1. Cost-Effectiveness of a One-Time National Hepatitis C Screening Program: Impact of a Selective Drug Reimbursement Policy CADTH Symposium April 14, 2015 William W. L. Wong Assistant Professor / Decision Modeller Toronto Health Economics and Technology Assessment (THETA) Collaborative Leslie Dan Faculty of Pharmacy University of Toronto

2. The Team PHAC (Public Health Agency of Canada) Tom Wong Ping Yan Dena Schanzer Dana Paquette THETA (Toronto Health Economics and Technology Assessment Collaborative) William Wong Hong-Anh Tu Murray Krahn Toronto Centre for Liver Disease, University Health Network Jordan Feld David Wong Funding: This study was supported by Public Health Agency of Canada (PHAC).

3. Objective PHAC is now reviewing its screening guidance for HCV One-time national hepatitis C screening program? CDEC recommended treatment for F2 – F4 patients only What is the impact of this selective drug reimbursement policy in terms of cost- effectiveness?

4. Overview Background: hepatitis C and screening Cost-effectiveness of screening for hepatitis C Results One-time screening cost-effectiveness results Impact of a selective drug reimbursement policy Discussion and conclusion

5. BACKGROUND

6. Hepatitis C In Canada, around 0.5% of the population, has evidence of current or past HCV infection (HCV) Age 14 – 49: 0.4% Age 50 – 79: 0.8% Only 30% aware of the infection

7. Hepatitis C: Natural History Around 75% progressing to chronicity (Chronic hepatitis C (CHC)). 10-20% of whom will silently progress to cirrhosis at risk of dying prematurely of liver failure and/or liver cancer A recent disease burden study from Ontario 1, ranked hepatitis C first among all infectious diseases in heath burden Managing CHC is difficult because it is often asymptomatic Disease is often discovered when symptoms of late stage liver disease have become apparent and the prognosis is poor Complications may be reduced by offering treatment in a timely manner [1] Kwong et. al.

8. Treatment for chronic hepatitis C is rapidly evolving 2010 2015 Peginterferon plus ribavirin (PR) PR plus direct- acting antiviral (DAA) Interferon-free regimens

9. Current: Screening Target Screening 1 Injection drug user—this should include anyone who has ever injected drugs Patient on haemodialysis Patient with persistently elevated ALT Recipients of blood components or solid organs before 1992 Person with significant exposure to blood of HCV (+) individual Prisoners in correctional facilities Infants of HCV infected mothers HIV positive individuals Individuals with tattoos (especially performed in prisons) … [1] PHAC

10. Screening recommendation in US In the U.S.A, CDC revised screening recommendations have already included persons who are born between 1945 and 1965 It is very helpful to ascertain if these US recommendations are cost effective in Canada, considering differences in epidemiology and in the health care system.

11. COST-EFFECTIVENESS OF SCREENING FOR HEPATITIS C

12. Research Questions 1.What is the cost-effectiveness of one-time screening for HCV regardless of other risk factors for all adults born during 1945 – 1965? 2.What is the cost-effectiveness of one-time screening for HCV regardless of other risk factors for all adults born during 1945 – 1985?

13. Methods Cost-utility analysis, state transition model Primary outcome: number of Quality adjusted life years (QALYs), with strategies compared by incremental cost per QALY (ICER) Target population: 25–64 year-olds, and 45–64 year-olds individuals currently living in Canada Perspective: provincial Ministry of Health in Canada Time Horizon: Life-time, weekly cycle length. Discount rate 5%

14. Strategies (1)“No screening”; (2)“Screen-and-treat* with pegylated interferon plus ribavirin (PR)”; (3)“Screen-and-treat* with PR- based direct- acting antiviral agents (DAA)”; and (4)“Screen-and-treat* with interferon-free DAA.” *“Case finding” strategy: Individuals are offered one-time screening for HCV infection through their primary care physician at a visit scheduled for another purpose. Screening involves a blood test for HCV antibody. All positive antibody tests will be followed by an HCV RNA test to confirm infection.

15. Treatments Considered TreatmentDescription PRpegIFN alfa-2a plus ribavirin180 mcg /200mg (PEGASYS RBV) SIMSimeprevir 150 mg (GALEXOS) SOFSofosbuvir 400mg (Sovaldi) ABT-450paritaprevir/ritonavir + ombitasvir + dasabuvir (VIEKIRA PAK / Holkira PAK) In the “Screen and treat with interferon-free DAA”, Genotype 1 CHC: 12 weeks of ABT-450-based combination therapy; Genotype 2 and 3 CHC: 12 – 24 weeks of sofosbuvir in combination with ribavirin (SOF/RBV); For genotype 4, 5 and 6 CHC - 48 weeks of PR.

16. ECONOMIC MODEL

17. Screening Model F0 F1 F2 F3 F4 Advanced liver disease CHC- unrelated Death From all states F0 F1 F2 F3 F4 F0 F1 F2 F3 F4 Start of simulation HCV - F0 F1 F2 F3 F4 F0-F3 SVR F4 SVR Undiagnosed CHC diagnosed CHC On treatment Responder Non-responder

18. Advanced liver disease HCCDecompensation liver-transplant CHC-related Death CHC-unrelated Death From all states From all F4 states post- transplant

19. Data inputs ParameterSource Fibrosis distributionClinical data from Toronto Western Hospital Fibrosis progressionThein et al 2008 (meta-analysis) Cirrhosis progressionvan der Meer AJ et al. JAMA. 2012 (included Canadian patients) Probability to receive treatmentClinical data from Toronto Western Hospital Efficacy and safetyPublished Clinical trials All-cause treatment discontinuationPublished Clinical trials Proportion of patients eligible for short PR therapy Published Clinical trials MortalityUS study based on cancer registries and systematic review Chronic Hepatitis C and liver- transplant related costs Canadian costing studies (Krajden et al. 2010, Taylor et al. 2002)

20. RESULTS

21. Base case results: Age 25-64 Compared to Common baseline (No Screening) Age rangeStrategyCostQALYs∆Cost∆QALYsICER Sequential ICER 25-64 No screening $71,32713.7653--- - Screen & treat with PR $71,45013.7685$1240.0032$38,117* Screen & treat IFN- Free DAA (ABT-450) $71,59313.7729$2660.0077$34,783 Screen & treat with PR-based DAA (simeprevir) $71,59313.7716$2670.0063$42,398Dominated *Extendedly dominated; cost IFN-Free therapy assumed at $50,000

22. Base case results: Age 45-64 Compared to Common baseline (No Screening) Age rangeStrategyCostQALYs∆Cost∆QALYsICER Sequential ICER 45-64 No screening $83,33512.1027--- - Screen & treat with PR $83,47612.1068$1410.0041$34,359 Screen & treat with PR-based DAA (simeprevir) $83,67212.1104$3370.0077$44,034$55,151* Screen & treat IFN- Free DAA (ABT-450) $83,67312.1122$3380.0095$35,562$36,471 *Extendedly dominated; cost IFN-Free therapy assumed at $50,000

23. CEA By Age range

24. One way sensitivity analysis

25. Probabilistic Sensitivity Analysis

26. CADTH Therapeutic Review

27. Worst case scenario F0 and F1 CHC patients will not receive any treatment at the time of screening. We lose follow up on those CHC patients even though they progress to F2 or higher in their later years

28. Restricted treatment (F2-F4) Compared to Common baseline (No Screening) Age rangeStrategyCostQALYs∆Cost∆QALYsICER Sequential ICER 25-64 No screening $71,32713.7649--- - Screen & treat with PR $71,45113.7676$1240.0026$47,466$47,466* Screen & treat with PR- based DAA (simeprevir) $71,55613.7698$2300.0048$47,573$47,573* Screen & treat IFN-Free DAA (ABT-450) $71,55713.7709$2300.0060$38,298 45-64 No screening $83,33412.1024--- - Screen & treat with PR $83,47312.1061$1390.0036$38,333$38,333* Screen & treat with PR- based DAA (simeprevir) $83,63212.1090$2980.0065$45,636$45,636* Screen & treat IFN-Free DAA (ABT-450) $83,63412.1107$3000.0082$36,348 *Extendedly dominated; cost IFN-Free therapy assumed at $50,000

29. Comparison Compared to Common baseline (No Screening) Age rangeStrategyICER (Treat all)ICER (Treat F2 – F4) 25-64 No screening - - Screen & treat with PR $38,117*$47,466 Screen & treat with PR-based DAA (simeprevir) $42,398$47,573 Screen & treat IFN-Free DAA (ABT-450) $34,783$38,298 45-64 No screening -- Screen & treat with PR $34,359$38,333 Screen & treat with PR-based DAA (simeprevir) $44,034$45,636 Screen & treat IFN-Free DAA (ABT-450) $35,562$36,348 *Extendedly dominated; cost IFN-Free therapy assumed at $50,000

30. DISCUSSION & CONCLUSION

31. Limitations Our analysis also assumed that the probability of being treated and the distribution of fibrosis states of CHC patients in Canada was similar to that at a single tertiary care hospital. We also did not consider every possible screening strategy. For example, we have not investigated the economic benefit of screening high-risk groups such as immigrants from high burden countries, emergency room or hospitalized populations, skin piercing practitioners, and low-income groups

32. Limitations The CHC-related costs used was not fibrosis-specific, it may over estimate the cost of mild/no fibrosis and underestimate the cost of severe fibrosis The utilities of CHC patients who have late stage liver disease used by the model have a very small sample size, and may not cover the full spectrum of the severity of the disease We study the worst-case scenario for the restricted treatment. Ideally, F0 and F1 CHC patients can still benefit from the one- time screening if the follow-up program was well established.

33. Conclusion A selective drug reimbursement policy have some impact on a one-time national screening program for hepatitis C. However, our analysis suggested that a selective one-time hepatitis C screening program would still likely be cost- effective. The screening programs we have evaluated will identify the asymptomatic yet chronically infected individuals and offer medical treatment if needed according to the published guidelines optimally before advanced liver disease is present. Early recognition and linkage of infected individuals to care, treatment can save and prolong the lives of CHC-infected patients Huge impact on budget: Can We Afford to Cure Hepatitis C?

34. Budget: Treat all $4-5 billion in the next 10 years

35. Budget: Treat only F2-F4 $3-4 billion in the next 10 years

36. QUESTIONS