PROGRESSIVE EDUCATION
SOCIETY’S
MODERN COLLEGE OF PHARMACY
NIGDI, PUNE- 411044
STUDIES OF VACCINE SAFETY
PHARMACOEPIDEMIOLOGY
PRESENTED BY:
PD 503 - DEEKSHA CHAVAN
PD 523 - PUSHKAR PANCHABHAI
PD 526 - ANVAY SHASTRI
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INTRODUCTION
• A vaccine is a biological preparation that improves immunity to a particular disease.
• Vaccines are among the most cost-effective and prevalent public health interventions.
• Morbidity and mortality declined where immunizations are practiced.
• Vaccine safety is prime for
1. Public
2. Manufacturer
3. Immunization providers
4. Recipients of vaccines
• No vaccine is completely safe or completely effective, while all known vaccines adverse events
are minor and self-limited; some vaccines have been associated with rare but serious health
effects.
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INTRODUCTION
• Knowledge and research capacity has been limited by:
1. Inadequate understanding of biological mechanisms underlying adverse events.
2. Insufficient information from case reports and case series.
3. Limitations of existing surveillance systems to provide evidence of causation.
• To overcome these limitations:
Epidemiology is vital in providing scientific methodology for assessing vaccine safety.
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IMPORTANCE OF VACCINE SAFETY
• Decrease in disease risks and increased attention on vaccine risk.
• Public confidence in vaccine safety is critical.
1. Higher standard of safety.
2. Vaccines are generally healthy.
3. Lower risk tolerance = need to search for a rare reaction.
4. Vaccination is universally recommended and mandated.
• Ongoing safety monitoring needed for the development of the sound policies and
recommendations.
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METHODS OF MONITORING VACCINE SAFETY
• There are two methods of monitoring vaccines:
1. Pre-licensure
2. Post-licensure
3. Pre-licensure monitoring:
• Vaccines like other pharmaceutical products, undergo extensive safety and efficacy evaluations
in the laboratory.
• Pre-licensure studies are carried out on:
a) Animals
b) Humans
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METHODS OF MONITORING VACCINE SAFETY
• Pre-licensure human studies:
a) Phases : I, II, III Trials
b) common reactions are identified.
c) Vaccines are tested in thousands of people before being licensed and allowed in the market.
• Most trials involve patients but screening and prevention trials are often recruit healthy
volunteers.
Phase I : This stage checks that treatment is safe and finds the best dose to use.
Phase II : This stage tells how well a test or treatment works.
Phase III : This stage compares the new treatment with the current treatment.
These are large scale trials.
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If the vaccine is known to shown to be safe and effective in Phase - III ,the
manufacturer applies for a license from FDA
Licensing Review
The FDA licenses the vaccine itself During the application FDA reviews :
and licenses the manufacturing 1.The Clinical trial results
plant where the vaccine will be 2.Product labelling
made 3.The Manufacturing plant
4.The Manufacturing protocol
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POST-LICENSURE
MONITORING
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POST-LICENSURE
MONITORING
• Identifies rare reactions
• Monitor increases in known reactions
• Identify risk factors for reactions
• Identify vaccine lots with unusual rates or types of events
• Identify signals
• Phase IV studies can be an FDA requirement for licensure
• These trials include tens of thousands of volunteers and may address questions of
long-term effectiveness and safety or examine unanswered questions identified in
Phase III clinical trials.
• Manufacturers must submit samples of each vaccine lot and results of their own
tests for potency and purity to the FDA before
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VACCINE ADVERSE EVENT REPORTING
SYSTEM (VAERS)
1. The vaccine adverse event reporting system (VAERS) is a
national reporting system, jointly administered by CDC &
FDA
2. VARERS was created in 1990 to unify the collection of all
reports of adverse events after vaccination.
3. VAERS is a passive reporting system and accepts reports
from the health professionals, vaccine manufactures, and the
general public.
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ADE CLASSIFICATION
Frequency (Common, Rare)
Extent (Local, Systemic)
Severity ( Hospitalization,
Disability and Death)
Causality and Preventability
(Intrinsic to vaccine, faulty
production or faulty
administration) 11
CLASSIFICATION
Adverse events are divided after vaccination into :
1. Vaccine- induced
2. Vaccine- potentiated
3. Programmatic error
4. Coincidental
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CLASSIFICATION
1. VACCINE-INDUCED:
Due to intrinsic characteristic of the vaccine preparation &
individual response of the vaccine, these events would not
have occurred without vaccination.
Ex: Vaccine-associated paralytic poliomyelitis after oral
polio vaccine.
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CLASSIFICATION
2. VACCINE-POTENTIATED:
Would have occurred anyway, but were precipitated by the vaccination.
Ex: First febrile seizure in a predisposed child.
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CLASSIFICATION
3. PROGRAMMATIC ERROR:
Due to technical errors in vaccine preparation, handling (or)
administration.
4. COINCIDENTAL:
Associated temporally with vaccination by chance or due to underlying
illness.
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METHODOLOGIC PROBLEMS:
1. Signal Detection
2. Assessment Of Causality
3. Exposure
4. Outcome
5. Analyses, Confounding & Bias
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METHODOLOGIC PROBLEMS:
1. SIGNAL DETECTION:
• Vaccines are biologic rather than chemical in nature.
• Variation in rate of adverse events by manufacturer or even lot
might be expected.
• Surveillance systems need to detect such potential aberrations in a
timely manner.
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METHODOLOGIC PROBLEMS:
Many vaccinations are administered to individuals: simultaneously or
as combination vaccine, unless the number of persons who also
receive that exact permutation of vaccine exposures is known, it may
be difficult if not impossible to know if an aberration has occurred.
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VACCINE SAFETY SURVEILLANCE SYSTEM:
• Examine multiple exposures (e.g. different vaccine antigens,
manufacturers, lot numbers ) and multiple disease outcomes.
• Monitor both previously known and unknown adverse events.
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METHODOLOGIC PROBLEMS:
2. ASSESSMENT OF CAUSALITY
• Vaccine specific clinical syndrome e.x.- Myopericarditis in healthy young
adults- smallpox vaccine : must be identified for assessing any adverse event
caused by vaccine.
• Information useful for assessing causality in individual case reports
includes ;
A) Previous general experience with vaccine
- Duration of Licensure
- Number of vaccines or non-vaccines.
B) Alternative etiologies
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METHODOLOGIC PROBLEMS:
C) Individual characteristics of the vaccines that may increase the
risk of
the adverse event.
D) Timing of events.
E) Characteristic of the event (e.g. lab findings)
F) Re-challenge.
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METHODOLOGIC PROBLEMS:
3. EXPOSURE :
• Misclassification of the exposure status occurs if there is poor
documentation of vaccination.
- Increases in number of licensed vaccines.
- Relative lack of combination vaccines.
• Leads to vaccination history misclassification.
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METHODOLOGIC PROBLEMS:
4. OUTCOME :
• Events being assessed are frequently extremely rare ( e.x.-
Encephalopathy, GBS )
• So identifying cases for interpretation of study findings is a major
challenge.
• Many adverse events caused by vaccine are poorly defined clinical
syndromes.
• The poor understanding & lack of diagnostic tools for these syndromes
limits clinical & epidemiological studies of these illness.
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METHODOLOGIC PROBLEMS:
5. ANALYSIS, CONFOUNDING & BIAS :
• Since vaccines can lead to series of outcomes, cohort studies can be
considered.
• In this adverse events and person-time risks are evaluated.
• When outcomes are rare, these studies become time consuming and
expensive.
• Case control studies are also carried out in case of rare adverse
events.
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METHODOLOGIC PROBLEMS:
• Once a vaccine is licensed, it is unethical to withhold the
vaccine in subsequent randomized trials as a means to
minimize cofounding and bias.
• To minimize recall bias, it is best to rely on data sources that
gather information on outcomes and vaccine exposure
independently.
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Thank You!
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