Comparing models of delivery for cancer genetics services among patients receiving primary care who meet criteria for genetic evaluation in two healthcare systems: BRIDGE randomized controlled trial.

BACKGROUND: Advances in genetics and sequencing technologies are enabling the identification of more individuals with inherited cancer susceptibility who could benefit from tailored screening and prevention recommendations. While cancer family history information is used in primary care settings to identify unaffected patients who could benefit from a cancer genetics evaluation, this information is underutilized. System-level population health management strategies are needed to assist health care systems in identifying patients who may benefit from genetic services. In addition, because of the limited number of trained genetics specialists and increasing patient volume, the development of innovative and sustainable approaches to delivering cancer genetic services is essential. METHODS: We are conducting a randomized controlled trial, entitled Broadening the Reach, Impact, and Delivery of Genetic Services (BRIDGE), to address these needs. The trial is comparing uptake of genetic counseling, uptake of genetic testing, and patient adherence to management recommendations for automated, patient-directed versus enhanced standard of care cancer genetics services delivery models. An algorithm-based system that utilizes structured cancer family history data available in the electronic health record (EHR) is used to identify unaffected patients who receive primary care at the study sites and meet current guidelines for cancer genetic testing. We are enrolling eligible patients at two healthcare systems (University of Utah Health and New York University Langone Health) through outreach to a randomly selected sample of 2780 eligible patients in the two sites, with 1:1 randomization to the genetic services delivery arms within sites. Study outcomes are assessed through genetics clinic records, EHR, and two follow-up questionnaires at 4 weeks and 12 months after last genetic counseling contactpre-test genetic counseling. DISCUSSION: BRIDGE is being conducted in two healthcare systems with different clinical structures and patient populations. Innovative aspects of the trial include a randomized comparison of a chatbot-based genetic services delivery model to standard of care, as well as identification of at-risk individuals through a sustainable EHR-based system. The findings from the BRIDGE trial will advance the state of the science in identification of unaffected patients with inherited cancer susceptibility and delivery of genetic services to those patients. TRIAL REGISTRATION: BRIDGE is registered as NCT03985852 . The trial was registered on June 6, 2019 at clinicaltrials.gov .

Patient Interactions With an Automated Conversational Agent Delivering Pretest Genetics Education: Descriptive Study.

BACKGROUND: Cancer genetic testing to assess an individual's cancer risk and to enable genomics-informed cancer treatment has grown exponentially in the past decade. Because of this continued growth and a shortage of health care workers, there is a need for automated strategies that provide high-quality genetics services to patients to reduce the clinical demand for genetics providers. Conversational agents have shown promise in managing mental health, pain, and other chronic conditions and are increasingly being used in cancer genetic services. However, research on how patients interact with these agents to satisfy their information needs is limited. OBJECTIVE: Our primary aim is to assess user interactions with a conversational agent for pretest genetics education. METHODS: We conducted a feasibility study of user interactions with a conversational agent who delivers pretest genetics education to primary care patients without cancer who are eligible for cancer genetic evaluation. The conversational agent provided scripted content similar to that delivered in a pretest genetic counseling visit for cancer genetic testing. Outside of a core set of information delivered to all patients, users were able to navigate within the chat to request additional content in their areas of interest. An artificial intelligence-based preprogrammed library was also established to allow users to ask open-ended questions to the conversational agent. Transcripts of the interactions were recorded. Here, we describe the information selected, time spent to complete the chat, and use of the open-ended question feature. Descriptive statistics were used for quantitative measures, and thematic analyses were used for qualitative responses. RESULTS: We invited 103 patients to participate, of which 88.3% (91/103) were offered access to the conversational agent, 39% (36/91) started the chat, and 32% (30/91) completed the chat. Most users who completed the chat indicated that they wanted to continue with genetic testing (21/30, 70%), few were unsure (9/30, 30%), and no patient declined to move forward with testing. Those who decided to test spent an average of 10 (SD 2.57) minutes on the chat, selected an average of 1.87 (SD 1.2) additional pieces of information, and generally did not ask open-ended questions. Those who were unsure spent 4 more minutes on average (mean 14.1, SD 7.41; P=.03) on the chat, selected an average of 3.67 (SD 2.9) additional pieces of information, and asked at least one open-ended question. CONCLUSIONS: The pretest chat provided enough information for most patients to decide on cancer genetic testing, as indicated by the small number of open-ended questions. A subset of participants were still unsure about receiving genetic testing and may require additional education or interpersonal support before making a testing decision. Conversational agents have the potential to become a scalable alternative for pretest genetics education, reducing the clinical demand on genetics providers.

BRCA1/2 Variants Identified Through Tumor Genomic Profiling: Assessing Genetic Counseling Outcomes.

PURPOSE: As tumor genomic profiling (TGP) is increasingly used to help guide cancer treatment, BRCA variants, which may or may not be reflective of the germline genome, are being identified. As TGP use increases, it is becoming an important tool for referral to genetic counseling and identifying patients with hereditary cancer syndromes such as hereditary breast and ovarian cancer. This study explores genetic counseling referral patterns and germline implications of patients found to have pathogenic BRCA1/2 variants identified through TGP. METHODS: Participants include patients at Huntsman Cancer Institute undergoing TGP through a single commercial laboratory between March 2014 and July 2018. A retrospective chart review was conducted for 62 patients found to have pathogenic variants (PVs) in BRCA1/2 on TGP. Data on genetic counseling referrals and uptake, germline test results, family history, and patient demographics were collected. RESULTS: In the study time frame, 1,899 patients underwent TGP. Testing identified 67 PVs in BRCA1 (23 variants) or BRCA2 (44 variants) in 62 patients. Thirty-five patients first received a referral to a genetic counselor following TGP with 33 patients completing genetic counseling. Of the 30 patients who pursued germline genetic testing following TGP, 11 were discovered to have a previously unknown germline BRCA PV. Nine of these patients were the first in their family diagnosed with hereditary breast and ovarian cancer. CONCLUSION: This study represents one institution's experience with genetic counseling referrals, uptake, and germline results following TGP. For some patients, TGP will be the first indicator of an underlying hereditary condition. Identifying patients with PVs (which may be germline) through TGP is an important new genetic counseling referral tool that can have important implications for the patient and their family.

Implications of Multigene Panel Testing on Psychosocial Outcomes: A Comparison of Patients With Pancreatic and Breast or Ovarian Cancer.

PURPOSE: National Comprehensive Cancer Network guidelines for germline genetic testing have included pancreatic cancer in the context of additional family cancer history for many years but this was not recommended for patients with pancreatic ductal adenocarcinoma (PDAC) independent of a family history until 2019. This hypothesis-generating study reports the results from multigene panel testing for PDAC patients at an academic medical center. PATIENTS AND METHODS: This prospective longitudinal feasibility study examined responses to genetic counseling and multigene panel testing among PDAC and breast or ovarian cancer (BrOv) patients between October 2016 and November 2017. Pre- and post-test surveys assessed perceptions of genetic risk and testing, recall, comprehension, and emotional reactions to results using open-ended and closed-ended items. RESULTS: Forty-six BrOv and 33 PDAC patients were enrolled, and 44 BrOv and 31 PDAC participants underwent genetic testing. Seven pathogenic variants were identified in six BrOv participants (13.6%), and three pathogenic variants were identified in three PDAC participants (9.7%). The majority of both cohorts expressed similar attitudes about the importance of genetic testing for their personal and family medical management and expressed accurate understanding of implications of their results. Although sample size was small, there were no significant differences between the BrOv and PDAC cohorts for positive or negative emotions. CONCLUSION: This study points to high rates of positive emotions and low rates of negative emotions following genetic test results, suggesting that the emotional reactions to genetic test results are similar for patients with BrOv and PDAC, despite poor prognosis with PDAC diagnoses. Because of the unique needs of the PDAC population following diagnosis, a multidisciplinary approach to germline genetic testing following diagnosis may result in best patient and family member outcomes.

The Effects of At-Birth Adoption on Atypical Behavior and Anxiety: A Nonhuman Primate Model.

OBJECTIVE: Adopted children tend to show an increased risk for a variety of psychopathological outcomes, even when adoption occurs at birth, which some suggest is a result of nonrandom assignment of adoptees and parents. This study uses a nonhuman primate model, in which adoptions were randomly assigned, to investigate the behavioral and physiological outcomes associated with at-birth adoption. METHOD: Immediately following birth, rhesus monkey infants were randomly assigned to be reared by either their biological mother (n = 113) or by an unrelated, lactating, adoptive mother (n = 34). At 6 months of age, infant behavior and physiology were assessed during a stressful series of mother-infant separations. Four years later, stress-related behaviors were measured following confrontation by an unfamiliar intruder, an ecologically meaningful stressor. RESULTS: When compared to infants reared by their biological mothers, adopted infants exhibited more behavioral withdrawal and higher plasma adrenocorticotropic hormone (ACTH) concentrations in response to separation. These behavioral differences persisted 4 years later during a stressful intruder challenge, with adoptees exhibiting more behavioral withdrawal, stereotypies, and impulsive approaches of the potentially aggressive intruder. CONCLUSION: Compared to infants reared by their biological mothers, adopted infants exhibited more behavioral inhibition, impulsivity, and higher ACTH concentrations, even when subjects were randomly assigned to be adopted or to remain with their biological mother. To the extent that these findings generalize to humans, they suggest that the overall risk for psychopathology in adopted individuals persists even after random assignment to adoption conditions.