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CSPH Works-in-Progress Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous Thromboembolism Associated with Major Urologic Cancer.

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Presentation on theme: "CSPH Works-in-Progress Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous Thromboembolism Associated with Major Urologic Cancer."— Presentation transcript:

1 CSPH Works-in-Progress Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous Thromboembolism Associated with Major Urologic Cancer Surgery Ye Wang, PhD Center for Surgery and Public Health August, 2014

2 Presentation Overview Background PhD Dissertation Project Q & A Current Project at the Center

3 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 2008 Spyropoulos et al., J Manag Care Pharm /3 deaths occur in patients undergoing invasive procedures Prevention of post-surgical VTE in patients with cancers Prevention of post-surgical VTE in patients with cancers

4 Thromboprophylaxis for VTE ≤4cm Thromboprophylaxis advocated for VTE according to the ACCP: ACCP = American College of Chest Physicians Gould et al., Chest 2012 Mechanical device i.e., intermittent pneumatic compression Pharmacological agents i.e., injectable anticoagulants

5 Cost-Effectiveness of Thromboprophylaxis ≤4cm Reduced incidence of VTE Increased costs Thromboprophylaxis Complications

6 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

7 Optimize the allocation of limited health care resources IdentifyMeasureCompare Costs (e.g., resource consumption) Consequences (e.g., clinical or humanistic outcomes) Cost-Effectiveness Analysis (continued) Gunter, Am J Manag Care 1999

8 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 Recommended: Quality-adjusted life years (QALYs) Comparisons across various diseases and health interventions Cost-Effectiveness Analysis (continued)

9 Incremental Cost-Effectiveness Ratio (ICER) ICER = (Costs Intervention B – Costs Intervention A ) ( Effectiveness Intervention B – Effectiveness Intervention A ) Direct Costs Procedures Hospitalization Follow-up Visits/Tests Complications Indirect Costs Lost Wages Lost Productivity Caregiving Societal Costs Benefits Physical Health Mental Health QALYs (calculated by utilities) $ Non-Societal Costs Siegel et al., JAMA 1996

10 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

11 QALYs years One QALY Quality of Life (utilities)

12 QALYs (continued) Time Intervention A Death Intervention B QALYsGained Quality of Life (utilities)

13 ✔ ✗ Cost-Effectiveness Analysis QALYs Gained QALYs Lost Increased Cost Saves Money Improves Health Costs Money Worsens Health Saves Money Worsens Health Cost Money Improves Health ? ? Decreased Cost Cost-Effectiveness Plane

14 Willingness-to-Pay (WTP) Thresholds Interpreting ICER (US Perspective) Less than $50,000 per QALY gainedGood Value $50,000 to $100,000 per QALY gainedSometimes Good Value Greater than $100,000 per QALY gainedRarely Good Value

15 Decision Tree Anticoagulation No Event Embolus Bleed Well Dead Disabled Dead Disabled Fatal Non-Fatal Fatal Non-Fatal Recursive with multiple recurrences Useful to short-term simulations Difficult to assign utilities Recursive with multiple recurrences Useful to short-term simulations Difficult to assign utilities

16 Markov Modeling WELLDEADDISABLED t DEADDISABLEDWELL Markov States (Cycle 0) (Cycle 1) t+1

17 Markov Modeling (continued) WELLDEADDISABLED t DEADDISABLEDWELL t+1 Markov States (Cycle 0) (Cycle 1)

18 Markov Modeling (continued) WELLDEADDISABLED t DEADDISABLEDWELL t+1 Markov States

19 Markov Modeling (continued) WELLDEADDISABLED t DEADDISABLEDWELL t+1 Markov States

20 Markov Modeling (continued) WELL DEADDISABLED Events can recur Simulate over a lifetime horizon Utilities dependent on the cycle length Events can recur Simulate over a lifetime horizon Utilities dependent on the cycle length Markov States

21 Markov Modeling (continued) WELL DEADDISABLED Markovian Assumption Markov States “memory-less”

22 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

23 Study 1 Utility evaluation for anticoagulant-related outcomes

24 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

25 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)

26 Descriptions Published literature Preference assessment guidelines Medical textbooks Expert opinions Gage et al., Arch Intern Med 1996 Torrance, J Health Econ 1986 Warrell et al., Oxford Textbook of Medicine 2003 Health State Descriptions

27 Methods – SG All 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 - p Choice 2: Standard Gamble Technique

28 p1 - p Standard Gamble Technique (continued) All health states were considered to be better than death:

29 p1 - p Standard Gamble Technique (continued) All health states were considered to be better than death: Indifferent – utility value

30 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.

31 Study 2 Cost-effectiveness of oral anticoagulants for stroke prevention in patients with atrial fibrillation

32 Methods – Treatment Options Treatment options: Dabigatran 150 mg twice daily Dabigatran 110 mg twice daily Rivaroxaban once daily Adjusted-dose warfarin

33 Base case A hypothetical cohort of patients, who were: 65 years old Newly diagnosed with atrial fibrillation Having no contraindications to anticoagulation

34 Model Information Model type: Markov model Perspective: The Singapore health care system Horizon: Lifetime Cycle length: Monthly

35 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)

36 Clinical inputs: Published clinical trials Utility inputs: Patient survey Cost inputs: Hospital databases Model Inputs

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

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

39 AF = atrial fibrillation, ICH = intracranial hemorrhage, RIND = reversible ischemic neurological deficit. Markov Model (continued)

40 Dominated Eliminated by extended dominance Results – Base-Case Analysis Rivaroxaban versus Warfarin: ICER = SGD 36,231/QALY Rivaroxaban versus Warfarin: ICER = SGD 36,231/QALY

41 Results – One-Way Sensitivity Analysis WTP threshold

42 42 Results – Two-Way Sensitivity Analysis

43 WTP threshold Rivaroxaban and warfarin were cost-effective in 91.29% and 8.05% of the 10,000 iterations, respectively. Results – Probabilistic Sensitivity Analysis

44 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.

45 Current Project at the CSPH Cost-Effectiveness Analysis of Thromboprophylaxis for the Prevention of Venous Thromboembolism Associated with Major Urologic Cancer Surgery

46 Urologic Cancer in the US ≤4cm National Caner Institute, Surveillance, Epidemiology, and End Results (SEER) Program 2014 %Ranking st th th th

47 Effect of VTE in patients with urologic cancer ≤4cm Lyman, Cancer 2011 Prevention of post-surgical VTE in patients with urologic cancer Prevention of post-surgical VTE in patients with urologic cancer

48 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 Physicians Gould et al., Chest 2012

49 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

50 Research Question Are thromboprophylaxis strategies cost-effective for the prevention of post-surgical VTE in patients with urologic cancer?

51 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

52 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 Radical prostatectomy Radical cystectomy Radical nephrectomy Partial nephrectomy

53 Model Information Model type: Markov model Perspective: Societal Horizon: Lifetime Cycle length: Monthly

54 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)

55 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

56 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

57 CTPH = chronic thromboembolic pulmonary hypertension; DVT = deep vein thrombosis; PE = pulmonary embolism; PTS = postthrombotic syndrome. Markov Model (continued)

58 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)

59 Thanks to Mentor & Other Staff at the CSPH Thank you! Questions and Comments Thank you! Questions and Comments

60 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


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