Document text
Evidence to Recommendations Framework :
Clesrovimab
Danielle Moulia, MPH
Co-Lead, Maternal/Pediatric RSV Work Group
Advisory Committee on Immunization Practices
April 16, 2025
1U.S. Centers for Disease Control and Prevention
Policy Question
•Should clesrovimab be recommended for all infants <8 months of age born
during or entering their first RSV season?
2
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?
3
EtR Domain: Public Health Problem
Is RSV -associated disease among infants <8 months of age of public health
importance?
4
RSV burden is high in children <5 years of age
58,000 –80,000 hospitalizations1,2,3
100–300 deaths4,5,6~2,000,000 medical encounters1Each year in the United States, RSV leads to approximately*:
5*Data on the burden of RSV disease in children under 5 are from before the 2023 -2024 RSV season, when RSV prevention products became available in the US.
References: 1) Hall et al, NEJM (2009): https://doi.org/10.1056/NEJMoa0804877 2) McLaughlin et al, J Infect Dis (2022): https://doi.org/10.1093/infdis/jiaa752 3)
CDC RSV -NET, unpublished data. 4) Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 5) Matias et al, Influenza Other Respi Viruses (2014):
https://doi.org/10.1111/irv.12258 6) Hansen et al, JAMA Network Open (2022): https://doi.org/10.1001/jamanetworkopen.2022.0527
In the absence of RSV prevention products:
•Most infants (68%) are infected in the
first year of life and nearly all (97%) by
age 2 years2
•2-3% of young infants are hospitalized for
RSV3,4,5
-Highest rates occur in the first months of life,
and risk declines with increasing age in early
childhood3,5
-79% of children aged <2 years had no
underlying medical conditions3
-All infants are at risk for hospitalizationRSV is the leading cause of hospitalization in infants1
6
References: 1) Glezen et al, Arch Dis Child (1986): https://doi.org/10.1001/archpedi.1986.02140200053026 2) Suh et al. JID (2022):
https://doi.org/10.1093/infdis/jiac120 3) Hall et al, Pediatrics (2013): https://doi.org/10.1542/peds.2013 -0303 4) Langley & Anderson, PIDJ (2011):
https://doi.org/10.1097/INF.0b013e3182184ae7 5) CDC NVSN data6
2024 –2025 RSV seasonality may be returning to pre -
pandemic trends
Notes: Report was last updated on 3/26/2025 .
*All results presented are from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NRE VSS. The last three weeks of data in 2023 -24 may be less complete. NREVSS is an abbreviation for the National Respiratory and
Enteric Virus Surveillance System. For more information on NREVSS, please visit National Respiratory and Enteric Virus Surveillance System | CDC .
**Respiratory syncytial virus types A and B are not shown separately in this report.
***The NREVSS surveillance season runs from the first week in July through June of the following year.Percentage* of polymerase chain reaction test results positive for respiratory syncytial virus**,
by MMWR week — National Respiratory and Enteric Virus Surveillance System, United States,
July 2009 –March 2025
7
Pre-COVID -19
pandemic
seasonality
shown by grey
shaded area
Public Health Problem - Work Group Interpretation
•Is RSV -associated disease among infants <8 months of age of public
health importance?
NoProbably
NoProbably
YesYes VariesDon’t
know
8
EtR Domain: 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?
9
GRADE: PICO Question
Population all infants <8 months of age born during or entering their first RSV season
Intervention clesrovimab
Comparison no immunization
OutcomesBenefits
1. RSV-associated medically -attended lower respiratory tract infection (LRTI)
2. RSV-associated LRTI with hospitalization
3. RSV-associated LRTI with intensive care unit admission
4. All-cause medically -attended LRTI
5. All-cause LRTI with hospitalization
Harms
1. Serious adverse events
10Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation
GRADE: Outcomes, importance, and data sources
Outcome Importance1 Data sources
Benefits
1. RSV -associated medically -attended LRTI Critical Phase 2b/3 RCT2
2. RSV -associated LRTI with hospitalization Critical Phase 2b/3 RCT2
3. RSV -associated LRTI with ICU admission Critical Phase 2b/3 RCT2
4. All -cause medically -attended LRTI Important Phase 2b/3 RCT2
5. All -cause LRTI with hospitalization Important Phase 2b/3 RCT2
Harms
6. Serious adverse events (SAEs) Important Phase 2b/3 RCT2
1. Three options: Critical; Important but not critical; Not important for decision making
2. Protocol 004: A Phase 2b/3 Double -Blind, Randomized, Placebo -Controlled Study to Evaluate the Efficacy and Safety of Clesrovimab in Healthy
Preterm and Full -Term Infants – described in Zar et al., Open Forum Infectious Diseases (2025): https://doi.org/10.1093/ofid/ofae631.003 ; Sinha,
presentation to ACIP (2024): https://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/02 -RSV-Mat-Peds -Sinha -508.pdf ; and unpublished data
from manufacturer
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | LRTI: Lower respiratory tract infection |
RCT: randomized controlled trial | ICU: intensive care unit 11
GRADE Benefits : Efficacy estimates and concerns in
certainty assessment
Outcome Vaccine efficacy estimate1
% (95% CI)Concerns in certainty assessment
Benefits, through 150 days of follow -up
1. RSV -associated medically -attended LRTI 60.4 (44.1, 71.9) Not serious (indirectness)2
2. RSV -associated LRTI with
hospitalization90.9 (76.2, 96.5) Not serious (indirectness)2
3. RSV LRTI with ICU admission3100.0 (24.0, 100.0) Serious (imprecision)4
Not serious (indirectness)2
4. All -cause medically -attended LRTI 13.1 ( -0.6, 24.8) Serious (imprecision)5
Not serious (indirectness)2
5. All -cause LRTI with hospitalization 49.0 (26.7, 64.5) Not serious (indirectness)2
121. Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method.
2. Concern for indirectness: the trial excluded infants who were palivizumab -eligible and took place during a season with disrup ted seasonality due to COVID -19. This was
deemed not serious.
3. Outcome was not a trial endpoint and was assessed post -hoc.
4. Serious concern for imprecision: the number of study participants did not meet optimal information size.
5. Serious concern for imprecision: the confidence interval containing estimates for which different policy decisions might be considered.
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval | LRTI: lower respiratory tract infection | RCT:
randomized controlled trial | ICU: intensive care unit
GRADE Harms : Relative risk of serious adverse events
(SAEs) and concerns in certainty assessment
Outcome Relative risk1 (95% CI) Concerns in certainty assessment
Harms
Serious adverse events (SAEs)20.93 (0.77, 1.12) Serious (imprecision)3
1. Relative risk was calculated as the risk of a serious adverse event in the clesrovimab arm divided by the risk of a serious adverse
event in the placebo arm.
2. Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. Serious adverse ev ents
may be related or unrelated to the study intervention.
3. Serious concern for imprecision: too few infants were included in the trial to capture rare events.
13Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval
Summary of GRADE for clesrovimab
Abbreviations: LRTI: Lower respiratory tract infection | RCT: randomized control trial | ICU: intensive care unit | serious adverse events Outcome Importance Design
(# of studies)Findings Evidence
type
Benefits
1. RSV -associated
medically -attended LRTICritical RCT (1)Clesrovimab is effective in preventing RSV -associated
medically -attended LRTIHigh
2. RSV -associated LRTI
with hospitalizationCritical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI
with hospitalizationHigh
3. RSV -associated LRTI
with ICU admissionCritical RCT (1)Clesrovimab is effective in preventing LRTI with ICU
admissionModerate
4. All -cause medically -
attended LRTIImportant RCT (1)Clesrovimab is not effective in preventing all cause
medically -attended LRTIModerate
5. All -cause LRTI with
hospitalizationImportant RCT (1)Clesrovimab is moderately effective in preventing all cause
hospitalization with LRTIHigh
Harms
6. Serious adverse events Important RCT (1)SAEs were balanced between the clesrovimab group and
the placebo groupModerate
14
Additional benefits of clesrovimab not included in GRADE:
Efficacy for RSV -associated medically -attended LRTI and
hospitalization observed through 180 days
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence intervalOutcome Follow -up time: 150 days Follow -up time: 180 days
Events/
Clesrovimab
(n/N)Events/
Placebo
(n/N)Vaccine Efficacy %
(95% CI)Events/
Clesrovimab
(n/N)Events/
Placebo
(n/N)Vaccine Efficacy %
(95% CI)
RSV-associated medically -
attended LRTI60/2398 74/1201 60.4 (44.1, 71.9) 64/2398 77/1201 59.5 (43.3, 71.1)
RSV-associated LRTI with
hospitalization5/2398 27/1201 90.9 (76.2, 96.5) 5/2398 28/1201 91.2 (77.2, 96.6)
15
Additional benefits of clesrovimab not included in
GRADE
•If approved by FDA and recommended by CDC, there will be two approved1
and recommended2 long -acting monoclonal antibodies for prevention of
severe RSV disease in infants
•Multiple products with different binding sites are beneficial if resistance
mutations develop to either product
•Multiple manufacturers in the same market allow for:
-If one product has insufficient supply in the United States, the other product
reduces the risk of a shortage.3
-Competitive pricing of products may be created by market competition
1. In July 2023, the Food and Drug Administration (FDA) approved nirsevimab for the prevention of RSV –associated lower respirato ry tract infection among infants and children aged <24
months. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf ; 2. In August 2023, the Advisory Committee for Immunization Practices recommended nirsevimab
infants aged <8 months born during or entering their first RSV season and for infants and children aged 8 –19 months who are at i ncreased risk of severe RSV disease entering their second
RSV season. https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm ; 3. https://www.cdc.gov/han/2023/han00499.html16
Additional harms of clesrovimab not included in
GRADE: Solicited adverse events (AEs), days 1 –5 post
immunization
•Injection -site and systemic reactions were comparable between the
clesrovimab (29.9%) and placebo (30.9%) arms
-Irritability and somnolence were the most commonly reported solicited AEs
•Mostly Grade 1 (mild) or 2 (moderate)
-The proportions of participants with solicited AEs of Grade 3 (severe) were low
(≤0.2%) in both groups
-No Grade 4 (potentially life -threatening) solicited AEs
Grade 1= mild; Grade 2= moderate; Grade 3=severe; Grade 4=potentially life threatening; https://www.fda.gov/media/73679/download17
Additional harms of clesrovimab not included in
GRADE: Fever*, days 1 –5 post immunization
Study Events*/Clesrovimab
(n/N)Events*/Placebo
(n/N)
Protocol 004 89/2408† (3.7%) 48/1202 (4.0%)
*Fever defined as a temperature ≥ 100.4 °F
† Total N=2409; 2408 had temperature data available per communication with manufacturer on March 9, 2025 •Rates of fever were comparable between the clesrovimab (3.7%) and
placebo (4.0%) arms
18
Workgroup interpretation of benefits and harms of
clesrovimab
Benefits
•Efficacious long -acting, monoclonal antibody that can prevent severe RSV
disease in young infants during the duration of their first RSV season
•Second long -acting, monoclonal antibody RSV prevention product would
mitigate the risk of manufacturing shortages and loss of efficacy due to
resistance mutations
Harms
•Favorable safety profile with no observed increase in serious adverse events,
local or systemic reactions, including fever
•Rare serious adverse events unlikely to be detected in a trial due to sample
size
19
Benefits and Harms
•How substantial are the desirable anticipated effects?
-How substantial are the anticipated effects for each main outcome for
which there is a desirable effect?
20Minimal Small Moderate Large Varies Don’t know
Benefits and Harms
•How substantial are the undesirable anticipated effects?
-How substantial are the anticipated effects for each main outcome for
which there is an undesirable effect?
Minimal Small Moderate Large Varies Don’t know
21
Benefits and Harms
•Do the desirable effects outweigh the undesirable effects?
Favors intervention (clesrovimab)
Probably favors the intervention (clesrovimab)
Probably favors the comparison (no immunization)
Favors the comparison (no immunization)
Unclear
22
EtR Domain: Values
Do parents and caregivers feel that the desirable effects of clesrovimab are large
relative to the undesirable effects?
Is there important uncertainty about, or variability in, how much parents and
caregivers value the prevention of severe RSV disease?
23
Parent attitudes about RSV disease
•38% of respondents believe that their baby would have no symptoms or
mild symptoms if they got sick with RSV
•24% expressed uncertainty about the disease severity or treatability if their
baby got sick with RSV
•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)
CDC and University of Iowa/RAND survey, unpublished. 523 women who were actively pregnant or pregnant within last 12 months; conducted: 12/2022 —1/2023 24
Factors that may increase parental intent to receive RSV
immunization products for their infant
•Trust in pediatrician’s
recommendation and fear of RSV
infection was associated with
increased intent to receive
nirsevimab1
•Receiving information about
monoclonal antibodies and passive
immunization led to a positive impact
(68%) on willingness to receive the
immunization2
References: 1. Hinderstein et al., Pediatrics (2024): https://10.1542/peds.2024 -067532 ; 2.Lee Mortensen et al., Expert Rev Vaccines (2022):
https://10.1080/14760584.2022.2108799
25
Factors that may decrease parental intent to receive RSV
immunization products for their infant
•Parents deferring RSV immunization were concerned about adverse events and
wanted to wait until the product had been available for longer, wanted more time
to decide, or trusted their own prevention measures against RSV1,2,3,4,5
References: 1. Hinderstein et al., Pediatrics (2024): https://10.1542/peds.2024 -067532 ; 2.Lee Mortensen et al., Expert Rev Vaccines (2022):
https://10.1080/14760584.2022.2108799 ; 3. Wang et al., Vaccine (2025): https:/10.1016/j.vaccine.2024.126570 ; 4.Zornoza Moreno et al., Hum Vaccin Immunother (2024):
https://10.1080/21645515.2024.2357439 ; 5.Ocana de Sentuary et al., EClinicalMedicine (2025): https://10.1016/j.eclinm.2024.102986 26
50% of women 18 -49 years who have an infant <8 months received
nirsevimab for their infant, February 2025, United States
*Receipt of RSV vaccination during pregnancy was assessed by the NIS –ACM questionnaire among women 18 –49 years who reported havi ng an infant born since October 1, 2024. For infants born April 1, 2024, through September 30, 2024, maternal RSV
vaccination was not assessed, and these infants were assumed to be protected against RSV only if infant was reported to have received nirsevimab. The estimates of receipt of RSV vaccination during pregnancy for infants born since April 1, 2024 are not a n
assessment of maternal RSV vaccination coverage among pregnant women eligible for vaccination as shown with the Vaccine Safety Datalink , as they are based on all infants eligible for nirsevimab or maternal vaccination rather than eligible pregnancies
†Estimates of nirsevimab receipt by infants born since April 1, 2024, include those who were born shortly before or are enter ing their first RSV season and do not account for the mother's RSV vaccination status during pregnancy
‡Intent for nirsevimab receipt is assessed among infants who had not received nirsevimab and whose mother did not receive RSV vaccination during pregnancy. Estimates of nirsevimab intent among women interviewed in August and September 2024
included all women who reported having an infant <8 months, and could include infants born in February and March 2024.
Data Source: National Immunization Survey – Adult COVID Module https://www.cdc.gov/rsvvaxview/dashboard/nirsevimab -coverage -infants.html27Infant protection against RSV by maternal RSV vaccination* or receipt of nirsevimab †, and
intent‡ for nirsevimab receipt by women aged 18 –49 years who have an infant <8 months
during the RSV season (born since April 1, 2024), February, United States
Mother received RSV vaccination
during pregnancy
Infant received nirsevimab
Definitely will get nirsevimab for
infant
Probably will get nirsevimab for
infant or unsure
Probably or definitely will not get
nirsevimab for infant
Nirsevimab uptake may be higher in settings of increased
access
References: 1. Puckett et al., Hosp Pediatr (2025 ): https:// 10.1542/hpeds.2024 -008070.
71% of newborns received nirsevimab at a US
birthing center when it was universally offered1
28
•Do parents and caregivers feel that the desirable effects of clesrovimab
are large relative to the undesirable effects?Values
NoProbably
NoProbably
YesYes VariesDon’t
know
29Minority opinion Majority opinion
Values
•Is there important uncertainty about, or variability in, how much how
much parents and caregivers value the prevention of severe RSV
disease ?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
30Minority opinion Majority opinion
EtR Domain: Acceptability
Is clesrovimab acceptable to key stakeholders?
31
Pediatrician attitudes about nirsevimab may provide insight
into their potential attitudes about clesrovimab
*Porter Novelli View Health Care Practitioner survey was conducted from October 2 -10, 2024, among 200 U.S. pediatricians who reported offering at least some routine pediatric vaccines
to patients
Kang et al, CDC (2024); https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html329194.595.596.5
74.543
210.50.5
0% 20% 40% 60% 80% 100%I feel comfortable co-administering nirsevimab and one or more
vaccines to my pediatric patients in one visit.I feel confident discussing and recommending nirsevimab
immunization with my patient's parents/caregiversNirsevimab is effective against severe RSV disease in infantsNirsevimab is safe for infantsPediatrician attitudes about nirsevimab, Pediatrician survey*, October 2024, n=200
Strongly agree or agree
Neither agree nor disagree
Disagree or strongly disagree
•77% of pediatricians reported that their practice had ever offered nirsevimab
•The majority of pediatricians agreed that nirsevimab is safe for infants and effective against severe
disease in infants
RSV prevention through long -acting, monoclonal
antibodies endorsed by national organizations
•Nirsevimab is recommended by
-American Academy of Pediatrics1
-American Academy of Family Physicians2
-National Foundation for Infectious Diseases3
1)https://publications.aap.org/redbook/resources/25379/AAP -Recommendations -for-the-Prevention -of-RSV?autologincheck=redirected
2)https://www.aafp.org/news/health -of-the-public/rsv -antibody -aafp -approval.html
3)https://www.nfid.org/resource/contagious -chronicles -updated -recommendations -for-respiratory -season/33
Acceptability
•Is clesrovimab acceptable to key stakeholders?
No Probably No Probably Yes Yes Varies Don’t know
34Minority opinion Majority opinion
EtR Domain: Feasibility
Is clesrovimab feasible to implement among all infants <8 months of age
born during or entering their first RSV season?
35
Clesrovimab storage, handling, and administration
•Clesrovimab storage, handling, and administration is anticipated to be similar to
other routine immunizations for children
•Administered as an intramuscular injection using a single -dose, prefilled syringe
•Stored at refrigerator temperature (2 °C to 8 °C)
•May be kept at room temperature between 68 °F to 77 °F (20 °C to 25 °C) for a
maximum of 48 hours.
-After removal from the refrigerator, must be used within 48 hours or discarded
•Dosage is 0.7 mL for all infants born during or entering their first RSV season
regardless of weight
•Can be administered simultaneously with other vaccines
36
Implementation and access
•The Vaccines for Children (VFC) program is a federally funded program that
provides immunizations at no cost to children who might not otherwise be
immunized because of inability to pay.1
-If ACIP votes to include clesrovimab in VFC, it will be the second monoclonal
antibody to be included in the VFC program.
•Implementation pros and cons:
-Pro: Clesrovimab is a single dose regardless of weight
-Con: Stocking clesrovimab may be challenging for providers who also need to
stock nirsevimab for high -risk children 8 through 19 months entering their second
RSV season and prefer to stock a single RSV monoclonal antibody
1. CDC. Vaccines for Children .https://www.cdc.gov/vaccines -for-children/about/index.html37
*Respondents were instructed to select up to 3 response categories
** Private stock of nirsevimab for practices participating in the VFC (Vaccines for Children) program
*** Challenges knowing whether infant received nirsevimab at a birthing hospital
Yoonjae Kang, MPH; Fan Zhang, MD; Tara M Vogt, PhD, MPH; https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html44
33.5
30.5
30.5
24.5
20
20
15.5
7.5
8.547.4
38.3
26
27.9
28.6
21.4
20.1
13
7.8
7.832.6
17.4
45.7
39.1
10.9
15.2
19.6
23.9
6.5
10.9Parent/caregiver concerns around nirsevimab safety
Challenges knowing maternal RSV vaccination status to determine infant eligibility
Financial burden in purchasing of nirsevimab**
Challenges with reimbursement from private health insurance plans
Lack of demand from parents/caregivers
Challenges deterimining infant eligibility***
Parent/caregiver concerns around nirsevimab effectiveness
Challenges with Medicaid reimbursement
Supply/stock issues
Practice does not have or does not anticipate having challenges in offering nirsevimab
All pediatricians (n=200) Pediatricians whose practice had ever offered nirsevimab (n=154) Pediatricians whose practice had never offered nirsevimab (n=46)Frequency of main challenges* pediatricians reported or
anticipated in offering nirsevimab, Pediatrician survey, October
2024, n=200
38
Birthing hospital barriers to monoclonal antibody
administration
•In a series of CDC Learning Collaborative calls hosted by the Association for
Immunization Managers on nirsevimab administration in birthing
hospitals, common barriers included:
-Determining maternal RSV vaccination status
-Storage and handling
-Billing
-Cost of nirsevimab
-Nirsevimab supply/shortages
-Determining a newborn’s VFC eligibility
-Documenting nirsevimab receipt and care coordination
-VFC requirements can be difficult to implement and enrollment is burdensome
VFC: Vaccines for Children39
Feasibility
•Is clesrovimab feasible to implement among all infants <8 months of
age born during or entering their first RSV season?
40Minority opinion Majority opinionNo Probably No Probably Yes Yes Varies Don’t know
EtR Domain: Resource Use
Is clesrovimab a reasonable and efficient allocation of resources?
41
1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described her e: David W.
Hutton, Lisa A. Prosser, Angela M. Rose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -Dutra, Mila
M. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness of Nirsevimab for Respiratory Syncytial Virus in Infants and Youn gChildren. Pediatrics December
2024; 154 (6): e2024066461. 10.1542/peds.2024 -066461.
2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab
3. “No RSV immunizations for most infants " means the only RSV immunization is palivizumab for eligible high -risk infants
Abbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life yearRSV-associated outcomes averted: 50% coverage with
clesrovimab among an annual US birth cohort1
Comparison Outpatient
Visits
AvertedED Visits
AvertedHospital
Admissions
AvertedICU
Admissions
AvertedDeaths
AvertedQALYs
Gained
Clesrovimab2 vs. no RSV
immunizations for most
infants3121,022 43,480 20,198 4,444 20 3,413
42
Incremental cost effectiveness ratios (ICERs): 50%
coverage with clesrovimab among an annual US birth
cohort1
Comparison $/Outpatient
Visit Averted$/ED Visit
Averted$/Hospital
Admission
Averted$/ICU
Admission
Averted$/Death
Averted$/QALY
Gained
Clesrovimab2 vs. no
RSV i mmunizations for
most infants32,948 8,207 17,666 80,300 17,666,032 104,543
1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described here: Hutton et al,
Peds (2024);.https://doi.org/10.1542/peds.2024 -066461.
2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab
3. “No RSV immunizations for most infants " means the only RSV immunization is palivizumab for eligible high -risk infants
Abbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year43
One -way sensitivity analysis: 50% coverage with
clesrovimab among an annual US birth cohort1
$0 $50,000 $100,000 $150,000 $200,000 $250,000
Disease-Specific Inpatient Costs (per Inpatient Case)
RSV QALYS Lost
Clesrovimab cost/dose
Proportion of Outpatient Visits With an LRTI Diagnosis Age 0-5 Months
Proportion of Hospitalizations With an LRTI Diagnosis Age 0-5 Months
Proportion of Outpatient Visits With an LRTI Diagnosis Age 6-11 Months
Fraction Receiving Palivizumab Natural History
Outpatient Efficacy
RSV Mortality Per Hospitalization Age 0-5 Months
Efficacy 6-10 monthsIncremental Cost -Effectiveness Ratio ($/QALY gained)
Low High
1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described her e: David W. Hutton, Lisa A. Prosser, Angela M.
Rose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -Dutra, Mila M. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness
ofNirsevimab for Respiratory Syncytial Virus in Infants and Young Children. Pediatrics December 2024; 154 (6): e2024066461. 10. 1542/peds.2024 -066461.
Abbreviations: QALY : quality adjusted life year 44
Merck1 and University of Michigan – CDC2 Model
Comparison
•University of Michigan/CDC Model
-$/QALY gained: $ 104,543 (assumes $457/dose)
•Merck Model
-$/QALY gained: $7,372 -$42,691 (assumes $423 - $493/dose); $ 36,636 (assumes
$457/dose)
•Key differences in inputs
-Initial efficacy and waning trajectory
-Medical costs
-Adverse events
1. Klodeta Kura, John C Lang, Dawei Wang, et al. Merck’s technical report: Cost -effectiveness analysis of clesrovimab use in infants in the United states. (Version submitted to CDC
and ACIP for review, January 27, 2025)
2. Estimates provided by an updated UM -CDC model, where updates included vaccine efficacy, vaccine efficacy waning trajectory, a nd cost/dose. Original model and methods
described here: David W. Hutton, Lisa A. Prosser, Angela M. Rose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -
Dutra, Mila M. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness of Nirsevimab for Respiratory Syncytial Virus in Infa nts and Young Children. Pediatrics December 2024;
154 (6): e2024066461. 10.1542/peds.2024 -066461.
Abbreviations: QALY: quality adjusted life year 45
Resource use summary
•Clesrovimab cost $104,543 per QALY gained in the base case, with
sensitivity analyses ranging from cost saving to $215,000/QALY
•Cost effectiveness models sensitive to
-Inpatient costs
-Clesrovimab cost/dose
-QALYs lost due to RSV illness
Abbreviations: QALY : quality adjusted life year 46
Resource Use
•Is clesrovimab use among all infants under 8 months of age born during or
entering their first RSV season a reasonable and efficient allocation of
resources with an estimated cost of $458 on average ($365 VFC / $560
other) per dose?
47No Probably No Probably Yes Yes Varies Don’t know
Minority opinion Majority opinion
Abbreviations: VFC: Vaccines for Children
EtR Domain: Equity
What would the impact of clesrovimab be on health equity for infants?
48
Adjusted population -based hospitalization rates among
infants <6 months old with laboratory -confirmed RSV by race
and ethnicity, RSV -NET, 2018 –2019 to 2024 –2025
RSV-NET: unpublished data. Surveillance was conducted during October –April for the 2018 –19 and 2019 –20 seasons and during May –April for 2021 –22 onwards. Rates were
adjusted for RSV testing practices and test sensitivity. Black, White, Asian/Pacific Islander children were categorized as no n-Hispanic; Hispanic children could be of any
race.*2020 –21 season experienced limited to no RSV circulation **2024 –25 data available through February 1, 2025 050010001500200025003000
2018–2019 2019–2020 2020–2021* 2021–2022 2022–2023 2023–2024 2024–2025**Rate per 100,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian or Pacific Islander
Hospitalization rates among infants <6 months old differ by race and ethnicity
but this difference varies by seasonRSV immunization products availableRSV circulation impacted by COVID -19 pandemic
49
Adjusted population -based ICU admission rates among
infants <6 months old with laboratory -confirmed RSV by race
and ethnicity, RSV -NET, 2018 –2019 to 2024 –2025
RSV-NET: unpublished data. Surveillance was conducted during October –April for the 2018 –19 and 2019 –20 seasons and during May –April for 2021 –22 onwards. Rates were
adjusted for RSV testing practices and test sensitivity. Black, White, Asian/Pacific Islander children were categorized as no n-Hispanic; Hispanic children could be of any race.
*2020 –21 season experienced limited to no RSV circulation; **2024 –25 data available through February 1, 2025 ICU admission rates among infants <6 months old differ by race and ethnicity
but this difference varies by seasonRSV immunization products availableRSV circulation impacted by COVID -19 pandemic
01002003004005006007008009001000
2018–2019 2019–2020 2020–2021* 2021–2022 2022–2023 2023–2024 2024–2025**Rate per 100,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian or Pacific Islander
50
RSV rates of severe disease by race and ethnicity
•RSV hospitalization rates were up to 7x higher among Alaska Native and American
Indian children compared to children aged less than 1 year1
-This study was limited to specific populations and might not be broadly representative of risk in all
Alaska Native and American Indian children
•National studies of death certificates found higher rates among non -Hispanic Black
and Hispanic children compared to non -Hispanic White children2
•Hospitalization rates using NVSN data have shown mixed results3
-Several studies have shown no differences by race or ethnicity4-7
-Even when significant, relative risk for non -Hispanic Black and Hispanic children mildly increased
compared to non -Hispanic, White children (e.g., relative risk of 1.2 -2.2)6-7
1. Atwell et al. 2023 Aug 1;152(2):e2022060435
2. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266
3. NVSN analyses compared incidence rates of non -Hispanic Black, non -Hispanic White, and
Hispanic children
Abbreviations: NVSN: New Vaccine Surveillance Network 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 group51
Equity
•What would be the impact of clesrovimab on health equity?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
52Minority opinion Majority opinion
EtR Summary
53
Work group considerations and interpretation
•Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV disease
through 150 days
•Serious adverse events appeared balanced between the clesrovimab and placebo
arms, however rare adverse events are unlikely to be detected in a trial of this size
•Work group discussion also highlighted:
•Clesrovimab has demonstrated a shorter half -life than nirsevimab (421vs 712days),
however efficacy against severe RSV appeared sustained through 150 days
• Clesrovimab and nirsevimab trial outcomes had different definitions , making direct comparisons
in efficacy difficult
1. Maas et al. https://www.sciensano.be/sites/default/files/pk_sna_and_efficacy_against_rsv_malri_from_a_phase_1b2a_study_of_the_monoclonal_ antibody_clesrovimab_mk -1654_in_infants.pdf
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf54
•The work group highlighted the benefits of multiple RSV antibody products
and multiple manufacturers, including:
-If RSV develops resistance to one product or one product has insufficient supply,
another is available
-Potential for decrease in price
•The leading cause of hospitalization in infants (RSV) can be prevented
through immunization. However, for RSV immunizations to have public
health impact, they must be administered early:
-For infants born outside the RSV season, high uptake prior to season onset is
essential
-For infants born during the RSV season, administration should be within the first
week of life - ideally during the birth hospitalizationWork group considerations and interpretation,
continued
55
Evidence to Recommendations Framework
Summary
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most settingsThe balance
between
desirable
and undesirable
consequences
isclosely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere
isinsufficient
evidence
todetermine
thebalance of
consequences
56•What is the balance between the desirable effects relative to the undesirable effects?
Evidence to Recommendations Framework
Summary
Type of
recommendationWe do not
recommend the
interventionWe recommend
theintervention for
individuals based on
shared
clinical decision -
makingWe recommend
theintervention
57•Should clesrovimab be recommended for all infants <8 months of age born during or
entering their first RSV season?
Acknowledgements
Jefferson Jones
Mila Prill
Meredith McMorrow
Ruth Link -Gelles
Monica Godfrey
Michael Melgar
Amadea Britton
Amber Kautz
Lauren Roper
Monica Patton
Fiona Havers
Ben Silk Amber Winn
Alexa Churan
Melissa Shah
Amanda Payne
David Hutton
Jamison Pike
Andrew Leidner
Ismael Ortega -Sanchez
Naomi Tepper
Heidi Moline
Fatimah Dawood
Jenny MiluckyCoronavirus and Other
Respiratory Viruses Division
Immunization Services Division
RSV-NET
NIS-ACM
58
59
GRADE: Clesrovimab
60
Evidence retrieval, conducted as of December 3, 2024
Records screened
(n=182)
Studies or papers
irrelevant
(n=161)Full text studies
assessed for eligibility
(n=21)Studies excluded
(n=20)
9 trial description
5 wrong population
2 wrong intervention
1 wrong comparator
3 wrong outcomesRecords included in
evidence synthesis
(n=1)
*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.govAdditional records identified
through other sources
(n = 2)
61Records identified through
database searching
(n = 180)*
Protocol 004: Phase 2b/3, double -blinded, placebo -
controlled trial
•3,614 healthy preterm infants (gestational age ≥29 weeks to <35 weeks) and full -term
infants (GA ≥35 weeks) born during or entering their first RSV season
-Randomized 2:1 (2,411 clesrovimab , 1,203 placebo)
-Enrolled at birth up to 1 year (median age at randomization: 3.1 months)
•Multi -country: Argentina, Belgium, Canada, Chile, China, Colombia, Denmark, Finland,
France, Italy, Japan, Korea, Malaysia, Mexico, Peru, Philippines, Poland, Thailand, Turkey,
UK, USA, South Africa
-Over 2/3 of infants enrolled were from the Northern Hemisphere
•Primary efficacy outcomes followed for 150 days, safety, and pharmacokinetics
-Secondary efficacy outcomes with follow -up through 150 and 180 days
62
GRADE evidence type
•High certainty: We are very confident that the true effect lies close to that
of the estimate of the effect.
•Moderate certainty: We are moderately confident in the effect estimate:
The true effect is likely to be close to the estimate of the effect, but there is
a possibility that it is substantially different.
•Low certainty: Our confidence in the effect estimate is limited. The true
effect may be substantially different from the effect estimate.
•Very low certainty: We have very little confidence in the effect estimate.
The true effect is likely to be substantially different from the estimate of the
effect .
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we have in the estimates
of effect across each outcome.
63
GRADE evidence type
•Initial evidence type (certainty level) determined by study design
-Initial evidence is high certainty: A body of evidence from randomized controlled
trials
-Initial evidence is low certainty: A body of evidence from observational studies
•Evidence type may be downgraded due to risk of bias, inconsistency, indirectness,
and imprecision. Evidence type may be upgraded or downgraded due to other
considerations including publication bias or indications of dose -response gradient,
large or very large magnitude of effect, and opposing residual confounding.
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we have in the estimates
of effect across each outcome.
64
Benefits
65
Case definitions for benefits
Outcomes ≥ 1 signs/symptomsAND ≥ 1 indicator of
LRTI/severityRSV-positive RT -PCR NP
sampleSetting
1. RSV -associated
medically -attended LRTIAt least one sign/symptom
on examination:
• Cough
• Difficulty
breathingAt least one of:
• Rales/crackles
• Wheezing
• Chest wall
indrawing/retra
ctions
• Hypoxemia*
• Tachypnea**
• Dehydration
due to
respiratory
symptomsRequired Outpatient or inpatient
clinical setting
2. RSV -associated LRTI with
hospitalizationInpatient clinical setting
3. RSV -associated LRTI with
ICU admissionInpatient clinical setting
4. All -cause medically -
attended LRTINot required Outpatient or inpatient
clinical setting
5. All -cause LRTI -associated
hospitalization Inpatient clinical setting
* Hypoxemia was defined as SpO2 <95% on room air at sea level, <92% on room air at altitude≥1800 m. In room air - oxygen saturation <95% at altitudes
≤1800 meters or <92% at altitudes >1800 meters
** Tachypnea was defined as RR≥60 breaths per minute for <2 months of age;≥50 breaths per minute for 2 to 12 months of age; or≥4 0 breaths per minute
for >12 to 24 months of age
Abbreviations: LRTI: lower respiratory tract infection | ICU: intensive care unit | RT -PCR: reverse transcription polymerase chain reaction | N P:
nasopharyngeal | RR: respiratory rate66
Outcome 1: RSV -associated medically -attended LRTI1
through 150 days of follow -up
Study Events1/Clesrovimab
n/N (%)Events1/Placebo
n/N (%) Efficacy2
(95% CI)
Protocol 004 60/23983 (2.5%) 74/12013 (6.2%) 60.4% (44.1, 71.9)
1.Defined by the presence of the following seen in an outpatient or inpatient clinical setting: cough or difficulty breathing A ND ≥ 1 indicator of LRTI or
severity (wheezing, chest wall in -drawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory symp toms); AND RSV
positive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample.
2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. The model included the following
covariates: hemisphere at randomization, gestational age group and age group at randomization. The lower bound of the 95% CI was >25%, meeting
the statistical criterion for success.
3.Patients were randomized 2:1 to the clesrovimab and placebo arms.
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 67
GRADE: RSV -associated medically -attended LRTI
through 150 days of follow -up (n=1 study)
•Measure of effect
-Efficacy: 60.4% (95% CI: 44.1, 71.9)
•Absolute risk (using 23.1% seasonal incidence1): 140 fewer cases per 1,000 immunized (166 fewer
to 102 fewer)
–Number needed to immunize: 7 (6 to 10)
•Absolute risk (using 11.0% seasonal incidence2): 66 fewer cases per 1,000 immunized (79 fewer to
49 fewer)
–Number needed to immunize: 15 (13 to 20)
•Absolute risk (using 6.2% seasonal incidence [phase 2b/3 trial placebo arm]): 37 fewer cases per
1,000 immunized (44 fewer to 27 fewer)
–Number needed to immunize: 27 (22 to 37)
•Concerns in certainty assessment
-Not serious (indirectness): trial excluded infants who were palivizumab eligible
•Final evidence type: High
1. Lively 2019 JPIDS , 5 years from 3 NVSN sites from Nov -Apr season, included if with acute respiratory infection (ARI, not restricted to LRTI). 2. Assumes 47.5%
of ARI are LRTI ( Rainisch 2020 Vaccine )
Abbreviations: LRTI: lower respiratory tract infection | CI = confidence interval 68
Outcome 2: RSV -associated LRTI with hospitalization1
through 150 days of follow -up
Study Events1/Clesrovimab
n/N (%)Events1/Placebo
n/N (%)Efficacy2
(95% CI)*
Protocol 004 5/23983 (0.2%) 27/12013 (2.2%) 90.9% (76.2, 96.5)
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 1.Defined by the presence of the following seen in an inpatient clinical setting: cough or difficulty breathing AND ≥ 1 indicator of LRTI (rhonchi,
rales/crackles, wheezing) AND ≥1 indicator of severity (chest wall indrawing/retractions, hypoxemia, tachypnea, dehydration d ue to respiratory
symptoms); AND RSV positive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample.
2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method.
3.Patients were randomized 2:1 to the clesrovimab and placebo arms.
69
GRADE: RSV-associated LRTI with hospitalization
through 150 days of follow -up (n=1 study)
•Measures of effect
-Efficacy: 90.9% (95% CI: 76.2, 96.5)
-Absolute risk (using 1.3% seasonal incidence*): 12 fewer cases per 1,000
immunized (13 fewer to 10 fewer)
•Number needed to immunize: 83 (77 to 100)
-Absolute risk (using 2.2% seasonal incidence [phase 2b/3 trial placebo arm]): 20
fewer cases per 1,000 immunized (22 fewer to 17 fewer)
•Number needed to immunize: 50 (45 to 59)
•Concerns in certainty assessment
-Not serious (indirectness): trial excluded infants who were palivizumab eligible
•Final evidence type: High
*NVSN data 2016 -2020 (unpublished), included if with acute respiratory infection
Abbreviations: LRTI: lower respiratory tract infection 70
Outcome 3: RSV -associated LRTI with ICU admission1
through 150 days of follow -up
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval | ICU: intensive care unit | PICU: pediatric intensive care unit | NICU:
neonatal intensive care unitStudy Events1/Clesrovimab
(n/N)Events1/Placebo
(n/N)Efficacy2
(95% CI)
Protocol 004 0/23983 44/12013100% (24, 100)
1.Defined as hospital admission for respiratory illness AND RSV -positive RT -PCR nasopharyngeal (NP) sample AND with evidence of adm ission in ICU in the associated serious
adverse event (SAE) narrative by looking for one or more of these following key terms: ICU, PICU, NICU, mechanical ventilatio n, ventilator, intubation, intubated, intensive
care, intensive care unit, intensive treatment unit, critical care unit.
2.Estimates and 95% CI were estimated by an exact method.
3.Patients were randomized 2:1 to the clesrovimab and placebo arms.
4.Onset of all 4 cases were prior to day 150. No cases occurred between days 150 -180.
71
GRADE: RSV-associated LRTI with ICU admission
through 150 days of follow -up (n=1 study)
•Measures of effect
-Efficacy: 100% (95% CI: 24, 100)
-Absolute risk (using 0.33% seasonal incidence [phase 2b/3 trial placebo arm]) : 330
fewer per 100,000 (from 79 to 330 fewer)
•Number needed to immunize: 303 (from 303 to 1,265)
•Concerns in certainty assessment
-Not serious (indirectness): trial excluded infants who were palivizumab eligible
-Serious (imprecision): number of study participants did not meet optimal
information size for this outcome
•Evidence type: Moderate
72Abbreviations: ICU: intensive care unite | LRTI: lower respiratory tract infection | CI: confidence interval
Outcome 4: All-cause medically attended LRTI1
through 150 days of follow -up
Study Events1/Clesrovimab
n/N (%)Events1/Placebo
n/N (%)Efficacy2
(95% CI)
Protocol 004 526/23983 (21.9%) 296/12013 (24.6%) 13.1% ( -0.6, 24.8)
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 1.Defined as outpatient and inpatient medically -attended LRTI due to any cause, defined by the presence of the following seen in an outpatie nt or
inpatient clinical setting: cough or difficulty breathing AND 1 or more of the following: wheezing, chest wall in -drawing/retrac tions, rales/crackles,
hypoxemia, tachypnea, dehydration due to respiratory symptoms.
2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method.
3.Patients were randomized 2:1 to the clesrovimab and placebo arms.
73
GRADE: All -cause medically -attended LRTI through 150
days of follow -up (n=1 study)
•Measures of effect
-Efficacy: 13.1% (95% CI: -0.6, 24.8)
-Absolute risk (using 24.6% seasonal incidence in phase 2b/3 controls): 26 fewer
cases per 1,000 vaccinated (61 fewer to 1 more)
•Number needed to immunize: 38 (16 to *)
•Concerns in certainty assessment
-Not serious (indirectness): trial excluded infants who were palivizumab eligible
-Serious (imprecision): width of the confidence interval contains estimates for
which different policy decisions might be considered
•Evidence type: Moderate
*Upper bound of the confidence interval could not be calculated.
Abbreviations: LRTI: lower respiratory tract infection | | CI: confidence interval 74
Outcome 5: All-cause hospitalization with LRTI1
through 150 days of follow -up
Study Events1/Clesrovimab
n/N (%)Events1/Placebo
(n/N)Efficacy2
(95% CI)
Protocol 004 60/23983 (2.5%) 58/12013 (4.8%) 49.0% (26.7, 64.5)
1.Defined by the presence of the following seen in an inpatient clinical setting: cough or difficulty breathing AND ≥ 1 indicator of LRTI (rhonchi,
rales/crackles, wheezing) AND ≥1 indicator of severity (chest wall indrawing/retractions, hypoxemia, tachypnea, dehydration d ue to respiratory
symptoms)
2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method.
3.Patients were randomized 2:1 to the clesrovimab and placebo arms.
75Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval | RT -PCR: reverse transcription polymerase chain reaction | IC U: intensive
care unit | PICU: pediatric intensive care unit | NICU: neonatal intensive care unit
GRADE: All -cause hospitalization with LRTI through
150 days of follow -up (n=1 study)
•Measures of effect
-Efficacy: 49.0% (95% CI: 6.7, 64.5)
-Absolute risk (using 4.1% seasonal incidence [phase 2b/3 trial controls]): 20 fewer
cases per 1,000 immunized (27 fewer to 11 fewer)
•Number needed to immunize: 50 (37 to 91)
•Concerns in certainty assessment
-Not serious (indirectness): trial excluded infants who were palivizumab eligible
•Evidence type: High
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 76
Harms
77
Outcome 6: Serious adverse events (SAEs)1 through
365 days post -dose
Study Events1/Clesrovimab
n/N (%)Events1/Placebo
n/N (%)RR
(95% CI)
Protocol 004 278/24092 (11.5%) 149/12022 (12.4%) 0.93 (0.77, 1.12)
Abbreviations: RR: risk ratio | CI: confidence interval 1.Defined as an adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention care, intensive care unit,
intensive treatment unit, critical care unit. Serious adverse events may be related or unrelated to the study intervention.
2.Patients were randomized 2:1 to the clesrovimab and placebo arms.
78
GRADE: Serious adverse events through 365 days
post -dose (n=1 study)
•Measures of effect
-Relative Risk: 0.93 (95% CI: 0.77 to 1.12)
-Absolute risk: 9 fewer cases per 1,000 immunized (29 fewer to 16 more)
•Concerns in certainty assessment
-Serious (imprecision): T oo few infants included in the trial to capture rare serious
adverse events
•Evidence type: Moderate
79Abbreviations: CI: confidence interval
Summary of GRADE for clesrovimab
Outcome Importance Design
(# of studies)Findings Evidence
type
Benefits
1. RSV -associated
medically -attended LRTICritical RCT (1)Clesrovimab is effective in preventing RSV -associated
medically -attended LRTIHigh
2. RSV -associated LRTI
with hospitalization Critical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI
with hospitalizationHigh
3. RSV -associated LRTI
with ICU admissionCritical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI
with ICU admissionModerate
4. All -cause medically -
attended LRTI Important RCT (1)Clesrovimab is not effective in preventing all cause medically -
attended LRTIModerate
5. All -cause LRTI with
hospitalization Important RCT (1)Clesrovimab is moderately effective in preventing all -cause
hospitalization with LRTIHigh
Harms
6. Serious adverse events
(SAEs)Important RCT (1)SAEs were not more common in intervention group than
placebo groupModerate
Abbreviations: LRTI = lower respiratory tract infection | RCT = randomized controlled trial80