient acceptance of PGx testing offered through the community pharmacy was very high, but the addition of MTM did not impact patient-reported perceptions about PGx testing or medication adherence.

Independent Community Pharmacists' Experience in Offering Pharmacogenetic Testing.

OBJECTIVE: 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.

The Potential Benefit of Expedited Development and Approval Programs in Precision Medicine.

BACKGROUND: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued growth of precision medicine drugs and devices. To facilitate the development and approval process of drugs for serious unmet needs, four expedited approval programs have been developed in the US: priority review, accelerated approval, fast track, and breakthrough therapy programs. METHODS: To determine if expedited approval programs are fulfilling the intended goals, we reviewed drug approvals by the US Food and Drug Administration (FDA) between 2011 and 2017 for new molecular entities (NMEs). RESULTS: From 2011 through 2017, the FDA approved 250 NMEs, ranging from 27 approvals in 2013 to 46 in 2017. The NME approvals spanned 22 different disease classes; almost one-third of all NMEs were for oncology treatments. CONCLUSIONS: As these pathways are utilized more, additional legislative changes may be needed to re-align incentives to promote continued development of innovative drugs for serious unmet needs in a safe, efficacious, and affordable manner.

Individualizing pharmacogenomic test results in the context of the microbiome.

The field of pharmacogenetic testing was hailed as one of the early successful clinical applications arising from the personalized (or precision) medicine revolution. Substantial progress has been made to identify genes and genetic variants involved in drug response and establish clinical implementation programs. Yet, drug response is a complex trait and recent work has highlighted the key role played by the gut microbiome. As the study of the gut microbiome and pharmacogenetics converge, it may be possible to generate more precise predictions of drug response and improve health outcomes to treatments. Substantial effort will be needed to understand the dynamic impact of the microbiome and the interplay with host genetics and how to implement expanded pharmacogenetic testing.

Toward digital-based interventions for medication adherence and safety.

INTRODUCTION: Adherence to the prescribed use of medications is a major problem for many patients. Whether intentional or unintentional, the failure to take medications as prescribed results in an array of health problems, hospitalizations, and increased health expenditures. AREAS COVERED: The paper reviews the different types of interventions to promote the appropriate use of medications from provider-based to digital-based interventions. These interventions often combine passive and interactive approaches and may include bio-surveillance/monitoring. Many studies have evaluated these interventions in a variety of conditions and patient population, demonstrating mixed outcomes. EXPERT OPINION: The complexity of the underlying causes of poor medication adherence may warrant personalized interventions that combine passive/interactive and personal/digital options. Enriching patient trials may enable observation of larger effect sizes.

The enduring importance of family health history in the era of genomic medicine and risk assessment.

Improving disease risk prediction and tailoring preventive interventions to patient risk factors is one of the primary goals of precision medicine. Family health history is the traditional approach to quickly gather genetic and environmental data relevant to the patient. While the utility of family health history is well-documented, its utilization is variable, in part due to lack of patient and provider knowledge and incomplete or inaccurate data. With the advances and reduced costs of sequencing technologies, comprehensive sequencing tests can be performed as a risk assessment tool. We provide an overview of each of these risk assessment approaches, the benefits and limitations and implementation challenges.

Promoting Wellness Through Mobile Health Technology in a College Student Population: Protocol Development and Pilot Study.

BACKGROUND: The health and well-being of college students has garnered widespread attention and concern in recent years. At the same time, the expansion and evaluation of digital technologies has grown in recent years for different target populations. OBJECTIVE: This protocol aims to describe a pilot feasibility study on wearables to assess student interest and to gather baseline data from college freshmen, for the academic year 2019 to 2020. METHODS: All full-time college freshmen residing in a single residence hall were eligible to participate. Study invitations were sent by post and email 5 weeks prior to move-in. Web-based enrollment and in-person attendance at study orientation sessions were mandatory. We provided the incoming freshmen with a wearable and study app. Wearable data and weekly survey data will be collected through the study app and analyzed. We have collected demographic, enrollment, and attrition data and the number and type of support requests from students. RESULTS: The planning phase of the WearDuke initiative was completed in 2018 to 2019, and the pilot study was launched in July 2019. Of the 175 students invited, 120 enrolled and 114 started the study; 107 students remained active participants till the end of the fall semester. For Apple Watch participants (the majority of study population), weekly survey completion rates ranged from 70% (74/106) to 96% (95/99). CONCLUSIONS: Halfway through the pilot, we noticed that the initiative has been received positively by the students with minimal attrition. The short- and long-term benefits may be substantial for students, the campus, the utilization of health services, and long-term health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16474.

Clinical Utilization of Pharmacogenetics in Psychiatry - Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry.

INTRODUCTION: The use of pharmacogenomic (PGx) testing to guide decisions and improve patient outcomes has increased in recent years. PGx testing represents a decision support tool that may inform dosing, increase the likelihood of treatment response, and identify patients at risk for medication side effects. METHODS: This is a narrative review of utilization of PGx testing in psychiatry from stakeholders including, pharmacists, genetic counselors, implementation scientists, industry, and clinicians. RESULTS: While many limitations exist to streamline use of PGx testing in psychiatry, various stakeholders are crucial to clinical implementation. DISCUSSION: PGx testing can assist in medication selection and improve patient outcomes; however, more data are needed to understand when and how to incorporate PGx testing into psychiatric practice.

Pharmacogenomic Testing In Pediatrics: Navigating The Ethical, Social, And Legal Challenges.

For the past several years, the implementation of pharmacogenetic (PGx) testing has become widespread in several centers and clinical practice settings. PGx testing may be ordered at the point-of-care when treatment is needed or in advance of treatment for future use. The potential benefits of PGx testing are not limited to adult patients, as children are increasingly using medications more often and at earlier ages. This review provides some background on the use of PGx testing in children as well as mothers (prenatally and post-natally) and discusses the challenges, benefits, and the ethical, legal, and social implications of providing PGx testing to children.

A stepwise approach to implementing pharmacogenetic testing in the primary care setting.

Pharmacogenetic testing can help identify primary care patients at increased risk for medication toxicity, poor response or treatment failure and inform drug therapy. While testing availability is increasing, providers are unprepared to routinely use pharmacogenetic testing for clinical decision-making. Practice-based resources are needed to overcome implementation barriers for pharmacogenetic testing in primary care.The NHGRI's IGNITE I Network (Implementing GeNomics In pracTicE; www.ignite-genomics.org) explored practice models, challenges and implementation barriers for clinical pharmacogenomics. Based on these experiences, we present a stepwise approach pharmacogenetic testing in primary care: patient identification; pharmacogenetic test ordering; interpretation and application of test results, and patient education. We present clinical factors to consider, test-ordering processes and resources, and provide guidance to apply test results and counsel patients. Practice-based resources such as this stepwise approach to clinical decision-making are important resources to equip primary care providers to use pharmacogenetic testing.

Awareness of family health history in a predominantly young adult population.

Family health history (FHH) is a key predictor of health risk and is universally important in preventive care. However, patients may not be aware of the importance of FHH, and thus, may fail to accurately or completely share FHH with health providers, thereby limiting its utility. In this study, we conducted an online survey of 294 young adults and employees based at a US university setting regarding their knowledge, sharing behaviors, and perceived importance of FHH, and use of electronic clinical tools to document and update FHH. We also evaluated two educational interventions (written and video) to promote knowledge about FHH and its importance to health. We found that 93% of respondents were highly aware of their FHH, though only 39% reported collecting it and 4% using an online FHH tool. Seventy-three percent of respondents, particularly women, had shared FHH with their doctor when prompted, and fewer had shared it with family members. Participants in the video group were significantly more likely to understand the benefits of FHH than those in the written group (p = 0.02). In summary, educational resources, either video or written, will be helpful to promote FHH collection, sharing, and use of online FHH tools.