Patients' ratings of genetic conditions validate a taxonomy to simplify decisions about preconception carrier screening via genome sequencing

Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment. However, expert perceptions of condition attributes used to classify these conditions may differ from those used by patients. To understand whether expert and patient perceptions differ, we asked women who had received preconception genetic carrier screening in the last 3 years to fill out a survey to rate the attributes (predictability, controllability, visibility, and severity) of several autosomal recessive or X-linked genetic conditions. These conditions were classified into one of five taxonomy categories developed by subject experts (significantly shortened lifespan, serious medical problems, mild medical problems, unpredictable medical outcomes, and adult-onset conditions). A total of 193 women provided 739 usable ratings across 20 conditions. The mean ratings and correlations demonstrated that participants made distinctions across both attributes and categories. Aggregated mean attribute ratings across categories demonstrated logical consistency between the key features of each attribute and category, although participants perceived little difference between the mild and serious categories. This study provides empirical evidence for the validity of our proposed taxonomy, which will simplify patient decisions for results they would like to receive from preconception carrier screening via genome sequencing

Description and pilot results from a novel method for evaluating return of incidental findings from next-generation sequencing technologies

To develop, operationalize, and pilot test a transparent, reproducible, and evidence informed method to qualify when to report incidental findings from next generation sequencing technologies

A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation

Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research

Genome sequencing and carrier testing: decisions on categorization and whether to disclose results of carrier testing

We are investigating the use of genome sequencing for preconception carrier testing. Genome sequencing could identify one or more of thousands of X-linked or autosomal recessive conditions that could be disclosed during preconception or prenatal counseling. Therefore, a framework that helps both clinicians and patients understand the possible range of findings is needed to respect patient preferences by ensuring that information about only the desired types of genetic conditions are provided to a given patient

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Biobank Recruitment: Motivations for Nonparticipation

Molecular data, essential for genomics research, can be captured more efficiently in large-scale, population-based biobanks of genetic material rather than by individual studies. Biobanks also offer improved quality and reliability of genetic samples and access through automated sample retrieval. However, it is challenging to adequately inform participants of the broad nature of the research and participation risks and benefits. In addition, recent studies suggest concerns about data sharing and return of research results, or future research topics (eg, stereotypical or potentially stigmatizing traits). We evaluated the interest in participating in a biobank and reasons for nonparticipation

Universal Screen for Lynch Syndrome in an Integrated Health Care System: Assessment of Patient Perspectives and Sharing Results With At-Risk Relatives

Background/Aims: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC). Evidence-based recommendations promote universal tumor screening for LS among all new cases of CRC over selective screening based on family history or age of diagnosis. Maximal reduction in morbidity and mortality from universal tumor screening depends on patients with a positive screen following up with genetic counseling and testing to confirm a diagnosis of LS and sharing results with at-risk relatives. Methods: Participants included 165 Kaiser Permanente Northwest members aged 39 to 91 years who had undergone surgery for CRC. Tumor samples were screened for microsatellite instability and participants surveyed before and after receiving screening results to assess perspectives on screening and sharing results with at-risk relatives. Results: Most patients reported no family history of CRC; 14.1% had a first-degree relative and 7.4% had a second- or third-degree relative with CRC. However, most (93%) wanted to know their risk for hereditary CRC. Overall, most patients endorsed potential benefits and few barriers to screening, though 62% indicated a worry about the cost of additional testing and surveillance. Before receiving screening results, most patients indicated they would likely share their result with their parents (90%), siblings (96%) and children (97%), where applicable. Of the 25 patients with a positive microsatellite instability screen, 96.0% reported they shared their results with at least one relative. Most patients endorsed motivations to share results, namely: so family members could act to reduce their risk of CRC (76%) and it was their responsibility to let family members know they might be at higher risk of CRC (68%). None of the patients indicated that strained family relationships would prevent them from sharing results, and few indicated that they would not share their results because it would worry relative(s) (8%) or because discussing their results could hurt relationship(s) (4%). Conclusion: Given universal tumor screening will target all new cases of CRC, it is important to understand motivations among patients not identified via high-risk factors such as family history or age of diagnosis. These findings provide insight into patient attitudes and perspectives toward LS screening to guide successful implementation of screening programs

Stakeholder perspectives on implementing a universal lynch syndrome screening program: A qualitative study of early barriers and facilitators

Background: Evidence-based guidelines recommend that all newly diagnosed colon cancers be screened for Lynch syndrome (LS). Best practices for implementing universal tumor screening have not been extensively studied. Purpose We interviewed a range of stakeholders in an integrated health care system to identify initial factors that might promote or hinder the successful implementation of a universal (LS) screening program. Methods: We conducted interviews with health plan leaders, managers, and staff. Interviews were audio recorded and transcribed. Thematic analysis began with a grounded approach and was also guided by the Practical Robust Implementation and Sustainability Model (PRISM). Results: We completed 14 interviews with leaders/managers and staff representing involved clinical and health plan departments. While in general stakeholders supported the concept of universal screening, they identified several internal (organizational) and external (environment) factors that promote/hinder implementation. Facilitating factors included: 1) perceived benefits of screening for patients and organization; 2) collaboration between departments; and 3) availability of organizational resources. Barriers were also found, including: 1) lack of awareness of guidelines; 2) lack of guideline clarity; 3) staffing and program “ownership” concerns; and 4) cost uncertainties. Analysis also revealed nine important infrastructure-type considerations for successful implementation. Conclusion: We found that clinical, laboratory, and administrative departments supported universal tumor screening for LS. Requirements for successful implementation may include interdepartmental collaboration and communication; patient and provider/staff education; and significant infrastructure and resource support related to laboratory processing and systems for electronic ordering and tracking

Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers

BACKGROUND Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. METHODS A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient‐specific and cancer‐specific factors and survey responses were analyzed. RESULTS The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. CONCLUSIONS The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision‐making and guide the successful implementation of screening programs. Cancer 2015;121:3281–3289. © 2015 American Cancer Society