Vaccines Have Become Controversial

How Are Vaccine Recommendations Made?

William Schaffner, MD
Professor of Preventive Medicine, Department of Health Policy
Professor of Medicine (Infectious Diseases)
Vanderbilt University Medical Center
 Potential Conflicts of Interest
Merck: Former member, Data Safety Monitoring
Board (DSMB)
Clinical trials of experimental vaccines

Pfizer: Member, DSMB

Roche Diagnostics: Consultant

“Never in the history of human progress has
a better and cheaper method of preventing
illness been developed than immunization
at its best”

Dr. Geoffrey Edsall

 Immunization Successes
Selected as one of 10 great public health
achievements of the 20th century

• Smallpox eradication (globally)

• Polio elimination (most of the world)
• Measles elimination (western hemisphere)
• Rubella elimination (western hemisphere)

CDC, MMWR 1999;48:241-243

 Estimated Return on Investment of
Childhood Vaccines
• For each birth cohort vaccinated against 13
diseases in accordance with the schedule of DtaP,
Hib, IPV, MMR, hep B, Varicella, Hepatitis A,
Pneumo-7, and Rotavirus vaccines:
– 42,000 lives are saved
– 20M cases of disease are prevented
– 13.6 billion dollars in direct costs are saved
– 68.9 billion dollars in direct plus indirect (societal) costs are
saved
– For each dollar invested in these vaccinations, $10.20 is saved

See presentation: by Fangjun Zhou – Tuesday Mar 29, Workshop D2 11:30am

Preliminary results of updated analysis from Zhou et al, Arch of Ped and Adolesc Med 2005
VACCINES HAVE TWO FUNCTIONS

• Protection of the individual vaccinated

clinical function

• Protection of the community against communicable

diseases
public health function

Interrupt transmission, protection of the frail

Permits the elimination of diseases
 Unsung Triumph of the U.S.
Infant, Childhood and Adolescent
Immunization Program

Elimination of Disparities
Income, race, geography
urban-rural
The Advisory Committee on
Immunization Practices

What is its role?

How does it work?
 Food and Drug Administration (FDA)

• Charged with licensing pharmaceuticals

and vaccines that are safe and effective

• After a vaccine is licensed, the ACIP

creates recommendations about which
populations should be immunized.
Advisory Committee on Immunization Practices
(ACIP)

• Established in 1964 to guide vaccination

practices in public health clinics

• Advisory to Director, CDC

and Secretary, DHHS
 ACIP
• “Harmonized” recommendations with:
– American Academy of Pediatrics (AAP)
– American Academy of Family Physicians (AAFP)
– American College of Obstetricians and
Gynecologists (ACOG)

– American College of Physicians (ACP)

• These organizations are key to distributing the

ACIP recommendations to their members
 ACIP
• Members
– 15 voting members
vaccinology, state and local public health,
pediatrics, family medicine, internal medicine,
infectious diseases

one member must be a lay person representing

the public

4-year terms
 ACIP Members
Conflict of Interest
• Required to eliminate all but research
relationships with vaccine manufacturers
(i.e. no lecturing, advisory boards, patents,
etc.)

• Research relationships are declared

• Member abstains from voting on issues

related to any vaccine manufactured by
the company
 ACIP
• Ex-Officio
– Centers for Medicare and Medicaid Services (CMS)
– Department of Defense (DOD)
– Department of Veterans Affairs (DVA)
– Food and Drug Administration (FDA)
– Health Resources and Services Administration
(HRSA)
– Indian Health Service (IHS)
– National Institutes of Health (NIH)
– National Vaccine Program Office (NVPO)
 ACIP
• Liaison Representatives
AAFP NACCHO BIO
AAP APhA PhRMA
ACHA AOA AHIP
ACOG SAM NVAC
ACP IDSA HICPAC
AGS NFID
AMA SHEA
NMA APTR

CANADA, MEXICO, U.K. – Immunization Committees

 ACIP

Members
Ex
Liaison
Officio

Press

Liaison

The Public
 ACIP
• Three meetings per year (Feb., June, Oct.)
• Working Groups
– Disease epidemiology, morbidity, mortality
– Vaccine immunogenicity, efficacy, safety
– Cost-effectiveness
– Feasibility
• Recommendations
– Clinical and public health guidance
– Dual function: protect individual and
community
 ACIP Evidence Evaluation
• Grading of Recommendations, Assessment,
Development and Evaluation (GRADE)

• Evidence to Recommendations (ETR)

framework

N.B. The quality of the evidence is graded, NOT

the Recommendations
 ACIP
Working Groups
Vaccines Other
• Influenza • General recommendations
• HPV • Adult immunizations
• Japanese Encephalitis • Harmonized schedule
• Meningococcal • Combination vaccines
• Pneumococcal • Evidence-based
• Rotavirus recommendations
• Zoster (shingles) • Vaccines during pregnancy
• Anthrax and breastfeeding
 ACIP General Observation – 1.
• The relationships of the ACIP with vaccine
manufacturers is both professionally genial as well as
scientifically critical

• The amount of data presented to the ACIP is

voluminous – yet more data always are desired

• ACIP strives to vote on recommendations as quickly as

possible after a new vaccine is licensed

• Vaccine safety is always paramount – and monitored

over time
 ACIP General Observation – 2.
• ACIP avoids preferential recommendations
(almost always)

• ACIP revises recommendations

• Harmonization of recommendations with

professional organizations is important

• ACIP acts as the Vaccines for Children

authorization committee (appropriations must
follow!)
 Vaccines for Children Program - 1
Initiative: Rosalynn Carter and Betty Bumpers

Aug, 1993: Congress passed the Omnibus Budget

Reconciliation Act (OBRA), creating VFC
Became operational Oct 1, 1994
An entitlement program
 Vaccines for Children Program - 2
Eligible children:
Younger than age 19
Medicaid – eligible
Uninsured or Underinsured
American Indian or Alaska Native
 Dual Function: Protect Individual and Community
Historical Example: Measles Vaccine -1

• Measles:
400,000 cases reported/year
4,000 measles encephalitis
400 deaths!
otitis media, pneumonia
• Measles vaccine licensed 1963
95%-98% protection
long-term immunity
• ACIP recommendation: universal, routine
vaccination of all children
 Dual Function: Protect Individual and Community
Historical Example: Measles Vaccine - 2

• Cases decreased: 22,000 – 75,000/year

• 1978 CDC: Measles Elimination Program

• Eliminate indigenous measles from US

• 1984-88: 3,750 cases/year

58% among vaccinated children

• Investigation:
Use-effectiveness of measles vaccine 90-92%
Why would the clinical trials show
up to 98% effectiveness, but…
when used in the “real world” only
provide 90-92% protection?
 Two Theories:
• The children were somehow immune
impaired

• Vaccine handling in the office reduced the

effectiveness of the vaccine
 Two Theories:
• The children were somehow immune
impaired
Re-immunization of children who were non-
responders resulted in 98+% protection

• Vaccine handling in the office reduced the

effectiveness of the vaccine
Vaccine handling of this temperature-sensitive
vaccine was sometimes slovenly in doctors’
offices
 Dual Function: Protect Individual and Community
Historical Example: Measles Vaccine - 3
• Dilemma: Can public health goal of measles
elimination be achieved?

• Note: Cases reduced by 99%

Measles control achieved
Great clinical protection

• How tolerant are “we” of 3,750 cases/year?

• If intolerant, what to do?

 Dual Function: Protect Individual and Community
Historical Example: Measles Vaccine - 4

• 1989 ACIP recommended all children receive 2 doses of

measles vaccine

• 1993 Transmission of indigenous measles

interrupted in US

• Although clinical result had been achieved, the public

health (community) goal required additional effort
 ACIP Decisions – June, 2019
Human papillomavirus vaccine
• Harmonized catch-up vaccination of women and men to
age 26
• Vaccination of adults age 27-45: shared clinical decision
making

Pneumococcal vaccines
• Discontinue routine PCV13 in immunocompetent adults
age 65+ in favor of shared clinical decision making

Hepatitis A vaccine
• Unimmunized adolescents should receive catch up
vaccination
• Everyone with HIV infection
 VACCINE RESEARCH
Pertussis AIDS
RSV TB
Group B Streptococcal Malaria
C. difficile
West Nile Universal Influenza
Campylobacter
E. Coli Cholera
Zika Anthrax
Norovirus Tularemia
Gonorrhea
 VACCINE RESEARCH
Edible vaccines New Targets
Alzheimer’s
Needle-free vaccines Smoking
Nasal Cocaine
Inhaler Cancers
Skin Patches
Micro-needles
Oral
 Disease is bad…

Vaccines are good!

W.S.
When meditating over a disease, I never think
of finding a remedy for it, but, instead, a
means of preventing it.
Louis Pasteur
 REFERENCES
Pickering LK, Orenstein, Sun W, Baker CJ.
FDA licensure of and ACIP recommendations for vaccines.
Vaccine 2017; 35: 5027-5036

Walton LR, Orenstein WA, Pickering LK.

The History of the United States Advisory Committee on
Immunization Practices (ACIP). Vaccine 2015; 33: 405-414

Smith JC, Snider DE, Pickering LK.

Immunization policy development in the United States: The
Role of the Advisory Committee on Immunization Practices.
Ann Int Med 2009; 150: 45-49