Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

Abbott, Michael; McKenzie, Lynda; Moran, Blanca Viridiana Guizar; Heidenreich, Sebastian; Hernández, Rodolfo; Hocking-Mennie, Lynne; Clark, Caroline; Gomes, Joana Castro; Lampe, Anne Katrin; Baty, D.; McGowan, Ruth; Miedzybrodzka, Zosia; Ryan, Mandy

doi:10.1007/s12687-021-00541-4

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…The diagnostic utility for genome sequencing with panel analysis was similar to exome sequencing in our clinical service, as suggested here and reported in published meta-analysis [18] whereas in this study and others, the cost of genome sequencing and data storage was around three times greater than that for exomes [21]. In future, cost differences may fall as sequencing and data storage improve and variant analysis becomes more automated.…”

Section: Discussionsupporting

confidence: 84%

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

et al. 2022

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NHS genetics centres in Scotland sought to investigate the Genomics England 100,000 Genomes Project diagnostic utility to evaluate genome sequencing for in rare, inherited conditions. Four regional services recruited 999 individuals from 394 families in 200 rare phenotype categories, with negative historic genetic testing. Genome sequencing was performed at Edinburgh Genomics, and phenotype and sequence data were transferred to Genomics England for variant calling, gene-based filtering and variant prioritisation. NHS Scotland genetics laboratories performed interpretation, validation and reporting. New diagnoses were made in 23% cases – 19% in genes implicated in disease at the time of variant prioritisation, and 4% from later review of additional genes. Diagnostic yield varied considerably between phenotype categories and was minimal in cases with prior exome testing. Genome sequencing with gene panel filtering and reporting achieved improved diagnostic yield over previous historic testing but not over now routine trio-exome sequence tests. Re-interpretation of genomic data with updated gene panels modestly improved diagnostic yield at minimal cost. However, to justify the additional costs of genome vs exome sequencing, efficient methods for analysis of structural variation will be required and / or cost of genome analysis and storage will need to decrease.

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Section: Discussionsupporting

confidence: 84%

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

et al. 2022

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“…Several studies demonstrate the utility of whole-exome (WES) [ 61 , 62 ] or whole-genome (WGS) [ 63 , 64 ] sequencing, as well as including other omics, such as RNA-seq or methylation profiles, increasing the diagnostic yield particularly on undiagnosed individuals with a suspected genetic condition [ 65 , 66 ]. Nevertheless, the improvement in diagnostic efficiency comes with several shortcomings, such as cost and time/analysis load [ 24 , 67 ] that are expected to be solved in the near future as technology improves in efficiency. However, it is important to recognise diagnostic limitations for each technology and it is at this point at which genetic (or genomic) counsellors provide an added value.…”

Section: Current Needs and Future Directions Of Genetic Counselling For Rare Diseasesmentioning

confidence: 99%

Current Status of Genetic Counselling for Rare Diseases in Spain

et al. 2021

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Genetic Counselling is essential for providing personalised information and support to patients with Rare Diseases (RD). Unlike most other developed countries, Spain does not recognize geneticists or genetic counsellors as healthcare professionals Thus, patients with RD face not only challenges associated with their own disease but also deal with lack of knowledge, uncertainty, and other psychosocial issues arising as a consequence of diagnostic delay. In this review, we highlight the importance of genetic counsellors in the field of RD as well as evaluate the current situation in which rare disease patients receive genetic services in Spain. We describe the main units and strategies at the national level assisting patients with RD and we conclude with a series of future perspectives and unmet needs that Spain should overcome to improve the management of patients with RD.

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“…7,9 Diagnostic testing for rare diseases can be done by a variety of methods, including karyotyping, fluorescence in situ hybridization, chromosomal microarray analysis, single-gene tests, and multigene (gene panel) tests. 12 Genome-wide sequencing (GWS) can shorten the diagnostic odyssey for rare diseases, with improved diagnostic yield compared with sequential testing for specific subsets of genetic disorders. 4,[13][14][15] GWS includes sequencing all protein-coding regions of genes (whole-exome sequencing) or entire genomes (whole-genome sequencing).…”

Section: Introductionmentioning

confidence: 99%

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada

Weymann,

Buckell,

Fahr

et al. 2024

JAMA Netw Open

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ImportanceEtiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs.ObjectiveTo measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases.Design, Setting, and ParticipantsThis cohort study was a quasiexperimental retrospective analysis across 3 distinct English and Canadian cohorts, completed in 2023. Mixed-effects generalized linear regression was used to estimate associations between GWS and costs in the 2 years before and after GWS. Difference-in-differences regression was used to estimate associations of genetic diagnosis and costs. Costs are in 2019 US dollars. GWS was conducted in a research setting (Genomics England 100 000 Genomes Project [100KGP] and Clinical Assessment of the Utility of Sequencing and Evaluation as a Service [CAUSES] Research Clinic) or clinical outpatient setting (publicly reimbursed GWS in British Columbia [BC], Canada). Participants were children with developmental disorders, seizure disorders, or both undergoing GWS between 2014 and 2019. Data were analyzed from April 2021 to September 2023.ExposuresGWS and genetic diagnosis.Main Outcomes and MeasuresAnnual health care costs and diagnostic costs per child.ResultsStudy cohorts included 7775 patients in 100KGP, among whom 788 children had epilepsy (mean [SD] age at GWS, 11.6 [11.1] years; 400 female [50.8%]) and 6987 children had an intellectual disability (mean [SD] age at GWS, 8.2 [8.4] years; 2750 female [39.4%]); 77 patients in CAUSES (mean [SD] age at GWS, 8.5 [4.4] years; 33 female [42.9%]); and 118 publicly reimbursed GWS recipients from BC (mean [SD] age at GWS, 5.5 [5.2] years; 58 female [49.2%]). GWS diagnostic yield was 143 children (18.1%) for those with epilepsy and 1323 children (18.9%) for those with an intellectual disability in 100KGP, 47 children (39.8%) in the BC publicly reimbursed setting, and 42 children (54.5%) in CAUSES. Mean annual per-patient spending over the study period was $5283 (95% CI, $5121-$5427) for epilepsy and $3373 (95% CI, $3322-$3424) for intellectual disability in the 100KGP, $724 (95% CI, $563-$886) in CAUSES, and $1573 (95% CI, $1372-$1773) in the BC reimbursed setting. Receiving a genetic diagnosis from GWS was not associated with changed costs in any cohort.Conclusions and RelevanceIn this study, receiving a genetic diagnosis was not associated with cost savings. This finding suggests that patient benefit and cost-effectiveness should instead drive GWS implementation.

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Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

Cited by 7 publications

References 44 publications

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

Current Status of Genetic Counselling for Rare Diseases in Spain

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada

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