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. 2022 Oct;24(10):2014-2027.
doi: 10.1016/j.gim.2022.06.004. Epub 2022 Jul 14.

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

Bart S Ferket  1 , Zach Baldwin  2 , Priyanka Murali  3 , Akila Pai  4 , Kathleen F Mittendorf  5 , Heidi V Russell  6 , Flavia Chen  7 , Frances L Lynch  8 , Kristen Hassmiller Lich  9 , Lucia A Hindorff  10 , Renate Savich  11 , Anne Slavotinek  12 , Hadley Stevens Smith  13 , Bruce D Gelb  14 , David L Veenstra  2
Affiliations

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

Bart S Ferket et al. Genet Med. 2022 Oct.

Abstract

Purpose: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.

Methods: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.

Results: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.

Conclusion: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.

Keywords: Cost-effectiveness analysis; Decision modeling; Economic evaluation; Exome sequencing; Genome sequencing.

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Conflict of interest statement

Conflict of Interest K.F.M. has received institutional support from GE Healthcare. D.L.V has received institutional support from Foundation Medicine. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of study selection process.
Numbers of articles of each step of the review process are indicated. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for study inclusion flow diagrams, reasons for exclusion of records after preliminary screening, ie, screening of titles and abstracts were not tracked.
Figure 2
Figure 2. Graphical representation used for development of conceptual frameworks.
ES, exome sequencing; GS, genome sequencing; ICER, incremental cost-effectiveness ratio.
See this image and copyright information in PMC

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