The Cost Effectiveness of RSV Prophylaxis: Using Decision
Analysis to Build a Better Guideline
Melony E. S. Sorbero, PhD, MS, MPH
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Purpose
• To evaluate the cost effectiveness of current AAP
recommendation for use of RSV prophylaxis.
• Focus on premature infants without CLD.
• Identify more cost-effective alternative
recommendations.
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Background
• Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract illness in young children.
• Generally resolves uneventfully in otherwise healthy children.
• High risk populations may develop severe and sometimes fatal lower respiratory tract infections.
• RSV infection annually contributes up to 126,300 pediatric hospitalizations in the U.S.
• Estimated annual hospitalization costs for RSV pneumonia in children <=4 years: $300 - $400 million (1998 $)+.
• Annual mortality due to RSV in infants and children is estimated to range from 200 ++ to over 2,700 +++.
(+Howard et al. J of Peds 2000; ++Shay DK et al. J Infect Dis 2001; +++ Institute of Medicine. In:New Vaccine Development: Establishing Priorities: Vol I. Wash DC Nat Aca Press 1986)
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Background
• There may also be long-term health consequences due to severe RSV infections:
– Increased risk of asthma and other respiratory conditions– Duration of increased risk up to 10 years
• A causal relationship between morbidity and severe RSV infection has not been shown.
(Meissner HC at al. Pediatr Infect Dis J. 1999; Sigurs et al. Am J Resp Crit Care Med 2000; Sampalis J Pediatr 2003 )
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Background
• Prematurity increases risk of severe RSV infection.
(Stevens TP et al. Arch Ped Adoles Med 2000)
20.60%
14.60%
11.30%
6.40%
0%
5%
10%
15%
20%
25%
Percent RSV Hospitalization
=< 26 W. 27 - 28 W. > 28 - 30 W. > 30 - 32 W.
Gestational Age at Birth
RSV Hospitalization Rate by Gestational Age at Birth
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Background
• Worldwide RSV epidemics occur yearly– United States: November – April– Peak: January – March (most areas)– Peak: 2 – 3 months earlier (Southeast)
• 80% RSV admissions occur within 4 months discharge from NICU.
42%
27%
15%
41%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Probability of hospitalization
Jan. Feb. - Apr. May - Aug. Sept. - Dec.
Month of Discharge
Respiratory Illness Hospitalization Rate by Month of Discharge from NICU in Infants <= 32 Weeks GA
(Cunningham CK, McMillan JA, Gross SJ Pediatrics 1991)
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Background
• No vaccine available for RSV.
• 2 products available in U.S. for passive immuno-prophylaxis against
RSV.
• Respiratory Syncytial virus immunoglobulin intravenous (RSV-IGIV)
(RespiGam; MedImmune, Inc, Gaithersburg, MD), containing high-
titer RSV antibodies.
• Palivizumab, (Synagis; MedImmune, Inc, Gaithersburg, MD), is a
humanized monoclonal antibody that binds to the F-protein of RSV.
• Require monthly treatments during RSV season.
• Synagis less costly and more effective of two.
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American Academy of Pediatrics (AAP) Recommendations for Prophylaxis Use
• Released in 1998; updated in 2003.
• Infants younger than age 2 years who currently receive or have recently
required medical therapy for CLD.
• Infant born 28 weeks gestation who are 12 months old at the start of
the RSV season.
• Infants born at 29 to 32 weeks who are 6 months old at the start of the
RSV season.
• Infants born between 32 and 35 weeks of gestation with risk factors.
(Red Book, 2000)
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Synagis
• Efficacy of Synagis in prevention of severe RSV
infection in premature infants without CLD: 82%.
• Synagis is available in 50 and 100 mg vials.
• The cost is $725 per 50 mg and $1370 per 100 mg vial.
• Synagis has a shelf life of 6 hours making drug wastage nearly inevitable.
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Study Design
• Developed decision analytic model.
• Societal perspective.
• Two versions: w/ and w/o asthma.
• Impact of asthma modeled with semi-Markov processes.
• Conducted CEA on models with asthma; CBA on models w/o
asthma.
• Seven hypothetical cohorts of premature infants without CLD born
at 24 – 32 weeks gestational age (GA).
• Assumed discharged from NICU at 36 weeks post-conceptual age.
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Model Assumptions
• Risk of RSV hospitalization obtained from published literature.– Gestational age specific probabilities – Seasonal pattern of hospitalization
• Efficacy of palivizumab adapted from IMpact study.
• Costs: year 2002 dollars
• Costs include:– Hospital costs– Cost of pulmonary clinic visits for Synagis injections – Emergency room visit cost– Drug costs– Cost of hours missed from work by parents for visits and
hospitalization
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Models with Asthma
• Increased risk of asthma varies with chronologic age.
• Duration for increased asthma risk: 10 years
• Includes quality of life adjustment for asthma.
• Incorporates national estimates of annual asthma cost
• Future benefits and costs discounted at 3%
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0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
24 - 26 27 28 29 - 30 31 32
Gestational Age at Birth (Weeks)
Expe
cted
Cos
ts ($
)
$ 2,184
$ 678
$ 7,298
$ 8,000
$ 4,092
Synagis: AAP Recommendations:Infants: = < 28 weeks if = < 12 months old at the start of the RSV season
Synagis: AAP Recommendations:Infants: 29 - 32 weeks if = < 6 months old at the start of the RSV season
Synagis
NoSynagis
$ 1,548
Effect of Gestational Age on Expected Costs
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Incremental Cost-Effectiveness Ratio
• Incremental cost-effectiveness ratio (ICER):Cost1 – Cost2 =
QALY1 – QALY2
Cost (Synagis) – Cost (No Synagis)
QALY (Synagis) – QALY (No Synagis)
• Current suggested “standards” for ICER :
– Accepted zone : $200,000
– Not generally accepted zone: > $200,000 / QALY
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0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
2,000,000
24 - 26 27 28 29 - 30 31 32
Gestational Age at Birth (Weeks)
Incre
men
tal C
ost /
QALY
($ / Q
ALY)
Acceptable Zone =< $ 200,000 / QALY
$830,152/ QALY
$1,500,351 / QALY
$ 906,310/ QALY
$1,855,000/ QALY
With Drug Wastage
$685,720/ QALY
$1,268,679/ QALY
$657,780/ QALY
$1,481,965/ QALY
Without Drug Wastage
Effect of Gestational Age on ICER
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Why is the ICER so high?
• Substantial difference in costs, even without drug wastage
• Very small difference in QALYs:– No proven mortality benefit– No proven long-term quality of life improvement– Change in quality of life due to asthma is small: .03
• Treating many infants at low risk for hospitalization
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Large variation within GA in ICER
$0
$500,000
$1,000,000
$1,500,000
$2,000,000
$2,500,000
$3,000,000
$3,500,000
Month of Discharge
ICE
R
24-26 weeks
27 weeks
28 weeks
29-30 weeks
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Improving the Recommendation’s Cost Effectiveness
• Simulations modifying the AAP guidelines
• Assume no drug wastage
• Restrict to 1st RSV season
• Younger age cutoffs (Discharged Sept. through March)
• Restrict to infants born 27 weeks GA or less if discharged before RSV season; up to 30 weeks GA if discharged during RSV season
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ICER by GA and Month of Discharge with new Recommendation
$0
$100,000
$200,000
$300,000
$400,000
$500,000
$600,000
Jan.
Feb.
Mar
.Apr.
May
June
July
Aug.
Sept.
Oct
.Nov.
Dec.
Month of Discharge
ICE
R
26 weeks
27 weeks
28 weeks
30 weeks
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ICER by GA with New Recommendation
$0
$50,000
$100,000
$150,000
$200,000
$250,000
$300,000
26 weeks 27 weeks 28 weeks 29-30 weeks
Month of Discharge
ICE
R ICER
$103,053
$171,224
$216,830
$280,083
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Conclusion
• In our model for premature infants without CLD, incremental Cost / QALY:
– Was high for all gestational ages; Many ICER were over $1 million.
– Large amount of variation across months.
• Simulations identified more cost-effective options.
• Pursue strategies to minimize drug wastage.
• AAP guidelines could be revisited to make them more cost effective.
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Limitations
• Some costs were based on local estimates.
• May have underestimated cost from family members missing work due to infant hospitalized with RSV.
• Unclear whether causal relationship between severe RSV infection and asthma and other long-term health consequences; need for additional research.
• Decrease in quality of life due to asthma based on adults.
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University of Rochester Collaborators
• Department of Pediatrics, Division of Neonatology/Infectious Disease
Dr. Nahed El Hassan Dr. Timothy Stevens Dr. Caroline Hall
• Department of Community and Preventive Medicine
Dr. Andrew Dick
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