Cadth 2015 d1 oral apr14_final
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Transcript of Cadth 2015 d1 oral apr14_final
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. WongAssistant Professor / Decision Modeller
Toronto Health Economics and Technology Assessment (THETA) CollaborativeLeslie Dan Faculty of Pharmacy
University of Toronto
The Team
PHAC (Public Health Agency of Canada)Tom WongPing YanDena SchanzerDana Paquette
THETA (Toronto Health Economics and Technology Assessment Collaborative)William WongHong-Anh TuMurray Krahn Toronto Centre for Liver Disease, University Health NetworkJordan FeldDavid Wong
Funding: This study was supported by Public Health Agency of Canada (PHAC).
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?
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
BACKGROUND
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
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 Ontario1, 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.
Treatment for chronic hepatitis C is rapidly evolving
2010 2015
Peginterferon plus
ribavirin (PR)
PR plus direct-
acting antiviral
(DAA)
Interferon-free
regimens
Current: Screening• Target Screening1
• 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
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.
COST-EFFECTIVENESS OF SCREENING FOR HEPATITIS C
Research Questions1. 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?
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%
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.
Treatments ConsideredTreatment DescriptionPR pegIFN alfa-2a plus ribavirin180 mcg /200mg
(PEGASYS RBV)SIM Simeprevir 150 mg (GALEXOS)SOF Sofosbuvir 400mg (Sovaldi)ABT-450 paritaprevir/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.
ECONOMIC MODEL
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
Advanced liver disease
HCCDecompensation
liver-transplant
CHC-related Death
CHC-unrelated Death
From all states
From all F4 states
post-transplant
Data inputsParameter Source
Fibrosis distribution Clinical data from Toronto Western Hospital
Fibrosis progression Thein et al 2008 (meta-analysis)
Cirrhosis progression van der Meer AJ et al. JAMA. 2012 (included Canadian patients)
Probability to receive treatment Clinical data from Toronto Western Hospital
Efficacy and safety Published Clinical trials
All-cause treatment discontinuation
Published Clinical trials
Proportion of patients eligible for short PR therapy
Published Clinical trials
Mortality US 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)
RESULTS
Base case results: Age 25-64
Compared to Common baseline (No Screening)
Age range Strategy Cost QALYs ∆Cost ∆QALYs ICERSequential
ICER
25-64
No screening
$71,327
13.7653 - - -
-
Screen & treat with
PR$71,45
013.768
5 $124 0.0032 $38,117* $38,117*Screen & treat IFN-Free DAA (ABT-450)
$71,593
13.7729 $266 0.0077 $34,783 $34,783
Screen & treat with PR-based
DAA (simeprevir)
$71,593
13.7716 $267 0.0063 $42,398 Dominated
*Extendedly dominated; cost IFN-Free therapy assumed at $50,000
Base case results: Age 45-64
Compared to Common baseline (No Screening)
Age range Strategy Cost QALYs ∆Cost ∆QALYs ICERSequential
ICER
45-64
No screening
$83,335
12.1027 - - -
-
Screen & treat with
PR$83,47
612.106
8 $141 0.0041 $34,359 $34,359Screen & treat with PR-based
DAA (simeprevir
)$83,67
212.110
4 $337 0.0077 $44,034 $55,151*
Screen & treat IFN-Free DAA (ABT-450)
$83,673
12.1122 $338 0.0095 $35,562 $36,471
*Extendedly dominated; cost IFN-Free therapy assumed at $50,000
CEA By Age range
25-34 35-44 45-54 55-64$0
$10,000
$20,000
$30,000
$40,000
$50,000
$60,000
ICER of screen and treat with PR
ICER for Screen and Treat PR-based DAA
ICER for Screen and Treat IFN-Free DAA
Age range
ICER
($/Q
ALY
)
One way sensitivity analysis
CHC related Utilities
Discount rate
Prevalence
Cost of CHC non-therapy
Cost of therapy
Known to be CHC infected
Therapy Efficiency
Cost of screening
Screeening acceptance
Cohort Firbrosis distribution
Therapy Algorithm related viral logic response
20000 25000 30000 35000 40000 45000 50000
Tornado Diagram: Screen and treat with IFN-Free DAA VS. no screening
ICER ($/QALY)
Probabilistic Sensitivity Analysis
0 10000 20000 30000 40000 50000 60000 70000 80000 90000 1000000
0.10.20.30.40.50.60.70.80.9
1
Acceptability Curve (No screening VS. Screen and treat with IFN-
Free DAA)
no screening screen and treat with IFN-Free DAA
Weight on Effect. (WTP)
% C
ost
-Eff
ect
ive
CADTH Therapeutic Review
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
Restricted treatment (F2-F4) Compared to Common baseline (No Screening)
Age range Strategy Cost QALYs ∆Cost ∆QALYs ICERSequential
ICER
25-64
No screening $71,327 13.7649 - - -
-
Screen & treat with PR $71,451 13.7676 $124 0.0026 $47,466 $47,466*
Screen & treat with PR-based
DAA (simeprevir) $71,556 13.7698 $230 0.0048 $47,573 $47,573*
Screen & treat IFN-Free DAA (ABT-450) $71,557 13.7709 $230 0.0060 $38,298 $38,298
45-64
No screening $83,334 12.1024 - - -
-
Screen & treat with PR $83,473 12.1061 $139 0.0036 $38,333 $38,333*
Screen & treat with PR-based
DAA (simeprevir) $83,632 12.1090 $298 0.0065 $45,636 $45,636*
Screen & treat IFN-Free DAA (ABT-450) $83,634 12.1107 $300 0.0082 $36,348 $36,348
*Extendedly dominated; cost IFN-Free therapy assumed at $50,000
Comparison Compared to Common baseline (No Screening)
Age range
Strategy ICER (Treat all) ICER (Treat F2 – F4)
25-64
No screening - -Screen & treat
with PR $38,117* $47,466Screen & 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 $38,333Screen & 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
DISCUSSION &CONCLUSION
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
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.
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?
Budget: Treat all
1 2 3 4 5 6 7 8 9 10$0
$500,000,000
$1,000,000,000
$1,500,000,000
$2,000,000,000
$2,500,000,000
$3,000,000,000
Budget
Scenerio 1: All Fibrosis Level: G1: SIM; G2: SOF; G3: SOF; G4:SOF
Scenerio 2: All Fibrosis Level: G1: SOF; G2: SOF; G3: SOF; G4:SOF
Scenerio 3: All Fibrosis Level: G1: SOF+LDV; G2: SOF+LDV; G3: SOF+LDV; G4:SOF+LDV
Scenerio 4: All Fibrosis Level: G1: PTVR/OBV/DSV ; G2: SOF+LDV; G3: SOF+LDV; G4:SOF+LDV
$4-5 billion in the next 10 years
Budget: Treat only F2-F4
1 2 3 4 5 6 7 8 9 10$0
$200,000,000
$400,000,000
$600,000,000
$800,000,000
$1,000,000,000
$1,200,000,000
$1,400,000,000
$1,600,000,000
$1,800,000,000
$2,000,000,000
Budget
Scenerio 5: F2-F4 Only: G1: SIM; G2: SOF; G3: SOF; G4:SOF
Scenerio 6: F2-F4 Only: G1: SOF; G2: SOF; G3: SOF; G4:SOF
Scenerio 7: F2-F4 Only: G1: SOF+LDV; G2: SOF+LDV; G3: SOF+LDV; G4:SOF+LDV
Scenerio 8: F2-F4 Only: G1: PTVR/OBV/DSV ; G2: SOF+LDV; G3: SOF+LDV; G4:SOF+LDV
$3-4 billion in the next 10 years
QUESTIONS