The Cost Effectiveness of RSV
Prophylaxis: Using Decision
Analysis to Build a Better Guideline
Melony E. S. Sorbero, PhD, MS, MPH
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
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•
•
•
•
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.
RSV Hospitalization Rate by Gestational Age at Birth
25%
20.60%
20%
Percent RSV
Hospitalization
14.60%
15%
11.30%
10%
6.40%
5%
0%
=< 26 W.
27 - 28 W.
> 28 - 30 W.
> 30 - 32 W.
Gestational Age at Birth
(Stevens TP et al. Arch Ped Adoles Med 2000)
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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.
Respiratory Illness Hospitalization Rate by
Month of Discharge from NICU in Infants <= 32 Weeks GA
45%
42%
41%
40%
35%
30%
27%
Probability of 25%
hospitalization 20%
15%
15%
10%
5%
0%
Jan.
Feb. - Apr.
May - Aug.
Sept. - Dec.
Month of Discharge
(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 hightiter 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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Effect of Gestational Age on Expected Costs
9,000
8,000
$ 8,000
Expected Costs ($)
7,000
$ 7,298
6,000
5,000
Synagis: AAP Recommendations:
Infants: 29 - 32 weeks if = < 6 months old at the
start of the RSV season
Synagis: AAP Recommendations:
Infants: = < 28 weeks if = < 12 months old at
the start of the RSV season
4,000
$ 4,092
3,000
Synagis
No
Synagis
$ 2,184
$ 1,548
2,000
$ 678
1,000
0
24 - 26
27
28
29 - 30
Gestational Age at Birth (Weeks)
31
32
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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: > $200,000 / QALY
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Incremental Cost / QALY ($ / QALY)
Effect of Gestational Age on ICER
2,000,000
1,800,000
$1,500,351
/ QALY
1,600,000
$1,855,000
/ QALY
With Drug Wastage
1,400,000
1,000,000
800,000
600,000
400,000
$1,481,965
/ QALY
$ 906,310
/ QALY
1,200,000
$1,268,679
/ QALY
$830,152
/ QALY
$685,720
/ QALY
$657,780
/ QALY
Without Drug
Wastage
200,000
Acceptable Zone =< $ 200,000 / QALY
0
24 - 26
27
28
29 - 30
Gestational Age at Birth (Weeks)
31
32
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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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$3,500,000
$3,000,000
$2,500,000
$2,000,000
$1,500,000
$1,000,000
$500,000
$0
N
ov
.
.
Se
pt
y
Ju
l
ay
M
ar
.
24-26 weeks
27 weeks
28 weeks
29-30 weeks
M
Ja
n.
ICER
Large variation within GA in ICER
Month of Discharge
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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
$600,000
26 weeks
27 weeks
28 weeks
30 weeks
$400,000
$300,000
$200,000
$100,000
$0
Ja
n.
Fe
b.
M
ar
.
A
pr
.
M
ay
Ju
ne
Ju
ly
A
ug
Se .
pt
.
O
ct
N .
ov
.
D
ec
.
ICER
$500,000
Month of Discharge
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ICER by GA with New Recommendation
$300,000
$280,083
$250,000
ICER
$200,000
$216,830
$150,000
ICER
$171,224
$100,000
$103,053
$50,000
$0
26 weeks
27 weeks
28 weeks
29-30 weeks
Month of Discharge
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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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