CSPH Works-in-Progress

Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous

Thromboembolism Associated with Major Urologic Cancer Surgery

Ye Wang, PhDCenter for Surgery and Public Health

August, 2014

Presentation Overview

• Background

• PhD Dissertation Project

• Q & A

• Current Project at the Center

Background – Disease Burden in the US

≤4cm

Venous thromboembolism (VTE):

• Deep vein thrombosis (DVT)

• Pulmonary embolism (PE)

Annual incidence:

• > 250,000 clinically evident cases

• ≈ 25,000 deaths per year

Annual VTE-associated health care expenses:

• $1.9 to 4.2 billion

• > $ 5.0 billion in patients with cancers

Heit et al., Arch Intern Med 2008Spyropoulos et al., J Manag Care Pharm 2007

1/3 deaths occur in patients undergoing invasive procedures

Prevention of post-surgical VTE in patients with cancers

Thromboprophylaxis for VTE

≤4cm

Thromboprophylaxis advocated for VTE according to

the ACCP:

ACCP = American College of Chest Physicians

Gould et al., Chest 2012

• Mechanical devicei.e., intermittent pneumatic compression

• Pharmacological agentsi.e., injectable anticoagulants

Cost-Effectiveness of Thromboprophylaxis

≤4cm

Reduced incidence of VTE

Increased costs

Thromboprophylaxis

Complications

Cost-Effectiveness Analysis

≤4cm

The economic, clinical and humanistic outcomes model:

Any disease management should aim to achieve balanced outcomes so that gains in one outcome would not sacrifice the opportunity gains in other outcomes and that the overall gains can be maximized and optimized.

Gunter, Am J Manag Care 1999

Optimize the allocation of limited health care resources

Identify Measure Compare

Costs (e.g., resource consumption) Consequences (e.g., clinical or humanistic outcomes)

Cost-Effectiveness Analysis (continued)

Gunter, Am J Manag Care 1999

Four types of cost-effectiveness analysis:

• Cost-minimization analysis

• Cost-effectiveness analysis

• Cost-benefit analysis

• Cost-utility analysis

Siegel et al., JAMA 1996

Recommended:• Quality-adjusted life

years (QALYs)

• Comparisons across various diseases and health interventions

Cost-Effectiveness Analysis (continued)

Incremental Cost-Effectiveness Ratio (ICER)

ICER =

(CostsIntervention B – CostsIntervention A)

(EffectivenessIntervention B – EffectivenessIntervention A)

Direct CostsProceduresHospitalizationFollow-up Visits/TestsComplications

Indirect CostsLost WagesLost ProductivityCaregiving

SocietalCosts

BenefitsPhysical HealthMental Health

QALYs(calculated by utilities)

$

Non-SocietalCosts

Siegel et al., JAMA 1996

Utility

Best possible health state

1

Worst possible health state

Death 0

Quality of Life (Utility)

0.4 Symptomatic Metastatic Prostate Cancer

0.2 Above the Knee Amputation

0.6 Severe Congestive Heart Failure

0.8 Disability after Hip Fracture

QALYs

0.5

2 years

One QALY

Quality of Life (utilities)

QALYs (continued)

Time

Intervention A

Death Death

Intervention B

QALYsGained

Quality of Life (utilities)

✔

✗

Cost-Effectiveness Analysis

QALYsGained

QALYsLost

Increased Cost

Saves MoneyImproves Health

Costs MoneyWorsens Health

Saves MoneyWorsens Health

Cost MoneyImproves Health

?

?

Decreased Cost

Cost-Effectiveness Plane

Willingness-to-Pay (WTP) Thresholds

Interpreting ICER(US Perspective)

Less than $50,000 per QALY gained Good Value

$50,000 to $100,000 per QALY gained Sometimes Good Value

Greater than $100,000 per QALY gained Rarely Good Value

Decision Tree

Anticoagulation

No Event

Embolus

Bleed

Well

Dead

Disabled

Dead

Disabled

Fatal

Non-Fatal

Fatal

Non-Fatal

Recursive with multiple recurrencesUseful to short-term simulationsDifficult to assign utilities

Markov Modeling

WELL DEADDISABLEDt

DEADDISABLEDWELL

Markov States

(Cycle 0)

(Cycle 1)

t+1

Markov Modeling (continued)

WELL DEADDISABLEDt

DEADDISABLEDWELLt+1

Markov States

(Cycle 0)

(Cycle 1)

Markov Modeling (continued)

WELL DEADDISABLEDt

DEADDISABLEDWELLt+1

Markov States

Markov Modeling (continued)

WELL DEADDISABLEDt

DEADDISABLEDWELLt+1

Markov States

Markov Modeling (continued)

WELL

DEADDISABLED

Events can recurSimulate over a lifetime horizonUtilities dependent on the cycle length

Markov States

Markov Modeling (continued)

WELL

DEADDISABLED

Markovian Assumption

Markov States

“memory-less”

PhD Dissertation Project

Part I. Patient-Reported Outcomes of Anticoagulants

• Psychometric properties (validation) of a medication adherence scale

• Evaluation of patients’ knowledge, satisfaction, and barriers to anticoagulant therapy

• …

Part II. Pharmacoeconomics of Anticoagulants• Utility evaluation for anticoagulant-related outcomes• Cost-effectiveness of oral anticoagulants for stroke

prevention in patients with atrial fibrillation

Study 1

Utility evaluation for anticoagulant-related outcomes

Study Design

Study design:• Cross-sectional patient survey

Sample size:• 100 patients

Inclusion criteria• ≥ 21 years old• Taking warfarin• Able to comprehend English or Chinese

Utility elicitation methods:• Standard gamble technique

Health States

Seven long-term health states

• Well on warfarin• Well on dabigatran• Well on rivaroxaban• Major ischemic stroke• Minor ischemic stroke• Intracranial hemorrhage (ICH)• Current health state

Four short-term health states

• Transient ischemic attack (TIA)• Major extracranial hemorrhage (ECH)• Minor ECH• Myocardial infarction (MI)

DescriptionsPublished literature

Preference assessment guidelines

Medical textbooks

Expert opinions

Gage et al., Arch Intern Med 1996Torrance, J Health Econ 1986Warrell et al., Oxford Textbook of Medicine 2003

Health State Descriptions

Methods – SGAll health states were considered to be better than death:

Choice 1: Staying in the health state under evaluation for the rest of the patient’s life

p 1 - pChoice 2:

Standard Gamble Technique

p 1 - p

Standard Gamble Technique (continued)

All health states were considered to be better than death:

p 1 - p

Standard Gamble Technique (continued)

All health states were considered to be better than death:

Indifferent – utility value

Results – A Brief Summary

Three best health states (mean ± SD)• Well on rivaroxaban (0.90 ± 0.15)• Well on warfarin (0.86 ± 0.17)• Well on dabigatran (0.83 ± 0.18)

Two health states worse than death (mean ± SD)• ICH (-0.09± 0.51)• Major ischemic stroke (-0.01 ± 0.53)

ICH = intracranial hemorrhage; SD = standard deviation.

Study 2

Cost-effectiveness of oral anticoagulants for stroke prevention in patients with atrial fibrillation

Methods – Treatment Options

Treatment options:

• Dabigatran 150 mg twice daily

• Dabigatran 110 mg twice daily

• Rivaroxaban once daily

• Adjusted-dose warfarin

Base case

A hypothetical cohort of patients, who were:

• 65 years old

• Newly diagnosed with atrial fibrillation

• Having no contraindications to anticoagulation

Model Information

Model type:• Markov model

Perspective:• The Singapore health care system

Horizon:• Lifetime

Cycle length:• Monthly

Model Information

Outcomes:• Direct medical costs • QALYs• ICERs

Willingness-to-pay (WTP) threshold: • Singapore’s 2012 per-capita gross domestic product

(SGD 65,000/QALY)

Software: • TreeAge Pro Suite 2013 (TreeAge Software, Inc.,

Williamstown, MA)

Clinical inputs:• Published clinical trials

Utility inputs:• Patient survey

Cost inputs:• Hospital databases

Model Inputs

AF = atrial fibrillation, ECH = extracranial hemorrhage, ICH = intracranial hemorrhage, MI = myocardial infarction, RIND = reversible ischemic neurological deficit, TIA = transient ischemic attack.

Markov Model

AF = atrial fibrillation, ECH = extracranial hemorrhage, ICH = intracranial hemorrhage, MI = myocardial infarction, RIND = reversible ischemic neurological deficit, TIA = transient ischemic attack.

Markov Model

AF = atrial fibrillation, ICH = intracranial hemorrhage, RIND = reversible ischemic neurological deficit.

Markov Model (continued)

Dominated

Eliminated by extended dominance

Results – Base-Case Analysis

Rivaroxaban versus Warfarin:ICER = SGD 36,231/QALY

Results – One-Way Sensitivity Analysis

WTP threshold

42

Results – Two-Way Sensitivity Analysis

WTP threshold

Rivaroxaban and warfarin were cost-effective in 91.29% and 8.05% of the 10,000 iterations, respectively.

Results – Probabilistic Sensitivity Analysis

Results – A Brief Summary

Base-case analysis• Rivaroxaban was the optimal choice compared to warfarin.

• The ICER of dabigatran 150 mg versus warfarin exceeded the WTP threshold.

• Dabigatran 110 mg was dominated by warfarin and rivaroxaban.

Probabilistic sensitivity analysis• Using a WTP threshold of SGD 65,000/QALY, rivaroxaban

and warfarin were cost-effective in 91.29% and 8.05% of the 10,000 iterations, respectively.

Current Project at the CSPH

Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous Thromboembolism Associated with Major Urologic Cancer Surgery

Urologic Cancer in the US

≤4cm

National Caner Institute, Surveillance, Epidemiology, and End Results (SEER) Program 2014

Percentage of new cancer cases in the US in 2014

Prostate cancerBladder cancerKidney cancerTesticles cancerOthers

% Ranking14.00 1st 4.50 6th 3.80 8th 0.50 25th

77.20 -

Effect of VTE in patients with urologic cancer

≤4cm

Lyman, Cancer 2011

Prevention of post-surgical VTE in patients with urologic cancer

Thromboprophylaxis for VTE (continued)

≤4cm

Paucity of studies on VTE in the urologic literature

The ACCP recommendations for major urologic cancer

surgery are extrapolated from General Surgery

Ideal use of VTE prophylaxis remains unclear

ACCP = American College of Chest PhysiciansGould et al., Chest 2012

Effectiveness of Thromboprophylaxis for VTE

≤4cm

Study design:• Retrospective data analysis (the Premier)

Inclusion criteria:• Adults (≥18 years old)• Admitted due to major urologic cancer surgery

Major urologic cancer surgery:• Radical prostatectomy• Radical nephrectomy• Partial nephrectomy• Radical cystectomy

Research Question

Are thromboprophylaxis strategies cost-effective for the prevention of post-surgical VTE in patients with

urologic cancer?

Methods – Treatment Options

Mechanical prophylaxis:• Intermittent pneumatic compression (IPC)

Pharmacological prophylaxis (injectable anticoagulants):• Low dose unfractionated heparin (LDUH)• Enoxaparin• Dalteparin• Tinzaparin• Fondaparinux• Argatroban

Comparator:• No prophylaxis

Base case

A hypothetical cohort of patients, who are:

• 65 years old

• Undergoing major urologic cancer surgery

• Radical prostatectomy

• Radical cystectomy• Radical nephrectomy• Partial nephrectomy

Model Information

Model type:• Markov model

Perspective:• Societal

Horizon:• Lifetime

Cycle length:• Monthly

Model Information

Outcomes:• Direct & indirect medical costs • QALYs• ICERs

WTP threshold: • US$50,000/QALY-gained

Software: • TreeAge Pro Suite 2014 (TreeAge Software, Inc.,

Williamstown, MA)

Clinical inputs:• Published literature

Utility inputs:• Published literature

Cost inputs:• The Perspective Database (Premier, Inc, Charlotte, NC)

Model Inputs

Direct medical costs:• Prophylaxis strategy• Complications (minor & major)

Indirect medical costs:• Health care for recovery

CTPH = chronic thromboembolic pulmonary hypertension; DVT = deep vein thrombosis; IPC = intermittent pneumatic compression; LDUH = low dose unfractionated heparin; PE = pulmonary embolism; PTS = postthrombotic syndrome.

Markov Model

CTPH = chronic thromboembolic pulmonary hypertension; DVT = deep vein thrombosis; PE = pulmonary embolism; PTS = postthrombotic syndrome.

Markov Model (continued)

Further work (specific to this project)

Collect Data:• Costs• Utilities• Probabilities

Perform data analyses:• Base-case analysis• Sensitivity analyses (one-way, multiple-way and

probabilistic sensitivity analyses)

Thanks to Mentor & Other Staff at the CSPH

Thank you!

Questions and Comments

Thank you!

Questions and Comments

Methods – Health state descriptions (cont’d)

• One side of your body is totally paralyzed and/or one side of your face droops.

• You are not able to walk or take care of yourself (e.g., bathing, dressing and feeding) without help.

• You are not able to perform most of your usual activities. • Your speech is unclear, and people have difficulty understanding

you. • You find it hard to write, but you may think clearly.

Major ischemic stroke

The descriptions for each health state consisted of one to six bullet points that described the health state’s important attributes.

An Example of health state descriptions