Understanding the CDC’s Advisory

Committee on Immunization Practices

(ACIP)
José R. Romero, MD
FAAP, FIDSA, FPIDS, FAAAS
Arkansas Secretary of Health
Arkansas Department of Health
Professor, Pediatrics and Pediatric Infectious Diseases
University of Arkansas for Medical Sciences
 ACIP Origin and History
• 1964- ACIP established by the Surgeon
General of the US Public Health Service
• May 25-26, 1964- First meeting
• 1972- Designated a Federal Advisory Cmte
 Federal Advisory Committee Act
• Federal Advisory Committee Act (FACA)-
enacted on October 6, 1972
• Mechanism to seek advice and
recommendations of US citizens in the Federal
Government’s decision-making process
- Committees provide relevant, objective advice
- Meetings open to public
- All documents available for public inspection
• Currently approximately 1000 Federal Advisory
Committees in the US, advising 50 agencies
- 21 federal advisory committees at CDC
 Role of the ACIP
Vaccine development and testing

Submission to FDA for Biologics

License Application (BLA)

Vaccines and Related ADVISES

Biological Products
Advisory Committee
FDA Licensure
(VRBPAC)

ADVISES
Advisory Committee on
CDC
Immunization Practices
(ACIP) consideration

Recommendations for
use published in MMWR

Modified from Pickering LK,

Orenstein WA, Development of
pediatric vaccine recommendations
Uptake and financing and policies. Semin Pediatr Infect
Dis. 2002;13;148-154.
 Role of the ACIP
Provide advice and guidance to the Director of
the Centers for Disease Control and Prevention
and the Office of the Secretary of the
Department of Health and Human Services on
most effective means to prevent vaccine-
preventable diseases in the civilian population of
the United States
- Vaccines and related agents (e.g. antisera,
immune globulins, antiviral agents)
- FDA licensed vaccines (and unlicensed vaccines,
if warranted)
 Role of the ACIP
Provide advice and guidance to the Director of
the Centers for Disease Control and Prevention
and the Office of the Secretary of the
Department of Health and Human Services on
most effective means to prevent vaccine-
preventable diseases in the civilian population of
the United States
- Vaccines and related agents (e.g. antisera,
immune globulins, antiviral agents)
- FDA licensed vaccines (and unlicensed vaccines,
if warranted)
 ACIP Charter Language
• For each vaccine, the committee advises on
population groups and/or circumstances in
which a vaccine or related agent is
recommended
• Committee deliberations on use of vaccines to
control disease in the US shall include
consideration of disease epidemiology and
burden of disease, vaccine efficacy and
effectiveness, vaccine safety, the quality of
evidence reviewed, economic analyses and
implementation issues
 ACIP Charter Language
• The committee may revise or withdraw their
recommendation(s) regarding a particular
vaccine as new information on disease
epidemiology, vaccine effectiveness or safety,
economic considerations or other data become
available
 ACIP Structure
Voting members- 15
14 members- Expertise in specific disciplines
Chair and Vice Chair (unofficial)
1 consumer representative
Member Expertise and Perspective
Pediatrics State/Local Health Depts
Internal Medicine Public Health
Family Medicine Nursing
Obstetrics/Gynecology Immunology
Infectious Diseases Vaccine research and policy
Geriatrics Economics/Cost-effectiveness
Preventive Medicine Consumer concerns
 ACIP Structure
Voting members
Terms- 4 year, overlapping
Chair- 3 additional years
External to the federal government
ACIP Steering Committee nominates
candidates
HHS selects and appoints
Conflicts of interest screened
On appointment
Annually
At each ACIP meeting
 ACIP Structure
Ex-Officio members
8 members- Represent other government
agencies involved in immunization
Centers for Medicaid and Medicare Services (CMS)
Department of Defense (DOD)
Department of Veterans Affairs (DVA)
Food and Drug Administration (FDA)
Health Resources & Services Administration (HRSA)
Indian Health Service (IHS)
National Institute of Health (NIH)
National Vaccine Program Office (NVPO)
 ACIP Structure
Liaison Organizations
• 31 organizations with broad involvement in
immunization
Representatives funded by organization they represent
Bring the perspective of the parent organization
Keep parent organization and membership appraised
• Members serve on work groups
• Attend and participate in ACIP meetings
• Four (AAFP, AAP, ACOG, ACP) assist with
development and publication of “harmonized”
immunization schedules
Childhood and Adolescent Immunization
Schedule
 ACIP Recommendations Process
ACIP Meetings
• Three, 2-day meetings annually
February, June, October
• Meetings open to the public
Meeting slides, live webcast archive, minutes are
available to the public on ACIP website
• ACIP recommendations become final when:
Approved by CDC Director
Adopted by HHS/CDSC
Published in Morbidity and Mortality Weekly Report
 ACIP Work Groups
1. Immunization Schedules 8. Herpes Zoster Vaccine
2. General Best Practices 9. Orthopoxviruses Vaccines
3. Influenza 10. Rabies vaccines
4. COVID-19 Vaccines 11. Tick Borne Encephalitis
Vaccine
5. Dengue Vaccine
12. Cholera Vaccine
6. Ebola Vaccine
13. Pneumococcal Vaccines
7. Hepatitis Vaccines

First 4 Work Groups are permanent Last 3 Work Groups are being constituted
 ACIP Work Groups
Establishing a Work Group
• Anticipation of licensure of new vaccine or new
indication for an existing vaccine.
- Work Groups begin reviewing 12-18 months prior
to a potential decision on licensure/indication
• Updates to existing recommendations are
anticipated based on new data (safety,
effectiveness, and/or programmatic issues,
e.g. vaccine administration)
• Review of existing ACIP recommendations on
a regular basis, every 7 years
 ACIP Work Groups
Work Group Terms of Reference (TOR)
• Each Work Group (WG) operates under
specific Terms of Reference
determined by the WG Chair and WG Lead at
the time of the formation of the Work Group.
- Background
- Purpose or Objectives
- Activities
• TOR updated annually or when major changes
to activities expected
- Shared with ACIP members during ACIP meetings
 ACIP Work Groups
Roles and Responsibilities: Liaison Reps
• Communicate the perspective of the parent
organization/agency they represent at the WG
• Provide updates their organization/agency to
ensure that partners are informed of key
discussions or issues under consideration
Roles and Responsibilities: Consultants
• Provide scientific expertise to the WG
 ACIP Work Groups
Pharmaceutical Company Interaction with
Work Groups
• Pharmaceutical company (PC) presentations
to WGs provide critical information
• WGs should provide opportunities for PCs
with biological licensing application to FDA for
a vaccine product update if new data available
ALL information provided to WG is confidential
After presentation and questions the PC exits call
• All presentation topics by PCs on the ACIP
meeting agenda should be to the WG first
 ACIP Work Groups
Confidentiality
• WGs serve a key scientific role in support of
vaccine policy development by the ACIP
• Conflicts of interest (COI) could interfere with
the effective functioning of a WG
• To avoid undue influence or the appearance/
perception of a COI in WG discussions,
screening is conducted on establishment of a
WG and annually
- Balance of ensuring limited potential conflicts of
interest & need for expertise in the subject matter
- Goal is to be transparent about potential conflicts
ACIP Work Groups
 ACIP Recommendations Process
Work Group Teleconferences
• Work Groups hold teleconferences 1 to 2 times
a month, lasting 60 to 90 minutes
-WG Chair and Lead generally meet for 30-60 mins
prior to meeting(s)
-Material(s) for discussion provided prior to meeting
-Meeting minutes provided, reviewed, and approved
by WG members
-Meetings are confidential and closed to the public
ACIP Recommendations Process
GRADE Approach
• ACIP adopted Grading of Recommendations
Assessment, Development and Evaluation
(GRADE) approach in October 2010
Evaluation of quality of evidence
• Quality of evidence of benefits and harms is
only 1 factor in developing a recommendation
Other factors include values & health economic data
Charter “consideration of disease epidemiology &
burden of disease, vaccine efficacy and effective-
ness, vaccine safety, economic analysis and
implementation issues”
ACIP Recommendations Process
GRADE Approach
• Develop policy questions
• Consider critical outcomes
• Review and summarize evidence of benefits
and harms
• Evaluate quality of evidence
• Assess population benefit
• Evaluate values and preferences
• Review health economic data
• Considerations for formulating recommendations
 ACIP Recommendations Process
GRADE Approach
• Review and summarize evidence of benefits & harms
• Evaluate quality of evidence

Evidence Type Study Design

1 Randomized controlled trials (RCTs) or overwhelming

evidence from observational studies
2 RCTs with important limitations, or exceptionally strong
evidence from observational studies
3 Observational studies, or RCTs with notable limitations
4 Clinical experience and observations, observational
studies with important limitations, or RCTs with several
major limitations
 ACIP Recommendations Process
GRADE Approach
• Review and summarize evidence of benefits & harms
• Evaluate quality of evidence
High/Evidence Type 1: We are very confident that the true effect
lies close to that of the estimate of the effect.
Moderate/Evidence Type 2: 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/Evidence Type 3: Our confidence in the effect estimate is
limited: The true effect may be substantially different from the
estimate of the effect.
Very low/Evidence Type 4: We have very little confidence in the
effect estimate: The true effect is likely to be substantially different
from the estimate of effect
 ACIP Recommendations Process
ACIP and Grade Approach
• Review and summarize evidence of benefits & harms
• Evaluate quality of evidence
Outcome Design (# studies) Risk of bias Inconsistency Indirectness Imprecision Evidence type

BENEFIT
RCT (_) No serious No serious No serious No serious SCORE 1-4
Serious Serious Serious Serious
Observational (_) No serious No serious No serious No serious SCORE 1-4
Serious Serious Serious Serious
HARMS
Mild Adverse RCT (_) No serious No serious No serious No serious SCORE 1-4
Events Serious Serious Serious Serious
Observational (_) No serious No serious No serious No serious SCORE 1-4
Serious Serious Serious Serious
Serious adverse RCT (_) No serious No serious No serious No serious SCORE 1-4
events Serious Serious Serious Serious
Observational (_) No serious No serious No serious No serious SCORE 1-4
Serious Serious Serious Serious
 ACIP Recommendations Process
Health Economic Analyses in Vaccine
Decision Making
• ACIP Charter: “deliberations… shall include
consideration of… economic analysis.”
• 2008: Formal criteria established for presenta-
tion to ACIP cost-effectiveness analysis
Ensure standardization and quality of data presented
• United States: No use of a CE “threshold” to
determine if a vaccine should be routinely
recommended
 ACIP Recommendations Process
Economic Analyses and ACIP
• Economic analysis should be undertaken for
all new vaccines being considered by the
committee, among other considerations
• Studies conducted by various teams
CDC, academic research institutions, and vaccine
manufacturers
ACIP Recommendations Process
Evidence to Recommendations (EtR)
Framework
• EtR frameworks have been developed by the
GRADE Working Group of the ACIP
EtR frameworks assist users of recommendations by
enabling them to understand the judgements made
by the panel and the evidence supporting those
judgments
• ACIP adopted EtR framework in February 2018
Additional structure and clarity for the full spectrum of
criteria evaluated during formulation of recommendations
ACIP Recommendations Process
ACIP EtR Framework Categories
• PROBLEM (Statement of)
-Public health importance
-Burden of disease
• BENEFITS & HARMS
-Balance of desirable and undesirable effects
-Certainty in evidence
• VALUES & PREFERENCES of target pop
• ACCEPTIBILITY to stakeholder population
• RESOURCE USE
-Health economic analysis
• FEASIBILITY
-Implementation considerations
 ACIP Recommendations Process
ACIP EtR Framework Criteria
• PROBLEM
Criteria:
Is the problem of public health importance?
 ACIP Recommendations Process
ACIP EtR Framework Criteria
• BENEFITS & HARMS
Criteria:
How substantial are the desirable anticipated effects?
How substantial are the undesirable anticipated effects?
Do the desirable effects outweigh the undesirable
effects?
What is the overall certainty of this evidence for the
critical outcomes?
 ACIP Recommendations Process
ACIP EtR Framework Criteria
• VALUES
Criteria:
Does the target population feel that the desirable effects
are large relative to the undesirable effects?
Is there important uncertainty about or variability in the
how much people value the main outcomes?
• ACCEPTIBILITY
Criteria:
Is the intervention acceptable to key stakeholders?
 ACIP Recommendations Process
ACIP EtR Framework Criteria
• RESOURCE USE
Criteria:
Is the intervention a reasonable and efficient allocation
of resources?
• FEASIBILITY
Criteria:
Is the intervention feasible to implement?
ACIP Recommendations Process
ACIP EtR Framework