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.

Clinical and Counseling Experiences of Early Adopters of Whole Exome Sequencing.

Currently, there are limited data regarding the practice of genetic counseling for whole exome sequencing (WES). Improved understanding of how genetic counselors and other providers are educating, counseling, and communicating results may identify practice trends, and patient or provider needs. Between April 2013 and December 2014, we surveyed providers who ordered WES testing from GeneDx, a CLIA-certified laboratory. Forty-nine respondents completed the survey; 41 % of participants reported board certification in genetic counseling. Pre-test and post-test counseling was completed in all but one case each. Pre-test counseling lasted less than 1 h for 53 % of cases and 1 to 2 h for 43 %. Topics discussed with all patients included consent for testing, and incidental findings; other topics were variable. In contrast to pre-test counseling, 59 % reported post-test counseling lasting 1 to 2 h and 33 % less than an hour; post-testing counseling was significantly longer in cases with a definitive diagnosis than those without (p = 0.0129). The survey findings indicate some variability regarding the amount of time spent on counseling and the topics discussed during pre-test counseling. Additional exploration, patient and provider educational resources, and potentially more specific guidelines regarding counseling for WES may be warranted.

Information-seeking and sharing behavior following genomic testing for diabetes risk.

As the practice of medicine has become more patient-driven, patients are increasingly seeking health information within and outside of their doctor's office. Patients looking for information and support are often turning to the Internet as well as family and friends. As part of a study to understand the impact of delivery method of genomic testing for type 2 diabetes risk on comprehension and health-related behaviors, we assessed participants' information-seeking and sharing behaviors after receiving their results in-person with a genetic counselor or online through the testing company's website. We found that 32.6 % of participants sought information after receiving the genomic test results for T2DM; 80.8 % of those that did seek information turned to the Internet. Eighty-eight percent of participants reported that they shared their T2DM risk results, primarily with their spouse/partner (65 %) and other family members (57 %) and children (19 %); 14 % reported sharing results with their health provider. Sharing was significantly increased in those who received results in-person from the genetic counselor (p = 0.0001). Understanding patients' interests and needs for additional information after genomic testing and with whom they share details of their health is important as more information and clinical services are available and accessed outside the clinician's office. Genetic counselors' expertise and experience in creating educational materials and promoting sharing of genetic information can facilitate patient engagement and education.

Patient beliefs and behaviors about genomic risk for type 2 diabetes: implications for prevention.

Type 2 diabetes is a major health burden in the United States, and population trends suggest this burden will increase. High interest in, and increased availability of, testing for genetic risk of type 2 diabetes presents a new opportunity for reducing type 2 diabetes risk for many patients; however, to date, there is little evidence that genetic testing positively affects type 2 diabetes prevention. Genetic information may not fit patients' illness representations, which may reduce the chances of risk-reducing behavior changes. The present study aimed to examine illness representations in a clinical sample who are at risk for type 2 diabetes and interested in genetic testing. The authors used the Common Sense Model to analyze survey responses of 409 patients with type 2 diabetes risk factors. Patients were interested in genetic testing for type 2 diabetes risk and believed in its importance. Most patients believed that genetic factors are important to developing type 2 diabetes (67%), that diet and exercise are effective in preventing type 2 diabetes (95%), and that lifestyle changes are more effective than drugs (86%). Belief in genetic causality was not related to poorer self-reported health behaviors. These results suggest that patients' interest in genetic testing for type 2 diabetes might produce a teachable moment that clinicians can use to counsel behavior change.

Community pharmacists' experience with pharmacogenetic testing.

OBJECTIVE: Appendix 1 Statements of knowledge of correct medication use Appendix 2 Statements of self-efficacy of correct medication use Appendix 3 Statements of skills of correct medication use To characterize the experiences and feasibility of offering pharmacogenetic (PGx) testing in a community pharmacy setting. DESIGN: Pharmacists were invited to complete a survey about PGx testing for each patient who was offered testing. If the patient consented, pharmacists were also asked to complete a follow-up survey about the process of returning PGx testing results to patients and follow-up with the prescribing provider. SETTING: Community pharmacies in North Carolina from August through November 2014. PARTICIPANTS: Pharmacists at five community pharmacies. MAIN OUTCOME MEASURES: Patient consent for testing, time to introduce PGx testing initially and communicate results, interpretation of test results, and recommended medication changes. RESULTS: Of the 69 patients offered testing, 56 (81%) consented. Pre-test counseling typically lasted 1-5 minutes (81%), and most patients (55%) did not have any questions about the testing. Most pharmacists reported test results to patients by phone (84%), with discussions taking less than 1 minute (48%) or 1-5 minutes (52%). Most pharmacists believed the patients understood their results either very well (54%) or somewhat well (41%). Pharmacists correctly interpreted 47 of the 53 test results (89%). All of the incorrect interpretations were for patients with test results indicating a dosing or drug change (6/19; 32%). Pharmacists reported contacting the ordering physician for four patients to discuss results indicating a dosage or drug change. CONCLUSION: The provision of PGx services in a community pharmacy setting appears feasible, requiring little additional time from the pharmacist, and many patients seem interested in PGx testing. Additional training may be necessary to improve test result interpretation, as well as for communication with both patients and ordering physicians.

Comparison of delivery strategies for pharmacogenetic testing services.

The number and use of pharmacogenetic tests to assess a patient's likelihood of response or risk of an adverse event is expanding across medical specialties and becoming more prevalent. During this period of development and translation, different approaches are being investigated to optimize delivery of pharmacogenetic services. In this paper, we review pre-emptive and point-of-care delivery approaches currently implemented or being investigated and discuss the advantages and disadvantages of each approach. The continued growth in knowledge about the genetic basis of drug response combined with development of new and less expensive testing technologies and electronic medical records will impact future delivery systems. Regardless of delivery approach, the currently limited knowledge of health professionals about genetics generally or PGx specifically will remain a major obstacle to utilization.

Genomic counseling: next generation counseling.

Personalized medicine continues to expand with the development and increasing use of genome-based testing. While these advances present new opportunities for diagnosis and risk assessment, they also present challenges to clinical delivery. Genetic counselors will play an important role in ushering in this new era of testing; however, it will warrant a shift from traditional genetic counseling to "genomic counseling." This shift will be marked by a move from reactive genetic testing for diagnosis of primarily single-gene diseases to proactive genome-based testing for multiple complex diseases for the purpose of disease prevention. It will also require discussion of risk information for a number of diseases, some of which may have low relative risks or weak associations, and thus, may not substantially impact clinical care. Additionally, genomic counselors will expand their roles, particularly in the area of health promotion to reduce disease risk. This additional role will require a style of counseling that is more directive than traditional counseling and require greater knowledge about risk reducing behaviors and disease screening.

Public trust in genomic risk assessment for type 2 diabetes mellitus.

Patient trust in personal medical information is critical to increasing adherence to physician recommendations and medications. One of the anticipated benefits of learning of one's genomic risk for common diseases is the increased adoption of screening, preventive care and lifestyle changes. However, the equivocal results thus far reported of the positive impact of knowledge of genomic risk on behavior change may be due to lack of patients' trust in the results. As part of a clinical study to compare two methods of communication of genomic risk results for Type 2 diabetes mellitus (T2DM), we assessed patients' trust and preferred methods of delivery of genomic risk information. A total of 300 participants recruited from the general public in Durham, NC were randomized to receive their genomic risk for T2DM in-person from a genetic counselor or online through the testing company's web-site. Participants completed a baseline survey and three follow-up surveys after receiving results. Overall, participants reported high levels of trust in the test results. Participants who received their results in-person from the genetic counselor were significantly more likely to trust their results than those who reviewed their results on-line (p = 0.005). There was not a statistically significant difference in levels of trust among participants with increased genetic risk, as compared to other those with decreased or same as population risk (p = 0.1154). In the event they undergo genomic risk testing again, 55 % of participants overall indicated they would prefer to receive their results online compared to 28 % that would prefer to receive future results in-person. Of those participants preferring to receive results online, 77 % indicated they would prefer to have the option to speak to someone if they had questions with the online results (compared to accessing results online without the option of professional consultation). This is the first study to assess satisfaction with genomic risk testing by the method of delivery of the test result. The higher rate of trust in results delivered in-person suggests that online access reports may not result in serious consideration of results and lack of adoption of recommended preventive recommendations.

Characterization of Research Support of Genome Editing Technologies and Transition to Clinical Trials.

Genome editing technologies have become widely used research tools. To assess the rate of growth with respect to federal funding of gene editing projects, we analyzed publicly available data retrieved from the NIH RePORTER and Clinicaltrials.gov databases. We identified 6,111 awards between 1977 and 2023, the majority being extramural, investigator-driven R (noneducational) awards (66.7%). There was an average growth rate of 40% between 2008 and 2022, and the biggest increase in awards was observed between 2017 and 2018 (doubling from 140 to 280). Five administering institutes/centers accounted for more than 60% of awards with the highest number of awards from the National Cancer Institute (20.0%). The majority of clinical trials involving some type of genome editing (75%) started in or after 2020. This analysis illuminates the rapid and widespread growth of gene editing research across disciplines and the eventual launch of clinical trials using gene editing tools.

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.

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.

Managing incidental genomic findings: legal obligations of clinicians.

PURPOSE: Clinical whole-exome and whole-genome sequencing will result in a broad range of incidental findings, but clinicians' obligations to identify and disclose such findings are a matter of debate. We sought legal cases that could offer insights into clinicians' legal liability. METHODS: We searched for cases in which incidental findings were related to the cause of action, using the search engines WestLaw, WestLaw Next, Lexis, and Lexis Advance. RESULTS: We found no case law related to incidental findings from genetic testing but identified eight cases involving incidental findings in medical imaging. These cases suggest that clinicians may face liability for failing to disclose incidental findings that would have offered an opportunity for interventions to improve health outcome, if under the applicable standard of care, they fail to identify or appreciate the significance of the incidental finding or they negligently fail to notify other clinicians and/or the patient of the identified incidental finding. Other cases support liability for failure to refer appropriately to a clinician with greater expertise. CONCLUSIONS: Clinicians may face liability if they fail to disclose incidental information that could inform interventions to improve health outcome; information lacking clinical actionability is likely to have less import.

Promoting public awareness and engagement in genome sciences.

Public understanding of genetic concepts and associated ethical and policy issues can enable informed deliberation and decision-making. Effective strategies for increasing public understanding involve providing forums incorporating the unique perspectives and attitudes of the public, while allowing opportunities to learn first-hand from scientists about genome research and related applications. Through a partnership between the Duke Institute for Genome Sciences & Policy (IGSP) and the Museum of Life and Science in Durham, NC, we developed and piloted a program aimed to bridge the concepts of formal (public school) and informal (community-based science museum) science learning with the experiential context of family and participatory learning. Called Genome Diner, we piloted the program with 40 genetic/genomic researchers, 76 middle school students and their parents (n = 83) from Durham, NC. Program impact was assessed via pre/post surveys for each participant group. Following participation, parents were significantly more likely to correctly interpret the implications of a genome research finding, and both students and parents indicated higher interest in research as well as higher confidence in accessing and understanding genome research. Genetic literacy of parents and students was not affected by participation in the program, likely due to the relatively high knowledge scores pre-Diner: 88.3 % and 78.5 %, respectively. The interactive format of Genome Diner provided an opportunity for students and parents to explore and discuss interests and issues about genomic research alongside genome scientists, positively influencing attitudes toward genetic research and researchers themselves. These interactions are critical for maintaining public interest and knowledge about genomic research and applications.

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.

Enhancing geneticists' perspectives of the public through community engagement.

PURPOSE: Given the rapid pace of genetic and genomic research and technology development, public engagement on scientific issues may be mutually beneficial to the research community and the general public. The public may benefit from a greater understanding of concepts and new applications, and researchers can build awareness of public knowledge, perceptions, and potential concerns about genomic research and applications. METHODS: We developed and piloted a public engagement program called Genome Diner to facilitate dialog between genetic/genomic researchers (n = 40) and middle school students (n = 76) and their parents (n = 83) from the local community. Program impact was assessed through pre- and post-Diner surveys for each group. RESULTS: After participation in Genome Diner, researchers' views were positively affected regarding the (adult) public's level of understanding of genetic concepts, beliefs about relevance of research, and the importance of researcher-community interaction. CONCLUSION: Through an interactive discussion with students and parents, researchers gained valuable insight into public perspectives about genome research. The engagement format of the Genome Diner program presents a novel method of fostering trust and relationships between the two groups and to inform both the public and the researchers, whose work may depend on public opinion and participation.

Effect of genetic testing for risk of type 2 diabetes mellitus on health behaviors and outcomes: study rationale, development and design.

BACKGROUND: Type 2 diabetes is a prevalent chronic condition globally that results in extensive morbidity, decreased quality of life, and increased health services utilization. Lifestyle changes can prevent the development of diabetes, but require patient engagement. Genetic risk testing might represent a new tool to increase patients' motivation for lifestyle changes. Here we describe the rationale, development, and design of a randomized controlled trial (RCT) assessing the clinical and personal utility of incorporating type 2 diabetes genetic risk testing into comprehensive diabetes risk assessments performed in a primary care setting. METHODS/DESIGN: Patients are recruited in the laboratory waiting areas of two primary care clinics and enrolled into one of three study arms. Those interested in genetic risk testing are randomized to receive either a standard risk assessment (SRA) for type 2 diabetes incorporating conventional risk factors plus upfront disclosure of the results of genetic risk testing ("SRA+G" arm), or the SRA alone ("SRA" arm). Participants not interested in genetic risk testing will not receive the test, but will receive SRA (forming a third, "no-test" arm). Risk counseling is provided by clinic staff (not study staff external to the clinic). Fasting plasma glucose, insulin levels, body mass index (BMI), and waist circumference are measured at baseline and 12 months, as are patients' self-reported behavioral and emotional responses to diabetes risk information. Primary outcomes are changes in insulin resistance and BMI after 12 months; secondary outcomes include changes in diet patterns, physical activity, waist circumference, and perceived risk of developing diabetes. DISCUSSION: The utility, feasibility, and efficacy of providing patients with genetic risk information for common chronic diseases in primary care remain unknown. The study described here will help to establish whether providing type 2 diabetes genetic risk information in a primary care setting can help improve patients' clinical outcomes, risk perceptions, and/or their engagement in healthy behavior change. In addition, study design features such as the use of existing clinic personnel for risk counseling could inform the future development and implementation of care models for the use of individual genetic risk information in primary care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00849563.

Characterization of clinical study populations by race and ethnicity in biomedical literature.

OBJECTIVE: The importance of race and ethnicity in biomedical research has long been a subject of debate, recently heightened by data revealed by the completion of the sequencing of the human genome and the mapping of human genetic variation. We aimed to determine whether and how the reporting of race has changed over the last three decades and how the practice may differ given study location, where the journal of publication is based, and decade of publication. DESIGN: We analyzed a sample of studies published in the Journal of the American Medical Association, The Lancet, and the Canadian Medical Association Journal from 1980 to 2009. MAIN OUTCOME MEASURES: The number of articles that reported race by journal and decade and the descriptors used. RESULTS: Of 1867 articles analyzed, 17.30% reported race. The reporting of race and number of populations reported increased over time for all three journals. In addition, the diversity of race/ethnicity descriptors increased, with increased use of race/ethnicity combinations and nationality of research subjects. CONCLUSION: Though it has increased over the past few decades, the reporting of race/ethnicity of study populations is relatively low, ambiguous and inconsistent, likely influenced by the uncertain relevance of these variables to the study's outcomes, study location, researcher views, and the policies of journals and funding agencies. Thus, due to the inconsistent and ambiguous practice of reporting race/ethnicity, comparison of study outcomes can result in misleading conclusions. Improvements in standardization of terms and new approaches to characterize research participants related to race/ethnicity are imperative.

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.