Abstract
Precision medicine (PM) informed by next-generation sequencing (NGS) poses challenges for health technology assessment (HTA). To date, there has been limited reimbursement of genomic testing with NGS in Canada, particularly for whole-genome and whole-exome sequencing (WGS/WES). Through a structured literature review, we examine Canadian economic evidence and evidentiary challenges for the adoption of genomic testing. We searched Medline (PubMed) for published Canadian studies generating economic evidence for PM informed by NGS. Our search focused on studies examining the costs and/or value of NGS. We reviewed included studies and summarized results according to evaluation type, clinical context, NGS technology, and test strategy. We then grouped HTA challenges encountered by authors when evaluating NGS. Our review included twenty-five studies. To determine the economic impacts of NGS-informed PM in Canada, studies applied cost-effectiveness analysis (52%, n = 13), stated preference analysis (20%, n = 5), cost-consequence analysis (16%, n = 4), and healthcare resource utilization or costing analysis (12%, n = 3). NGS panels were the most common technology evaluated (n = 13), followed by WGS and/or WES (n = 8). The included studies highlighted multiple challenges when generating economic evidence, many of which remain unaddressed. Challenges were broadly related to (1) accounting for all NGS outcomes; (2) addressing uncertainty; and (3) improving consistency of economic approaches. Canadian studies are beginning to produce estimates of the economic impacts of NGS-informed PM, yet challenges for HTA remain. While solutions and real-world evidence are generated, lifecycle health technology management methods can be designed to better support resource allocation decisions for genomic testing in Canada.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agyeman AA, Ofori-Asenso R (2015) Perspective: does personalized medicine hold the future for medicine? J Pharm Bioallied Sci 7:239–244
AHS (2017) Breast Cancer Molecular Testing – Oncologist Alberta Health Services. https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-moleculartesting-bulletin.pdf. Accessed 29/10/2018
Barcenas CH, Raghavendra A, Sinha AK, Syed MP, Hsu L, Patangan MG Jr, Chavez-MacGregor M, Shen Y, Hortobagyi GH, Valero V, Giordano SH, Ueno NT, Tripathy D (2017) Outcomes in patients with early-stage breast cancer who underwent a 21-gene expression assay. Cancer 123:2422–2431
BC Cancer (2016) New genetic tests become standard of cancer care in BC. BC Cancer. http://www.bccancer.bc.ca/about/news-stories/news/2016/new-genetic-tests-become-standard-of-cancer-care-in-bc. Accessed 29 Oct 2018
Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic. Nature 501:355–364
Boycott K, Hartley T, Adam S, Bernier F, Chong K, Fernandez BA, Friedman JM, Geraghty MT, Hume S, Knoppers BM, Laberge AM, Majewski J, Mendoza-Londono R, Meyn MS, Michaud JL, Nelson TN, Richer J, Sadikovic B, Skidmore DL, Stockley T, Taylor S, van Karnebeek C, Zawati MH, Lauzon J, Armour CM, Canadian College of Medical Geneticists (2015) The clinical application of genome-wide sequencing for monogenic diseases in Canada: position statement of the Canadian College of Medical Geneticists. J Med Genet 52:431–437
Bridges JF et al (2011) Conjoint analysis applications in health—a checklist: a report of the ISPOR Good Research Practices for Conjoint Analysis Task Force. Value Health 14:403–413
Buchanan J, Wordsworth S, Schuh A (2013) Issues surrounding the health economic evaluation of genomic technologies. Pharmacogenomics 14:1833–1847
CADTH (2017) Guidelines for the economic evaluation of health technologies. Canada. 4th ed. Ottawa:
Carlson JJ, Sullivan SD, Garrison LP, Neumann PJ, Veenstra DL (2010) Linking payment to health outcomes: a taxonomy and examination of performance-based reimbursement schemes between healthcare payers and manufacturers. Health policy 96:179–190
Centre for Clinical Genomics (n.d.) CC Genomics Hereditary Cancer Panel. http://www.ccgenomics.ca/hcp-panel.html. Accessed 29 Oct 2018
Cheung MC, Chan KK, Sabharwal M, Fields A, Chambers A, Evans WK (2016) Comparing assessment frameworks for cancer drugs between Canada and Europe: what can we learn from the differences? ESMO open 1:e000124
Cuffe S, Hon H, Qiu X, Tobros K, Wong CKA, de Souza B, McFarlane G, Masroor S, Azad AK, Hasani E, Rozanec N, Leighl N, Alibhai S, Xu W, Issa AM, Liu G (2014) Cancer patients’ acceptance, understanding, and willingness-to-pay for pharmacogenomic testing. Pharmacogenet Genomics 24:348–355
Dragojlovic N, Elliott AM, Adam S, van Karnebeek C, Lehman A, Mwenifumbo JC, Nelson TN, du Souich C, Friedman JM, Lynd LD (2018a) The cost and diagnostic yield of exome sequencing for children with suspected genetic disorders: a benchmarking study. Genet Med 20:1013–1021
Dragojlovic N, Kim E, Elliott AM, Study C, Friedman JM, Lynd LD (2018b) Evaluating the use of parental reports to estimate health care resource utilization in children with suspected genetic disorders. J Eval Clin Pract 24:416–422
Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW (2015) Methods for the economic evaluation of health care programmes. Oxford university press
Faulkner E, Annemans L, Garrison L, Helfand M, Holtorf AP, Hornberger J, Hughes D, Li T, Malone D, Payne K, Siebert U, Towse A, Veenstra D, Watkins J (2012) Challenges in the development and reimbursement of personalized medicine—payer and manufacturer perspectives and implications for health economics and outcomes research: a report of the ISPOR Personalized Medicine Special Interest Group. Value Health 15:1162–1171
Génome Québec (2016) A new initiative to facilitate the implementation of personalized medicine in Canada. Génome Québec. http://www.genomequebec.com/267-en/news-a-new-initiative-to-facilitate-the-implementation-of-personalized-medicine-in-canada/. Accessed 29 Oct 2018
Hayeems RZ, Bhawra J, Tsiplova K, Meyn MS, Monfared N, Bowdin S, Stavropoulos DJ, Marshall CR, Basran R, Shuman C, Ito S, Cohn I, Hum C, Girdea M, Brudno M, Cohn RD, Scherer SW, Ungar WJ (2017) Care and cost consequences of pediatric whole genome sequencing compared to chromosome microarray. Eur J Hum Genet 25:1303–1312
Health Quality Ontario (2018) Health technology assessments methods and process guide: version 2.0. https://www.hqontario.ca/Portals/0/documents/evidence/reports/hta-methods-and-process-guide-en.pdf. Accessed 15 Feb 2019
Hollis A (2016) Sustainable financing of innovative therapies: a review of approaches. PharmacoEconomics 34:971–980
Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E, on behalf of the CHEERS Task Force (2013) Consolidated health economic evaluation reporting standards (CHEERS) statement. Cost Eff Resour Alloc 11:6
Husereau D, Marshall DA, Levy AR, Peacock S, Hoch JS (2014) Health technology assessment and personalized medicine: are economic evaluation guidelines sufficient to support decision making? Int J Technol Assess Health Care 30:179–187
Joly Y, Ramos–Paque E (2010) Approval of new pharmacogenomic tests: is the Canadian regulatory process adequate? CJLT 8:2
Laksman Z, Detsky AS (2011) Personalized medicine: understanding probabilities and managing expectations. J Gen Intern Med 26:204–206
Lilley M, Christian S, Blumenschein P, Chan S, Somerville M (2013) A centralized approach to out–of–province genetic testing leads to cost savings: the Alberta experience. Clin Genet 84:373–377
Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ (2011) The n–of–1 clinical trial: the ultimate strategy for individualizing medicine? Per Med 8:161–173
Macklin S, Durand N, Atwal P, Hines S (2018) Observed frequency and challenges of variant reclassification in a hereditary cancer clinic. Genet Med 20:346–350
Marshall DA, Deal K, Bombard Y, Leighl N, MacDonald KV, Trudeau M (2016) How do women trade-off benefits and risks in chemotherapy treatment decisions based on gene expression profiling for early-stage breast cancer? A discrete choice experiment. BMJ Open 6:e010981
Najafzadeh M, Johnston KM, Peacock SJ, Connors JM, Marra MA, Lynd LD, Marra CA (2013) Genomic testing to determine drug response: measuring preferences of the public and patients using Discrete Choice Experiment (DCE). BMC Health Serv Res 13:454
National Institutes of Health (2018) All of Us Research Program Operation Protocol. https://allofus.nih.gov/sites/default/files/aou operational protocol v1.7 mar 2018.pdf. Accessed 15/02/2019
Newborn Screening Ontario (n.d.) Newborn Screening Ontario Molecular Diagnostics. https://www.newbornscreening.on.ca/en/diagnostic–testing/molecular–diagnostics. Accessed 29/10/2018
Nshimyumukiza L, Beaumont JA, Duplantie J, Langlois S, Little J, Audibert F, McCabe C, Gekas J, Giguère Y, Gagné C, Reinharz D, Rousseau F (2018) Cell-free DNA–based non-invasive prenatal screening for common aneuploidies in a Canadian Province: a cost-effectiveness analysis. J Obstet Gynaecol Can 40:48–60
Okun N, Teitelbaum M, Huang T, Dewa CS, Hoch JS (2014) The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for down syndrome in Ontario, Canada. Prenat Diagn 34:350–356
Ontario Personalized Medicine Network (n.d.) Personalized Medicine Reports - Subcommittee 2: Evaluating Our Current Health Technology Assessment Capabilities in Light of Personalized Medicine Technologies. Ontario Genomics. http://www.ontariogenomics.ca/provincial-strategies/opmn/personalized-medicine-resources/. Accessed 29 Oct 2018
Pollard S, Sun S, Regier DA (2019) Balancing uncertainty with patient autonomy in precision medicine. Nat Rev Genet. 20:251–252
Presley CJ, Tang D, Soulos PR, Chiang AC, Longtine JA, Adelson KB, Herbst RS, Zhu W, Nussbaum NC, Sorg RA, Agarwala V, Abernethy AP, Gross CP (2018) Association of broad-based genomic sequencing with survival among patients with advanced non–small cell lung cancer in the community oncology setting. Jama 320:469–477
Regier D, Friedman J, Makela N, Ryan M, Marra C (2009) Valuing the benefit of diagnostic testing for genetic causes of idiopathic developmental disability: willingness to pay from families of affected children. Clin Genet 75:514–521
Regier DA, Friedman JM, Marra CA (2010) Value for money? Array genomic hybridization for diagnostic testing for genetic causes of intellectual disability. Am J Hum Genet 86:765–772
Regier DA, Peacock SJ, Pataky R, van der Hoek K, Jarvik GP, Hoch J, Veenstra D (2015) Societal preferences for the return of incidental findings from clinical genomic sequencing: a discrete–choice experiment. Can Med Assoc J 187:E190–E197
Regier DA, Weymann D, Buchanan J, Marshall DA, Wordsworth S (2018) Valuation of health and nonhealth outcomes from next-generation sequencing: approaches, challenges, and solutions. Value Health 21:1043–1047
Richards S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–423
Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, Kuntz KM, Meltzer DO, Owens DK, Prosser LA, Salomon JA, Sculpher MJ, Trikalinos TA, Russell LB, Siegel JE, Ganiats TG (2016) Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. Jama 316:1093–1103
Schork NJ (2015) Personalized medicine: time for one-person trials. Nature 520:609–611
Statistics Canada (2018) Table 18–10–0004–01 Consumer Price index, monthly, not seasonally adjusted. https://www150.statcan.gc.ca/t1/tbl1/en/cv.action?pid=1810000401. Accessed 01 Oct 2018
Stuart EA (2010) Matching methods for causal inference: a review and a look forward statistical science: a review. J Inst Math Stat 25:1
Tsiplova K, Zur RM, Marshall CR, Stavropoulos DJ, Pereira SL, Merico D, Young EJ, Sung WWL, Scherer SW, Ungar WJ (2017) A microcosting and cost–consequence analysis of clinical genomic testing strategies in autism spectrum disorder. Genet Med 19:1268–1275
Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI (2010) Cost–effectiveness analysis of recurrence score–guided treatment using a 21–gene assay in early breast cancer. Oncologist 15:457–465
Turnbull C et al (2018) The 100 000 genomes project: bringing whole genome sequencing to the NHS. BMJ 361:k1687
Weymann D, Laskin J, Roscoe R, Schrader KA, Chia S, Yip S, Cheung WY, Gelmon KA, Karsan A, Renouf DJ, Marra M, Regier DA (2017) The cost and cost trajectory of whole-genome analysis guiding treatment of patients with advanced cancers. Mol Genet Genom Med 5:251–260
Weymann D, Pataky R, Regier DA (2018) Economic evaluations of next–generation precision oncology: a critical review. JCO Precision Oncology 2:1–23
Wordsworth S, Buchanan J, Regan R, Davison V, Smith K, Dyer S, Campbell C, Blair E, Maher E, Taylor J, Knight SJL (2007) Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom. Genomic Medicine 1:35–45
Yuen T, Carter MT, Szatmari P, Ungar WJ (2018) Cost–effectiveness of genome and exome sequencing in children diagnosed with autism spectrum disorder Applied health economics and health policy 16:481–493
Funding
This work was supported by BC Cancer Foundation’s Strategic Priority Fund Awards. The Canadian Centre for Applied Research in Cancer Control is funded by the Canadian Cancer Society Grant No. 2015-703549.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Deirdre Weymann, Nick Dragojlovic, and Samantha Pollard report no conflicts of interest. Dean A. Regier has received travel support from Illumina to attend conferences in Boston, USA, and Barcelona, Spain.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Resource Allocation in Genetic and Genomic Medicine
Electronic supplementary material
ESM 1
(DOC 199 kb)
Rights and permissions
About this article
Cite this article
Weymann, D., Dragojlovic, N., Pollard, S. et al. Allocating healthcare resources to genomic testing in Canada: latest evidence and current challenges. J Community Genet 13, 467–476 (2022). https://doi.org/10.1007/s12687-019-00428-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12687-019-00428-5