Establishing the Medical Actionability of Genomic Variants.

Actionability is an important concept in medicine that does not have a well-accepted standard definition, nor is there a general consensus on how to establish it. Medical actionability is often conflated with clinical utility, a related but distinct concept. This lack of clarity contributes to practice variation and inconsistent coverage decisions in genomic medicine, leading to the potential for systematic bias in the use of evidence-based interventions. We clarify how medical actionability and clinical utility are distinct and then discuss the spectrum of actionability, including benefits for the person, the family, and society. We also describe applications across the life course, including prediction, diagnosis, and treatment. Current challenges in assessing the medical actionability of identified genomic variants include gaps in the evidence, limited contexts with practice guidelines, and subjective aspects of medical actionability. A standardized and authoritative assessment of medical actionability is critical to implementing genomic medicine in a fashion that improves population health outcomes and reduces health disparities.

Positive impact of genetic counseling assistants on genetic counseling efficiency, patient volume, and cost in a cancer genetics clinic.

PURPOSE: Cancer genetics clinics have seen increasing demand, challenging genetic counselors (GCs) to increase efficiency and prompting some clinics to implement genetic counseling assistants (GCAs). To evaluate the impact of GCAs on Geisinger's cancer genetics clinic, we tracked GC time utilization, new patient volume, and clinic cost per patient before and after implementing a GCA program. METHODS: GCs used time-tracking software while completing preappointment activities. Electronic health records were reviewed for appointment length and number of patients per week. Internal salary data for GCs and GCAs were used to calculate clinic costs per patient. RESULTS: Time spent by GCs completing each preappointment activity (21.8 vs. 15.1 minutes) and appointment length (51.6 vs. 44.5 minutes) significantly decreased after GCA program implementation (p values < 0.001). New patients per week per GC significantly increased (7.9 vs. 11.4, p < 0.001). Weekly clinic cost per patient significantly decreased ($233 vs. $176, p = 0.03). CONCLUSION: Implementing a GCA program increased GC efficiency in preappointment activities and clinic appointments, increased patient volume, and decreased clinic cost per patient. Such a program can improve access to GC services and assist GCs in focusing on the direct patient care for which they are specially trained.

Effect of Sociodemographic Factors on Uptake of a Patient-Facing Information Technology Family Health History Risk Assessment Platform.

OBJECTIVE: Investigate sociodemographic differences in the use of a patient-facing family health history (FHH)-based risk assessment platform. METHODS: In this large multisite trial with a diverse patient population, we evaluated the relationship between sociodemographic factors and FHH health risk assessment uptake using an information technology (IT) platform. The entire study was administered online, including consent, baseline survey, and risk assessment completion. We used multivariate logistic regression to model effect of sociodemographic factors on study progression. Quality of FHH data entered as defined as relatives: (1) with age of onset reported on relevant conditions; (2) if deceased, with cause of death and (3) age of death reported; and (4) percentage of relatives with medical history marked as unknown was analyzed using grouped logistic fixed effect regression. RESULTS: A total of 2,514 participants consented with a mean age of 57 and 10.4% minority. Multivariate modeling showed that progression through study stages was more likely for younger (p-value = 0.005), more educated (p-value = 0.004), non-Asian (p-value = 0.009), and female (p-value = 0.005) participants. Those with lower health literacy or information-seeking confidence were also less likely to complete the study. Most significant drop-out occurred during the risk assessment completion phase. Overall, quality of FHH data entered was high with condition's age of onset reported 87.85%, relative's cause of death 85.55% and age of death 93.76%, and relative's medical history marked as unknown 19.75% of the time. CONCLUSION: A demographically diverse population was able to complete an IT-based risk assessment but there were differences in attrition by sociodemographic factors. More attention should be given to ensure end-user functionality of health IT and leverage electronic medical records to lessen patient burden.

Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework.

PURPOSE: This paper describes the implementation outcomes associated with integrating a family health history-based risk assessment and clinical decision support platform within primary care clinics at four diverse healthcare systems. METHODS: A type III hybrid implementation-effectiveness trial. Uptake and implementation processes were evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. RESULTS: One hundred (58%) primary care providers and 2514 (7.8%) adult patients enrolled. Enrolled patients were 69% female, 22% minority, and 32% Medicare/Medicaid. Compared with their respective clinic's population, patient-participants were more likely to be female (69 vs. 59%), older (mean age 57 vs. 49), and Caucasian (88 vs. 69%) (all p values <0.001). Female (81.3% of females vs. 78.5% of males, p value = 0.018) and Caucasian (Caucasians 90.4% vs. minority 84.1%, p value = 0.02) patient-participants were more likely to complete the study once enrolled. Patient-participant survey responses indicated MeTree was easy to use (95%), and patient-participants would recommend it to family/friends (91%). Minorities and those with less education reported greatest benefit. Enrolled providers reflected demographics of underlying provider population. CONCLUSION: Family health history-based risk assessment can be effectively implemented in diverse primary care settings and can effectively engage patients and providers. Future research should focus on finding better ways to engage young adults, males, and minorities in preventive healthcare.

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer.

PURPOSE: The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies. METHODS: A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed. RESULTS: No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs. CONCLUSION: MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.

Clinical utility of a Web-enabled risk-assessment and clinical decision support program.

PURPOSE: Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. METHODS: A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). PARTICIPANTS: consentable nonadopted adults with upcoming appointments. PRIMARY OUTCOME: agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. MEASURES: chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. RESULTS: Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. CONCLUSION: MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.

Randomized trial of DVD, telephone, and usual care for increasing mammography adherence.

The purpose of this study was to test an intervention to increase mammography screening in women 51-75 years of age who had not received a mammogram in the last 15 months. A total of 1681 women were randomized to (1) a mailed tailored interactive DVD, (2) a computer-tailored telephone counseling, or (3) usual care. Women with income below US$75,000 who were in the interactive DVD group had significantly more mammograms than women in usual care. Women with income above US$75,000 had significantly fewer mammograms than women with income less than US$75,000 regardless of group. Further investigation is needed to understand why women with income above US$75,000 did not show the same benefit of the intervention.

Randomized Trial of Telegenetics vs. In-Person Cancer Genetic Counseling: Cost, Patient Satisfaction and Attendance.

Telegenetics-genetic counseling via live videoconferencing-can improve access to cancer genetic counseling (CGC) in underserved areas, but studies on cancer telegenetics have not applied randomized methodology or assessed cost. We report cost, patient satisfaction and CGC attendance from a randomized trial comparing telegenetics with in-person CGC among individuals referred to CGC in four rural oncology clinics. Participants (n = 162) were randomized to receive CGC at their local oncology clinic in-person or via telegenetics. Cost analyses included telegenetics system; mileage; and personnel costs for genetic counselor, IT specialist, and clinic personnel. CGC attendance was tracked via study database. Patient satisfaction was assessed 1 week post-CGC via telephone survey using validated scales. Total costs were $106 per telegenetics patient and $244 per in-person patient. Patient satisfaction did not differ by group on either satisfaction scale. In-person patients were significantly more likely to attend CGC than telegenetics patients (89 vs. 79 %, p = 0.03), with bivariate analyses showing an association between lesser computer comfort and lower attendance rate (Chi-square = 5.49, p = 0.02). Our randomized trial of telegenetics vs. in-person counseling found that telegenetics cost less than in-person counseling, with high satisfaction among those who attended. This study provides support for future randomized trials comparing multiple service delivery models on longer-term psychosocial and behavioral outcomes.

Implementing family health history risk stratification in primary care: impact of guideline criteria on populations and resource demand.

UNLABELLED: The Genomic Medicine Model aims to facilitate patient engagement, patient/provider education of genomics/personalized medicine, and uptake of risk-stratified evidence-based prevention guidelines using MeTree, a patient-facing family health history (FHH) collection and clinical decision support (CDS) program. Here we report the number of increased risk (above population-level risk) patients identified for breast/ovarian cancer, colon cancer, hereditary syndrome risk, and thrombosis; the prevalence of FHH elements triggering increased-risk status; and the resources needed to manage their risk. STUDY DESIGN: hybrid implementation-effectiveness study of adults with upcoming well-visits in 2 primary care practices in Greensboro, NC. PARTICIPANTS: 1,184, mean age = 58.8, female = 58% (N = 694), non-white = 20% (N = 215). Increased Risk: 44% (N = 523). RECOMMENDATIONS: genetic counseling = 26% (N = 308), breast MRI = 0.8% (N = 10), breast chemoprophylaxis = 5% (N = 58), early/frequent colonoscopies = 19% (N = 221), ovarian cancer screening referral = 1% (N = 14), thrombosis testing/counseling = 2.4% (N = 71). FHH elements: 8 FHH elements lead to 37.3% of the increased risk categorizations (by frequency): first-degree-relative (FDR) with polyps age ≥60 (7.1%, N = 85), three relatives with Lynch-related cancers (5.4%, N = 65), FDR with polyps age <60 (5.1%, N = 61), three relatives on same side of family with same cancer (4.9%, N = 59), Gail score ≥1.66% (4.9%, N = 58), two relatives with breast cancer (one ≤age 50) (4.1%, N = 49), one relative with breast cancer ≤age 40 (4.1%, N = 48), FDR with colon cancer age ≥60 (1.7%, N = 20). MeTree identifies a high percentage of individuals in the general primary care population needing non-routine risk management/prevention for the selected conditions. Implementing risk-stratification in primary care will likely increase demand for related-resources, particularly colon screening and GC. Understanding the prevalence of FHH elements helps predict resource needs and may aid in guideline development.

Quality of family history collection with use of a patient facing family history assessment tool.

BACKGROUND: Studies have shown that the quality of family health history (FHH) collection in primary care is inadequate to assess disease risk. To use FHH for risk assessment, collected data must have adequate detail. To address this issue, we developed a patient facing FHH assessment tool, MeTree. In this paper we report the content and quality of the FHH collected using MeTree. DESIGN: A hybrid implementation-effectiveness study. Patients were recruited from 2009 to 2012. SETTING: Two community primary care clinics in Greensboro, NC. PARTICIPANTS: All non-adopted adult English speaking patients with upcoming appointments were invited to participate. INTERVENTION: Education about and collection of FHH with entry into MeTree. MEASURES: We report the proportion of pedigrees that were high-quality. High-quality pedigrees are defined as having all the following criteria: (1) three generations of relatives, (2) relatives' lineage, (3) relatives' gender, (4) an up-to-date FHH, (5) pertinent negatives noted, (6) age of disease onset in affected relatives, and for deceased relatives, (7) the age and (8) cause of death (Prim Care31:479-495, 2004.). RESULTS: Enrollment: 1,184. Participant demographics: age range 18-92 (mean 58.8, SD 11.79), 56% male, and 75% white. The median pedigree size was 21 (range 8-71) and the FHH entered into MeTree resulted in a database of 27,406 individuals. FHHs collected by MeTree were found to be high quality in 99.8% (N = 1,182/1,184) as compared to <4% at baseline. An average of 1.9 relatives per pedigree (range 0-50, SD 4.14) had no data reported. For pedigrees where at least one relative has no data (N = 497/1,184), 4.97 relatives per pedigree (range 1-50, SD 5.44) had no data. Talking with family members before using MeTree significantly decreased the proportion of relatives with no data reported (4.98% if you talked to your relative vs. 10.85% if you did not, p-value < 0.001.). CONCLUSION: Using MeTree improves the quantity and quality of the FHH data that is collected and talking with relatives prior to the collection of FHH significantly improves the quantity and quality of the data provided. This allows more patients to be accurately risk stratified and offered appropriate preventive care guided by their risk level. TRIAL NUMBER: NCT01372553.

Impact of the Cancer Risk Intake System on patient-clinician discussions of tamoxifen, genetic counseling, and colonoscopy.

The Cancer Risk Intake System (CRIS), a computerized program that "matches" objective cancer risks to appropriate risk management recommendations, was designed to facilitate patient-clinician discussion. We evaluated CRIS in primary care settings via a single-group, self-report, pretest-posttest design. Participants completed baseline telephone surveys, used CRIS during clinic visits, and completed follow-up surveys 1 to 2 months postvisit. Compared with proportions reporting having had discussions at baseline, significantly greater proportions of participants reported having discussed tamoxifen, genetic counseling, and colonoscopy, as appropriate, after using CRIS. Most (79%) reported CRIS had "caused" their discussion. CRIS is an easily used, disseminable program that showed promising results in primary care settings.

Patients' interest in discussing cancer risk and risk management with primary care physicians.

Little is known about patients' preferences for discussing cancer risks and risk management with primary care physicians. We sought to determine whether patients want to discuss such topics and what factors are associated with this interest. Participants (375 patients ages 40-85, of diverse race and education level) completed a telephone survey prior to scheduled physician visits. Survey included items on perceived health, perceived cancer risk, education level, and whether participants would like to discuss with a physician their breast, ovarian or colon cancer risk, tamoxifen, cancer genetic counseling, and colon cancer screening. Greater proportions were interested in discussing risks for each cancer, compared with those who were not (P < 0.0001). More participants were interested in discussing mammograms (80%) and cancer genetic counseling (60%) than tamoxifen (49%) or colon cancer screening modalities (43-53%). For many topics, poorer perceived health was associated with greater interest in future discussion; higher education level was associated with less interest.