Currently Viewing:
The American Journal of Managed Care Special Issue: HCV
Real-World Outcomes of Ledipasvir/Sofosbuvir in Treatment-Naïve Patients With Hepatitis C
Zobair M. Younossi, MD, MPH, FACG, AGAF, FAASLD; Haesuk Park, PhD; Stuart C. Gordon, MD; John R. Ferguson; Aijaz Ahmed, MD; Douglas Dieterich, MD; and Sammy Saab, MD, MPH
Sofosbuvir Initial Therapy Abandonment and Manufacturer Coupons in a Commercially Insured Population
Taruja D. Karmarkar, MHS; Catherine I. Starner, PharmD; Yang Qiu, MS; Kirsten Tiberg, RPh; and Patrick P. Gleason, PharmD
Improving HCV Cure Rates in HIV-Coinfected Patients - A Real-World Perspective
Seetha Lakshmi, MD; Maria Alcaide, MD; Ana M. Palacio, MD, MPH; Mohammed Shaikhomer, MD; Abigail L. Alexander, MS; Genevieve Gill-Wiehl, BA; Aman Pandey, BS; Kunal Patel, BS; Dushyantha Jayaweera, MD; and Maria Del Pilar Hernandez, MD
Does Patient Cost Sharing for HCV Drugs Make Sense?
Darius N. Lakdawalla, PhD; Mark T. Linthicum, MPP; and Jacqueline Vanderpuye-Orgle, PhD
A Way Out of the Dismal Arithmetic of Hepatitis C Treatment
Jay Bhattacharya, MD, PhD, Center for Primary Care and Outcomes Research, Stanford University School of Medicine; Guest Editor-in-Chief for the HCV special issue of The American Journal of Managed
Currently Reading
Value of Expanding HCV Screening and Treatment Policies in the United States
Mark T. Linthicum, MPP; Yuri Sanchez Gonzalez, PhD; Karen Mulligan, PhD; Gigi A. Moreno, PhD; David Dreyfus, DBA; Timothy Juday, PhD; Steven E. Marx, PharmD; Darius N. Lakdawalla, PhD; Brian R. Edlin, MD; and Ron Brookmeyer, PhD
Costs and Spillover Effects of Private Insurers' Coverage of Hepatitis C Treatment
Gigi A. Moreno, PhD; Karen Mulligan, PhD; Caroline Huber, MPH; Mark T. Linthicum, MPP; David Dreyfus, DBA; Timothy Juday, PhD; Steven E. Marx, PharmD; Yuri Sanchez Gonzalez, PhD; Ron Brookmeyer, PhD; and Darius N. Lakdawalla, PhD
Coverage for Hepatitis C Drugs in Medicare Part D
Jeah Kyoungrae Jung, PhD; Roger Feldman, PhD; Chelim Cheong, PhD; Ping Du, MD, PhD; and Douglas Leslie, PhD

Value of Expanding HCV Screening and Treatment Policies in the United States

Mark T. Linthicum, MPP; Yuri Sanchez Gonzalez, PhD; Karen Mulligan, PhD; Gigi A. Moreno, PhD; David Dreyfus, DBA; Timothy Juday, PhD; Steven E. Marx, PharmD; Darius N. Lakdawalla, PhD; Brian R. Edlin, MD; and Ron Brookmeyer, PhD
Expanding screening for hepatitis C virus infection may generate substantial benefits for patients and society, but only when paired with expanded treatment policies.
Although Markov modeling as a tool for understanding chronic disease management policies is well established in the literature,41 the approach has limitations. First, as with any simulation, Markov models are not designed to generate predictions or forecasts. Similarly, as with all population-level studies, results from a Markov simulation cannot inform individual-level understanding of disease processes and outcomes.41,42 The results of our model should be approached as a guide for decision making rather than being predictive of real-world outcomes.
Second, each parameter carries a degree of uncertainty. We present sensitivity analyses and alternative model scenarios in the eAppendix in order to characterize this uncertainty. The model also assumes that parameter estimates are stable for the duration of the simulation and that this is a reasonable representation of HCV disease progression in the modeled risk groups.
Third, the model does not capture some important dynamics of the HCV epidemic. For example, the model does not account for the recent outbreak of HCV due to the increase in intravenous drug use among rural youth.43,44 In addition, the model does not capture the “treatment cascade” that occurs as patients are lost to follow-up between screening, treatment, and, ultimately, the achievement of SVR.20 We also lack concrete data on the extent to which physicians adhere to treatment guidelines.31,45 Our results are therefore an upper bound on the value of increased screening.
Fourth, while NHANES provides reliable population-level estimates, it is subject to several limitations. Small sample sizes make subpopulation estimates less reliable. NHANES also excludes the incarcerated and homeless populations, each of which is thought to have high rates of HCV.1,46,47 In addition, because NHANES relies on self-reported behavioral data, such as sexual behavior and injection drug use, there is a risk of underreporting. Nonetheless, use of NHANES is preferable to parameters from the literature because its sample is representative of the housed, civilian population of the United States.  
Finally, more than half of new HCV infections occur in the PWID population, and evidence suggests that combining increased outreach efforts with prevention, testing, and antiviral treatment may have considerable effects on incidence and prevalence in this group.48 Effective prevention includes outreach, education, testing, needle and syringe access, and access to opioid substitution therapy.48,49 Our model does not incorporate the effect of outreach or prevention efforts, however, and assumes that effects on transmission are due to treatment effects alone. Future research should explicitly model the additional effects of programs that offer targeted outreach, screening, prevention, treatment, and wraparound services for high-risk populations.
Increasing screening for HCV infection may generate considerable value for society, but only when paired with access to treatment at earlier stages of the disease. This result highlights the importance of implementing policies to ensure patients who receive an HCV-positive diagnosis remain in the healthcare system until they receive treatment and achieve SVR. Resource constraints in the healthcare system require difficult allocation decisions, and HCV has been at the center of many recent debates. Our findings suggest that expansions in screening coupled with treatment of all infected patients could break even within 8 years and accrue an additional $823.53 billion in discounted net social benefits over a 20-year horizon. Thus, expanded screening and treatment may pay substantial dividends, but only when effective mechanisms are in place to ensure that patients are retained in care and able to access treatment.

The authors would like to thank Caroline Huber, MPH, and Chelsea Kamson, BA, for valuable research support. Caroline Huber is an employee of Precision Health Economics (PHE) and Chelsey Kamson was employed by PHE at the time of the research.

Author Affiliations: Precision Health Economics (MTL, KM, GAM), Los Angeles, CA; AbbVie, Inc (YSG, TJ, SEM), North Chicago, IL; Arete Analytics (DD), Andover, MA; Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California (DNL), Los Angeles, CA; Weill Cornell Medical College, Cornell University (BRE), New York, NY; National Development and Research Institutes (BRE), New York, NY; Department of Biostatistics, University of California (RB), Los Angeles, CA.

Source of Funding: Support for this research was provided by AbbVie, Inc.

Author Disclosures: Drs Juday, Marx, and Sanchez Gonzalez are employees and stockholders of Abbvie, Inc, which develops and markets treatments for hepatitis C virus. Mr Linthicum and Drs Moreno and Mulligan are employees of Precision Health Economics (PHE), a healthcare consultancy to life science firms. Dr Lakdawalla is the chief strategy officer and owns equity in PHE, and Drs Dreyfus and Brookmeyer are consultants for PHE. Dr Edlin reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MTL, YSG, KM, GAM, DD, TJ, SEM, DNL, BRE, RB); acquisition of data (KM, GAM); analysis and interpretation of data (MTL, YSG, KM, GAM, DD, TJ, SEM, DNL, BRE, RB); drafting of the manuscript (MTL, YSG, KM, GAM); critical revision of the manuscript for important intellectual content (MTL, YSG, KM, GAM, DD, TJ, SEM, DNL, BRE, RB); statistical analysis (KM, DD); obtaining funding (TJ, YSG); administrative, technical, or logistic support (MTL, KM, GAM); and supervision (GAM, YSG, TJ, DNL).

Address correspondence to: Mark T. Linthicum, MPP, Precision Health Economics, 11100 Santa Monica Blvd, Suite 500, Los Angeles, CA 90025. E-mail:

1. Edlin BR, Eckhardt BJ, Shu MA, Holmberg SD, Swan T. Toward a more accurate estimate of the prevalence of hepatitis C in the United States. Hepatology. 2015;62(5):1353-1363. doi: 10.1002/hep.27978.

2. CDC. Hepatitis C virus infection among adolescents and young adults—Massachusetts, 2002–2009. MMWR Morb Mortal Wkly Rep. 2011;60(17):537-541.

3. AASLD IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932-954. doi: 10.1002/hep.27950.

4. Eckman MH, Talal AH, Gordon SC, Schiff E, Sherman KE. Cost-effectiveness of screening for chronic hepatitis C infection in the United States. Clin Infect Dis. 2013;56(10):1382-1393. doi: 10.1093/cid/cit069.

5. National Health and Nutrition Examination Survey Data [waves 2003-2004 through 2011-2012]. CDC website. Acessed March 1, 2015.

6. Hagan H, Campbell J, Thiede H, et al. Self-reported hepatitis C virus antibody status and risk behavior in young injectors. Public Health Rep. 2006;121(6):710-719.

7. Rein DB, Smith BD, Wittenborn JS, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156(4):263-270. doi: 10.7326/0003-4819-156-4-201202210-00378.

8. Coffin PO, Scott JD, Golden MR, Sullivan SD. Cost-effectiveness and population outcomes of general population screening for hepatitis C. Clin Infect Dis. 2012;54(9):1259-1271. doi: 10.1093/cid/cis011.

9. Gordon SC, Hamzeh FM, Pockros PJ, et al. Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther. 2013;38(7):784-793. doi: 10.1111/apt.12454.

10. Gordon SC, Pockros PJ, Terrault NA, et al. Impact of disease severity on healthcare costs in patients with chronic hepatitis C (CHC) virus infection. Hepatology. 2012;56(5):1651-1660. doi: 10.1002/hep.25842.

11. Moorman AC, Xing J, Ko S, et al; CHeCS Investigators. Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): missed opportunities for intervention. Hepatology. 2015;61(5):1479-1484. doi: 10.1002/hep.27365.

12. Van Nuys K, Brookmeyer R, Chou JW, Dreyfus D, Dieterich D, Goldman DP. Broad hepatitis C treatment scenarios return substantial health gains, but capacity is a concern. Health Aff (Millwood). 2015;34(10):1666-1674. doi: 10.1377/hlthaff.2014.1193.

13. Doyle JS, Aspinall E, Liew D, Thompson AJ, Hellard ME. Current and emerging antiviral treatments for hepatitis C infection. Br J Clin Pharmacol. 2013;75(4):931-943. doi: 10.1111/j.1365-2125.2012.04419.x.

14. Younossi ZM, Singer ME, Mir HM, Henry L, Hunt S. Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients. J Hepatology. 2014;60(3):530-537. doi: 10.1016/j.jhep.2013.11.009.

15. Afdhal N, Reddy KR, Nelson DR, et al; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493. doi: 10.1056/NEJMoa1316366.

16. Afdhal N, Zeuzem S, Kwo P, et al; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898. doi: 10.1056/NEJMoa1402454.

17. Kowdley KV, Gordon SC, Reddy KR, et al; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888. doi: 10.1056/NEJMoa1402355.

18. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147(2):359-365.e351. doi: 10.1053/j.gastro.2014.04.045.

19. Ferenci P, Bernstein D, Lalezari J, et al; PEARL-III Study; PEARL-IV Study. ABT-450/r–ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983-1992. doi: 10.1056/NEJMoa1402338.

20. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V 3rd. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):e101554. doi: 10.1371/journal.pone.0101554.

21. Lutchman G, Kim WR. A glass half full: implications of screening for hepatitis C virus in the era of highly effective antiviral therapy. Hepatology. 2015;61(5):1455-1458. doi: 10.1002/hep.27718.

22. Kallman JB, Arsalla A, Park V, et al. Screening for hepatitis B, C and non-alcoholic fatty liver disease: a survey of community-based physicians. Aliment Pharmacol Ther. 2009;29(9):1019-1024. doi: 10.1111/j.1365-2036.2009.03961.x.

23. Leidner AJ, Chesson HW, Xu F, Ward JW, Spradling PR, Holmberg SD. Cost-effectiveness of hepatitis C treatment for patients in early stages of liver disease. Hepatology. 2015;61(6):1860-1869. doi: 10.1002/hep.27736.

24. Manos MM, Shvachko VA, Murphy RC, Arduino JM, Shire NJ. Distribution of hepatitis C virus genotypes in a diverse US integrated health care population. J Med Virol. 2012;84(11):1744-1750. doi: 10.1002/jmv.23399.

25. Williams IT, Bell BP, Kuhnert W, Alter MJ. Incidence and transmission patterns of acute hepatitis C in the United States, 1982-2006. Arch Intern Med. 2011;171(3):242-248. doi: 10.1001/archinternmed.2010.511.

26. Hepatitis C FAQs for health professionals. CDC website. Updated March 11, 2016. Accessed April 15, 2015.

27. Henderson DK. Managing occupational risks for hepatitis C transmission in the health care setting. Clin Microbiol Rev. 2003;16(3):546-568.

28. Grabowski HG, Vernon JM. Brand loyalty, entry, and price competition in pharmaceuticals after the 1984 Drug Act. J Law Econ. 1992;35(2):331-350.

29. Tirrell M. Pricing wars heat up over hepatitis C drugs. CNBC website. Published February 4, 2015. Accessed July 3, 2015.

30. Davis KL, Mitra D, Medjedovic J, Beam C, Rustgi V. Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol. 2011;45(2):e17-e24. doi: 10.1097/MCG.0b013e3181e12c09.

31. Cabana MD, Rand CS, Powe NR, et al. Why don’t physicians follow clinical practice guidelines?: a framework for improvement. JAMA. 1999;282(15):1458-1465.

32. Aetna. Pharmacy Clinical Policy Bulletins Aetna Non-Medicare Prescription Drug Plan: Subject: Hepatitis C. 2015. Accessed September 1, 2015.

33. Canary LA, Klevens RM, Holmberg SD. Limited access to new hepatitis C virus treatment under state Medicaid programs. Ann Intern Med. 2015;163(3):226-228. doi: 10.7326/M15-0320.

34. Prior authorization criteria: United American—essential (PDP). United American Medicare Part D website. Updated March 01, 2016. Accessed April 14, 2016.

35. Hirth RA, Chernew ME, Miller E, Fendrick AM, Weissert WG. Willingness to pay for a quality-adjusted life year: in search of a standard. Med Decis Making. 2000;20(3):332-342.

36. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-797. doi: 10.1056/NEJMp1405158.

37. Rein DB, Wittenborn JS, Smith BD, Liffmann DK, Ward JW. The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus. Clin Infect Dis. 2015;61(2):157-68. doi: 10.1093/cid/civ220.

38. Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52(6):793-800. doi: 10.1093/cid/ciq243.

39. Skarbinski J, Rosenberg E, Paz-Bailey G, et al. Human immunodeficiency virus transmission at each step of the care continuum in the United States. JAMA Intern Med. 2015;175(4):588-596. doi: 10.1001/jamainternmed.2014.8180.

40. Moreno G, Mulligan K, Huber C, et al. Costs and spillover effects of private insurers’ coverage of hepatitis C treatment. Am J Manag Care. 2016;x(x):In Press.

41. Briggs A, Sculpher M. An introduction to Markov modelling for economic evaluation. Pharmacoeconomics. 1998;13(4):397-409.

42. Amiri M, Kelishadi R. Comparison of models for predicting outcomes in patients with coronary artery disease focusing on microsimulation. Int J Prev Med. 2012;3(8):522-530.

43. Suryaprasad AG, White JZ, Xu F, et al. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006–2012. Clin Infect Dis. 2014;59(10):1411-1419. doi: 10.1093/cid/ciu643.

44. Jones CM, Logan J, Gladden RM, Michele K. Bohm MK. Vital signs: demographic and substance use trends among heroin users—United States, 2002–2013. MMWR Morb Mortal Wkly Rep. 2015;64(26):719-725.

45. Southern WN, Drainoni M-L, Smith BD, et al. Physician nonadherence with a hepatitis C screening program. Qual Manag Health Care. 2014;23(1):1-9. doi: 10.1097/QMH.0000000000000007.

46. He T, Li K, Roberts MS, et al. Prevention of hepatitis C by screening and treatment in U.S. prisons. Ann Intern Med. 2016;164(2):84-92. doi: 10.7326/M15-0617.

47. Rich JD, Allen SA, Williams BA. Responding to hepatitis C through the criminal justice system. N Engl J Med. 2014;370(20):1871-1874. doi: 10.1056/NEJMp1311941.

48. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57(suppl 2):S39-S45. doi: 10.1093/cid/cit296.

49. Edlin BR, Winkelstein ER. Can hepatitis C be eradicated in the United States? Antiviral Res. 2014;110:79-93. doi: 10.1016/j.antiviral.2014.07.015. 
Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up