Title: Rapid exome sequencing for the diagnosis of critically ill children in the NHS Genomic Medicine Service: Ensuring an equitable and effective parent and patient-centred service
Funder: Department of Health and Social Care

Abstract: Background In October 2019 rapid exome sequencing (ES) for critically ill children with a suspected underlying monogenic condition was implemented in the new NHS Genomic Medicine Service. Rapid ES can offer a pathway to faster diagnoses and much earlier decisions about treatment and management. This is the first time that rapid ES for critically ill children has been offered nationally in a fully public health service. Optimal clinical implementation in acute care settings requires consideration of multiple practical, organisational and counselling challenges. Our research is needed to ensure that rapid ES delivered through the Genomic Medicine Service is offered in a manner that is acceptable to parents and professionals, efficient to the NHS and maximises benefits to patients and parents across the country. Aim To examine the delivery of rapid ES in the NHS from the perspective of parents and professionals and provide recommendations for ongoing service delivery and future research that will improve quality of care for patients and parents. Methods The study will have oversight from a Steering Group and a Patient and Public Involvement Advisory Group (PPIAG). Our mixed-methods evaluation of the rapid ES service will be carried out in three phases. In phase 1 we will survey families affected with rare and undiagnosed conditions and conduct qualitative interviews with professionals involved in establishing the service. Understanding the anticipated challenges and research priorities of key stakeholders will allow us to refine our research questions and develop nuanced study materials. In Phase 2 we will focus on gaining a comprehensive understanding of rapid ES for critically ill children in clinical practice. We will undertake qualitative interviews with parents whose very sick child was offered rapid ES. Through these interviews we will explore the personal utility of the test and the information and support needs of parents at a very distressing time. We will also conduct a cross-sectional survey with professionals looking at challenges for service delivery and training needs. In addition, an assessment of referrals and clinical outcomes will consider equity of access and clinical utility. In phase 3 we will integrate study findings with a step-wise triangulation protocol that will bring together the findings from each research arm. Finally, we will develop and disseminate parent and patient-centred recommendations and resources. Anticipated Impact and Dissemination Our evaluation will benefit patients and parents through recommendations and resources to improve quality of care and equity of access and help to meet their information and support needs. The optimised clinical use of rapid ES will allow more parents to receive an accurate genetic diagnosis for their child, providing valuable information about the cause and prognosis of their child s illness. A summative report, peer reviewed research publications and lay summaries describing recommendations and guidance for best practice will be disseminated to lay organisations, healthcare providers, policy makers and commissioners. This work will also be an exemplar for evaluating other aspects of the Genomic Medicine Service and our findings may be useful to others internationally as they implement and refine similar services.

Lay abstract: Background Rapid exome sequencing (ES) is a new NHS test that has been offered to critically ill children since October 2019. Rapid ES is offered when the child has symptoms that suggest they may have a genetic condition that cannot be diagnosed using standard genetic tests. Rapid ES will increase the chance of quickly finding the cause of the child s illness. If a genetic condition is diagnosed this can give parents important information about the outlook for their child and help decisions about treatments and management. This is the first time that rapid ES for critically ill children has been offered nationally in a public health service. Our research is needed to ensure that rapid ES is offered in a way that is beneficial to patients, supportive of parents and can be accessed equally by all. We will make recommendations to address any challenges or barriers to delivering the service across England and look at how best to support decision making when parents are distressed. Study aims and design The aim of our study is to examine how rapid ES for critically ill children is being delivered by the NHS so that we can provide recommendations that will improve quality of care for patients and parents. To do this we will: Survey parents whose children are affected by rare genetic conditions. This will help us focus our research on the issues that are most important to parents. Interview parents whose children had rapid ES when they were critically ill to ask what they think of rapid ES and how support and information could be improved. Interview professionals involved in establishing the rapid ES service and survey professionals who care for critically ill children across England to look at how the rapid ES service is delivered and ask what challenges they face and what training and education is needed. Look at all of the tests done in a 12 month period (~700) to see if families from all over England have access to the test and whether the test changed the care children received. Gather all our findings together and make recommendations for best practice. Patient and public involvement We will embed patient and public involvement in our study. Our advisory groups will include representatives of national patient organisations and parents. The advisory groups will be actively involved throughout the study and will ensure that the recommendations are helpful to patients, parents and the NHS. Impact Our evaluation of rapid ES for critically ill children will bring benefits to patients and parents by delivering recommendations and information resources that will improve the service, promote equal access and meet the information and support needs of parents.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE