cost-effectiveness of left ventricular assist devices (lvads) as permanent implants for end-stage...

Cost-Effectiveness of Left Ventricular Assist Devices (LVADs) as Permanent Implants for End-Stage Heart Failure

David Samson Blue Cross and Blue Shield Association

Technology Evaluation Center, University at Albany

Thanks to: Alan M. Garber Stanford University

Gillian Sanders Duke University

Naomi Aronson Blue Cross and Blue Shield Association Technology Evaluation Center

Copyright 2004 Blue Cross Blue Shield Association

Copyright 2004 Blue Cross Blue Shield Association

Rose et al.NEJM, 2001;345:1435

REMATCH Trial

REMATCH: destination therapy, in contrast to bridge to transplant

129 patients with NYHA Class IV end-stage heart failure,

contraindications for heart transplantation, randomized to LVAD or

optimal medical management (OMM)

Median survival: LVAD - 408 d, OMM - 150 d ( 8.5 mo, p=0.001)

Rate of all serious adverse events per patient-yr:

LVAD - 6.45, OMM - 2.75, rate ratio (95% CI): 2.35 (1.86 - 2.95) Copyright 2004 Blue Cross Blue Shield Association

REMATCH Trial

Copyright 2004 Blue Cross Blue Shield Association

0.0

0.2

0.4

0.6

0.8

1.0

months from randomization

Su

rviv

al

0 6 12 18 24 30

LVAS, n=OMM, n=

6861

4128

3316

154

73

REMATCH, all cause mortalityFeb. 2002 update

LVASOMM

CDRH-FDA, CSDAP,03/04/02

REMATCH Trial

• 1 yr median NYHA Class: LVAD - II, OMM - IV (p<0.001)

• 1 yr mean SF-36 PF: LVAD - 46, OMM - 21 (p=0.01)

Copyright 2004 Blue Cross Blue Shield Association

Class I: No limitation on physical activity (sx > ordinary activity)

Class II: Slight limitation on physical activity (sx ordinary activity)

Class III: Marked limitation on physical activity (sx < ordinary activity)

Class IV: Inability to carry on physical activity (sx at rest)

REMATCH Trial

Copyright 2004 Blue Cross Blue Shield Association

Thoratec,FDA, CSDAP,03/04/02

Month

LVAD% NYHA

I/II

OMM% NYHA

I/II

0 0 0

1 54 0

3 68 3

6 80 9

9 82 0

12 71 0

18 44 0

24 71 33

Structural Components of CEA

• Time horizon, perspective: Lifetime (3 years), payor

• Patient population, setting: REMATCH patient selection, sites

• Strategies: LVAD, OMM

• Markov model: 2-state (analogous to 3-state)

• Quality of life focus: NYHA functional class categories

• Valuing of Costs: 2002 $ USCopyright 2004 Blue Cross Blue Shield Association

Markov Model

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Alive Dead

p11 1

NYHA III/IV

p11p22

Dead

NYHA I/II

p12

p12

p13 p231

p21

2-State:

3-State:

Cycle-Specific Calculation of QALYs, Costs

QALYt = St [(PI/II*UI/II)+(PIII/IV*UIII/IV)]t/12

Ct = St [(Prehosp*Crehosp)+(Poutpt*Coutpt)]

Copyright 2004 Blue Cross Blue Shield Association

• t = monthly cycle

• St = survival probability

• PI/II, PIII/IV = probability of being in NYHA class categories

• UI/II, UIII/IV = utility of being in NYHA class categories

• Prehosp, Poutpt = probability of being rehospitalized, outpatient

• Crehosp, Coutpt = cost of being rehospitalized, outpatient

Parameter Estimates

• Survival, LVAD:OMM HR=0.52 95% CI: 0.34, 0.78

• Survival extrapolation interpolation stop & drop, 2 setsto 0% @ 3 yr

parametric models

• NYHA I/II utility 0.81 0.50 - 1.00

• NYHA III/IV utility 0.55 0.30 - 0.80

Copyright 2004 Blue Cross Blue Shield Association

Parameter Estimates• LVAD Prehosp 0.22 0.10 - 0.35

• OMM Prehosp 0.15 0.05 - 0.30

• LVAD Cimplant $277,001 $125K - $425K

• LVAD/OMM Crehosp $39,896 $10K - $70K

• LVAD/OMM Coutpt $1,719 $250 - $3,250

• Discount, costs/utilities 3% 1% - 5%

Copyright 2004 Blue Cross Blue Shield Association

Results: Baseline, Sensitivity Analysis on Survival Relation

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CostDifference

QALYsDifference

ICER($/QALY)

95% CIL $304,652 0.226 $1,350,746

Baseline $338,882 0.422 $802,674

95% CIU $424,253 0.948 $447,645

Sensitivity Analysis on Survival Extrapolation

Copyright 2004 Blue Cross Blue Shield Association

Extrapolation MethodCost

DifferenceQALYs

DifferenceICER

($/QALY)

Linear interpolation $338,882 0.422 $802,674

Stop & drop $334,896 0.398 $840,738

Gompertz/exponential $334,711 0.395 $846,888

Exponential $362,866 0.566 $641,592

Sensitivity Analysis on Cost of Implantation

Copyright 2004 Blue Cross Blue Shield Association

Cost of Implantation ICER ($/QALY)

$125K $442,644

$200K $620,289

$275K $797,934

$350K $975,579

$425K $1,153,224

Sensitivity Analysis on Cost of Implantation

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Sensitivity Analysis on NYHA Utilities

Copyright 2004 Blue Cross Blue Shield Association

UtilityNYHA I/II

ICER($/QALY)

0.50 $1,588,874

0.75 $887,689

1.00 $615,890

UtilityNYHA III/IV

ICER($/QALY)

0.30 $708,363

0.55 $802,674

0.80 $925,955

Sensitivity Analysis on NYHA Utilities

Copyright 2004 Blue Cross Blue Shield Association

Sensitivity Analysis on NYHA Utilities

Copyright 2004 Blue Cross Blue Shield Association

Sensitivity Analysis on Rehospitalization/Outpatient Costs

Copyright 2004 Blue Cross Blue Shield Association

Cost ofRehospital-

izationICER

($/QALY)

$10K $701,399

$40K $803,026

$70K $904,652

Cost ofOutpatient

CareICER

($/QALY)

$250 $792,915

$1,750 $802,879

$3,250 $812,844

Sensitivity Analysis on Probability of Rehospitalization

Copyright 2004 Blue Cross Blue Shield Association

ProbabilityRehospital-

izationLVAD

ICER($/QALY)

0.10 $679,442

0.23 $802,879

0.35 $936,174

ProbabilityRehospital-

izationOMM

ICER($/QALY)

0.05 $867,072

0.18 $786,574

0.30 $706,076

Sensitivity Analysis on Discount Rate

Copyright 2004 Blue Cross Blue Shield Association

Discount Rate

UtilityICER

($/QALY)

CostICER

($/QALY)

0.01 $784,499 $806,703

0.03 $802,674 $802,674

0.05 $821,103 $798,770

Conclusions

• CEA results most sensitive to cost of LVAD implantation

• In 1-way and 2-way sensitivity analyses, ICERs < $500K/QALY depended on unrealistic assumptions, especially about cost of LVAD implantation

• Destination LVADs exceed common CE standards

• Results raise questions of resource use for end-of-life care

Copyright 2004 Blue Cross Blue Shield Association

References

• CDRH-FDA. Presentation to FDA-CSDAP, March 4, 2002.

• Frazier et al. Ann Surg, 1995;222(3):327-38.

• Frazier et al. Ann Thorac Surg, 1994;57:1416-22.

• Gelijns et al. Ann Thorac Surg, 1997;64:1312-9.

• Moskowitz et al. Ann Thorac Surg, 2001;71:S195-8.

• Moskowitz et al. Ann Thorac Surg, 1997;64:1764-9.

• Oz et al. Ann Surg, 2003;238(4):577-85.

• Rose et al. N Engl J Med, 2001;345(20):1435-43.

• Samson. TEC, 2004;19(2):1-36 (bcbs.com/tec/vol19/19_02.html)

• Thoratec. Presentation to FDA-CSDAP, March 4, 2002.Copyright 2004 Blue Cross Blue Shield Association