Centers for Disease Control and Prevention

Evidence to Recommendations Framework: 

Nirsevimab Updates

Jefferson Jones MD MPH FAAP, CDR USPHS

Co-Lead, Respiratory Syncytial Virus Vaccines - Pediatric/Maternal Work Group 

Coronavirus and Other Respiratory Viruses Division

National Center for Immunization and Respiratory Diseases

August 3, 2023
2

Evidence to Recommendations (EtR) Framework

Policy Questions

▪ Should one dose of nirsevimab be recommended for infants aged <8 months born 

during or entering their first RSV season (50 mg for infants <5 kg and 100 mg for 

infants ≥5 kg)?

▪ Should one dose of nirsevimab be recommended children aged 8–19 months who 

are at increased risk of severe RSV disease and entering their second RSV season 

(200 mg)?

▪ Given an average RSV season of 4–5 months, infants aged 8 months and children 

aged 20 months would be experiencing their second and third RSV seasons, 

respectively
3

Nirsevimab is a passive immunization

▪ Active immunity results from infection or vaccination, which triggers 

an immune response

▪ Passive immunity is when a person receives antibodies from an external 

source

– From mother to baby through transplacental or breastmilk transfer

– Direct administration of antibodies, such as IVIG or monoclonal 

antibodies 

IVIG= Intravenous Immunoglobulin Therapy

https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm
4

Evidence to Recommendations (EtR) Framework

PICO Question 1

▪

Population Infants aged <8 months born during or entering their first RSV 

season

Intervention Nirsevimab (1 injection prior to start of RSV season or at birth if 

born during season, 50 mg if <5 kg or 100 mg if ≥5 kg)

Comparison No nirsevimab prophylaxis

Outcomes ▪ Medically attended RSV-associated lower respiratory tract 

infection (LRTI)

▪ RSV-associated LRTI with hospitalization

▪ RSV-associated LRTI with ICU admission

▪ RSV-associated death

▪ All-cause medically attended LRTI

▪ All-cause LRTI-associated hospitalization

▪ Serious adverse events
5

Evidence to Recommendations (EtR) Framework

EtR Domain Question(s)

Public Health Problem ▪ Is the problem of public health importance?

Benefits and Harms ▪ How substantial are the desirable anticipated effects?

▪ How substantial are the undesirable anticipated effects?

▪ Do the desirable effects outweigh the undesirable effects?

Values ▪ Does the target population feel the desirable effects are large relative 

to the undesirable effects?

▪ Is there important variability in how patients value the outcome?

Acceptability ▪ Is the intervention acceptable to key stakeholders?

Feasibility ▪ Is the intervention feasible to implement?

Resource Use ▪ Is the intervention a reasonable and efficient allocation of resources?

Equity ▪ What would be the impact of the intervention on health equity?
EtR Domain: Public Health Problem

Is RSV-associated disease among infants <8 months of age entering their 

first RSV season and infants born during the RSV season of public health 

importance? 
7

Changes in seasonality of RSV transmission following 

SARS-CoV2 introduction— NREVSS1, 2017–2023

0

5

10

15

20

25

27 29 31 33 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25

Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

% PCR results RSV

-positive

Epidemiologic week

2017–18 2018–19 2019–20 2020–21 2021–22 2022–23

Abbreviation: PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm

* 3-week centered moving averages of percentage of RSV-positive PCR results nationwide. The black dotted line represents the threshold for a seasonal epidemic (3% RSV-positive laboratory PCR results). 
8

Epidemiology of RSV

▪ RSV is the most common cause of hospitalization in U.S. infants

– Highest hospitalization rates in first months of life

– Risk declines by month with increasing age in infancy and early childhood

▪ Prematurity and other chronic diseases increase risk of RSV-associated 

hospitalization, but most hospitalizations are in healthy, term infants

▪ Work group felt that RSV-associated disease in infants born or entering their 

first RSV season is of public health importance
EtR Domain: Benefits and Harms

Do the desirable effects outweigh the undesirable effects?
10

Efficacy estimates and concerns in certainty of 

assessment

Outcome Efficacy estimate* Concerns in certainty of assessment

Benefits

Medically attended RSV LRTI 79.0% (95% CI: 68.5%–86.1%) None

RSV LRTI with hospitalization 80.6% (95% CI: 62.3%–90.1%) None

RSV LRTI with ICU admission 90.0% (95% CI: 16.4%–98.8%) Serious (imprecision): Too few events

Death due to RSV respiratory 

illness

None recorded N/A

All-cause medically attendedLRTI34.8% (95% CI: 23.0–44.7%) None

All-cause LRTI-associated 

hospitalization

44.9% (95% CI:24.9%–59.6%) None

*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm
11

Relative risk of SAEs and concerns in certainty of 

assessment

Outcome Relative risk1 Concerns in certainty of assessment

Harms

Serious Adverse Events 

(SAEs)2

0.73 (95% CI: 0.59–0.89) Serious (imprecision)

1 Pooled phase 2b and phase 3 estimate comparing nirsevimab arm to placebo arm

2 Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. 

Adverse events include respiratory symptoms.
12

Summary of GRADE for nirsevimab

OutcomeImportance Design

(# of studies)

FindingsEvidence

type

1

Benefits

Medically attended RSV 

LRTI Critical RCT (2) Nirsevimab is effective in preventing medically attended RSV LRTI High

RSV-associted LRTI with 

hospitalization Critical RCT (2) Nirsevimab is effective in preventing medically attended 

RSV LRTI with hospitalization High

RSV-associated LRTI with 

ICU admission Critical RCT (2) Nirsevimab is likely effective in preventing medically attended RSV LRTI with ICU admission Moderate

RSV-associated death Critical RCT (2) No RSV-associated deaths reported -

All-cause medically 

attended LRTI Important RCT (2) Nirsevimab is effective in preventing all cause medically attended LRTI High

All-cause LRTI-associated 

hospitalization Important RCT (2) Nirsevimab is effective in preventing all cause hospitalization with respiratory disease High

Harms

Serious adverse eventsCritical RCT (2) SAEs were likely not more common in intervention group 

than placebo group Moderate
13

Additional safety data provided at Antimicrobial Drugs 

Advisory Committee meeting

▪ Most commonly reported adverse reaction were injection site reactions 

(0.3%) and rash (0.9%)

▪ FDA noted an imbalance in deaths between nirsevimab and the control 

arms but determined that the deaths were unlikely to be related to 

nirsevimab

https://www.fda.gov/advisory-committees/advisory-committee-calendar/june-8-2023-meeting-antimicrobial-drugs-advisory-committee-meeting-announcement-06082023
14

Nirsevimab phase 3b study (HARMONIE)1

▪ Enrolled 8,058 infants

– Age at enrollment: 49% <3 month, 24% 3-5 months, 28% ≥6 months

– 85% born at term, 50% born in season

▪ Conducted in France, UK, and Germany during August 8, 2022–February 28, 2023

▪ Randomized to nirsevimab or no injection

▪ Primary endpoint RSV hospitalization

– LRTI hospitalization with positive RSV test 

– RSV tests ordered by clinician and not on all patients with LRTI 

– Participants followed for at least 12 months after randomization

▪ At end of RSV season, preliminary efficacy results released

– Median post-randomization follow up time of 2.5 months 

1 Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510
15

HARMONIE preliminary results1

▪ Efficacy

– RSV hospitalization: 83% (95% CI 68%–92%)

– Severe disease (SaO2 <90% and oxygen given): 76% (95% CI 33%–93%)

– All-cause hospitalization with LRTI during RSV season: 58% (95% CI 

40%–71%)

▪ Safety

– Grade 1 AEs slightly higher in nirsevimab arm (29%) vs no intervention 

arm (25%)

– Number of Grade 2 and Grade 3 AEs similar between nirsevimab and 

control arm

SaO2= oxygen saturation; AE= adverse event

1 Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510/. Results analyzed as of 

2/28/2023 because RSV season had ended, and median duration of follow up was 2.5 months at that time.
16

Benefits and harms summary

▪ Overall GRADE evidence rating: moderate

▪ Downgraded based on imprecision for protection against ICU admissions 

because of few recorded events and imprecision of SAEs because rare 

events are unlikely to be detected

▪ The work group felt that the:

– Desirable anticipated effects of nirsevimab were moderate to large

– Undesirable anticipated effects of nirsevimab were minimal to small

– Desirable effects outweighed the undesirable effects and favored 

nirsevimab over no intervention
EtR Domain: Values

Criterion 1: Does the target population feel that the desirable effects are 

large relative to undesirable effects?

Criterion 2: Is there important uncertainty about, or variability in, how 

much people value the main outcomes?
18

Summary results of CDC and University of Iowa/RAND 

survey on RSV immunizations to prevent RSV disease in 

infants

▪ Only 33% of respondents thought their baby ‘definitely’ or ‘probably’ 

would get an RSV infection within one year after being born

▪ Despite being unsure or perceiving RSV risk to be low, respondents were 

worried their baby would need to be hospitalized if they got sick with RSV 

(mean response 4 of 5 with 5 being most worried)

▪ 70% of respondents said they ‘definitely’ or ‘probably’ would get an RSV 

antibody injection for their baby if safe and effective*

*If antibody injection was approved by FDA and recommended by CDC. 

CDC and University of Iowa/RAND survey, unpublished
19

Values summary

▪ The work group determined that the target population probably feels that the 

desirable effects are large relative to undesirable effects

▪ The work group varied in whether they felt there was important uncertainty about, 

or variability in, how much people value the main outcomes

*If antibody injection was approved by FDA and recommended by CDC. 

CDC and University of Iowa/RAND survey, unpublished
EtR Domain: Acceptability

Is immunization with nirsevimab acceptable to key stakeholders?
21

Acceptability Summary

▪ In a survey of U.S. pediatric providers, over 85% agreed that parents need 

more information about RSV, that immunization could help prevent RSV, 

and that immunization policy should ensure all children get access1

▪ The American Academy of Pediatrics and National Foundation For 

Infectious Diseases Roundtable have stated the need for safe and effective 

RSV prevention products2,3

▪ The work group felt that passive immunization with nirsevimab was 

probably acceptable to key stakeholders

1. https://admin.allianceforpatientaccess.org/wp-content/uploads/2023/01/AfPA-and-NCfIH_The-Indirect-Impact-of-RSV_Survey-Report_Jan-2023.pdf

2. AAP COID BGC Pediatrics 2014 Aug;134(2):415-20. 

3. https://www.nfid.org/wp-content/uploads/2022/04/NFID-RSV-Call-to-Action.pdf
EtR Domain: Feasibility

Is nirsevimab feasible to implement among all infants <8 months of age 

entering their first RSV season and infants born during the RSV season?
23

Work Group Feasibility Interpretation

▪ Considerations reviewed in separate presentation

▪ Work group felt that nirsevimab will probably be feasible to implement
EtR Domain: Resource Use

Is nirsevimab immunization among all infants <8 months of age entering 

their first RSV season and infants born during the RSV season a 

reasonable and efficient allocation of resources?
25

Updates to cost effectiveness model

▪ Cost of product 

– $495 list price

– $395 Vaccines for Children (VFC) program price

– Assuming 50% VFC and 50% private insurance, average price of $445

– Price not final

▪ Mortality assumptions modified to include individuals at increased risk of 

severe RSV disease

▪ Savings from not using palivizumab incorporated

▪ Other inputs unchanged1

1 Other inputs unchanged from previous model presented at February 23, 2023 ACIP meeting
26

Number needed to immunize with nirsevimab to 

prevent one health outcome

17 

48 

128 

581 

24 

194 

 -

 100

 200

 300

 400

 500

 600

 700

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Number needed to immunize to avoid
27

Cost per health event averted

Cost of $445 per dose

$2,662 $7,473 

$19,909 

$90,494 

$3,687 

$30,165 

 $-

 $10,000

 $20,000

 $30,000

 $40,000

 $50,000

 $60,000

 $70,000

 $80,000

 $90,000

 $100,000

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Cost per Event Averted
28

Cost effectiveness result and Work Group 

Interpretation

▪ Updated base case result: $102,811 per quality adjusted life year saved

▪ The work group felt nirsevimab is or probably is a reasonable and efficient 

use of resources
EtR Domain: Equity

What would be the impact of nirsevimab on health equity?
30

Equity Summary

▪ If recommended, ACIP will vote on VFC resolution for nirsevimab

▪ National studies of death certificates found higher rates among non-Hispanic black 

children compared with non-Hispanic White infants and children aged 1–4 years1

▪ ICU admission rates for RSV among Non-Hispanic Black infants <6 months old were 

1.2–1.6x higher than among Non-Hispanic White infants2

▪ RSV hospitalization rates 4–10x higher among Alaska Native and American Indian 

children aged <24 months than the rate in the general population3

▪ Studies of RSV hospitalization by race and ethnicity have differing results4–7

▪ The work group felt that nirsevimab would increase health equity

1. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255-S266. 2. Unpublished data from RSV-NET, CDC. 3. Atwell Pediatrics 2023, e2022060435. 4. Hall Pediatrics 2013 Aug;132(2):e341-8; 5. Hall NEJM 

2009;360(6):588–598. 6. Iwane Pediatrics 2004 Jun;113(6):1758-64, findings differed by age group. 7. Rha Pediatrics 2020 Jul;146(1):e20193611, findings differed by age group
31

EtR Summary: All infants 1st RSV season

EtR Domain Question(s) Work Group Judgments

Public Health 

Problem

▪ Is RSV-associated disease among infants <8 months of age 

entering their first RSV season and infants born during the 

RSV season of public health importance?

Yes

Benefits and 

Harms

▪ How substantial are the desirable anticipated effects?

▪ How substantial are the undesirable anticipated effects?

▪ Do the desirable effects outweigh the undesirable effects?

Moderate to large

Minimal to small

Yes

Values ▪ Does the target population feel the desirable effects are 

large relative to the undesirable effects?

▪ Is there important variability in how patients value the 

outcome?

Yes/probably yes

No consensus

Acceptability ▪ Is nirsevimab acceptable to key stakeholders? Yes/probably yes

Feasibility ▪ Is the intervention feasible to implement? Probably yes

Resource Use ▪ Is the intervention a reasonable and efficient allocation of 

resources? Yes/probably yes 

Equity ▪ What would be in the impact of the intervention on health 

equity? Probably increased
32

Evidence to Recommendations Framework

Summary: Work Group Interpretations

All infants 1st RSV season 

Balance of

consequences

Undesirable

consequences

clearly

outweigh

desirable

consequences

in most settings

Undesirable

consequences

probably

outweigh

desirable

consequences

in most settings

The balance

between

desirable 

and undesirable

consequences

is closely

balanced or

uncertain

Desirable

consequences

probably

outweigh

undesirable

consequences

in most settings

Desirable

consequences

clearly

outweigh

undesirable

consequences

in most settings

There 

is insufficient

evidence 

to determine 

the balance of

consequences

Minority opinion 
33

Evidence to Recommendations Framework

Summary: Work Group Interpretations

All infants 1st RSV season 

Type of

recommendation

We do not 

recommend the 

intervention

We recommend 

the intervention for 

individuals based on 

shared 

clinical decisionmaking

We recommend 

the intervention
2

nd indication

Should one dose of nirsevimab be recommended for children 8–19 

months of age with increased risk of severe disease entering their second 

RSV season?
35

Evidence to Recommendations (EtR) Framework

PICO Question 2

▪

Population Children aged 8–19 months who are at increased risk of severe RSV 

disease and who are entering their second RSV season

Intervention Nirsevimab (200 mg [2 x 100 mg] injection near start of second RSV

season)

Comparison No nirsevimab prophylaxis

Outcomes ▪ Medically attended RSV associated lower respiratory tract 

infection (LRTI)

▪ Medically attended RSV associated LRTI with hospitalization

▪ Medically attended RSV associated LRTI with ICU admission

▪ RSV-associated death

▪ All-cause Medically attended LRTI

▪ All-cause LRTI associated hospitalization

▪ Serious adverse events
36

Evidence to Recommendations (EtR) Framework

EtR Domain Question(s)

Public Health Problem ▪ Is the problem of public health importance?

Benefits and Harms ▪ How substantial are the desirable anticipated effects?

▪ How substantial are the undesirable anticipated effects?

▪ Do the desirable effects outweigh the undesirable effects?

Values ▪ Does the target population feel the desirable effects are large relative 

to the undesirable effects?

▪ Is there important variability in how patients value the outcome?

Acceptability ▪ Is the intervention acceptable to key stakeholders?

Feasibility ▪ Is the intervention feasible to implement?

Resource Use ▪ Is the intervention a reasonable and efficient allocation of resources?

Equity ▪ What would be the impact of the intervention on health equity?
EtR Domain: Public Health Problem

Is RSV disease among children who are at increased risk of severe disease 

in their 2nd RSV season of public health importance?
38

Risk groups previously proposed to receive nirsevimab 

when entering second RSV season

▪ Based on American Academy of Pediatrics recommendations for palivizumab for a 

child’s second RSV season1

▪ Assumed to be cost saving compared with palivizumab

▪ Proposed recommendation to receive nirsevimab when entering 2nd RSV season

– Children with chronic lung disease of prematurity if require medical support 

(chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during 

the 6-month period before the start of the second RSV season

– Children with severe immunocompromise

– Children with cystic fibrosis if manifestations of severe lung disease (previous 

hospitalization for pulmonary exacerbation in the first year of life or abnormalities 

on chest imaging that persist when stable) or weight for length < 10th percentile

1. American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncitial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book : 2021 

Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021.
39

Analyses conducted by CDC to evaluate risk factors for 

severe RSV disease during second RSV season

▪ Systematic review of literature

▪ Analysis of MarketScan national claims database
40

Systematic review of literature on risk factors for 

severe disease during second RSV season

▪ Included any studies that compared RSV hospitalization rates among 

children with risk factors to a healthy control group among children aged 

6–24 months

▪ Among 3,825 abstracts, 6 studies identified

▪ Chronic lung disease, congenital heart disease, and neuromuscular disease 

analyzed in these studies

▪ Studies indicated increased risk of hospitalization for these risk factors

▪ No studies evaluating other risk factors identified
41

Analysis of MarketScan national claims database for 

select risk factors for severe RSV disease during second 

RSV season, 2015-2021

▪ Using ICD-9-CM/ICD-10-CM codes, identified children with and without 

select conditions (chronic lung disease, congenital heart disease, Down 

syndrome, neuromuscular disease, pulmonary malformations, 

immunodeficiency, cystic fibrosis) and children that were hospitalized with 

RSV

▪ Compared rates of RSV hospitalization among children with a chronic 

conditions to children without chronic condition

▪ Increased rates of hospitalization seen for all conditions

▪ RSV testing may be more common for children with risk conditions, 

inflating RSV-specific hospitalization rates 
42

Increased incidence of RSV-associated severe disease 

in American Indian and Alaska Native children

1 Atwell 2023 Pediatrics 2023 Jul 14;e2022060435. 2 Karron et al. J Infect Dis 1999. 3Holman et al. Pediatrics 2004. 4 Lowther et al. J Ped Infect Dis 2000 5American Academy of 

Pediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book : 2021 Report of the Committee 

on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021.

▪ Several prior studies have documented increased incidence of RSV-associated 

hospitalizations among American Indian and Alaska Native children1,2,3,4

– One study found that rates of RSV-associated hospitalization in AI/AN children 

were 4-10 times average rates of U.S. children aged 12-23 months from NVSN1

– These studies have been conducted in specific populations and may not be 

broadly representative of risk in all AI/AN children

– Findings of these studies do not separate environmental, sociocultural, or other 

factors that may increase severe disease risk

▪ Some AI/AN communities are also in remote areas that make transportation of 

children with severe RSV to appropriate healthcare facilities more challenging5
43

Public health problem work group interpretation

▪ Evidence for RSV burden among children aged 8–19 months entering their 

second with specific risk conditions is limited

▪ The work group felt nirsevimab should be recommended to the same 

groups that AAP recommends for palivizumab for the second RSV season

▪ The work group also felt that nirsevimab should be recommended to 

Alaska Native and American Indian children entering their second RSV 

season

▪ The work group felt that RSV disease among children who are at increased 

risk of severe disease1in their 2nd RSV season was of public health 

importance

1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and 

American Indian and Alaska Native children 
EtR Domain: Benefits and Harms

Do the desirable effects outweigh the undesirable effects?
45

Efficacy based on extrapolation of pharmacokinetic 

data

▪ A pharmacokinetic trial was conducted that randomized children at 

increased risk of severe RSV disease to palivizumab or nirsevimab

▪ In the second RSV season, 220 participants received nirsevimab and 42 

received palivizumab

▪ Among those that received nirsevimab, two pharmacokinetic endpoints have 

been reported

– Day 150 nirsevimab concentrations compared with phase 3 (Melody) 

efficacy trial among late pre-term and term infants that showed efficacy

– Proportion of participants that had area under the curve nirsevimab 

concentrations above target based on efficacy trial data of 12.8 

mg*day/ml

Domachowske J, Madhi SA, Simões EAF, Atanasova V, Cabañas F, Furuno K, et al. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. New 

England Journal of Medicine. 2023;386(9): 892–894. doi: 10.1056/NEJMc2112186
46

Observed nirsevimab concentrations 150 days post-dose

▪ Among recipients of 

nirsevimab, day 150 

concentrations higher 

in those who received 

200 mg in second RSV 

season (labeled trial 

05) than infants who 

received 50mg (if <5kg) 

or 100mg (if >5kg) in 

phase 3 Melody trial 

(labeled trial 04)

Source: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting. 

The dashed line is EC90 value of 6.8 μg/mL determined based on RSV challenge studies in cotton rat model. 

Abbreviations: CHD, hemodynamically significant congenital heart disease; CLD, chronic lung disease of prematurity; EC90, 90% effective 

concentration; GA, gestational age. Trial 04: MELODY trial among late pre-term and term infants. Trial 05: Pharmacokinetics study among infants at 

increased risk of severe RSV disease.
47

Area under the curve (AUC) nirsevimab concentration 

and safety results

▪ Among recipients of nirsevimab in second season, most had AUC 

nirsevimab concentrations above the target threshold

– 97.7% (129/132) of infants with chronic lung disease

– 100% (58/58) of infants with congenital heart disease

▪ No adverse events judged as related to nirsevimab or palivizumab in 

second RSV season follow up period

Source: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting
48

Summary of GRADE for nirsevimab dose for second season

OutcomeImportance Design

(# of studies)

FindingsEvidence

type

Benefits

Medically attended (MA) 

RSV LRTI Critical 1 Nirsevimab might be effective in preventing MA RSV LRTI Low

RSV LRTI with 

hospitalization Critical No available data

RSV LRTI with ICU 

admission Critical No available data

RSV-associated death Critical No available data

All cause medically 

attended LRTI Important

No available data

All cause hospitalization 

with respiratory disease Important No available data

Harms

Serious adverse events 

(SAEs) Critical 1

Prevalence of SAEs was not significantly different in the 

intervention and control groups Very low
49

Benefits and harms summary

▪ Overall evidence rating: Very low certainty (type 4)

▪ Downgraded based on indirectness because pharmacokinetic data used as 

surrogate for efficacy, population did not include children that matches 

proposed indication, study small in size, and no placebo group was 

included for comparison

▪ The work group felt1that the:

– Desirable anticipated effects were moderate

– Undesirable anticipated effects were minimal

– Desirable effects outweighed the undesirable effects and favored 

nirsevimab over no intervention

1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and 

American Indian and Alaska Native children 
EtR Domains: Values, Acceptability, and 

Feasibility
51

Values summary

▪ No additional data was available for values specific to populations at 

increased risk for severe disease

▪ The work group determined that the target population feels or probably 

feels that the desirable effects are large relative to undesirable effects1

▪ The work group also felt that there was probably not important 

uncertainty or variability in how much people valued the main outcomes1

1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and 

American Indian and Alaska Native children 
52

Acceptability summary

▪ No additional data was available for acceptability specific to infants and 

young children at increased risk

▪ The work group felt that prevention with nirsevimab was, or probably was 

acceptable to key stakeholders1

1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and 

American Indian and Alaska Native children 
53

Feasibility summary

▪ Additional visit to provider might be needed for administration of 

nirsevimab prior to beginning of 2nd RSV season

▪ The work group felt that nirsevimab was probably feasible to implement 

among children aged 8–19 months at increased risk of severe RSV disease 

entering their second RSV season1

1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and 

American Indian and Alaska Native children 
EtR Domain: Resource Use
55

Inputs to cost effectiveness model for second RSV 

season 

▪ Theoretical groups of children with increased risk created with 2x, 4x, 6x, 10x 

higher risk than the general population aged 8–19 months in October

– Increased incidence of RSV-associated hospitalization and increased mortality 

per hospitalization

– Increased incidence of RSV-associated hospitalization but held mortality per 

hospitalization constant

– No increase in incidence of outpatient and ED visits, healthcare costs, or 

quality adjusted life years lost with RSV disease1

▪ Cost updated to $890 nirsevimab costs (2x $445/dose)

▪ Mortality estimates modified to include high-risk individuals

▪ Other inputs unchanged1

1Same assumption as previous model presented at February 23, 2023 ACIP meeting
56

Updated cost effectiveness results for children 8–19 

months entering second RSV season

Incremental Cost-Effectiveness Ratio ($ / quality adjusted life year)

Increased Risk 

category

RSV Hospitalization incidence 

increased

RSV hospitalization incidence and 

mortality per hospitalization increased

1x (base) $1,557,544 $1,557,544 

2x $1,147,756 $836,270 

4x $726,983 $280,740 

6x $512,337 $118,912 

10x $294,775 $25,328 
57

Resource Use Work Group Interpretation

▪ The work group felt that nirsevimab use among children aged 8–19 

months entering their second RSV season who are at increased risk of 

severe disease1is probably a reasonable and efficient allocation of 

resources.

1For groups recommended to receive palivizumab in their second RSV season by the American 

Academy of Pediatrics and American Indian and Alaska Native children 
EtR Domain: Equity
59

Equity summary and Work Group interpretation

▪ Equity issues differ by chronic condition among infants and young children

▪ AI/AN children have higher hospitalization incidence rates than general population 

during second RSV season 

▪ Non-Hispanic Black and Hispanic populations higher rates of preterm birth than 

non-Hispanic White population1

▪ The work group felt that nirsevimab use would probably increase health equity2

1https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm

2For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and American Indian 

and Alaska Native children 
60

Summary: Children at high risk entering 2nd RSV season

EtR Domain Question(s) Work Group Judgments

Public Health 

Problem

▪ Is RSV disease among children 8–19 months who are at 

increased risk of severe disease of public health importance? Yes

Benefits and 

Harms

▪ How substantial are the desirable anticipated effects?

▪ How substantial are the undesirable anticipated effects?

▪ Do the desirable effects outweigh the undesirable effects?

Moderate

Minimal

Favors nirsevimab

Values ▪ Does the target population feel the desirable effects are 

large relative to the undesirable effects?

▪ Is there important variability in how patients value the 

outcome?

Probably yes

Probably no

Acceptability ▪ Is nirsevimab acceptable to key stakeholders? Yes / Probably yes

Feasibility ▪ Is the intervention feasible to implement? Probably yes

Resource Use ▪ Is the intervention a reasonable and efficient allocation of 

resources?

$890: Probably yes

Equity ▪ What would be in the impact of the intervention on health 

equity?

Probably increased
61

Evidence to Recommendations Framework

Summary: Work Group Interpretations

Children at increased risk of severe disease entering 2nd RSV season1

Balance of

consequences

Undesirable

consequences

clearly

outweigh

desirable

consequences

in most settings

Undesirable

consequences

probably

outweigh

desirable

consequences

in most settings

The balance

between

desirable 

and undesirable

consequences

is closely

balanced or

uncertain

Desirable

consequences

probably

outweigh

undesirable

consequences

in most settings

Desirable

consequences

clearly

outweigh

undesirable

consequences

in most settings

There 

is insufficient

evidence 

to determine 

the balance of

consequences

1For groups recommended to receive palivizumab in their second RSV season by the American 

Academy of Pediatrics and American Indian and Alaska Native children 
62

Evidence to Recommendations Framework

Summary: Work Group Interpretations

Children at increased risk of severe disease entering 

2nd RSV season1

Type of

recommendation

We do not 

recommend the 

intervention

We recommend 

the intervention for 

individuals based on 

shared 

clinical decisionmaking

We recommend 

the intervention

1For groups recommended to receive palivizumab in their second RSV season by the American 

Academy of Pediatrics and American Indian and Alaska Native children 
63

Acknowledgements 

Meredith McMorrow

Lauren Roper

Katherine Fleming-Dutra

Mila Prill

Amanda Payne

Danielle Moulia

Morgan Najdowski

David Hutton

Jamie Pike

Ismael Ortega-Sanchez

Andrew Leidner

Sara Oliver

Monica Godfrey

Evelyn Twentyman

Rebecca Morgan

Doug Campos-Outcalt

Sherry Farr

Karrie Finn-Downing

Melissa Glidewell

Eric Griggs

Emilia (Emily) Koumans

Matt Oster

Eghosa (Ivy) Oyegun

Francena Scott

Olga Varechtchouk

Lori Moore

Roua El Kalach

Eric Larson

Harris LaTreace

Michelle Ruslavage

Hannah Rosenblum

James Singleton

Carla Black

Sarah Meyer

Derrell Powers

Raigan Wheeler

Michael Melgar

Amadea Britton

Erica Reott

Samuel Graitcer

Jeanne Santoli

Jill Moses

Jamie Mells

Dawona Hough

Paul Lucas

Michelle Banks

Arthur Bayo

Nancy Fenlon

Rebecca Miller

Elizabeth Walker

Suzanne Johnson-DeLeon

JoEllen Wolicki

Elizabeth Greene

Neil Murthy

Patricia Wodi

Sarah Cutchin

Elisha Hall

Sarah Schillie

Andrew Kroger

Melissa Barnett

Dale Babcock

Rosa Herrera

Richard Quartarone

Stuart Myerburg

Melissa Taylor

Sarah Morales

Barbara Mahon

All members of the ACIP 

Mat/Peds RSV Work Group
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.
Back up slides
GRADE 

Indication: one dose of nirsevimab for infants aged <8 months born 

during or entering their first RSV season
67

GRADE: Medically attended RSV LRTI (n=2 studies)

▪ Measures of effect

– Efficacy: 79.0% (68.5% to 86.1%)

– Absolute risk (using 23.1% seasonal incidence*): 177 fewer cases per 1,000 immunized 

(195 fewer to 152 fewer)

• Number needed to immunize: 6 (5 to 7)

– Absolute risk (using 11.0% seasonal incidence**): 86 fewer cases per 1,000 immunized 

(94 fewer to 74 fewer)

• Number needed to immunize: 12 (11 to 14)

– Absolute risk (using 5.4% seasonal incidence [phase 3 trial controls]): 42 fewer cases per 

1,000 immunized (46 fewer to 37 fewer)

• Number needed to immunize: 24 (22 to 27)

▪ Concerns in certainty assessment

– None

▪ Evidence type: High (type 1)

67

*Lively 2019 JPIDS, 5 years from 3 NVSN sites from Nov-Apr season, included if with acute respiratory infection (ARI, not 

restricted to LRTI). **Assumes 47.5% of ARI are LRTI (Rainisch 2020 Vaccine)
68

GRADE: RSV-associated LRTI with hospitalization (n=2 

studies)

▪ Measures of effect

– Efficacy: 80.6% (62.3% to 90.1%)

– Absolute risk (using 1.3% seasonal incidence*): 10 fewer cases per 

1,000 immunized (12 fewer to 8 fewer)

• Number needed to immunize: 100 (83 to 125)

– Absolute risk (using 2% seasonal incidence [phase 3 trial controls]): 16 

fewer cases per 1,000 immunized (18 fewer to 12 fewer)

• Number needed to immunize: 63 (56 to 83)

▪ Concerns in certainty assessment

– None

▪ Evidence type: High (type 1)

68

*NVSN data 2016-2020 (unpublished), included if with ARI
69

GRADE: RSV-associated LRTI with ICU admission (n=2 

studies)

▪ Measures of effect

– Efficacy: 90.0% (16.4% to 98.8%)

– Absolute risk (using 0.35% seasonal incidence*): 3 fewer cases per 

1,000 immunized (3 fewer to 1 fewer)

• Number needed to immunize: 317 (289 to 1,754)

– Absolute risk (using 0.1% seasonal incidence [phase 3 trial controls]): 

0.9 fewer cases per 1,000 immunized (1.0 fewer to 0.2 fewer)

• Number needed to immunize: 1,111 (1,010 to 6,250)

▪ Concerns in certainty assessment

– Serious (imprecision): Too few events

▪ Evidence type: Moderate (type 2)

69

*Arriola 2019 JPIDS for proportion of hospitalizations admitted to ICU, NVSN data 2016-2020 (unpublished), included if with ARI
70

GRADE: All-cause medically attended LRTI (n=2 

studies)

▪ Measures of effect

– Efficacy: 34.8% (23.0 to 44.7%)

– Absolute risk (using 13.9% seasonal incidence [phase 3 trial controls]): 

46 fewer cases per 1,000 immunized (60 fewer to 30 fewer)

• Number needed to immunize: 21 (17 to 33)

▪ Concerns in certainty assessment

– None

▪ Evidence type: High (type 1)

70
71

GRADE: All-cause LRTI-associated hospitalization (n=2 

studies)

▪ Measures of effect

– Efficacy: 44.9% (24.9% to 59.6%)

– Absolute risk (using 3.7% seasonal incidence in phase 3 controls): 16 

fewer cases per 1,000 vaccinated (22 fewer to 9 fewer)

• Number needed to immunize: 63 (45 to 111)

▪ Concerns in certainty assessment

▪ Evidence type: High (type 1) 71
72

GRADE: SAEs (n=2 studies)

▪ Measures of effect

– Relative Risk: 0.73 (0.59 to 0.89)

– Absolute risk: 28 fewer cases per 1,000 immunized (43 fewer to 12 

fewer)

▪ Concerns in certainty assessment

– Serious (imprecision)

▪ Evidence type: Moderate (type 2)

72
GRADE 

Indication: one dose of nirsevimab for children aged 8-19 months who are 

at increased risk of severe RSV disease and entering their second RSV 

season
74

GRADE Summary

a Very serious concern for indirectness, due to use of a surrogate outcome, the was surrogate established in 1st season while trial is in 2nd season, and population that does not match proposed indication.

b Pharmacokinetic extrapolation was used and based on comparable pharmacokinetic levels from efficacy in infants <12 months of age for prevention of the first medically attended RSV LRTI to pharmacokinetic levels in children ≤24 

months with chronic lung disease (CLD) or congenital heart disease (CHD) entering their second RSV season. Based on pharmacokinetic and efficacy data from the phase 2b and phase 3 (MELODY) trials, a target area under the curve 

nirsevimab concentration of > 12.8 mg*day/ml was established. For the CLD cohort, 129/132 (98%) participants met the target nirsevimab concentration, and for the CHD cohort, 58/58 (92%) participants met the target. Additionally, 

the concentration of nirsevimab 150 days after injection was higher compared with the 150-day concentration in the phase 3 trial nirsevimab arm population.

c Serious concern for indirectness as the comparison group is palivizumab rather than placebo.

d Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered.

e 180 trial participants received nirsevimab in both the first and second season. 40 received palivizumab in the first season and nirsevimab in the second season

Certainty assessment No of patients Effect

Certainty Importance

No of 

studies

Study 

design

Risk of bias Inconsistency Indirectness Imprecision Other 

considerations

Nirsevimab Palivizumab Relative 

(95% CI)

Absolute 

(95% CI)

Medically attended lower respiratory tract infection

1 randomized 

trial

not serious not serious not serious very seriousa none Pharmacokinetic extrapolation 

was used and based on 

comparable pharmacokinetic 

levels from efficacy in infants 

<12 months of age for 

prevention of the first 

medically attended RSV LRTI to 

pharmacokinetic levels in 

children ≤24 months with 

chronic lung disease (CLD) or 

congenital heart disease (CHD) 

entering their second RSV 

seasonb

n/a n/a ⨁⨁◯◯

Low

CRITICAL

Serious adverse events

1 randomized 

trial

not serious not serious seriousc very seriousd none 21/220e 0/42 (0%) RR 8.4

(0.52 to 

135.5)f

86 more per 

1,000 (from 6 

fewer to 1,000 

more)g

⨁◯◯◯

Very low

Important
Updated cost effectiveness analysis
Economic Analysis of Nirsevimab in 

Pediatric Populations

David W. Hutton, PhD, MS

Associate Professor, Health Management and Policy, School of Public Health

Associate Professor of Global Public Health, School of Public Health

Associate Professor, Industrial and Operations Engineering, College of Engineering

University of Michigan

Highlighted portions of presentation represent changes from Feb 2023 ACIP presentation 
Research Team

University of Michigan

• David Hutton, PhD

• Lisa Prosser, PhD

• Angela Rose, MPH

• Kerra Mercon, MS

• Jefferson Jones, MD, MPH, FAAP

• Mila Prill, MSPH

• Meredith McMorrow, MD, MPH, FAAP

• Jamison Pike, PhD

• Katherine Fleming-Dutra, MD, FAAP

• Ismael Ortega-Sanchez, PhD

• Fiona Havers, MD

• Betsy Gunnels, MSPH

• Andrew Leidner, PhD

77
Conflicts of interest statements

• Authors have no known conflict of interests.

78
Methods: Study question

• Determine the cost-effectiveness of nirsevimab by:

• Evaluating the population burden of disease in pediatric US population in 

terms of 

• annual resource utilization 

• total cases

• total costs 

• deaths

• quality-adjusted life years

• Comparing the incremental cost-effectiveness ratio of nirsevimab to no 

prevention.

• Running scenario analyses outcomes that explore key areas of 

uncertainty.

• Perspective: Societal

79
Methods: Intervention(s)

• Target population: US pediatric < 7 months of age entering their first 

RSV season

• Secondary analysis high-risk infants in their second RSV season (7-18 months 

old)

• Interventions:

1. No nirsevimab (Natural history)

2. Nirsevimab against RSV illness

• Time horizon: 1 RSV season

• Analytic horizon: lifetime

• Discount rate: 3%

80
Methods: Decision Tree Model

81

No 

Prophylaxis

Nirsevimab

Infection 

Hospitalization

ED

None of the above

Outpatient

Alive

Dead

Infection

Adverse 

Events

Systemic Reaction

Injection Site Reaction

None of the above

Serious Adverse Event Infection 

Infection
Methods: Epidemiology

Hospitalization

Base Case Range Source

Respiratory syncytial virus (RSV) 

incidence, per 100,000 See Above See Above CDC NVSN, 

December 2016 to September 2020

Proportion with LRTI

Age 0-5 months 1.0 0.5-1.0 Rainisch, 2020

Age 6-11 months 1.0 0.5-1.0 Rainisch, 2020

82 CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to September 2020

 -

 1,000

 2,000

 3,000

 4,000

0 2 4 6 8 10 12 14 16 18 20 22

Hospitalization rate 

per 100,000 

children

Age in months
Methods: Epidemiology

ED and Outpatient

Respiratory syncytial virus (RSV) 

incidence, per 100,000 

Base Case Range Source

Emergency Department

Age 0-5 months 7,500 5,500 – 7,500 Lively 2019 (base case and range)5, Hall 

2009 (range)6

Age 6-11 months 5,800 5,700 – 5,800

Age 12 -23 months 3,200 3,200 – 5,300 Hall 2009 (base case and range)6, Lively 

2019 (range)5

Proportion with LRTI

Age 0-5 months 0.65 0.25-1.0 Rainisch, 20204

Age 6-11 months 0.5 0.25-1.0 Rainisch, 20204

Medically attended outpatient

Age 0-5 months

21,600

13,200 – 21,600 Lively 2019 (base case and range)5, Hall 

2009 (range)6

Age 6-11 months 24,600 17,700 – 24,600

Age 12 -23 months

18,440

6,600 – 29,620 Jackson 2021 (base case and range)7, 

Hall 2009 (range)6

Proportion with LRTI

Age 0-5 months 0.65 0.25-1.0 Rainisch, 20204

Age 6-11 months 0.3 0.1-1.0 Rainisch, 20204

83
Methods: Epidemiology

Mortality

Base 

Case

Range Source

RSV mortality per 

hospitalization

Age 0-5 months 0.10% 0.04-0.20% Hansen 2022, 

Doucette 2016

Age 6-11 months 0.10% 0.04-0.20% Hansen 2022, 

Doucette 2016

Age 12-23 months 0.3% 0.28%-0.34% Gupta 2016

84

New Mortality estimates are based on recent study by Hansen to be appropriate for 

the entire US population instead of just non-high-risk individuals.
Seasonality

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar

Fraction of Annual Infections

85

Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015-2019)
Methods: Nirsevimab Efficacy

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00%

0 2 4 6 8 10 12 14

Efficacy

Month

86

Average efficacy first 6 

months = trial efficacy 

Sigmoid decay to 

final efficacy

Zero efficacy
Methods: Efficacy

Variable Base case 

value

Range for 

sensitivity 

analysis

Source

Nirsevimab

Initial efficacy (months 0-5) 

against RSV-associated LRTI 79.0% 68.5% -86.1%

Efficacy months 6-10 25.0% 0.0% - 50.0%

Efficacy after 10 months 0.0%

87
Methods: Provision of Nirsevimab

• Base case:

• At birth for those born 

• October 1 – March 31

• October for those born in 

• April (~6-month visit)

• June (~4-month visit)

• August (~2-month visit)

• November for those born in

• May (~6-month visit)

• July (~4-month visit)

• September (~2-month visit)

• 50% coverage in the population

88
Methods: Medical Costs

Variable Value Range Source

Disease-specific 

hospitalization costs (per 

hospitalization) 

Age 0-11 months $11,487 4,804 - 86,646

Bowser 2022

Age 12- 23 months $11,469 4,804 - 86,646

Disease-specific ED costs 

(per ED visit) $563 544 – 581 Bowser 2022

Disease-specific 

outpatient costs (per 

outpatient visit)

$82 46-118 Bowser 2022

89

• Bowser, 2022 is a systematic review using studies from 2014-2021

• Funded by Sanofi

• All numbers updated to 2022 dollars using GDP Deflator
Methods: Productivity Costs

Variable Value Range Source

Productivity burden of RSV 

Disease (caregiver losses)

Days of lost productivity

Outpatient* 2.5 0-5

Fragaszy, 2018; Petrie, 2016; 

Van Wormer, 2017

ED* 2.5 0-5

Fragaszy, 2018; Petrie, 2016; 

Van Wormer, 2017

Hospitalization^ 7.4 0-14

Lifetime productivity for 

those <1 year old (lost from 

death)

1,795,936 Grosse, 2019

90

*Productivity for outpatient and ED based on adult influenza

^Hospitalization productivity loss = length of hospitalization + 2 days
Methods: Intervention Cost

Variable Value Range Source

Immunization-related costs

Nirsevimab, per dose $445 $50-$600 Assumption

91

Both assume no additional visits, but do include costs of administration

Manufacturer has suggested $495 list price and $395 for VFC

We assume 50% VFC*

* 50% VFC based on:

Benefits from Immunization During the Vaccines for Children Program Era — United 

States, 1994–2013
Methods: Palivizumab

92

• Assumption: Nirsevimab policy will lead to 100% reduction in palivizumab 

use. 

• Savings assumptions: current Palivizumab use

– 1.6% are high-risk (palivizumab-eligible)

– 75% uptake in high-risk

– 4.17 palivizumab doses/person on average

– $1,228/palivizumab dose
Methods: RSV 

Health-Related Quality-of-Life

LRTI quality adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)

Outpatient: Child 3.1 1.8 16.6

Outpatient: Caregiver 1.5 0 9.1

ED: Child 4.9 2.9 16.6

ED: Caregiver 2.5 0 9.1

Hospitalized: Child 6.2 3.7 26.5

Hospitalized: Caregiver 2.4 0 13.6

93

Measured in 

Days Lost

Most 

Likely
Methods: Additional Inputs

• Also included nirsevimab adverse events

• Systemic reactions

• Injection site reactions

• Serious adverse events

• Medical costs

• Productivity costs

• Quality-adjusted life-years lost

94
Methods: Uncertainty analyses

• One-way sensitivity

• Scenarios:

• Upper respiratory infection effect 

• Timing of administration

• Additional Scenario:

• High-risk children entering the second RSV season

95
Results: Base Case

• Base Case:

• Population of 1,000 births

• 50% uptake in the nirsevimab group

• First RSV season

• $500/dose

• Nirsevimab only impacts LRTI

96
Results: Health outcomes

97

Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group

URTI- Upper respiratory tract infection; LRTI- Lower respiratory tract infection

 -

 100,000

 200,000

 300,000

 400,000

 500,000

 600,000

 700,000

 800,000

 900,000

 Natural History Nirsevimab Natural History Nirsevimab Natural History Nirsevimab

Outpatient Emergency Department Inpatient

Number of Events in Cohort

URTI LRTI
Results: Health outcomes

98 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group

107,252.7

38,204.1

14,341.3

3,155.1

77,442.9

9,465.2

0.0

20,000.0

40,000.0

60,000.0

80,000.0

100,000.0

120,000.0

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Events Averted per year

Nirsevimab
Results: Health outcomes

99

17 

48 

128 

581 

24 

194 

 -

 100

 200

 300

 400

 500

 600

 700

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Number needed to Prophylax to avoid

Nirsevimab
Results: Costs

100 Base costs of nirsevimab: $445/dose, Cost of palivizumab for high-risk included in “Natural History”

Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group

$0

$200

$400

$600

$800

$1,000

$1,200

$1,400

$1,600

$1,800

$2,000

Natural

History

Nirsevimab Natural

History

Nirsevimab Natural

History

Nirsevimab Natural

History

Nirsevimab Natural

History

Nirsevimab Natural

History

Nirsevimab

Intervention Outpatient ED Inpatient Deaths Total

Total Costs in Cohort

Millions

Medical Productivity
Results: Health outcomes

101 Base costs of nirsevimab: $445/dose

$2,662 

$7,473 

$19,909 

$90,494 

$3,687 

$30,165 

 $-

 $10,000

 $20,000

 $30,000

 $40,000

 $50,000

 $60,000

 $70,000

 $80,000

 $90,000

 $100,000

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Cost per Event Averted

Nirsevimab
Results: QALYs lost

102

Adverse 

Events Outpatient ED Inpatient Deaths Total Grand

Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total

Natural History 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151 

Nirsevimab 52 6,246 3,127 2,774 1,387 565 224 949 10,586 4,738 15,324 

Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group
Results: Cost-effectiveness

103

Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group

Base costs of nirsevimab: $445/dose, Cost of palivizumab for high-risk included in “Natural History”

 $1,550

 $1,600

 $1,650

 $1,700

 $1,750

 $1,800

 $1,850

 $1,900

 (18,500) (18,000) (17,500) (17,000) (16,500) (16,000) (15,500) (15,000)

Costs 

Millions

QALYs (lost) from RSV 

Natural History Nirsevimab
Results: Cost-effectiveness

104

Overall Costs ($) QALYs ICER ($/QALY)Vs. NH

Natural History 1,585,172,002 18,151 

Nirsevimab 1,875,840,158 15,324 102,811 

Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group

Base costs of nirsevimab: $445/dose, Cost of palivizumab for high-risk included in “Natural History”
Sensitivity: Tornado nirsevimab

105 Base cost of $445/dose

$0 $50,000 $100,000 $150,000 $200,000 $250,000

nirsevimab cost/dose

Disease-specific inpatient costs (per inpatient case) Age 0-5 months

RSV QALYS Lost

Initial Efficacy

Fraction Receiving Palivizumab Natural History

RSV-related QALYs lost Outpatient Child

Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months

Disease-specific inpatient costs (per inpatient case) Age 6-11 months

RSV-related QALYs lost Outpatient Caregiver

Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months

Incremental Cost-Effectiveness Ratio

Low High
 $-

 $50,000

 $100,000

 $150,000

 $200,000

 $250,000

$0 $100 $200 $300 $400 $500 $600

ICER

Total Cost of Nirsevimab (drug + administration)

Sensitivity: Cost nirsevimab

106 Base cost of $500/dose
Results: Alternative Scenarios

107

No Palivizumab 

Savings

Palivizumab 

Savings

Low-Risk Mortality $205,639 $118,522 

Overall Average Mortality $182,397 $102,811

Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group

Base costs of nirsevimab: $445/dose, Cost of palivizumab for high-risk included in “Natural History”
Scenario: Upper respiratory infection effect

108

202,821.0

62,596.7

14,341.3

3,155.1

77,442.9

9,465.2

0.0

50,000.0

100,000.0

150,000.0

200,000.0

250,000.0

Outpatient ED Inpatient ICU Inpatient Day ICU Day

Events Averted per year

Nirsevimab
 $-

 $50,000

 $100,000

 $150,000

 $200,000

 $250,000

$0 $100 $200 $300 $400 $500 $600

ICER

Total Cost of Nirsevimab (drug + administration)

Scenario: Upper respiratory infection effect

Nirsevimab 109 is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.

$48,208/QALY
Scenario: Timing analysis

110

• Cost-effectiveness of an infant receiving nirsevimab as a newborn in 

• Oct-Feb

• Oct-March

• Oct-April

• With varying efficacy in months 6-10

• 0%

• 25%

• 50%

Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
111

Scenario: Timing and efficacy in months 6-10

Very minor differences, Slightly higher ICERs for Oct-Apr

Base cost of $445/dose

ICER= Incremental cost-effectiveness ratio

 $-

 $20,000

 $40,000

 $60,000

 $80,000

 $100,000

 $120,000

0% efficacy 25% efficacy 50% efficacy

ICER

Oct-Feb Oct-Mar Oct-Apr
Higher-risk children entering the second RSV 

season

112

• Immunization in October (under 19 months old in October)

• Incidence of RSV-associated hospitalization and mortality per 

hospitalization: 

• 1x, 2x, 4x, 6x, 10x higher

• Cost

• $890 nirsevimab costs (2x $445/dose)

Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
Second Season, High-Risk 

113

0

10

20

30

40

50

Inpatient ICU Inpatient Days ICU Days

Events Averted per 1000 

Children given nirsevimab

Events Averted

Base 2x 4x 6x 10x
Second Season, High-Risk 

114

Cost is $890 per overall course, 2 doses @ $445 each

Increased 

Risk Incidence Incidence and mortality, given hospitalization

1x (base) $1,557,544 $1,557,544 

2x $1,147,756 $836,270 

4x $726,983 $280,740 

6x $512,337 $118,912 

10x $294,775 $25,328 
Limitations

• Model Structure

• No risk groups

• No dynamic transmission. No impact of the vaccine on transmission and 

indirect effects

• Uncertain inputs

• Nirsevimab cost 

• QALYs lost 

• Upper respiratory tract infections

• Palivizumab utilization

115
Summary

• Nirsevimab has the potential to be cost-effective

• Results sensitive to:

• Cost per dose (Cost-Saving – 200,000 $/QALY)

• Inpatient costs (Cost-saving – 125,000 $/QALY)

• Efficacy (45,000 – 170,000 $/QALY)

• URTI/LRTI 

• Proportion of infections with LRTI

• Or efficacy of nirsevimab against URTI

• QALYs lost (20,000 – 200,000 $/QALY)

• Hospitalization, Outpatient, ED

• Child, Parent

116

URTI: Upper Respiratory Tract Infection

LRTI: Lower Respiratory Tract Infection

QALY: Quality-Adjusted Life-Year
Thank You

• Please send comments to:

• dwhutton@umich.edu

117
Appendix

118
Methods: Epidemiological model

119

Seasonality

Incidence

• Outpatient

• ED

• Hospitalizations

Nirsevimab

Waning 

Protection

Health Effects

• Outpatient

• ED

• Hospitalizations

• Deaths

Economic Effects

• Intervention

• Disease

• Societal

• QALYs

• ICER

Interventions

Epidemiology

Timing

Cost Burden/

• Outpatient

• ED

• Hospitalizations

Health Economics

Health Burden/

• Outpatient

• ED

• Hospitalizations
Methods: Inputs

• Incidence

• Raw reported incidence may be underreported because of imperfect PCR 

sensitivity, so we consider an additional scenario in sensitivity analysis:

• based on CDC Unpublished re-analysis of raw data from Zhang et al study which found 

decreased RSV PCR sensitivity in light of paired serology testing (adjustment factor: 

87.6%).

120
Methods: Inputs

Variable Value Range Source

Probabilities of Pediatric Adverse 

Events: Nirsevimab

Systemic Reaction 0.005 Sanofi/AstraZeneca ACIP 

data request

Probability of outpatient visit 

given Systemic Reaction

1x 

Outpatient 

Visit

- Assumption; Deluca et al 

(under review)

Anaphylaxis 0 0 – 0.0000010 Sanofi/AstraZeneca ACIP 

data request

Injection Site Reaction 0.002 Sanofi/AstraZeneca ACIP 

data request

Probability of outpatient visit 

given Injection Site Reaction

0.1 Assumption; Deluca et al 

(under review)

Serious Adverse Event 0.000001 Prosser, 200612

121

* ISR grade 3 not reported by arm. We assumed the ISR grade 3 rates by arm were proportional to ISR of any severity by arm. Range is 

based on 95% CI based on binomial proportion from the base value.
Methods: Inputs

Variable Value Range Source

Pediatric Quality-Adjusted LifeYears lost due to adverse events

Systemic reaction 0.0056 0.00051-0.0061 Deluca et al (under 

review)

Anaphylaxis 0.0137 0.0135-0.0139

Serious Adverse Event 0.141 0.092-0.199 (Guillain-Barre) Prosser, 

200612

122 * No SAEs were reported in the nirsevimab trial. Values in the table above are based on the incidence of Guillian-Barre syndrome 

following influenza vaccination. 
Methods: Inputs

Variable Value Range Source

Costs due to adverse events^

Medical Costs

Cost of outpatient visit for systemic 

reaction

$313 $27 - $1,337 Marketscan unpublished; 

Deluca et al (under review)

Cost of outpatient visit for injection 

site reaction

$326 $48 - $1,101 Marketscan unpublished; 

Deluca et al (in Press)

Anaphylaxis medical costs $7,706 $89 - $23,414 Marketscan unpublished; 

Deluca et al (In Press)

Serious Adverse Event $36,163.76 $10372.31 - $122,145.60 Prosser, 200612

Productivity Costs

Recipient time for office visit (fraction 

of day)

0.25

Parent time for anaphylaxis (days) 1 1-3 Shimabukuro, 202113

Daily productivity 190 169.41 – 211.03 Grosse, 201914

123

^ Costs updated to 2022$ using GDP deflator

* Daily productivity rate calculated by dividing mean annual total productivity (both market and non-market) for each age group by 365.25 days

Deluca EK, Gebremariam A, Rose A, Biggerstaff M, Meltzer MI, Prosser LA. Cost-Effectiveness of Routine Annual Influenza Vaccination by Age and Risk Status. Vaccine. 2023. In press
Health-Related Quality-of-Life

• Sources

• Glaser (2022)

• Estimate based on comparison of utility losses between premature children who had RSV vs. 

premature children without RSV and their caregivers

• Used as base case for hospitalization for children and their caregivers

• Regnier (2013) 

• Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with 

pertussis 

• Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED 

and outpatient in base case

• JIVE RSV Utilities Survey (2021)

• Estimates QALY losses for hospitalization and outpatient visits for child and caregiver

• Estimates may be impacted by COVID-related concerns about respiratory viruses

• Inform upper bound of range

124
Validation

231

66

8

225 

65 

13 

0

50

100

150

200

250

Outpatient Clinic

Visits

Rates of Medically

ED Visits Hospitalizations

-Attended RSV 

(per 1000 births)

Rainisch et al, Vaccine, 2020 JIVE model

125
Results: Costs

Medical Productivity

InterventionOutpatientEDInpatientTotal RSV MedicalTotal Health SystemOutpatientEDInpatientDeathsTotal ProductivityTotal

Natural History 225,005,528 69,409,019 137,189,260 548,601,655 755,199,934 980,205,462 356,863,932 102,733,556 59,598,851 85,770,201 604,966,541 1,585,172,002 

Nirsevimab 815,695,065 60,614,296 115,680,370 383,861,494 560,156,160 1,375,851,225 311,646,183 86,626,721 41,701,850 60,014,178 499,988,933 1,875,840,158 

126 Base cost of $445/dose

Cohort:entire annual US birth cohort, assuming 50% uptake in nirsevimab group