REG Cost-Effectiveness

Workshop (Part II)

Jonathan D. Campbell; Piyameth Dilokthornsakul

Workshop Objectives

• Introductions• Cystic fibrosis model example

• What can we do with CEA models? What can’t we do?• Unveil the cost-effectiveness model black box.

• Review current evidence gaps in respiratory health technology assessment

• Collectively propose study designs and other solutions toward HTA respiratory evidence

• Who would like to participate in a REG working group?• Research priorities of a cost-effectiveness REG working group and action items

for initiating a working group?

Forecasting the Lifetime Outcomes and

Cost of Ivacaftor in Patients with Cystic

Fibrosis in the United States

Piyameth Dilokthornsakul; Ryan N. Hansen; Jonathan D. Campbell

4

CF Model Objectives• To forecast lifetime outcomes and cost to compare ivacaftor plus usual care

versus usual care alone

• To indirectly compared the long-run projected impact of ivacaftor to the non-

CF U.S. population.

5

Model and assumptions• Lifetime Markov model

• CF patients aged 6 or more

• U.S. payer perspective with 3% discount for cost and outcomes

• Incorporated exacerbation in each health state

• Assumption:• Progressive approach in usual care alone• Efficacy of ivacaftor after 2 years

• Inputs from literatures outside USA• Cost of ivacaftor after patent expired

Scenarios Description (Efficacy after 2 years) Treatment duration

Base-case scenario 50% efficacy LifetimeOptimistic scenario Full efficacy LifetimeIntermediate scenario 66% efficacy LifetimeConservative scenario Patients stop the treatment Two years

Health state 1: Mild lung disease

%FEV1≥ 70

Health state 2: Moderate lung

disease40 ≤ %FEV1<70

Health state 3:Severe lung

disease%FEV1<40

Health state 4:Lung

transplantation

Health state 5:Death

6

InputsInputs Data sources References

Clinical Efficacy of ivacaftor Two landmark randomized controlled trials

Ramsey BW. N Engl J Med. 2011;365(18):1663-1672Davies JC. Am J Respir Crit Care Med. 2013;187(11):1219-1225

Clinical Transition probabilities Australian study3 (Usual care) van Gool K. Value Health. Mar-Apr 2013;16(2):345-355

Clinical Mortality U.S. life tablesA previous study for relative risk of death in CF patients with certain FEV1

Karem E. N Engl J Med. 1992; 326:1187-91

Economics Cost U.S. studies for treatment costREDBOOK for cost of medication

Lieu TA. Pediatrics. Jun 1999;103(6):e72Bentley TS. U.S. organ and tissue transplant cost estimates and discussion. Brookfield, WI: Miilliman;2011

Patient-centered Utility A U.K. study Whiting P. Health Technol Assess. Mar 2014;18(18):1-106

7

Analysis• One-way sensitivity analysis

• Probabilistic sensitivity analysis

• Simple budget impact analysis• For the first 3, 5, and 10 years of ivacaftor use

Model example

9

Results: Base-case and scenarioFindings(Ivacaftor +UC Vs. UC)

Base-case scenario(50% efficacy)

Optimistic scenario(100% efficacy)

Intermediate scenario(66% efficacy)

Conservative scenario(Stop treatment)

Incremental estimated life expectancy

5.31(4.45 to 6.08)

8.61(8.19 to 8.99)

5.74(5.05 to 6.35)

0.14(0.08 to 0.23)

Incremental QALYs 4.52(3.69 – 5.40)

7.45(6.49 to 8.41)

4.89(4.12 to 5.60)

0.12(0.06 to 0.19)

Incremental costs ($) $3,740,480($2,199,261 to $4,915,629)

$3,837,481($1,627,340 to $5,481,593)

$3,751,831($2,0418,971 to $4,978,556)

$507,043($-43,931to $737,964)

Abbreviations: QALY; quality-adjusted life years, UC; usual care

10

Results: One-way

Baseline %FEV1 predicted for moderate lung disease (Incremental QALY)

Cost of ivacaftor(Incremental cost)

11

$- $1,000,000 $2,000,000 $3,000,000 $4,000,000 0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1 Cost Effectiveness Acceptibility Curve

Ivacaftor Usual CareWillingness-to-pay ($)

Prob

abili

ty o

f bei

ng c

ost-

effe

ctiv

e

Results: Probabilistic

-0.5000 -0.4000 -0.3000 -0.2000 -0.1000 0.0000 0.1000 0.2000 0.3000

$(4,000,000)

$(3,000,000)

$(2,000,000)

$(1,000,000)

$-

$1,000,000

$2,000,000

Incremental cost and QALYs for Ivacaftor vs Usual Care in patients with cystic fibrosis

QALYCo

st (

$)

12

Results• Budget impact analysis

Time horizon Budget impact (per member per month)

3 years $0.091 ($0.069 to $0.113)

5 years $0.088($0.067 to 0.109)

10 years $0.081 ($0.061 to $0.100)

Gaps of knowledge in COPD CEA studies

• 24 published studies in last 5 years identified the following gaps:• Most of studies use clinical trials as efficacy data, they might not be representative of the real-world population

(Efficacy and Effectiveness issue)

• A lack of quality of life evidence in exacerbation state.

• A limitation of Markov assumption which transition probabilities are assumed to be constant overtime. It might not be similar to real-world.

• Several models use lung function as a proxy of COPD severity. However, other factors could be predictors of disease severity but are not captured in the model (i.e. GOLD A-D vs. GOLD 1-4).

• A lack of information on the long-term effect of interventions when the time horizon of the model was longer than that of clinical trials

Gaps of knowledge in asthma CEA studies

• 25 published studies in last 5 years identified the following gaps: • A lack of information on the impact of adherence on effectiveness and cost-effectiveness for evidence used in

the CEA model

• A lack of sufficient and sensitive health-related quality-of-life preference scores (utility) data in pediatrics, during exacerbation, mild severity, or uncontrolled asthma populations

• A lack of indirect cost estimation, especially for pediatric populations

• A lack of information on the long-term effect of interventions when the time horizon of the model was longer than that of clinical trials

• Other gaps of knowledge• A lack of CEAs on asthma patients who smoke, who have exercise-induced bronchoconstriction

• A lack of CEAs related to the minimal effective dose of inhaled corticosteroid

REG Research Priorities for CEA

• Collectively propose study designs and other solutions toward HTA respiratory evidence gaps.

• Should REG develop a working group and identify funding to address this line of research?

• Do we also have interest in acting as internal consultants to other REG working groups within cost-effectiveness applications?

• Should REG develop and validate global asthma and chronic obstructive pulmonary disease policy models that could be tailored for use by HTA stakeholders in their real-world value assessment of existing and emerging interventions?

Policy Models

• Well-designed Health Care Policy Models with robust inputs are powerful tools for analyzing health care policy and clinical trial investment decisions.

• Such models are frequently used by the National Cancer Institute, the Congressional Budget Office, and other policy analysts when short-run trial-based or observational evidence is not enough to address all of the relevant policy issues.

Cost-Effectiveness Working Group Members and Action Items• Members

• Action Items

Jonathan D Campbell, PhD Assistant Professor Director, Pharmaceutical Outcomes Research Graduate Program Center for Pharmaceutical Outcomes Research University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences | Anschutz Medical Campus Department of Clinical Pharmacy p: 303.724.2886 | f: 303.724.0979 Jon.Campbell@ucdenver.edu | www.ucdenver.edu/pharmacy Mail Stop C238 12850 E. Montview Blvd, V20-1205 Aurora, CO 80045

Piyameth Dilokthornsakul, PharmDLecturerCenter of Pharmaceutical Outcomes ResearchFaculty of Pharmaceutical Sciences, Naresuan UniversityMuang, Phitsanulok, ThailandTel: 66-86-7354746E-mail: piyamethd@gmail.com