Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial
Publication: Annals of Internal Medicine
Volume 170, Number 4
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Abstract
Background:
The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of a composite outcome including myocardial infarction (MI), stroke, and death.
Objective:
To determine the cost-effectiveness of alirocumab in these circumstances.
Design:
Decision analysis using the Cardiovascular Disease Policy Model.
Data Sources:
Data sources representative of the United States combined with data from the ODYSSEY Outcomes trial.
Target Population:
U.S. adults with a recent first MI and a baseline low-density lipoprotein cholesterol level of 1.81 mmol/L (70 mg/dL) or greater.
Time Horizon:
Lifetime.
Perspective:
U.S. health system.
Intervention:
Alirocumab or ezetimibe added to statin therapy.
Outcome Measures:
Incremental cost-effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained.
Results of Base-Case Analysis:
Compared with a statin alone, the addition of ezetimibe cost $81 000 (95% uncertainty interval [UI], $51 000 to $215 000) per QALY. Compared with a statin alone, the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe, replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY.
Results of Sensitivity Analysis:
The price of alirocumab would have to decrease from its original cost of $14 560 to $1974 annually to be cost-effective relative to ezetimibe.
Limitation:
Effectiveness estimates were based on a single randomized trial with a median follow-up of 2.8 years and should not be extrapolated to patients with stable coronary heart disease.
Conclusion:
The price of alirocumab would have to be reduced considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely, independent cost-effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market.
Primary Funding Source:
University of California, San Francisco, and Institute for Clinical and Economic Review.
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References
1.
Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-99. [PMID: 25773378]
2.
Kazi DS, Moran AE, Coxson PG, Penko J, Ollendorf DA, Pearson SD, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. JAMA. 2016;316:743-53. [PMID: 27533159]
3.
Schwartz GG, Szarek M, Bhatt DL, Bittner V, Diaz R, Edelberg J, et al. The ODYSSEY Outcomes trial: alirocumab in patients after acute coronary syndrome. Presented at ACC.18, the American College of Cardiology's 67th Annual Scientific Session and Expo, Orlando, Florida, 10–12 March 2018.
4.
Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097-2107. [PMID: 30403574]
5.
Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362:590-9. [PMID: 20089957]
6.
Moran AE, Odden MC, Thanataveerat A, Tzong KY, Rasmussen PW, Guzman D, et al. Cost-effectiveness of hypertension therapy according to 2014 guidelines. N Engl J Med. 2015;372:447-55. [PMID: 25629742]
7.
Weinstein MC, Coxson PG, Williams LW, Pass TM, Stason WB, Goldman L. Forecasting coronary heart disease incidence, mortality, and cost: the Coronary Heart Disease Policy Model. Am J Public Health. 1987;77:1417-26. [PMID: 3661794]
8.
Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016;316:1093-103. [PMID: 27623463]
9.
Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey public use files, 1998–2008. Accessed at http://meps.ahrq.gov/mepsweb/ on 1 January 2010.
10.
Bureau of Labor Statistics. Consumer Price Index for all urban consumers. Accessed at https://data.bls.gov/timeseries/CUUR0000SAM?output_view=pct_12mths on 25 April 2018.
11.
California Office of Statewide Health Planning and Development. California public patient discharge data: Office of Statewide Health Planning and Development, 2008. Accessed at www.oshpd.ca.gov/HID/Data_Request_Center/ on 1 January 2016.
12.
California Office of Statewide Health Planning and Development. Hospital financial data: Office of Statewide Health Planning and Development, 2003. Accessed at https://oshpd.ca.gov/data-and-reports/request-data/ on 1 January 2016.
13.
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-97. [PMID: 26039521]
14.
Kazi DS, Garber AM, Shah RU, Dudley RA, Mell MW, Rhee C, et al. Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome. Ann Intern Med. 2014;160:221-32. [PMID: 24727840]
15.
Khazeni N, Hutton DW, Garber AM, Hupert N, Owens DK. Effectiveness and cost-effectiveness of vaccination against pandemic influenza (H1N1) 2009. Ann Intern Med. 2009;151:829-39. [PMID: 20008759]
16.
Khazeni N, Hutton DW, Garber AM, Owens DK. Effectiveness and cost-effectiveness of expanded antiviral prophylaxis and adjuvanted vaccination strategies for an influenza A (H5N1) pandemic. Ann Intern Med. 2009;151:840-53. [PMID: 20008760]
17.
Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Murray CJ, et al. Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the Global Burden of Disease 2010 study. Circulation. 2014;129:1483-92. [PMID: 24573352]
18.
Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Flaxman A, et al. The global burden of ischemic heart disease in 1990 and 2010: the Global Burden of Disease 2010 study. Circulation. 2014;129:1493-501. [PMID: 24573351]
19.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2197-223. [PMID: 23245608]
20.
National Center for Health Statistics. National Health and Nutrition Examination Survey, 2005-2012. Accessed at https://wwwn.cdc.gov/nchs/nhanes/Default.aspx on 11 December 2018.
21.
National Center for Health Statistics. National Health Interview Survey, 2009-2011. Accessed at ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Datasets/NHIS/ on 12 June 2012.
22.
National Center for Health Statistics. National Hospital Discharge Survey, 2010. Accessed at ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Datasets/NHDS/ on 29 March 2012.
23.
National Center for Health Statistics. CDC WONDER: underlying cause of death, 1999-2010. Accessed at http://wonder.cdc.gov/ucd-icd10.html on 13 February 2013.
24.
SSR Health. US Brand Rx Net Price. Accessed at http://www.ssrhealth.com/research-archive/ on 1 March 2018.
25.
IBM Watson Health. IBM Miromedex Red Book. Accessed at https://truvenhealth.com/Training/Product/IBM-Micromedex-Clinical-Knowledge/IBM-Micromedex-RED-BOOK on 20 April 2018.
26.
U.S. Census Bureau. American Fact Finder. Sex by age. Universe: total population 2010 Census summary file 1. Accessed at https://factfinder.census.gov/faces/tableservices/jsf/pages/productview.xhtml?pid=DEC_10_SF1_PCT12&prodType=table on 11 December 2018.
27.
Singh J. Exploratory analysis for population projection data. Accessed at https://rpubs.com/jayant_singh/population-projections on 11 December 2018.
28.
U.S. Census Bureau. Statistical Abstract of the United States, 1998. vol 118. Washington, DC: Government Printing Office; 1998:136.
29.
Hlatky MA, Kazi DS. PCSK9 Inhibitors: economics and policy. J Am Coll Cardiol. 2017;70:2677-2687. [PMID: 29169476]
30.
Sabatine MS, DeFerrari GM, Giugliano RP, Huber K, Lewis BS, Ferreira J, et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease. Circulation. 2018;138:756-766. [PMID: 29626068]
31.
Navar AM, Taylor B, Mulder H, Fievitz E, Monda KL, Fievitz A, et al. Association of prior authorization and out-of-pocket costs with patient access to PCSK9 inhibitor therapy. JAMA Cardiol. 2017;2:1217-1225. [PMID: 28973087]
32.
Kazi DS, Lu CY, Lin GA, DeJong C, Dudley RA, Chen R, et al. Nationwide coverage and cost-sharing for PCSK9 inhibitors among Medicare Part D plans. JAMA Cardiol. 2017;2:1164-1166. [PMID: 28903137]
33.
Kazi DS, Penko J, Ollendorf DA, Coxson PG, Bibbins-Domingo K. Effect of money-back guarantees on the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibitors. Ann Intern Med. 2018;168:896-898. [PMID: 29610832]
34.
Institute for Clinical and Economic Review. Alirocumab for treatment of high cholesterol: effectiveness and value. Preliminary new evidence update. Accessed at https://icer-review.org/wp-content/uploads/2018/03/Alirocumab-Preliminary-New-Evidence-Update_03102018.pdf on 1 November 2018.
35.
Berkort B. Regeneron/Sanofi heart drug succeeds in major trial. Will insurers pay? Accessed at www.reuters.com/article/us-regeneron-pharms-sanofi-cholesterol/regeneron-sanofi-heart-drug-succeeds-in-major-trial-will-insurers-pay-idUSKCN1GM0IK on 29 November 2018.
36.
Cortez M, Spalding R. Regeneron, Sanofi cut heart drug's price to spur greater use. Accessed at www.bloomberg.com/news/articles/2018-03-10/regeneron-sanofi-cut-heart-drug-s-price-as-trial-disappoints on 29 November 2018.
37.
Walker J. Regeneron and Sanofi plan to cut cholesterol drug price in exchange for wider coverage. Accessed at www.wsj.com/articles/regeneron-and-sanofi-plan-to-cut-cholesterol-drug-price-in-exchange-for-wider-coverage-1520690400 on 29 November 2018.
38.
Herper M. Regeneron and Express Scripts reach a deal on embattled cholesterol drug. Accessed at www.forbes.com/sites/matthewherper/2018/05/01/lets-make-a-deal-drugmakers-try-to-reignite-a-dormant-cholesterol-drug-with-price-cut/#2c86b62d5f38 on 29 November 2018.
39.
Herper M. In unprecedented move, Amgen cuts price of cholesterol drug Repatha by 60%. Accessed at www.forbes.com/sites/matthewherper/2018/10/24/in-unprecedented-move-amgen-cuts-price-of-cholesterol-drug-repatha-by-60/#21c2d73bc257 on 1 November 2018.
40.
Navarese EP, Kolodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163:40-51. [PMID: 25915661]
41.
Committee on Ethical and Scientific Issues in Studying the Safety of Approved Drugs. Ethical and Scientific Issues in Studying the Safety of Approved Drugs. Washington, DC: National Academies Pr; 2012.
42.
Felli JC, Hazen GB. Sensitivity analysis and the expected value of perfect information. Med Decis Making. 1998;18:95-109. [PMID: 9456214]
43.
Maddox TM, Reid KJ, Rumsfeld JS, Spertus JA. One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors. BMC Cardiovasc Disord. 2007;7:28. [PMID: 17850662]
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Published In
Annals of Internal Medicine
Volume 170 • Number 4 • 19 February 2019
Pages: 221 - 229
History
Published online: 1 January 2019
Published in issue: 19 February 2019
Keywords
Copyright
© 2019 American College of Physicians.
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Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Ann Intern Med.2019;170:221-229. [Epub 1 January 2019]. doi:10.7326/M18-1776
Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Ann Intern Med.2019;170:221-229. [Epub 1 January 2019]. doi:10.7326/M18-1776
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Time to update the $100,000 threshold for cost effectiveness
1- Kazi DS, Penko J, Coxson PG, Guzman D, Wei PC, Bibbins-Domingo K. Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Ann Intern Med 2019;170:221-229.
2- Mark DB, Hlatky MA, Califf RM, Naylor CD, Lee KL, Armstrong PW, Barbash G, White H, Simoons ML, Nelson CL, Clapp-Channing N. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. New England journal of medicine. 1995 May 25;332(21):1418-24.
Authors' Response
To provide researchers and policy-makers some guidance on this thorny issue, the American Heart Association and American College of Cardiology have defined high-value interventions as those with an incremental cost-effectiveness ratio (ICER) of less than 50,000/QALY and low-value interventions as those with an ICER of 150,000 per QALY or higher.2 These values were adapted from the World Health Organization’s Choosing Interventions that are Cost-Effective (WHO CHOICE) project, which classifies interventions into three categories of cost-effectiveness: highly cost-effective, with an ICER < gross domestic product (GDP) per capita; cost-effective, with an ICER between 1 and 3 times GDP per capita; and not cost-effective, with an ICER >3 times GDP per capita. Since the US per capita GDP is approximately $60,000, the WHO CHOICE framework would suggest that interventions between $60,000 and $180,000 per QALY would be cost-effective in the US. However, this GDP-based framework is fraught with its own theoretical and practical limitations,3 and unanswered questions include whether this threshold should vary based on the number of people eligible for the intervention. For instance, would we be willing to pay more for a new treatment that benefits a thousand patients with a rare disease than one for 10 million US adults at risk of major cardiovascular events?
We chose the $100,000 per QALY for our base-case analysis as it is the approximate mid-point of the ranges recommended by the organizations above.4 In line with the recommendations of the Second Panel of Cost Effectiveness in Health and Medicine, we presented additional analyses using the $50,000 per QALY and $150,000 per QALY thresholds in the online Supplement (Appendix Table 5).4,5
Identifying an explicit willingness-to-pay threshold would require our society to have a thoughtful conversation about the trade-offs of increasing or reducing the amount of money we spend on health care, and, by extension, a national consensus on how much we value health relative to other societal priorities. More importantly, we would have to be willing to forego interventions that do not meet our pre-determined threshold of cost-effectiveness. Although we do not appear to have the political appetite for this difficult conversation at the present time, clarifying our priorities in a time of economic uncertainty would enhance our health system’s ability to efficiently – and possibly equitably – allocate resources to improve the health of our population.
Dhruv S. Kazi, MD, MSc, MS
Beth Israel Deaconess Medical Center, Boston, MA
Kirsten Bibbins-Domingo, PhD, MD, MAS
University of California San Francisco, San Francisco, CA
References
1. PCORI Help Center. What Is PCORI’s Official Policy On Cost And Cost-Effectiveness Analysis? Patient-Centered Outcomes Research Institute.Available at https://help.pcori.org/hc/en-us/articles/213716587-What-is-PCORI-s-official-policy-on-cost-and-cost-effectiveness-analysis- . Accessed March 29, 2019.
2. Anderson JL, Heidenreich PA, Barnett PG, Creager MA, Fonarow GC, Gibbons RJ, Halperin JL, Hlatky MA, Jacobs AK, Mark DB, Masoudi FA, Peterson ED, Shaw LJ. ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63: 2304–22.
3. Marseille, Elliot, Larson, Bruce, Kazi, Dhruv S, Kahn, James G & Rosen, Sydney. (2015). Thresholds for the cost–effectiveness of interventions: alternative approaches. Bulletin of the World Health Organization, 93 (2), 118 - 124. World Health Organization.
4. Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Kazi DS, Penko J, Coxson PG, Guzman D, Wei PC, Bibbins-Domingo K. Ann Intern Med. 2019 Jan 1. doi: 10.7326/M18-1776.
5. 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 KE, Ganiats TG. Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses. Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016;316(10):1093-1103. doi:10.1001/jama.2016.12195