Diverse Participant Recruitment for Infant Sequencing in the BabySeq Project.

Purpose: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implemented. We conducted interviews with parents from URG to better understand their perspectives on GS research, develop strategies to reduce barriers to enrollment, and facilitate research participation.

Methods: Semi-structured interviews with 50 parents from URG.

The BabySeq Project: A clinical trial of genome sequencing in a diverse cohort of infants.

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States.

Evaluation of pharmacogenetic automated clinical decision support for clopidogrel.

Clopidogrel requires activation to have antiplatelet effects. Pharmacogenetic testing to identify patients with impaired function can be coupled with clinical decision support (CDS) alerts to guide antiplatelet prescribing. We evaluated the impact of alerts on clopidogrel prescribing.

Primary Care Providers' Experiences With an Active Elective Genetic Testing Program.

Elective genetic testing (EGT) programs that provide pharmacogenomic information to guide medication management and screen for medically actionable disease predispositions are emerging in a number of health systems. Primary care providers (PCPs) are at the forefront of test initiation, patient education, and management of EGT results. However, little research has examined the experiences of PCPs in health systems offering clinical EGT.

Attitudes, knowledge, and risk perceptions of patients who received elective genomic testing as a clinical service.

Purpose: Elective genomic testing (EGT) is increasingly available clinically. Limited real-world evidence exists about attitudes and knowledge of EGT recipients.

Methods: After web-based education, patients who enrolled in an EGT program at a rural nonprofit health care system completed a survey that assessed attitudes, knowledge, and risk perceptions.

Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse.

Design and pilot results from the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study.

Background: As a mega-biobank linked to a national healthcare system, the Million Veteran Program (MVP) can directly improve the health care of participants. To determine the feasibility and outcomes of returning medically actionable genetic results to MVP participants, the program launched the MVP Return of Actionable Results (MVP-ROAR) Study, with familial hypercholesterolemia (FH) as an exemplar actionable condition.

Methods: The MVP-ROAR Study consists of a completed single-arm pilot phase and an ongoing randomized clinical trial (RCT), in which MVP participants are recontacted and invited to receive clinical confirmatory gene sequencing testing and a telegenetic counseling intervention.

Evaluating the utility of multi-gene, multi-disease population-based panel testing accounting for uncertainty in penetrance estimates.

Panel germline testing allows for the efficient detection of deleterious variants for multiple conditions, but the benefits and harms of identifying these variants are not always well understood. We present a multi-gene, multi-disease aggregate utility formula that allows the user to consider adding or removing each gene in a panel based on variant frequency, estimated penetrances, and subjective disutilities for testing positive but not developing the disease and testing negative but developing the disease. We provide credible intervals for utility that reflect uncertainty in penetrance estimates.

Familial communication and cascade testing following elective genomic testing.

Familial communication of results and cascade genetic testing (CGT) can extend the benefits of genetic screening beyond the patient to their at-risk relatives. While an increasing number of health systems are offering genetic screening as an elective clinical service, data are limited about how often results are shared and how often results lead to CGT. From 2018 to 2022, the Sanford Health system offered the Sanford Chip, an elective genomic test that included screening for medically actionable predispositions for disease recommended by the American College of Medical Genetics and Genomics for secondary findings disclosure, to its adult primary care patients.

Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program.

Objective: The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research results.

Materials And Methods: Here we describe the development and utility of an informatics application for participant recruitment and enrollment management for the Veterans Affairs Million Veteran Program Return Of Actionable Results Study, a randomized controlled pilot trial returning individual genetic results associated with familial hypercholesterolemia.

Results: The application is developed in Python-Flask and was placed into production in November 2021.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need).

The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care.

Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRSs in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. The study processes used to test patients, report their PRS results to them and their primary care providers (PCPs), and promote the use of those results in clinical decision-making are modeled on common practices in primary care.

Attitudes about pharmacogenomic testing vary by healthcare specialty.

To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Providers reported comfort ordering PGx testing and its perceived utility on web-based surveys before and after genetics education. Primary quantitative analyses compared primary care providers (PCPs) to specialty providers at both timepoints.

gene-based clinical decision support reduces statin-associated muscle symptoms risk with simvastatin.

variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. The authors conducted a retrospective chart review on 20,341 patients who had genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.

Public perspective on medications to delay Alzheimer's disease symptoms.

Disease-modifying treatments for Alzheimer's disease are emerging. Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD-related genetic testing. Invitations to a web-based survey were posted on social media sites.

Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

Purpose: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain.

Methods: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns.

Parents' decision-making regarding whether to receive adult-onset only genetic findings for their children: Findings from the BabySeq Project.

Purpose: Most professional guidelines recommend against genetic screening for adult-onset only (AO) conditions until adulthood, yet others argue that there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing.

Methods: We conducted interviews with parents (N = 24) who were given the option to receive actionable AO results for their children.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale.

Workforce Considerations When Building a Precision Medicine Program.

This paper describes one healthcare system's approach to strategically deploying genetic specialists and pharmacists to support the implementation of a precision medicine program. In 2013, Sanford Health initiated the development of a healthcare system-wide precision medicine program. Here, we report the necessary staffing including the genetic counselors, genetic counseling assistants, pharmacists, and geneticists.

Progression of precision statin prescribing for reduction of statin-associated muscle symptoms.

Statins are among the most commonly prescribed medications, and improve patient outcomes by lowering cholesterol levels, but also have side effects. Variations in statin response can be attributed to a handful of factors that include pharmacogenetics. While not a true review article, this work was written using various search engines and terms and previous and newly published Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statins to provide a historical perspective in addition to the current status of statin-related pharmacogenetics and future perspectives.

Parental Attitudes Toward Standard Newborn Screening and Newborn Genomic Sequencing: Findings From the BabySeq Study.

With increasing utility and decreasing cost of genomic sequencing, augmentation of standard newborn screening (NBS) programs with newborn genomic sequencing (nGS) has been proposed. Before nGS can be integrated into newborn screening, parents' perspectives must be better understood. Using data from surveys administered to parents of healthy newborns who were enrolled in the BabySeq Project, a randomized clinical trial of nGS alongside NBS, this paper reports parents' attitudes regarding population-based NBS and nGS assessed 3 months after results disclosure.