Transcript Dr. William Wong

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
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).
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 costeffectiveness?
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
•
•
A recent disease burden study from Ontario1, ranked hepatitis C first
among all infectious diseases in heath burden
•
•
•
at risk of dying prematurely of liver failure and/or liver cancer
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
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 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?
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)
(2)
(3)
(4)
•
“No screening”;
“Screen-and-treat* with pegylated interferon
plus ribavirin (PR)”;
“Screen-and-treat* with PR- based directacting antiviral agents (DAA)”; and
“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 Considered
Treatment
Description
PR
pegIFN alfa-2a plus ribavirin180 mcg /200mg (PEGASYS
RBV)
Simeprevir 150 mg (GALEXOS)
Sofosbuvir 400mg (Sovaldi)
paritaprevir/ritonavir + ombitasvir + dasabuvir (VIEKIRA
PAK / Holkira PAK)
SIM
SOF
ABT-450
•
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
Start of
simulation
HCV -
Responder
Undiagnosed CHC
diagnosed CHC
On treatment
Non-responder
F0
F0
F0
F1
F1
F1
F2
F2
F2
F2
F3
F3
F3
F3
F4
F4
F4
F0
F0-F3
SVR
F1
From all states
CHCunrelated
Death
Advanced liver
disease
F4
SVR
F4
Advanced liver disease
From all F4 states
Decompensation
HCC
liver-transplant
CHC-related
Death
From all states
posttransplant
CHC-unrelated
Death
Data inputs
Parameter
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 livertransplant 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
25-64
Strategy
Cost
QALYs
∆Cost
∆QALYs
ICER
No screening
Screen &
treat with PR
Screen &
treat IFNFree DAA
(ABT-450)
$71,327
13.7653
-
-
-
Sequential
ICER
-
$71,450
13.7685
$124
0.0032
$38,117*
$38,117*
$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
45-64
Strategy
Cost
QALYs
∆Cost
∆QALYs
ICER
No screening
Screen &
treat with PR
Screen &
treat with
PR-based
DAA
(simeprevir)
$83,335
12.1027
-
-
-
Sequential
ICER
-
$83,476
12.1068
$141
0.0041
$34,359
$34,359
$83,672
12.1104
$337
0.0077
$44,034
$55,151*
$83,673
12.1122
$338
0.0095
$35,562
$36,471
Screen &
treat IFNFree DAA
(ABT-450)
*Extendedly dominated; cost IFN-Free therapy assumed at $50,000
CEA By Age range
ICER of screen and treat with PR
$60,000
ICER($/QALY)
$50,000
$40,000
ICER for Screen and Treat PR-based
DAA
$30,000
$20,000
ICER for Screen and Treat IFN-Free
DAA
$10,000
$0
25-34
35-44
45-54
Age range
55-64
One way sensitivity analysis
Tornado Diagram: Screen and treat with IFN-Free DAA VS. no screening
20000
CHC related Utilities
Discount rate
Prevalence
Cost of CHC non-therapy
Cost of therapy
Known to be CHC infected
Therapy Efficiency
Cost of screening
Screeening acceptance
Cohort Firbrosis distribution
Therapy Algorithm related viral logic response
25000
30000
ICER ($/QALY)
35000
40000
45000
50000
Probabilistic Sensitivity Analysis
Acceptability Curve
(No screening VS. Screen and treat with IFN-Free
DAA)
1
0.9
% Cost-Effective
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0
10000
20000
30000
40000
50000
60000
70000
80000
Weight on Effect. (WTP)
no screening
screen and treat with IFN-Free DAA
90000 100000
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
25-64
45-64
Strategy
Cost
QALYs
∆Cost
∆QALYs
ICER
Sequential
ICER
No screening
Screen &
treat with PR
Screen &
treat with PRbased DAA
(simeprevir)
Screen &
treat IFN-Free
DAA (ABT-450)
No screening
Screen &
treat with PR
Screen &
treat with PRbased DAA
(simeprevir)
Screen &
treat IFN-Free
DAA (ABT-450)
$71,327
13.7649
-
-
-
-
$71,451
13.7676
$124
0.0026
$47,466
$47,466*
$71,556
13.7698
$230
0.0048
$47,573
$47,573*
$71,557
$83,334
13.7709
12.1024
$230
-
0.0060
-
$38,298
-
$38,298
-
$83,473
12.1061
$139
0.0036
$38,333
$38,333*
$83,632
12.1090
$298
0.0065
$45,636
$45,636*
$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
25-64
45-64
Strategy
ICER (Treat all)
ICER (Treat F2 – F4)
No screening
Screen & treat
with PR
Screen & treat
with PR-based DAA
(simeprevir)
-
-
$38,117*
$47,466
$42,398
$47,573
$34,783
$38,298
-
-
$34,359
$38,333
$44,034
$45,636
$35,562
$36,348
Screen & treat
IFN-Free DAA
(ABT-450)
No screening
Screen & treat
with PR
Screen & treat
with PR-based DAA
(simeprevir)
Screen & treat
IFN-Free DAA
(ABT-450)
*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 onetime 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 costeffective.
• 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
Budget
$3,000,000,000
$4-5 billion
in the next 10 years
$2,500,000,000
$2,000,000,000
$1,500,000,000
$1,000,000,000
$500,000,000
$0
1
2
3
4
5
6
7
8
9
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
10
Budget: Treat only F2-F4
Budget
$2,000,000,000
$1,800,000,000
$3-4 billion
in the next 10 years
$1,600,000,000
$1,400,000,000
$1,200,000,000
$1,000,000,000
$800,000,000
$600,000,000
$400,000,000
$200,000,000
$0
1
2
3
4
5
6
7
8
9
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
10
QUESTIONS