Rare diseases affect an estimated 8% of the Scottish population. Although 80% of rare conditions are believed to have a genetic cause many patients remain undiagnosed. This has a significant impact on quality of life for patients and families who face a ‘diagnostic odyssey’ of clinical and genetic testing.
New developments in genomic medicine, such as whole genome sequencing (WGS), may increase the number of patients who receive a genetic diagnosis for their condition. A recent study from the 100,000 Genomes Project established the effectiveness of WGS in the diagnosis of rare diseases. However, there is limited economic evidence to support the provision of WGS in clinical practice in Scotland.
We are currently working on a Chief Scientist Office (CSO) funded economic evaluation of WGS for the diagnosis of rare conditions in Scotland. We have recently had an article published which outlines findings from the Scottish Genomes Partnership’s (SGP) involvement in the 100,000 Genomes Project. In the article we report:
- Preliminary cost estimates for standard genetic testing.
- A micro-costing of trio-based WGS in Scotland.
- Findings from interviews with patients and families in the SGP study.
The costs of standard genetic testing
We estimated the costs of standard genetic testing by attaching unit costs to patients’ genetic testing histories. We also accounted for costs of hospital attendances due to the rare disease. We found high variation in costs for standard genetic testing of patients with undiagnosed rare conditions.
The average cost was £1,841 but ranged from £90 to £6,784. Neurological and neurodevelopmental disorders had the highest costs. This was due to high numbers of single gene tests.The cost of trio-based Whole Genome Sequencing
We used the protocol from Scotland’s participation in the 100,000 Genomes Project to estimate the cost of trio-based WGS (genomic sequencing of a child plus two parents) for the diagnosis of rare diseases. Using micro-costing, the cost of WGS was estimated at £6,625 per family trio (typically a child plus two parents). Micro-costing allowed us to estimate the staff time, consumables and equipment used at each stage of the WGS process.
Around 50% of the overall cost of WGS was the sequencing itself, with a further 25% for data analysis and storage. This suggests that reducing these costs could have a large impact on the overall cost of delivering WGS in clinical practice.The value of Whole Genome Sequencing to service users
We also looked at the value of WGS to service users. We interviewed six parents of children with undiagnosed rare conditions and three affected adults. It was found that service users valued WGS for a variety of reasons:
- The chance of a diagnosis and ending the long and stressful diagnostic journey provided peace of mind and closure.
- The information provided by WGS enabled more informed decision making.
- Contributing to genomic research could help others in the future.
The evidence from this research shows that WGS is more expensive than standard genetic testing for the diagnosis of rare conditions. However, it remains to be seen whether the additional cost of WGS is justified by its increased diagnostic yield. Our future research will explore this using cost-effectiveness analysis modelling. This will compare various genetic and genomic testing strategies in terms of their costs and diagnostic yield.
Costs - We are currently updating the costs of standard genetic testing. Access to patients’ medical records is allowing us to estimate the costs more precisely. We are also updating the costs to reflect what WGS might look like beyond the 100,000 Genomes Project in Scotland.
Benefits - We are developing a valuation survey to measure and value the wide range of benefits of WGS to patients and families with undiagnosed rare conditions. This includes factors such as waiting times for genomic test results, the value of information and emotional benefits from WGS.
Bringing the costs and benefits together, we will develop a user-perspective cost-benefit analysis. Comparing the costs of WGS to its broader value to service users can help ensure that a holistic and patient centred approach is taken when measuring the benefits of WGS. The results of our health economic analysis will be used to guide the development of a Scottish genetic and genomic testing strategy.
Abbott, M., McKenzie, L., Moran, B.V.G., Heidenreich, S., Hernández, R., Hocking-Mennie, L., Clark, C., Gomes, J., Lampe, A., Baty, D., McGowan, R., Miedzybrodzka, Z. and Ryan, M. (2021) 'Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland', Journal of Community Genetics, [Epub ahead of print].
The article will be part of a Special Issue of the Journal of Community Genetics focusing on 'Resource Allocation in Genomic Medicine'.
Many thanks to Michael Abbott of HERU for his work developing this blog post. Michael is a staff member at HERU who is also undertaking a PhD which aims to elicit patient preferences for genomic medicine using a discrete choice experiment to measure and value the broad range of health and non-health outcomes which patients with rare conditions value.
HERU is supported by the Chief Scientist Office (CSO) of the Scottish Government Health and Social Care Directorates (SGHSC). The views expressed here are those of the Unit and not necessarily those of the CSO.