Combined population genomic screening for three high-risk conditions in Australia: a modelling study

Paul Lacaze; Clara Marquina; Jane Tiller; Adam Brotchie; Yoon-Jung Kang; Melissa A Merritt; Robert C Green; Gerald F Watts; Kristen J Nowak; Ranjit Manchanda; Karen Canfell; Paul James; Ingrid Winship; John J McNeil; Zanfina Ademi

doi:10.1016/j.eclinm.2023.102297

Combined population genomic screening for three high-risk conditions in Australia: a modelling study

EClinicalMedicine. 2023 Nov 8:66:102297. doi: 10.1016/j.eclinm.2023.102297. eCollection 2023 Dec.

Authors

Paul Lacaze¹, Clara Marquina², Jane Tiller¹, Adam Brotchie¹, Yoon-Jung Kang³, Melissa A Merritt³, Robert C Green⁴, Gerald F Watts^{5

6}, Kristen J Nowak^{7

8}, Ranjit Manchanda^{9

10}, Karen Canfell³, Paul James^{11

12

13}, Ingrid Winship^{12

13}, John J McNeil¹, Zanfina Ademi^{1

2}

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
² Health Economics and Policy Evaluation Research (HEPER) Group, Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
³ The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council NSW, Sydney, NSW 2011, Australia.
⁴ Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School, Boston, MA, 02114, USA.
⁵ School of Medicine, University of Western Australia, Perth, WA 6009, Australia.
⁶ Departments of Cardiology and Internal Medicine, Royal Perth Hospital, Perth, WA, 6001, Australia.
⁷ Public and Aboriginal Health Division, Western Australia Department of Health, East Perth, WA, 6004, Australia.
⁸ Centre for Medical Research, The University of Western Australia, Crawley, WA, 6009, Australia.
⁹ Wolfson Institute of Population Health, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
¹⁰ Department of Health Services Research, Faculty of Public Health & Policy, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
¹¹ Parkville Familial Cancer Centre, Peter McCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
¹² Department of Genomic Medicine, Royal Melbourne Hospital City Campus, Parkville, VIC, 3050, Australia.
¹³ Department of Medicine, University of Melbourne, Parkville, VIC, 3050, Australia.

Abstract

Background: No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system.

Methods: This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18-40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100-$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis).

Findings: Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208).

Interpretation: Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration.

Funding: Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604).

Keywords: Cost-effectiveness analysis; Genomic testing; Genomics; Health-economic evaluation; Population screening; Prevention; Public health.