Title: Delivering genomic sequencing in clinical practice: a patient-centred evaluation of the new NHS Genomic Medicine Service
Funder: Department of Health and Social Care

Abstract: Background Next-generation sequencing technologies including whole genome sequencing (WGS) are being used to aid diagnosis of children and adults with rare diseases. Most rare diseases affect children and it takes on average six years for these patients to get a diagnosis. Genome sequencing has the potential to reduce this 'diagnostic odyssey'; the diagnostic yield of WGS in previously unsolved paediatric cases is around 40%. A diagnosis can ensure more accurate treatment, a clearer prognosis and information about recurrence. However, research has identified potential psychological harms including frustration and isolation at the lack of information, loss of hope for recovery and loss of disease community. Health professionals have also raised concerns around 'mainstreaming' of genomics, particularly if it is offered by non-genetic specialists. Aims and objectives The new NHS Genomic Medicine Service ('Service') will become operational from January 2019. I will use behavioural science methods to evaluate the new Service in relation to paediatric rare diseases. The three principal objectives are to: 1. Understand patient-provider communication around offering WGS for paediatric rare disease and around return of results and deliver recommendations for enhancing this communication process. 2. Examine longitudinally the processes, outcomes and impact (benefits and harms) on patients and families of undergoing and receiving WGS results for rare diseases, and identify ways to mitigate any harms and maximise benefits and efficiency going forward. 3. Identify any challenges and barriers that are preventing the NHS from achieving mainstream adoption of genomics, and identify actions to be taken that will support equitable and successful implementation of genomic medicine across all hospitals and specialist providers. Methods This will be a longitudinal mixed-methods study with data collection and analysis occurring simultaneously. Four discrete but related studies will be conducted. Observations (20-30) of the pre-test counselling appointment and results disclosure appointment will be conducted using an ethnographic approach. Follow-up interviews will take place with both the professional and patient/parents. A longitudinal mixed-methods study will be conducted with parents. This will involve surveys administered over 3 time-points (time of testing, results disclosure, and 12 months after results) using validated measures of informed decision-making, decisional conflict, test related distress and uncertainty. Follow up interviews with parents will take place. Finally, a cross-sectional survey will be administered to health providers who may order genomic tests for paediatric patients, to understand if and how genomics is being mainstreamed including emerging barriers and challenges.Timelines for delivery This is a four year study. This research is extremely timely given that the new Service will begin imminently. This proposal has a short trajectory in terms of patient benefit as findings can be implemented almost immediately. Recommendations for policy and practice will be published from year 3 onwards. Anticipated impact and dissemination Evaluating the new Service as it is rolled out across the country will directly benefit patients by identifying best-practices, minimising potential harms, and ensuring WGS is implemented in a responsible manner that benefits patients. Findings will be disseminated through papers, conferences, a dissemination workshop, social media and support group meetings.

Lay abstract: Background Genome sequencing (where a person's entire genetic code is mapped) is set to dramatically transform patient care and medical outcomes. From January 2019, genome sequencing will be available as part of routine clinical care in the NHS. One area where genome sequencing is set to have a profound impact is the diagnosis of rare diseases in children, helping to end the 'diagnostic odyssey' that many families go through. However, as the technology is new, very little is known about the clinical, social, behavioural and psychological impact. Why is this research needed? We do not know how clinical teams communicate with patients and their families when offering genome sequencing and delivering test results. We do not know how patients and families experience a diagnostic, negative or inconclusive result, including the long-term impact of that result. Moreover, we don't yet know whether the NHS will achieve mainstream, comprehensive and equitable adoption of genomics. In this Fellowship I will evaluate service users' and health professionals' experiences of the new NHS Genomic Medicine Service, focusing specifically on the use of whole genome sequencing (WGS) to diagnose rare diseases in children. Aim To evaluate the new NHS Genomic Medicine Service, focusing on paediatric rare diseases, and deliver feedback and recommendations for practice to improve patient-care. Design and methods This is a four year mixed-methods study using observations, interviews and questionnaires. Recruitment will take place across a minimum of five sites (participation confirmed). Studies 1 & 2: I will conduct observations of pre-test counselling appointments for genome sequencing (Study 1) and results disclosure appointments (Study 2) to understand overarching structures of the appointments. At both appointment types I will conduct interviews with the professionals and parents to explore their implicit goals and gain insight into how the appointment unfolded from their perspectives. Study 3: I will administer surveys to parents of children with rare diseases undergoing genome sequencing at three time-points; 1) at the time of testing, 2) when they receive their results (diagnostic, negative or inconclusive) and 3) 12 months after receiving results. The surveys will assess informed decision-making, perceived value of the result, immediate impact and longer-term clinical, social, educational, behavioural and psychological outcomes. Surveys will be followed by in-depth interviews with a subset of survey responders. Study 4: I will administer a survey to healthcare providers across the UK who may order genomic tests for paediatric rare disease patients. The aim of the survey is to understand their experiences of delivering the new Service. Patient and public involvement (PPI) This research has been co-designed with parents of children with rare diseases and patient advocates who have prioritised the research aims and questions to ensure they address the questions of most relevance and future impact to them. Two parent representatives will sit on the advisory team to ensure PPI throughout the duration of the research. Dissemination This work will be disseminated to health professionals and policy-makers through academic publications, conference presentations, a policy report, a workshop in year 4, and to patients and public through social-media, patient group meetings and plain language summaries of papers. Why is this research important to patients/the NHS? This research will: Identify best-practices and deliver recommendations for how clinicians can improve communication with patients/families; Improve services by providing evidence on the impact of genome sequencing (clinical, social, psychological etc) on patients/families including any negative consequences; and Identify any potential challenge and barriers to delivering the service equitably.It is important to do this research now as the new Service is about to begin. Findings and recommendations for best practices can be fed back to professionals and policy makers.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE