Comparative Effectiveness of Aflibercept Bevacizumab and Ranibizumab for DME Supported through a cooperative agreement from the National Eye Institute National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Department of Health and Human Services EY1423 ID: 778749
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Diabetic Retinopathy Clinical Research Network
Comparative Effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for DMESupported through a cooperative agreement from the National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services EY14231, EY14229, EY018817
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Slide2Anti-VEGF Treatment Options for Diabetic Macular Edema
Aflibercept 2.0-mg (EYLEA®)Better vision outcomes at 1 year for individuals with worse vision~ U.S. cost per injection (2014): $1850Bevacizumab 1.25-mg (Avastin®)Not approved for DME by FDA~ U.S. cost per
injection (2014): $60Typically repackaged into plastic syringesRanibizumab 0.3-mg (Lucentis)~ U.S. cost per injection (2014): $1170
Slide3Relevance: Comparing Efficacy vs. Cost-effectiveness
Comparing efficacy is most relevant to the doctor-patient relationshipFor example, primary outcome of DRCR.net Protocol TWhen initial visual acuity loss was mild prior to initiating anti-VEGF therapy for DME, there were no apparent differences, on average, in visual acuity outcomes at 1 year after initiating therapy with aflibercept, bevacizumab, or ranibizumabAt worse levels of initial visual acuity, aflibercept was more effective at improving vision at 1 yearComparing cost-effectiveness is most relevant to some payers and policymakers
Slide4Relevance: Efficacy vs. Cost-effectiveness
In 2010, about 2 billion dollars spent for anti-VEGF for ophthalmologic purposes – 1/6th entire Medicare Part B drug budget Example:July 2011: UK National Health Service (NHS) decided not to reimburse ranibizumab as a treatment of DME April 2013: Novartis agrees to a discounted price to the UK government (details are “commercial in confidence”); NHS decides to reimburse ranibizumabGiven increasing public health importance of DME and large differences in costs among different treatment alternatives for DME, a post-hoc cost-effectiveness analysis of different anti-VEGF agents for DME was undertaken by DRCR.net
Slide5Cost-Effectiveness Plane
Better
Health(QALYs)Higher CostWorseHealth(QALYs)Lower Cost
Slide6Cost-Effectiveness Plane
Incremental
Benefit(QALYs Gained)IncrementalCostSAVES MONEY,IMPROVES HEALTHCOSTS MONEY,WORSENS HEALTHSAVES MONEY,WORSENS HEALTHCOSTS MONEY,IMPROVES HEALTH√?
x
x
/?
More Favorable
Less Favorable
A
DOMINANT
DOMINATED
B
Slide7Cost-Effectiveness Ratio
Incremental Cost-Effectiveness Ratio (ICER):High ratios are “Bad”, low ratios are “Good”No explicit threshold, but generally . . .<$50,000/QALY considered good value>$250,000/QALY considered too expensiveAdditional Costs you pay for B vs. A ($$$)Additional Health Benefits you get from B vs. A (QALYs)
Slide8Purpose
Determine cost-effectiveness of anti-VEGF treatment options for patients with newly-diagnosed diabetic macular edema involving the center of the macula with visual acuity loss (20/32 or worse)
Slide9Costs
“Societal” perspectiveDirect medical costs based on actual resource use from the trial and CMS allowablesCosts of each interventionNumber of treatments per year from DCRC.net Protocol TTapering of treatments without average visual acuity loss as published from DRCR.net Protocol ICosts of managing side effectsCosts of caring for patients who are blind from DME
Slide10Health-Related Quality of Life
Time spent in each health state is weighted by a quality multiplier to reflect quality of life
DeathPerfect Health01
Slide11Sample
Quality Adjustments.92 – moderate angina.90 – asymptomatic HIV
.87 – migraine.84 – ulcer .82 – severe angina.78 – atrioventricular blockage.61 – mild schizophrenia.45 – severe clinical depression.40 – symptomatic, drug-resistant prostate cancer.29 – severe chronic schizophrenia.07 – post-cardiac arrest, moderately impaired.53 – AIDS DeathPerfect Health01
Slide12Health-Related Quality of Life
Note: Protocol T did not elicit participants’ quality-of-life directly But, other researchers studied large populations and found relationships between best-corrected visual acuity and quality-of-life weights used for this studyBrownTied to better-seeing eyeEx: 20/20 BCVA = 0.97 20/200 BCVA = 0.66RESTORE Trial (ranibizumab vs. laser for DME)Tied to eye treated with anti-VEGFUtility scores for side effects (MI, CVA, death)Determined ICER of each intervention relative to one another
Slide13Results – Utility, Year 1
Mean cumulative QALYs over 1 year A vs B A vs R R vs B ABR Difference (P-value
)
Difference (P-value)
Difference
(P
-value)
All participants
0.869
0.849
0.857
0.020 (0.03)
0.011 (0.22)
0.008 (0.40)
Visual acuity
20/50 or worse at
baseline
0.835
0.823
0.829
0.012 (0.33)
0.006 (0.63)
0.006 (0.59)
Visual acuity
20/32 to 20/40 at
baseline
0.901
0.875
0.884
0.026 (0.02)
0.017 (0.18)
0.009 (0.55)
A: aflibercept, B: bevacizumab, R: ranibizumab
Slide14Results – Costs, Year 1
Slide15Results – Costs, Year 1
Slide16Results – Costs, Year 1
Slide17Results – Costs, Year 1, All Participants
Slide18Results – Costs, Year 1, Initial Visual Acuity 20/50 Or Worse
Slide19Results – Costs, Year 1, Initial Visual Acuity 20/32 to 20/40
Slide20Results – Cost-effectiveness, 1 Yr
Cost(2015 USD)Utility(QALYs)Cost-effectiveness vs. bevacizumab ($/QALY)*All patients Bevacizumab$4,1000.849–Ranibizumab$18,6000.857$1,730,000Aflibercept
$26,100
0.869$1,100,000Baseline visual acuity 20/50 or worse
Bevacizumab
$5,000
0.823
–
Ranibizumab
$20,400
0.829
$2,450,000
Aflibercept
$28,100
0.835
$1,870,000
Baseline visual acuity
20/32 to 20/40
Bevacizumab
$3,200
0.875
–
Ranibizumab
$16,900
0.884
$1,500,000
Aflibercept
$24,100
0.901
$798,000
Slide21Results – Cost-effectiveness Projections
Slide22Results – Cost-effectiveness, 10 Yr
Cost(2015 USD)Utility(QALYs)Cost-effectiveness vs. bevacizumab ($/QALY)*All patients Bevacizumab$39,8006.80–Ranibizumab$79,4006.87$603,000Aflibercept$102,5006.98
$349,000
Baseline visual acuity 20/50 or worse
Bevacizumab
$40,700
6.60
–
Ranibizumab
$81,200
6.65
$817,000
Aflibercept
$104,500
6.82
$287,000
Baseline visual acuity
20/32 to 20/40
Bevacizumab
$38,900
7.01
–
Ranibizumab
$77,700
7.09
$506,000
Aflibercept
$100,600
7.14
$474,000
Slide23Injection Cost Thresholds, 1 Yr
1-year horizon Current drug cost per dose (2015 USD) All patients Ranibizumab$1,170
Aflibercept
$1,850 Baseline visual acuity
20/50 or worse
Ranibizumab
$1,170
Aflibercept
$1,850
Slide24Injection Cost Thresholds, 1 Yr
1-year horizon Current drug cost per dose (2015 USD) Cost producing cost-effectiveness of $100,000/QALYAll patients Ranibizumab$1,170 $100Aflibercept
$1,850
$240Baseline visual acuity
20/50 or worse
Ranibizumab
$1,170
$94
Aflibercept
$1,850
$250
Slide25Injection Cost Thresholds, 1 Yr
1-year horizon Current drug cost per dose (2015 USD) Cost producing cost-effectiveness of $100,000/QALYRelative reduction from current costAll patients Ranibizumab$1,170 $10091%
Aflibercept
$1,850 $24087%
Baseline visual acuity
20/50 or worse
Ranibizumab
$1,170
$94
92%
Aflibercept
$1,850
$250
87%
Slide26Injection Cost Thresholds, 10 Yr
10-year horizon Current drug cost per dose (2015 USD) Cost producing cost-effectiveness of $100,000/QALYRelative reduction from current costAll patients Ranibizumab$1,170 $230
80%
Aflibercept$1,850 $570
69%
Baseline visual acuity
20/50 or worse
Ranibizumab
$1,170
$190
84%
Aflibercept
$1,850
$700
62%
Slide27Limitations
Extrapolating the findings of the DRCR.net trial beyond year oneUsing best-corrected visual acuity alone as a surrogate for the impact of DME on health-related quality-of-lifeVisual needs may be varied from patient to patient
Utilities assigned to best-corrected visual acuity alone may underestimate impact on health-related quality of life
Slide28Conclusions
Over 1-year study period, for individuals with worse initial visual acuity, incremental cost-effectiveness ratios (ICERs) of aflibercept and ranibizumab when compared with bevacizumab were $1.9 million and $2.5 million per quality-adjusted life-year (QALY)Overall ICERs projected over 10 years when compared with bevacizumab were $350,000/QALY for aflibercept and $600,000/QALY for ranibizumab
Slide29Conclusions (continued)
For treatment of eyes with worse initial visual acuity, anti-VEGF agent cost per injection would have to decrease by 62% for aflibercept or 84% for ranibizumab for those therapies to have ICERs of $100,000/QALY relative to bevacizumab if evaluated over a 10-year time horizon
Slide30Relevance
Aflibercept 2.0-mg and ranibizumab 0.3-mg are unlikely to be cost-effective relative to bevacizumab for treatment of DME unless their prices decline substantiallyThese results highlight the challenges when safety and efficacy results (of importance to patients and physicians providing their treatment) are at odds with cost-effectiveness results (of importance to some payers and policymakers)
Slide31Thank You on Behalf of Diabetic Retinopathy Clinical Research Network (DRCR.net)
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52 clinical study sitesStudy participants who volunteered to participate in this trialDRCR.net Data and Safety Monitoring CommitteeDRCR.net investigators and staff