Reflections on the Cost of Low-Cost Whole Genome Sequencing: Framing the Health Policy Debate

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

Parents' experiences of an abnormal ultrasound examination - vacillating between emotional confusion and sense of reality

<p>Abstract</p> <p>Background</p> <p>An ultrasound examination is an important confirmation of the pregnancy and is accepted without reflection to any prenatal diagnostic aspects. An abnormal finding often comes unexpectedly and is a shock for the parents. The aim was to generate a theoretical understanding of parents' experiences of the situation when their fetus is found to have an abnormality at a routine ultrasound examination.</p> <p>Methods</p> <p>Sixteen parents, mothers and fathers, whose fetus had been diagnosed with an abnormality during an ultrasound scan in the second or third trimester, were interviewed. The study employed a grounded theory approach.</p> <p>Results</p> <p>The core category <it>vacillating between the emotional confusion and sense of reality </it>is related to the main concern <it>assessment of the diagnosis impact on the well-being of the fetus</it>. Two other categories <it>Entering uncertainty </it>and <it>Involved in an ongoing change and adaptation </it>have each five sub-categories.</p> <p>Conclusions</p> <p>Parents are aware of that ultrasound examination is a tool for identifying abnormalities prenatally. The information about the abnormality initially results in broken expectations and anxiety. Parents become involved in ongoing change and adaptation. They need information about the ultrasound findings and the treatment without prolonged delay and in a suitable environment. The examiner who performs the ultrasound examination must be aware of how anxiety can be intensified by environmental factors. All parents should to be offered a professional person to give them <it>s</it>upport as a part of the routine management of this situation.</p

Lynch syndrome: barriers to and facilitators of screening and disease management

Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health

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

Misunderstandings Concerning Genetics Among Patients Confronting Genetic Disease

Critical questions arise about misunderstandings of genetics. We interviewed for 2 h each, 64 individuals who had or were at risk for Huntington's disease (HD), breast cancer or Alpha‐1 antitrypsin deficiency. These individuals revealed various misunderstandings that can affect coping, and testing, treatment and reproductive decisions. A therapeutic misconception about testing appeared: that testing would be helpful in and of itself. Many believed they could control genetic disorders (even HD), yet these beliefs were often incorrect, and could impede coping, testing, and treatment. Misunderstandings about statistics and genetics often fueled each other, and reflected denial, and desires for hope and control. Emotional needs can thus outweigh understandings of genetics and statistics, and providers’ input. Individuals often maintained non‐scientific beliefs, though embarrassed by these. These data have implications for care, and public and professional education. Misunderstandings’ persistence, despite realization of their inaccuracy, suggests that providers need to address not just cognitive facts, but underlying emotional issues

The ECOUTER methodology for stakeholder engagement in translational research.

BACKGROUND: Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes (as a patient or member of the public). Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others (the many 'publics' of engagement) brings them closer to the research but also brings the research closer to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. METHODS: In practice, engagement faces numerous challenges and is often time-consuming, expensive and 'thorny' work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER (Employing COnceptUal schema for policy and Translation Engagement in Research) methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, "How could it be otherwise?" ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of 'keeping open' the possible considerations that might emerge and including reflexive use of qualitative analytic methods. RESULTS: This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to 'open up' engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: (1) engagement and knowledge exchange; (2) analysis of mindmap contributions; (3) development of a conceptual schema (i.e. a map of concepts and their relationship); and (4) feedback, refinement and development of recommendations. CONCLUSION: ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it

Factors Influencing Surgical Treatment Decisions for Breast Cancer: A Qualitative Exploration of Surgeon and Patient Perspectives

Background: The rate of mastectomy is much higher in Newfoundland and Labrador than in any other province in Canada, even for women diagnosed at an early stage. In this paper, we present qualitative data from women who have made a decision for surgical treatment and from breast surgeons in an effort to better explicate factors influencing breast cancer (BCA) surgical decision-making. Methods: The study’s descriptive, qualitative design involved holding interviews with breast surgeons and holding focus groups and interviews with women who were offered the choice of breast-conserving surgery (BCS) or mastectomy (MT). Results: Participants included 35 women and 13 surgeons. High interest in MT and increasing requests for prophylactic contralateral MT were evident. A host of factors—clinical, demographic, psychosocial, education-related, and cultural—influenced the decisions. A key factor for women was fear of recurrence and a need to “just get rid of it,” but the experiences of others also influenced the decisions. Life stage and family considerations also factored prominently into women’s decisions. Conclusions: Women with early-stage BCA more often chose MT and often demanded prophylactic removal of the healthy breast. Findings highlight the importance of ensuring that women at average risk are appropriately counselled about the low likelihood of a subsequent contralateral BCA and the lack of survival benefit associated with prophylactic contralateral MT. Findings also revealed other areas of presurgical discussion that might help women think through their personal circumstances and values so as to encourage informed surgical decisions