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

Regimen Treatment history Components Treatment duration SVR (%) R: 24 − 293,4 PR: 7 − 153,4 NR: 53,4 BOC + pegIFN/RBV 4-w eek lead‑in + 24/44 w eeks 63 − 661 TPV + pegIFN/RBV 24/48 w eeks 69 − 752 R: 69 − 753 PR: 40 − 523 R: 83 − 884 PR: 54 − 594 NR: 29 − 334

R: Relapsers; PR: Partial responders; NR: Non Responders

38 − 441.2 Treatment experienced PegIFN/RBV 48 w eeks TPV + pegIFN/RBV 4-w eek lead‑in + 44 w eeks, or 48 w eeks w ithout lead-in Dual therapy Treatment naïve PegIFN/RBV 48 w eeks Triple therapy Treatment naïve Treatment experienced BOC + pegIFN/RBV 4-w eek lead‑in + 32/44 w eeks

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

Regimen Treatment history Components Treatment duration SVR (%) Naïve SOF + pegIFN/RBV 12 w eeks 901 N Naïve SOF + pegIFN/RBV 12 w eeks 902 A Naïve SOF + pegIFN/RBV x 24 w eeks 932 A Naïve SOF + pegIFN/RBV 12 + 12 w eeks 912 A Experienced SOF + RBV 12 w eeks 103 E Naïve SOF + RBV 12 w eeks 843 E Naïve SOF + RBV 24 w eeks 904 S Naïve SOF + RBV x 24 w eeks 714 S Naïve SOF + low dose RBV 24 w eeks 554 S Naïve SOF + RBV 24 w eeks 765 P New generation +/- pegINF/RBV

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

1. Harvoni SPC, www.ema.eu (2014) 2. Viekirax SPC, www.ema.eu (2015)

Regimen Treatment history Components Treatment duration SVR (%) Naïve SOF + LEDA 12 or 24 w eeks 97-991 Experienced SOF + LEDA 12 or 24 w eeks 91-992 Naïve SOF + LEDA 8 or 12 w eeks 93-953 Naïve OMB + PAR + RIT + DAS +/- RBV 12 or 24 w eeks 95-1004 Experienced OMB + PAR + RIT + DAS +/- RBV 12 or 24 w eeks 95-1004 GS combo Abbbie combo

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 kn2,3

Highly cost-effective Cost-effective Not cost-effective 77.621 kn

1 x GDP

232.864 kn

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

perspective

• Lifetime horizon
• Patients are initially distributed in 5 initial states according to

fibrosis stage

• First year in the model represents treatment cycle (only one line
• f treatment included)
• In subsequent years patient progress trough model based on

transitional probabilities

• Impact on potential disease eradication

as a result of high SVR

• Second line treatment cost in

unsuccessfully treated patients

Patient classification:

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

Localized settings

• Treatment cost1
• Medical cost per health state and side effect costs2
• Comparator in each scenario according to current clinical practice and reimbursement limitations1
• GT1a i GT1b ratio (25,9% GT1a vs. 76,1% GT1b)3
• Mortality rates4

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

Healthcare state QALY Mild chronic HCV (F0-F1) 0,98 Recovered history of mild 1 Moderate chronic HCV (F2-F3) 0,85 Recovered history of moderate 0,933 Compensated Cirrosis, chronic HCV 0,79 Recovered history of Compensated Cirrhosis 0,933 Decompensated Cirrosis 0,72 Hepatocelular carcinoma 0,72 Liver transplantation 0,825

• 0,06

Δ QALY

• 0,13

0,02 0,083 0,143

QALY per healthcare state

1. Liu et al. 2012

2,5% 3,7%

Healthcare state Cost Δ cost Mild chronic HCV (F0-F1) 676 kn Recovered history of mild 338 kn Moderate chronic HCV (F2-F3) 676 kn Recovered history of moderate 338 kn Compensated Cirrosis, chronic HCV 3.119 kn Recovered history of Compensated Cirrhosis 1.560 kn Decompensated Cirrosis 134.090 kn Hepatocelular carcinoma 210.302 kn Liver transplantation (first year) 812.118 kn Liver transplantation (subsequent year) 183.065 kn

• 338 kn
• 1.559 kn
• 338 kn

Costs per healthcare state

1. McAdam-Marx et al. 2011

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

Medical costs AE management cost Intervention: AbbVie regimen

354.045 kn 33.203 kn 218 kn 387.466 kn 15,65

Comparator: PegINF+RBV

75.363 kn 98.349 kn 2.172 kn 175.884 kn 14,1

Incremental

278.682 kn

• 65.146 kn
• 1.954 kn

211.582 kn 1,54

Total Cost Regimen Cost

137.264 kn

Regimen Other Cost QALYs ICER

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

Medical costs AE management cost Intervention: AbbVie regimen

374.438 kn 60.451 kn 291 kn 435.180 kn 14,17

Comparator: BOC+PegINF+RBV

242.778 kn 142.343 kn 3.030 kn 388.150 kn 12,42

Incremental

131.661 kn

• 81.892 kn
• 2.739 kn

47.030 kn 1,75

Comparator: TPV+PegINF+RBV

239.836 kn 133.841 kn 2.716 kn 376.393 kn 12,52

Incremental

134.602 kn

• 73.390 kn
• 2.426 kn

58.787 kn 1,65 35.677 kn

Regimen Regimen Cost Other Cost Total Cost QALYs ICER

26.898 kn

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

Medical costs AE management cost Intervention: AbbVie regimen

368.966 kn 62.968 kn 309 kn 432.243 kn 14,59

Comparator: PegINF+RBV

75.363 kn 170.221 kn 2.172 kn 247.755 kn 12,42

Incremental

293.603 kn

• 107.253 kn
• 1.862 kn

184.487 kn 2,17 85.105 kn

Regimen Regimen Cost Other Cost Total Cost QALYs ICER

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

Medical costs AE management cost Intervention: AbbVie regimen

397.959 kn 98.722 kn 458 kn 497.139 kn 13,22

Comparator: BOC+PegINF+RBV

242.778 kn 218.428 kn 3.030 kn 464.235 kn 10,89

Incremental

155.181 kn

• 119.706 kn
• 2.572 kn

32.904 kn 2,34

Comparator: TPV+PegINF+RBV

239.836 kn 199.356 kn 2.716 kn 441.909 kn 11,2

Incremental

158.123 kn

• 100.634 kn
• 2.258 kn

55.230 kn 2,02 14.083 kn 27.300 kn

Regimen Regimen Cost Other Cost Total Cost QALYs ICER

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

Medical costs AE management cost Intervention: AbbVie regimen

324.755 kn 16.869 kn 272 kn 341.895 kn 15,95

Comparator: PegINF+RBV

85.979 kn 38.680 kn 718 kn 125.377 kn 15,36

Incremental

238.776 kn

• 21.811 kn
• 446 kn

216.519 kn 0,60 361.296 kn

Regimen Regimen Cost Other Cost Total Cost QALYs ICER

Deterministic sensitivity analysis

GT4 Naive IFN eligible

Cost effectiveness scatter plot

GT4 Naive IFN eligible

GT4 Treatment experienced

• Comparator: No treatment.

Medical costs AE management cost Intervention: AbbVie regimen

324.755 kn 16.005 kn 272 kn 341.032 kn 14,96

Comparator: No treatment

0 kn 122.801 kn 0 kn 122.801 kn 12,63

Incremental

324.755 kn

• 106.796 kn

272 kn 218.230 kn 2,33 93.827 kn

Regimen Regimen Cost Other Cost Total Cost QALYs ICER

Deterministic sensitivity analysis

GT4 Treatment experienced

Cost effectiveness scatter plot

GT4 Treatment experienced

Conclusions

Highly cost-effective Cost-effective Not cost-effective GT1 Treatment Experienced F0 F1

excluded

ICUR = 14.083 kn GT1 Naive IFN eligible

F0 F1 excluded

ICUR = 85.105 kn GT4 Naive IFN eligible ICUR = 361.296 kn GT1 Treatment Experienced ICUR = 26.898 kn GT1 Naive IFN eligible ICUR = 137.264 kn GT4 Treatment Experienced ICUR = 93.827 kn

Questions that still remain…

• Would treatment of F0-F1 patients lead to disease

eradication and future HCV related costs?

• Would ICER for naive GT1 patients (F0-F1) be below highly

cost effective if second line treatment costs were included?

Thank you for your attention!