Should Scotland Provide Genome-Wide Sequencing for the Diagnosis of Rare Developmental Disorders?: A Cost-Effectiveness Analysis

Michael Abbott; Mandy Ryan; Rodolfo Andrés Hernández; Lynda McKenzie; Sebastian Heidenreich; Lynne Hocking; Caroline Clark; Morad Ansari; David Moore; Anne  Lampe; Ruth  McGowan; Jonathan Berg; Zosia Miedzybrodzka

doi:10.1007/s10198-024-01717-8

Should Scotland Provide Genome-Wide Sequencing for the Diagnosis of Rare Developmental Disorders? A Cost-Effectiveness Analysis

Michael Abbott^* (Corresponding Author), Mandy Ryan, Rodolfo Andrés Hernández, Lynda McKenzie, Sebastian Heidenreich, Lynne Hocking, Caroline Clark, Morad Ansari, David Moore, Anne Lampe, Ruth McGowan, Jonathan Berg, Zosia Miedzybrodzka

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Aims: This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.
Methods: Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing. The cost effectiveness of each strategy was expressed in terms of incremental cost per additional diagnosis. The impact of uncertainty on cost-effectiveness results was explored using deterministic and probabilistic sensitivity analysis.
Results: 2nd line ES was a cost-saving option, increasing diagnostic yield by 13.9% and decreasing cost by £1,027 per trio compared to standard genetic testing. Compared to ES, strategies involving GS increased costs significantly, with only a moderate or zero improvement in diagnostic yield. Sensitivity analysis indicated that significant reductions in cost or improvements in diagnostic yield are required before 1st-line GS becomes cost effective.
Conclusion 2nd -line ES (after chromosomal microarray; replacing gene panel testing) for the diagnosis of developmental disorders is a cost-saving option for the Scottish NHS. Ongoing economic evaluation is required to monitor the evolving cost and diagnostic yield of GS and ES over time.

Original language	English
Number of pages	10
Journal	European Journal of Health Economics
Early online date	9 Sept 2024
DOIs	https://doi.org/10.1007/s10198-024-01717-8
Publication status	E-pub ahead of print - 9 Sept 2024

Bibliographical note

The authors would like to thank the Scottish Genomes Partnership for their support with this work. Specifically, we thank, Christine Bell, Austin Diamond and Jon Warner for their collaboration. We thank Amy Rowlatt, Tessa Coupar, Courtney Elliot, Lorna McLean, Laura Taylor, Resifina Seyara, Florence Richards and Quinn Heppe for collecting the genetic testing data which was used to generate costs. We thank Professor Tim Aitman for his conceptualisation and management of the Scottish Genomes Partnership. We would also like to thank Edinburgh Genomics at the University of Edinburgh for their participation in the SGP project, the current NHS Scotland trio ES service, as well as their contribution to the generation of costs for this study. We also thank the members of our Project Advisory Group: Deborah Marshall, Sarah Wordsworth, Richard Herriot, Natalie Frankish, Sarah Ogilvie and Nicola Williams for providing comments on earlier versions of the cost-effectiveness model. Finally, this work would not be possible without the families, clinicians, nurses, research scientists, laboratory staff and wider members of the Scottish Genomes Partnership and Deciphering Developmental Disorders studies, to whom we give our grateful thanks.

Keywords

Cost effectiveness
Economic evaluation
Genetics
Genomics
Rare conditions

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10198-024-01717-8Licence: CC BY

Cite this

Abbott, M., Ryan, M., Hernández, R. A., McKenzie, L., Heidenreich, S., Hocking, L., Clark, C., Ansari, M., Moore, D., Lampe, A., McGowan, R., Berg, J., & Miedzybrodzka, Z. (2024). Should Scotland Provide Genome-Wide Sequencing for the Diagnosis of Rare Developmental Disorders? A Cost-Effectiveness Analysis . European Journal of Health Economics. Advance online publication. https://doi.org/10.1007/s10198-024-01717-8

Abbott, M , Ryan, M , Hernández, RA, McKenzie, L, Heidenreich, S, Hocking, L, Clark, C, Ansari, M, Moore, D, Lampe, A, McGowan, R, Berg, J & Miedzybrodzka, Z 2024, 'Should Scotland Provide Genome-Wide Sequencing for the Diagnosis of Rare Developmental Disorders? A Cost-Effectiveness Analysis ', European Journal of Health Economics. https://doi.org/10.1007/s10198-024-01717-8

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abstract = "Aims: This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.Methods: Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing. The cost effectiveness of each strategy was expressed in terms of incremental cost per additional diagnosis. The impact of uncertainty on cost-effectiveness results was explored using deterministic and probabilistic sensitivity analysis.Results: 2nd line ES was a cost-saving option, increasing diagnostic yield by 13.9% and decreasing cost by £1,027 per trio compared to standard genetic testing. Compared to ES, strategies involving GS increased costs significantly, with only a moderate or zero improvement in diagnostic yield. Sensitivity analysis indicated that significant reductions in cost or improvements in diagnostic yield are required before 1st-line GS becomes cost effective.Conclusion 2nd -line ES (after chromosomal microarray; replacing gene panel testing) for the diagnosis of developmental disorders is a cost-saving option for the Scottish NHS. Ongoing economic evaluation is required to monitor the evolving cost and diagnostic yield of GS and ES over time.",

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author = "Michael Abbott and Mandy Ryan and Hern{\'a}ndez, {Rodolfo Andr{\'e}s} and Lynda McKenzie and Sebastian Heidenreich and Lynne Hocking and Caroline Clark and Morad Ansari and David Moore and Anne Lampe and Ruth McGowan and Jonathan Berg and Zosia Miedzybrodzka",

note = "The authors would like to thank the Scottish Genomes Partnership for their support with this work. Specifically, we thank, Christine Bell, Austin Diamond and Jon Warner for their collaboration. We thank Amy Rowlatt, Tessa Coupar, Courtney Elliot, Lorna McLean, Laura Taylor, Resifina Seyara, Florence Richards and Quinn Heppe for collecting the genetic testing data which was used to generate costs. We thank Professor Tim Aitman for his conceptualisation and management of the Scottish Genomes Partnership. We would also like to thank Edinburgh Genomics at the University of Edinburgh for their participation in the SGP project, the current NHS Scotland trio ES service, as well as their contribution to the generation of costs for this study. We also thank the members of our Project Advisory Group: Deborah Marshall, Sarah Wordsworth, Richard Herriot, Natalie Frankish, Sarah Ogilvie and Nicola Williams for providing comments on earlier versions of the cost-effectiveness model. Finally, this work would not be possible without the families, clinicians, nurses, research scientists, laboratory staff and wider members of the Scottish Genomes Partnership and Deciphering Developmental Disorders studies, to whom we give our grateful thanks. ",

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T2 - A Cost-Effectiveness Analysis

AU - Abbott, Michael

AU - Ryan, Mandy

AU - Hernández, Rodolfo Andrés

AU - McKenzie, Lynda

AU - Heidenreich, Sebastian

AU - Hocking, Lynne

AU - Clark, Caroline

AU - Ansari, Morad

AU - Moore, David

AU - Lampe, Anne

AU - McGowan, Ruth

AU - Berg, Jonathan

AU - Miedzybrodzka, Zosia

N1 - The authors would like to thank the Scottish Genomes Partnership for their support with this work. Specifically, we thank, Christine Bell, Austin Diamond and Jon Warner for their collaboration. We thank Amy Rowlatt, Tessa Coupar, Courtney Elliot, Lorna McLean, Laura Taylor, Resifina Seyara, Florence Richards and Quinn Heppe for collecting the genetic testing data which was used to generate costs. We thank Professor Tim Aitman for his conceptualisation and management of the Scottish Genomes Partnership. We would also like to thank Edinburgh Genomics at the University of Edinburgh for their participation in the SGP project, the current NHS Scotland trio ES service, as well as their contribution to the generation of costs for this study. We also thank the members of our Project Advisory Group: Deborah Marshall, Sarah Wordsworth, Richard Herriot, Natalie Frankish, Sarah Ogilvie and Nicola Williams for providing comments on earlier versions of the cost-effectiveness model. Finally, this work would not be possible without the families, clinicians, nurses, research scientists, laboratory staff and wider members of the Scottish Genomes Partnership and Deciphering Developmental Disorders studies, to whom we give our grateful thanks.

PY - 2024/9/9

Y1 - 2024/9/9

N2 - Aims: This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.Methods: Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing. The cost effectiveness of each strategy was expressed in terms of incremental cost per additional diagnosis. The impact of uncertainty on cost-effectiveness results was explored using deterministic and probabilistic sensitivity analysis.Results: 2nd line ES was a cost-saving option, increasing diagnostic yield by 13.9% and decreasing cost by £1,027 per trio compared to standard genetic testing. Compared to ES, strategies involving GS increased costs significantly, with only a moderate or zero improvement in diagnostic yield. Sensitivity analysis indicated that significant reductions in cost or improvements in diagnostic yield are required before 1st-line GS becomes cost effective.Conclusion 2nd -line ES (after chromosomal microarray; replacing gene panel testing) for the diagnosis of developmental disorders is a cost-saving option for the Scottish NHS. Ongoing economic evaluation is required to monitor the evolving cost and diagnostic yield of GS and ES over time.

AB - Aims: This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.Methods: Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing. The cost effectiveness of each strategy was expressed in terms of incremental cost per additional diagnosis. The impact of uncertainty on cost-effectiveness results was explored using deterministic and probabilistic sensitivity analysis.Results: 2nd line ES was a cost-saving option, increasing diagnostic yield by 13.9% and decreasing cost by £1,027 per trio compared to standard genetic testing. Compared to ES, strategies involving GS increased costs significantly, with only a moderate or zero improvement in diagnostic yield. Sensitivity analysis indicated that significant reductions in cost or improvements in diagnostic yield are required before 1st-line GS becomes cost effective.Conclusion 2nd -line ES (after chromosomal microarray; replacing gene panel testing) for the diagnosis of developmental disorders is a cost-saving option for the Scottish NHS. Ongoing economic evaluation is required to monitor the evolving cost and diagnostic yield of GS and ES over time.

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KW - Economic evaluation

KW - Genetics

KW - Genomics

KW - Rare conditions

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