Academic research community (GECIP)

Genetic diseases (GDs) are highly complex and chronically debilitating. It is estimated that Mendelian disorders (diseases that are classically inherited) account for 10% of infant mortality and 20% of paediatric hospitalizations. Families with a child with a GD face many far-reaching lifetime health, social and economic impacts including: financial pressure, relationship strain, poorer parental health and uncertainty about recurrence. These impacts result in very substantial costs for Governments. Heritable GDs are now preventable, however, preconception carrier screening is not widely accessible. It is only available for a limited range of disorders such as cystic fibrosis, fragile X syndrome and spinal muscular atrophy in some countries. There is no public funding for preconception carrier screening, resulting in significant inequality of access and entrenching health, social and economic inequalities for affected families. Further, there is no comprehensive economic model of the potential health and economic benefits of preconception carrier screening to inform decisions about public funding. With the price of genomic testing rapidly falling, many more families could obtain an accurate assessment of their risk of having a child with a severe, early onset, incurable genetic disorder. Where the risk is high, it facilitates access to testing, such as IVF with pre-implantation genetic screening, to ensure the health of future children. For families with a known history of a serious genetic disorder, if it is shown there is a low risk of recurrence, it can restore reproductive confidence. This is a remarkable step forward from current practice where a majority of families, even those with a family history of a serious genetic disorder, have no well-informed advice of the risk to their future children. The project captures the impacts for government and provide much needed evidence, which will ultimately improve the lives of children and their families. Data from the 100,000 Genomics Project provides an opportunity to collect high-quality healthcare utilization and associated costs within the largest genome sequencing programme in the UK, in an NHS setting. The estimates can then be used as input parameter in purposeful constructed economic models to assess where the use of WGS is most likely to represent value for money for the NHS.

Genomic technologies have shown promise for stratifying disease management, identifying patients with rare disorders and identifying the causes of infections, all of which could improve both health and non-health outcomes in patients. The 100,000 Genomes Project (100KGP) presents both an ideal opportunity to systematically collect high-quality cost and health outcome data within the largest genome sequencing programme in the UK, in an NHS setting. This data, when used in the context of economic evaluations will be able to provide information on where the use of whole genome sequencing (WGS) is most likely to represent value for money for the NHS. This analysis will include the examination of both appropriate diagnostic points in the care pathway and the downstream consequences of testing (such as the use of targeted drug therapies). The 100KGP also provides a fantastic opportunity to address a range of methodological challenges facing health economists in this area.

Equity considerations associated with the use of genome sequencing in the UK National Health Service: a health economic analysis using data from the 100,000 Genomes Project

The UK is a global leader in genome sequencing: mapping the entire genetic code of an individual. Between 2013-2018 the Genomics England 100,000 Genomes Project sequenced 100,000 genomes from around 85,000 individuals, all of whom were National Health Service (NHS) patients affected by a suspected genetic disorder or cancer. In 2019, the NHS was the first public health service to announce the launch of a Genomic Medicine Service, which will build on the success of the 100,000 Genomes Project by offering sequencing to the 3.5 million adults and children in the UK with rare diseases.

A key concern when rolling out the new Genomic Medicine Service is equality of access to sequencing. Multiple factors could potentially impede equality of access, including ethnicity, employment status, local deprivation and other demographic factors. This MSc project will explore the extent to which each of these factors are associated with undergoing genome sequencing, with reference to secondary care resource use and costs. Data to address this research question will be provided via the Rare Disease Pilot Study of the 100,000 Genomes Project, which covers 4,875 participants (2,676 affected participants, and their relatives). Strong associations between any of these factors and genome sequencing would be suggestive of potential sources of inequity in the availability of sequencing. Identifying such sources, and the potential size of any effects, will be a vital first step to developing possible policy levers for improving equality of access to genome sequencing.

The 100,000 Genomes Project (100KGP) managed by Genomics England aimed to sequence the genomes of NHS patients in England with rare diseases or cancer, to improve our understanding of the causes and treatment of disease. The completion of this project led the National Health Service (NHS) in England to launch a new Genomic Medicine Service (GMS). This has resulted in the NHS being the first public health care service in the world to offer genome sequencing to patients with rare genetic diseases and cancer. Genome sequencing could provide more patients with diagnoses, provide better information on how their disorder might develop, and better guide treatment decisions for these patients. However, we don’t currently know if genome sequencing offers value for money for the NHS. In this project I will use data from the 100KGP on the hospital care received by patients with cancer, as well as data from genome sequencing, to evaluate the resource use and costs incurred when patients undergo genome sequencing. I will primarily focus on breast, colorectal, lung, ovarian and renal cancers, as well as childhood cancers (e.g. sarcoma).

This project is a health economics study, analysing routinely collected clinical and genetic data (known as real world data) in order to better understand current treatment effectiveness, and health-economic value for cancer patients with and without specific variants in a gene called FGFR (Fibroblast Growth Factor Receptor). The FGFR protein (encoded by the FGFR gene) effects cell growth and division. When mutated, these functions can go awry and lead to the development of a wide range of solid tumour and blood-based cancers.

We have identified a gap in the literature in analysis of patients with FGFR variants. This study will address that gap comparing the clinical outcomes, and also the costs of current standard-of-care treatment in the UK healthcare system, for patients with and without variants in the FGFR gene. We hope that this research will support feasibility analysis, and also potential reimbursement discussions for drug development pathways that that target FGFR-expressing cancers.

This study will assess and compare:

• Patient characteristics (genomic features and clinical presentation);

• A standard measure of cost: all-cause and disease related healthcare resource use (HCRU) and other associated costs in the real-world UK clinical setting; and

• A standard measure of clinical outcome – overall survival (OS) of cancer patients with and without a range of FGFR variants

The Genomics England dataset contains all of the above datasets including patients with FGFR variants. This analysis will make extensive use of this data to contribute to the existing limited literature and shed light to deepen our understanding on how different types of FGFR variants impact the patient, treatment options and healthcare costs.