A Discrete Event Simulation Model to Assess the Economic Value of a Hypothetical Pharmacogenomics Test for Statin-Induced Myopathy in Patients Initiating a Statin in Secondary Cardiovascular Prevention
- 78 Downloads
Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels. The potential economic value of a PGx test for statin-induced myopathy is unknown.
We developed a lifetime discrete event simulation (DES) model for patients 65 years of age initiating a statin after a first CVE consisting of either an acute myocardial infarction (AMI) or a stroke. The model evaluates the potential economic value of a hypothetical PGx test for diagnosing statin-induced myopathy. We have assessed the model over the spectrum of test sensitivity and specificity parameters.
Our model showed that a strategy with a perfect PGx test had an incremental cost-utility ratio of 4273 Canadian dollars ($Can) per quality-adjusted life year (QALY). The probabilistic sensitivity analysis shows that when the payer willingness-to-pay per QALY reaches $Can12,000, the PGx strategy is favored in 90% of the model simulations.
We found that a strategy favoring patients staying on statin therapy is cost effective even if patients maintained on statin are at risk of rhabdomyolysis. Our results are explained by the fact that statins are highly effective in reducing the CV risk in patients at high CV risk, and this benefit largely outweighs the risk of rhabdomyolysis.
DM contributed to the conception and design of the study, data acquisition, analysis and interpretation of data, drafting the article, and final approval. JRG, AD, MPD, JCT, ACI, FFA, AM, and JL contributed to the conception and design of the study analysis and interpretation of data, drafting the article, and final approval.
This research was supported by Genome Canada and Genome Québec. Jason R. Guertin is the recipient a of an establishment fund from the Centre de Recherche du CHU de Québec – Université Laval and from the Fondation du CHU de Québec.
Compliance with Ethical Standards
Conflict of interest
Dominic Mitchell, Jason R. Guertin, Anick Dubois, Marie-Pierre Dubé, Jean-Claude Tardif, Ange Christelle Iliza, Fiorella Fanton-Aita, Alexis Matteau, and Jacques LeLorier declare that they have no conflicts of interest that are directly relevant to the content of this review.
This article is distributed under the terms of the Creative Commons Attribution–NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any non-commercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- 1.Statistics Canada. Cholesterol levels of adults, 2012 to 2013. Statistics Canada, Ottawa, Canada. http://www.statcan.gc.ca/pub/82-625-x/2014001/article/14122-eng.htm. Accessed 6 Oct 2017.
- 2.Anderson TJ, Gregoire J, Hegele RA, Couture P, Mancini GB, McPherson R, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–67. https://doi.org/10.1016/j.cjca.2012.11.032.CrossRefPubMedGoogle Scholar
- 3.Morgan S, Smolina K, Mooney D, Raymond C, Bowen ML, Gorczynski C, et al. The Canadian Rx atlas, 3rd edition (The Canadian prescription drug atlas). Vancouver: Centre for Health Services and Policy Research; 2013.Google Scholar
- 12.Chai C, James H. Working out ’til you’re sick? Doctors warn of rhabdo, a deadly condition linked to over exercising. Global news, Canada, Montreal. 2014. http://globalnews.ca/news/1082282/doctors-warn-of-rhabdo-a-deadly-condition-linked-to-over-exercising/. Accessed 22 Nov 2017.
- 13.Mancini GBJ, Baker S, Bergeron J, Fitchett D, Frohlich J, Genest J, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Consensus Working Group Update (2016). Can J Cardiol. 2016;32(7):S35–65. https://doi.org/10.1016/j.cjca.2016.01.003.CrossRefPubMedGoogle Scholar
- 14.Swankhuizen M, Regier L. Statin intolerance ‐ management considerations. RxFiles, Saskatoon, Canada. 2013. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf. Accessed 24 Oct 2017.
- 15.Hovingh GK, Gandra SR, McKendrick J, Dent R, Wieffer H, Catapano AL, et al. Identification and management of patients with statin-associated symptoms in clinical practice: a clinician survey. Atherosclerosis. 2016;245:111–7. https://doi.org/10.1016/j.atherosclerosis.2015.12.015.CrossRefPubMedGoogle Scholar
- 16.Anderson TJ, Grégoire J, Pearson GJ, Barry AR, Couture P, Dawes M, et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32(11):1263–82. https://doi.org/10.1016/j.cjca.2016.07.510.CrossRefPubMedGoogle Scholar
- 17.Jansen ME, Rigter T, Rodenburg W, Fleur TMC, Houwink EJF, Weda M, et al. Review of the reported measures of clinical validity and clinical utility as arguments for the implementation of pharmacogenetic testing: a case study of statin-induced muscle toxicity. Front Pharmacol. 2017;8:555. https://doi.org/10.3389/fphar.2017.00555.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Pharmacogenomics Research Network. Pharmacogenomics of Statin Therapy Center. 2017. http://www.pgrn.org/pgx-of-statin-therapy.html. Accessed 9 Oct 2017.
- 19.Canada G. Personalized medicine strategies for molecular diagnostics and targeted therapeutics of cardiovascular disease. Ottawa: Génome Canada; 2018. https://www.genomecanada.ca/en/personalized-medicine-strategies-molecular-diagnostics-and-targeted-therapeutics-cardiovascular. Accessed 17 Jan 2018.
- 20.Québec G. Personalized medicine strategies for molecular diagnostics and targeted therapeutics of cardiovascular disease. Génome Québec, Montreal. 2018. http://www.genomequebec.com/159-en/project/personalized-medicine-strategies-for-molecular-diagnostics-and-targeted-therapeutics-of-cardiovascular-diseases.html. Accessed 17 Jan 2018.
- 22.Pedersen TR, Kjekshus J, Berg K, Haghfelt T, Faergeman O, Faergeman G, et al. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. Atheroscler Suppl. 2004;5(3):81–7. https://doi.org/10.1016/j.atherosclerosissup.2004.08.027.CrossRefPubMedGoogle Scholar
- 23.Caro JJ, Möller J, Karnon J, Stahl J, Ishak J. Discrete event simulation for health technology assessment. Boca Raton: CRC Press; 2016.Google Scholar
- 28.Dhamoon MS, Sciacca RR, Rundek T, Sacco RL, Elkind MS. Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study. Neurology. 2006;66(5):641–6. https://doi.org/10.1212/01.wnl.0000201253.93811.f6.CrossRefPubMedGoogle Scholar
- 30.Canadian Institute for Health Information. 30-Day stroke in-hospital mortality. In: Health Indicators Interactive Tool. Ottawa: Canadian Institute for Health Information. 2017. http://indicatorlibrary.cihi.ca/display/HSPIL/30-Day+Stroke+In-Hospital+Mortality. Accessed 15 Sep 2017.
- 33.Statistics Canada. Life tables, Canada, provinces and territories—2010 to 2012. Ottawa (Ontario); Statistics Canada; 2016. Cat No.: 84-537-XIE.Google Scholar
- 34.Statistique Canada. Indice des prix à la consommation, aperçu historique (1997 à 2016). 2017. http://www.statcan.gc.ca/tables-tableaux/sum-som/l02/cst01/econ46a-fra.htm. Accessed 15 Mar 2017.
- 36.Régie de l’assurance-maladie du Québec. Manuel des médecins omnipraticiens: rémunération à l’acte. Québec: RAMQ; 2017.Google Scholar
- 37.Régie de l’assurance-maladie du Québec. Liste des médicaments: dernière mise à jour le 3 mai 2017. Québec: RAMQ; 2017.Google Scholar
- 46.Guertin JR, Rahme E, LeLorier J. Use of continuous exposure variables when examining dose-dependent pharmacological effects - application to the association between exposure to higher statin doses and the incidence of diabetes. J Popul Ther Clin Pharmacol. 2017;24(1):5-15. https://doi.org/10.22374/1710-618.104.22.168.
- 49.Wouters H, Van Dijk L, Geers HC, Winters NA, Van Geffen EC, Stiggelbout AM, et al. Understanding statin non-adherence: knowing which perceptions and experiences matter to different patients. PLoS One. 2016;11(1):e0146272. https://doi.org/10.1371/journal.pone.0146272.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Public Health Agency of Canada. Tracking heart disease and stroke in Canada 2009. Ottawa: Public Health Agency of Canada; 2009.Google Scholar
- 51.Ontario Case Costing: OCC Costing Analysis Tool [online database]. Ministry of Health and Long Term Care. 2015. https://hsimi.ca/occp/occpreports/. Accessed 10 Apr 2015.
- 56.CADTH. Guidelines for the economic evaluation of health technologies: Canada, 4th ed. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2017.Google Scholar