Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service

Abstract

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). The GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: Our mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

Public and patient involvement in research to support genome services development in the UK

“…○ 1. Two of the co-applicants are from patient organisations (Genetic Alliance UK and Alstrom Syndrome UK) [39,43] and sit in the research team, bringing experience with a range of research projects and in setting up PPI advisory groups, and a broad perspective on rare disease. The Genetic Alliance UK representative leads on the PPI elements of the evaluation.…”

“…1. Two funding co-applicants and core members of the research team are from the patient organisations (Alstrom Syndrome UK and Antenatal Results and Choices (ARC)) [43,45] . The Director of ARC leads the PPI elements of the research.…”

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals’ views and experiences

“…Understanding the impact of delivering pES as a national service from the perspective of healthcare professionals is necessary for recognising areas of success and efficiency, highlighting areas for improvement, and identifying support needs. Optimising EXome PREnatal Sequencing Services (EXPRESS) (NIHR127829) is a national study examining the delivery of pES across England through the NHS GMS ( Hill et al, 2022 ). In the mixed methods study described here, we have used surveys and interviews with professionals to address the research question: What does delivery of a national pES service look like from the perspective of healthcare professionals, and what should it look like in the future?…”

Enhancement of phenotyping for fetal investigation using next‐generation sequencing

“…Such findings have led to the establishment of phenotype test directories (such as that introduced by the NHS England Genomic Service) to guide multidisciplinary team discussions on fetal case selection. Some consider this form of triage to be too rigid and to underestimate the genetic etiology in the fetus with abnormal prenatal ultrasound findings; in England, this is currently the subject of a prospective audit 9,10 .…”