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