Value of a Hypothetical Pharmacogenomic Test for the Diagnosis of Statin-Induced Myopathy in Patients at High Cardiovascular Risk
- 8 Downloads
We recently conducted two economic evaluations of a hypothetical pharmacogenomic test for statin-induced myopathy (SIM) in patients at high cardiovascular risk. Although the models differed in modeling technique and data inputs, both yielded similar results. We believe our approach to assessing the economic value of a diagnostic test was highly advantageous as it characterized the complete range of false-negative and false-positive test outcomes. We used a broad interpretation of test parameters that reflected physician and patient behavioral responses to the test results and accounted for patient adherence to treatment. Both economic evaluations indicated that a highly accurate pharmacogenomic test for SIM would provide a positive incremental net monetary benefit (INMB) for a provincial payer in Canada. However, the value of the test would depend on its ability to accurately diagnose patients when they experience musculoskeletal pain symptoms and guide patients with a test result indicating no SIM to adhere to treatment. Interestingly, our results indicated that a highly inaccurate test would still yield a positive INMB. We found this surprising result was driven by the imbalance of the risk of cardiovascular events outweighing the risk of rhabdomyolysis in patients at high cardiovascular risk. A highly accurate pharmacogenomic test for SIM in patients at high cardiovascular risk would provide economic value for payers. However, the economic and clinical value of the test would depend on the credibility of the test results and their success in influencing patients without SIM to adhere to therapy.
DM contributed to the conception and design of the study, data acquisition, analysis and interpretation of data, drafting the article, and final approval. JRG and JL contributed to the conception and design of the study, analysis and interpretation of data, drafting the article, and final approval.
Compliance with Ethical Standards
This research was supported by Genome Canada and Genome Québec. Jason R. Guertin is a recipient of an establishment fund from the Centre de recherche du CHU de Québec - Université Laval and from the Fondation du CHU de Québec.
Conflict of interest
Dominic Mitchell, Jason R. Guertin, and Jacques LeLorier have no conflicts of interest that are directly relevant to the content of this review.
- 1.Mohamad TN, All M, Faddah R. Primary and secondary prevention of coronary artery disease. In: Drugs and disease: cardiology. Medscape; 2017. https://emedicine.medscape.com/article/164214-overview. Accessed 24 Feb 2018.
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.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/10.22374/1710-6188.8.131.52.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2016;37(11):908–16. https://doi.org/10.1093/eurheartj/ehv641.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Statin benefits questioned for heart disease prevention: Cholesterol-lowering drugs heavily promoted to prevent strokes and heart attacks. CBC Radio Canada; 2013. http://www.cbc.ca/news/health/statin-benefits-questioned-for-heart-disease-prevention-1.1373093. Accessed 28 Feb 2018.
- 12.Mancini GB, Baker S, Bergeron J, Fitchett D, Frohlich J, Genest J, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference. Can J Cardiol. 2011;27(5):635–62. https://doi.org/10.1016/j.cjca.2011.05.007.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Mancini GBJ, Tashakkor AY, Baker S, Bergeron J, Fitchett D, Frohlich J, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus Update. Can J Cardiol. 2013;29(12):1553–68. https://doi.org/10.1016/j.cjca.2013.09.023.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.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.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Chai C, James H. Working out ’til you’re sick? Doctors warn of rhabdo, a deadly condition linked to over exercising. Montreal: Global News; 2014. http://globalnews.ca/news/1082282/doctors-warn-of-rhabdo-a-deadly-condition-linked-to-over-exercising/. Accessed 22 Nov 2017.
- 19.Swankhuizen M, Regier L. Statin intolerance—Management considerations. Saskatoon: RxFiles; 2013. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf. Accessed 24 Oct 2017.
- 21.Carr DF, O’Meara H, Jorgensen AL, Campbell J, Hobbs M, McCann G, et al. SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink. Clin Pharmacol Ther. 2013;94(6):695–701. https://doi.org/10.1038/clpt.2013.161.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Wilke RA, Ramsey LB, Johnson SG, Maxwell WD, McLeod HL, Voora D, et al. The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther. 2012;92(1):112–7. https://doi.org/10.1038/clpt.2012.57.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Stewart A. SLCO1B1 polymorphisms and statin-induced myopathy. PLoS Curr. 2013. https://doi.org/10.1371/currents.eogt.d21e7f0c58463571bb0d9d3a19b82203.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Regence. Medical policy manual: genetic testing for statin-induced myopathy. Portland: Regence; 2018.Google Scholar
- 26.Génome Canada. 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.
- 27.Génome Québec. Personalized medicine strategies for molecular diagnostics and targeted therapeutics of cardiovascular disease. Montreal: Génome Québec; 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.
- 28.Mitchell D, Guertin JR, Iliza AC, Fanton-Aita F, LeLorier J. Economic evaluation of a pharmacogenomics test for statin-induced myopathy in cardiovascular high-risk patients initiating a statin. Mol Diagn Ther. 2017;21(1):95–105. https://doi.org/10.1007/s40291-016-0238-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Mitchell D, Guertin JR, Dubois A, Dubé MP, Tardif JC, Iliza AC, et al. 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. Mol Diagn Ther. 2018. https://doi.org/10.1007/s40291-018-0323-2.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.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.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Berm EJJ, de Looff M, Wilffert B, Boersma C, Annemans L, Vegter S, et al. Economic evaluations of pharmacogenetic and pharmacogenomic screening tests: a systematic review. second update of the literature. PLoS One. 2016;11(1):e0146262. https://doi.org/10.1371/journal.pone.0146262.CrossRefPubMedPubMedCentralGoogle Scholar
- 48.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
- 53.Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012–22. https://doi.org/10.1093/eurheartj/ehv043.CrossRefPubMedPubMedCentralGoogle Scholar
- 57.Patel J, Superko HR, Martin SS, Blumenthal RS, Christopher-Stine L. Genetic and immunologic susceptibility to statin-related myopathy. Atherosclerosis. 2015;240(1):260–71. https://doi.org/10.1016/j.atherosclerosis.2015.03.025.CrossRefPubMedPubMedCentralGoogle Scholar
- 58.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.CrossRefPubMedPubMedCentralGoogle Scholar
- 64.B.C. PharmaCare. B.C. PharmaCare Drug Information Sheet for alirocumab (PRALUENT). Victoria: PharmaCare. Ministry of Health; 2016.Google Scholar
- 65.Sanofi-aventis Canada Inc. Praluent: product monograph including patient medication information, Laval; 2017.Google Scholar
- 66.Amgen Canada Inc. Repatha (evolocumab): product monograph including patient medication information, Mississauga; 2016.Google Scholar
- 67.CADTH. Guidelines for the economic evaluation of health technologies: Canada. 3rd ed. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2006.Google Scholar
- 68.CADTH. Guidelines for the Economic Evaluation of Health Technologies: Canada. 4th ed. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2017.Google Scholar
- 69.van Kempen BJ, Spronk S, Koller MT, Elias-Smale SE, Fleischmann KE, Ikram MA, et al. Comparative effectiveness and cost-effectiveness of computed tomography screening for coronary artery calcium in asymptomatic individuals. J Am Coll Cardiol. 2011;58(16):1690–701. https://doi.org/10.1016/j.jacc.2011.05.056.CrossRefPubMedPubMedCentralGoogle Scholar