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