Croatian perspective cost effectiveness analysis of interferon free - PowerPoint PPT Presentation

Croatian perspective cost effectiveness analysis of interferon free therapy for chronic HCV Neven Lovrinov, MSc.Pharm Terminal d.o.o. Croatia

HCV treatment cost – 2014 hot topic in media

SVR rates in HCV Treatment Regimen Treatment history Components SVR (%) duration 38 − 44 1.2 Treatment naïve PegIFN/RBV 48 w eeks Dual R: 24 − 29 3,4 therapy PR: 7 − 15 3,4 Treatment experienced PegIFN/RBV 48 w eeks NR: 5 3,4 4-w eek lead ‑ in + 63 − 66 1 BOC + pegIFN/RBV 24/44 w eeks Treatment naïve 69 − 75 2 TPV + pegIFN/RBV 24/48 w eeks R: 69 − 75 3 Triple 4-w eek lead ‑ in + BOC + pegIFN/RBV therapy 32/44 w eeks PR: 40 − 52 3 4-w eek lead ‑ in + R: 83 − 88 4 Treatment experienced 44 w eeks, or PR: 54 − 59 4 TPV + pegIFN/RBV 48 w eeks NR: 29 − 33 4 w ithout lead-in R: Relapsers; PR: Partial responders; NR: Non Responders 1. Poordad et al. 2011 2. Jacobson et al. 2011 3. Bacon et al. 2011 4. Zeuzem et al. 2011

SVR rates in HCV – new generation of direct acting antiviral Treatment Regimen Treatment history Components SVR (%) duration 90 1 N Naïve SOF + pegIFN/RBV 12 w eeks 90 2 A Naïve SOF + pegIFN/RBV 12 w eeks 93 2 A Naïve SOF + pegIFN/RBV x 24 w eeks 91 2 A Naïve SOF + pegIFN/RBV 12 + 12 w eeks New 10 3 E Experienced SOF + RBV 12 w eeks generation 84 3 E +/- Naïve SOF + RBV 12 w eeks pegINF/RBV 90 4 S Naïve SOF + RBV 24 w eeks 71 4 S Naïve SOF + RBV x 24 w eeks 55 4 S Naïve SOF + low dose RBV 24 w eeks 76 5 P Naïve SOF + RBV 24 w eeks 1. Lawitz et al. 2013 2. Kowdley et al. 2013 3. Gane et al. 2013 4. Osinusi et al. 2013 5. Sulkovski et al. 2014

SVR rates in HCV – new generation of direct acting antiviral Treatment Regimen Treatment history Components SVR (%) duration 97-99 1 Naïve SOF + LEDA 12 or 24 w eeks GS combo 91-99 2 Experienced SOF + LEDA 12 or 24 w eeks 93-95 3 Naïve SOF + LEDA 8 or 12 w eeks OMB + PAR + RIT + 95-100 4 Naïve 12 or 24 w eeks Abbbie DAS +/- RBV combo OMB + PAR + RIT + 95-100 4 Experienced 12 or 24 w eeks DAS +/- RBV 1. Harvoni SPC, www.ema.eu (2014) 2. Viekirax SPC, www.ema.eu (2015)

Is new Hep C treatment cost effective in local setup?

Which groups of patients could be treated with new Hep C treatment at cost effective ratio?

Clinical practice in Croatia prior new generation of treatment • Treatment naive patients – peginterferon / ribavirin • Treatment experienced (only genotip 1) – boceprevir / peginterferon / ribavirin – telaprevir / peginterferon / ribavirin

Challenges of interpreting CE in Croatia • CE analysis is not mandatory part of reimbursement submission • Costs of healthcare in the region differentiates from those in western societies • Lack of local micro-costing data in different diseases and disease staged

Cost-effectiveness threshold • WHO uses BDP multiplicators to define CE categories: • ICER < 1 x GDP per capita  highly cost-effective, • ICER 1 – 3 x GDP per capita  cost-effective, • ICER > 3 x GDP per capita  not cost-effective. • 2013. GDP per capita in Croatia 2013.= 10.249 Eur or 77.621 kn 2,3 Highly Not 77.621 kn 232.864 kn Cost-effective cost-effective cost-effective 1 x GDP 3 x GDP 1. WHO, www.who.int, 2015 2. DZS, www.dzs.hr, 2015 3. HNB, http://www.hnb.hr/tecajn/, 2015

CE model structure 1. Shepherd 2007; 2. Hartwell 2011

CE model structure • Closed-cohort health state-transition model from payers • Impact on potential disease eradication perspective as a result of high SVR • Lifetime horizon • Second line treatment cost in • Patients are initially distributed in 5 initial states according to unsuccessfully treated patients fibrosis stage • First year in the model represents treatment cycle (only one line of treatment included) • In subsequent years patient progress trough model based on transitional probabilities

Patient classification: Patient segment Genotype Fibrosis subgroup Naive IFN eligible 1 Fibrosis stage all Treatment experienced 4 Fibrosis stage 2+

Localized settings • Treatment cost 1 • Medical cost per health state and side effect costs 2 • Comparator in each scenario according to current clinical practice and reimbursement limitations 1 • GT1a i GT1b ratio (25,9% GT1a vs. 76,1% GT1b) 3 • Mortality rates 4 1. Reimbursent list – January 2015, www.hzzo.hr 2. The Campbell and Cochrane Economics Methods Group (CCEMG) and the Evidence for Policy and Practice Information and Coordinating Centre (EPPI-Centre) 3. Vince et al. 2006 4. Statistical yearbook of Republic of Croatia, 2011

International data • Healthcare state transition probabilities, • QALY’s per healthcare state, 1. Shepherd et al. 2007 2. Hartwell et al. 2011

QALY per healthcare state 3,7% 2,5% Healthcare state QALY Δ QALY Mild chronic HCV (F0-F1) 0,98 0,02 -0,13 Recovered history of mild 1 Moderate chronic HCV (F2-F3) 0,85 0,083 -0,06 Recovered history of moderate 0,933 Compensated Cirrosis, chronic HCV 0,79 0,143 Recovered history of Compensated Cirrhosis 0,933 Decompensated Cirrosis 0,72 Hepatocelular carcinoma 0,72 1. Liu et al. 2012 Liver transplantation 0,825

Costs per healthcare state Healthcare state Cost Δ cost Mild chronic HCV (F0-F1) 676 kn -338 kn Recovered history of mild 338 kn Moderate chronic HCV (F2-F3) 676 kn -338 kn Recovered history of moderate 338 kn Compensated Cirrosis, chronic HCV 3.119 kn -1.559 kn Recovered history of Compensated Cirrhosis 1.560 kn Decompensated Cirrosis 134.090 kn Hepatocelular carcinoma 210.302 kn 1. McAdam-Marx et al. 2011 Liver transplantation (first year) 812.118 kn Liver transplantation (subsequent year) 183.065 kn

Analyzed scenarios: • GT1 Naive IFN eligible • GT1 Treatment experienced • vs BOC+pegINF+RBV • vs TPV+pegINF+RBV • GT1 Naive IFN eligible F0 F1 excluded • GT1 Treatment experienced F0 F1 excluded • vs BOC+pegINF+RBV • vs TPV+pegINF+RBV • GT4 Naive IFN eligible • GT4 Treatment experienced

GT1 Naive IFN eligible • Comparator: PegINF + RBV Other Cost Regimen Regimen Cost Total Cost QALYs ICER AE management Medical costs cost 354.045 kn 33.203 kn 218 kn 387.466 kn 15,65 Intervention: AbbVie regimen 75.363 kn 98.349 kn 2.172 kn 175.884 kn 14,1 Comparator: PegINF+RBV 137.264 kn 278.682 kn -65.146 kn -1.954 kn 211.582 kn 1,54 Incremental

Deterministic sensitivity analysis GT1 Naive IFN eligible

Cost effectiveness scatter plot GT1 Naive IFN eligible

GT1 Treatment experienced • Treatment experienced: • Relapsers • Partial responders • Null responders • Comparator 1: PR + boceprevir; Comparator 2: PR + telaprevir Other Cost Regimen Regimen Cost Total Cost QALYs ICER AE management Medical costs cost 374.438 kn 60.451 kn 291 kn 435.180 kn 14,17 Intervention: AbbVie regimen 242.778 kn 142.343 kn 3.030 kn 388.150 kn 12,42 Comparator: BOC+PegINF+RBV 26.898 kn 131.661 kn -81.892 kn -2.739 kn 47.030 kn 1,75 Incremental 239.836 kn 133.841 kn 2.716 kn 376.393 kn 12,52 Comparator: TPV+PegINF+RBV 35.677 kn 134.602 kn -73.390 kn -2.426 kn 58.787 kn 1,65 Incremental

Deterministic sensitivity analysis GT1 Treatment experienced

Cost effectiveness scatter plot GT1 Treatment experienced (comparator PR+boceprevir)

GT1 Naive IFN eligible – F0 F1 excluded • According to existing reimbursement guideline in Croatia HCV treatment was reimbursed only for patients with F≥2 Other Cost Regimen Regimen Cost Total Cost QALYs ICER AE management Medical costs cost 368.966 kn 62.968 kn 309 kn 432.243 kn 14,59 Intervention: AbbVie regimen 75.363 kn 170.221 kn 2.172 kn 247.755 kn 12,42 Comparator: PegINF+RBV 85.105 kn 293.603 kn -107.253 kn -1.862 kn 184.487 kn 2,17 Incremental

Deterministic sensitivity analysis GT1 Naive IFN eligible – F0 F1 excluded

Cost effectiveness scatter plot GT1 Naive IFN eligible – F0 F1 excluded

GT1 Treatment experienced – F0 F1 excluded • Treatment experienced: • Relapsers • Partial responders • Null responders • Comparator 1: BOC+pegINF+RBV; Comparator 2: TEL+pegINF+RBV Other Cost Regimen Regimen Cost Total Cost QALYs ICER AE management Medical costs cost 397.959 kn 98.722 kn 458 kn 497.139 kn 13,22 Intervention: AbbVie regimen 242.778 kn 218.428 kn 3.030 kn 464.235 kn 10,89 Comparator: BOC+PegINF+RBV 14.083 kn 155.181 kn -119.706 kn -2.572 kn 32.904 kn 2,34 Incremental 239.836 kn 199.356 kn 2.716 kn 441.909 kn 11,2 Comparator: TPV+PegINF+RBV 27.300 kn 158.123 kn -100.634 kn -2.258 kn 55.230 kn 2,02 Incremental

Deterministic sensitivity analysis GT1 Treatment experienced – F0 F1 excluded

Cost effectiveness scatter plot GT1 Treatment experienced – F0 F1 excluded

GT4 Naive IFN eligible • Comparator: PegINF + RBV Other Cost Regimen Regimen Cost Total Cost QALYs ICER AE management Medical costs cost 324.755 kn 16.869 kn 272 kn 341.895 kn 15,95 Intervention: AbbVie regimen 85.979 kn 38.680 kn 718 kn 125.377 kn 15,36 Comparator: PegINF+RBV 361.296 kn 238.776 kn -21.811 kn -446 kn 216.519 kn 0,60 Incremental

Deterministic sensitivity analysis GT4 Naive IFN eligible

Cost effectiveness scatter plot GT4 Naive IFN eligible