Survey of genetic counselors and clinical geneticists' use and attitudes toward pharmacogenetic testing

Pharmacogenetic (PGx) testing aims to improve therapeutic outcomes through tailoring treatment based on a patient’s genetic risk for non-response and/or an adverse event. Given their expertise, geneticists could facilitate the use of PGx testing; however, , the preparedness and perceived role of the clinical genetics community is unclear. To assess the attitudes, preparedness, and perceived roles of geneticists in the delivery of PGx testing, we conducted a survey of 1500 randomly selected board-certified genetic counselors and clinical geneticists in the U.S (response rate: 37.8% (n=516)). Twelve percent of genetic counselors and 41% of clinical geneticists indicated that they had ordered or coordinated patient care for PGx testing, a seemingly high proportion at this early stage of adoption. Almost all respondents had some education on pharmacogenetics, though only 28% of counselors and 58% of clinical geneticists indicated they felt well-informed about PGx testing. About half of counselors (52%) and clinical geneticists (46%) felt they would play ‘some’ role in the delivery of PGx testing; 17% and 19%, respectively, felt that they would play ‘no’ or ‘a little’ role. At this early stage of PGx testing, the role of geneticists and genetic counselors is unclear. However, their experience may aid in readying PGx testing and informing delivery strategies into clinical practice

Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource

Supplemental Data Supplemental Data include 65 figures and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2017.04.015. Supplemental Data Document S1. Figures S1–S65 Download Document S2. Article plus Supplemental Data Download Web Resources ClinGen, https://www.clinicalgenome.org/ ClinGen Gene Curation, https://www.clinicalgenome.org/working-groups/gene-curation/ ClinGen Gene Curation SOP, https://www.clinicalgenome.org/working-groups/gene-curation/projects-initiatives/gene-disease-clinical-validity-sop/ ClinGen Knowledge Base, https://search.clinicalgenome.org/kb/agents/sign_up OMIM, http://www.omim.org/ Orphanet, http://www.orpha.net/consor/cgi-bin/index.php With advances in genomic sequencing technology, the number of reported gene-disease relationships has rapidly expanded. However, the evidence supporting these claims varies widely, confounding accurate evaluation of genomic variation in a clinical setting. Despite the critical need to differentiate clinically valid relationships from less well-substantiated relationships, standard guidelines for such evaluation do not currently exist. The NIH-funded Clinical Genome Resource (ClinGen) has developed a framework to define and evaluate the clinical validity of gene-disease pairs across a variety of Mendelian disorders. In this manuscript we describe a proposed framework to evaluate relevant genetic and experimental evidence supporting or contradicting a gene-disease relationship and the subsequent validation of this framework using a set of representative gene-disease pairs. The framework provides a semiquantitative measurement for the strength of evidence of a gene-disease relationship that correlates to a qualitative classification: “Definitive,” “Strong,” “Moderate,” “Limited,” “No Reported Evidence,” or “Conflicting Evidence.” Within the ClinGen structure, classifications derived with this framework are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. Detailed guidance for utilizing this framework and access to the curation interface is available on our website. This evidence-based, systematic method to assess the strength of gene-disease relationships will facilitate more knowledgeable utilization of genomic variants in clinical and research settings

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods/Design</p> <p>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 <it>either </it>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), <it>or </it>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.</p> <p>Discussion</p> <p>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.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00849563">NCT00849563</a></p

Clinical evaluation of computerized functional electrical stimulation after spinal cord injury: a multicenter pilot study

This study investigated the safety and effects of computerized functional electrical stimulation (FES) on spinal cord injured individuals. Nineteen subjects two to ten years postinjury, with clinically complete motor and sensory lesions between C4 and T10, participated. All subjects met the specific selection criteria. None had received lower extremity electrical stimulation before. In phase I, subjects received surface electrical stimulation to the quadriceps muscle bilaterally for resistive knee extension 3 times a week for four weeks. The resistance and number of completed lifts was recorded daily. In phase II, 36 sessions provided sequential surface electrical stimulation to the quadriceps, hamstrings, and gluteus muscles bilaterally in order for subjects to pedal a lower extremity ergometer with resistance varied depending on completed run time. For each session, heart rate, blood pressure, temperature, and work performance were recorded. Tests done before and after the training program included fasting blood chemistries, 24-hour urinalysis, arm-crank ergometer stress testing, and midthigh girth measurement. Results indicate that this form of FES is safe, that quadriceps strength and endurance is increased, that endurance for ergometer pedaling is increased, and that there may be a training effect as more work is done at a similar heart rate and systolic blood pressure and as muscle bulk is increased. The FES effect on cardiovascular conditioning and general health requires further research to precisely determine its benefits

A review and definition of ‘usual care’ in genetic counseling trials to standardize use in research

The descriptor 'usual care' refers to standard or routine care. Yet, no formal definition exists. The need to define what constitutes usual care arises in clinical research. Often one arm in a trial represents usual care in comparison with a novel intervention. Accordingly, usual care in genetic counseling research appears predominantly in randomized controlled trials. Recent standards for reporting genetic counseling research call for standardization, but do not address usual care. We (1) inventoried all seven studies in the Clinical Sequencing Evidence-Generating Consortium (CSER) about how genetic counseling was conceptualized, conducted, and whether a usual care arm was involved; (2) conducted a review of published randomized control trials in genetic counseling, comparing how researchers describe usual care groups; and (3) reviewed existing professionally endorsed definitions and practice descriptions of genetic counseling. We found wide variation in the content and delivery of usual care. Descriptions frequently detailed the content of usual care, most often noting assessment of genetic risk factors, collecting family histories, and offering testing. A minority included addressing psychological concerns or the risks versus benefits of testing. Descriptions of how care was delivered were vague except for mode and type of clinician, which varied. This significant variation, beyond differences expected among subspecialties, reduces the validity and generalizability of genetic counseling research. Ideally, research reflects clinical practice so that evidence generated can be used to improve clinical outcomes. To address this objective, we propose a definition of usual care in genetic counseling research that merges common elements from the National Society of Genetic Counselors' practice definition, the Reciprocal Engagement Model, and the Accreditation Council for Genetic Counselors' practice-based competencies. Promoting consistent execution of usual care in the design of genetic counseling trials can lead to more consistency in representing clinical care and facilitate the generation of evidence to improve it