Transcript
Page 1: Studies of vaccine safety (Pharmacoepidemiology)  V PharmD

SELECTED SPECIAL APPLICATIONS OF

PHARMACOEPIDEMIOLOGY

PHARMACOEPIDEMIOLOGY

AND

PHARMACOECONOMICS

By,

Sohel Memon(Doctor of Pharmacy)

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SELECTED SPECIAL APPLICATIONS OF PHARMACOEPIDEMIOLOGY

1. Studies of vaccine safety

2. Pharmacoepidemiology and risk

management

3. Drug induced birth defects.

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STUDIES OF VACCINE SAFETY

PHARMACOEPIDEMIOLOGY

AND

PHARMACOECONOMICS

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STUDIES OF VACCINE SAFETY

1. Introduction

2. Importance of vaccine safety

3. Methods of monitoring vaccines safety

4. VAERS

5. Casual link between ADE and Vaccine

6. ADE classifications

7. Methodologic Problems

8. Ad Hoc Epidemiologic Studies

9. Automated Large-Linked Databases

10. Role of Immunization provider

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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 & mortality declined where immunizations

are practiced. Vaccine safety is prime for:

- Public

- Manufacturer

- Immunization providers

- Recipients of vaccines No vaccine is completely safe or completely effective,

while all known vaccine adverse events are minor and self-limited, some vaccines have been associated with rare but serious health effects.

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Knowledge and research capacity has been limited by: Inadequate understanding of biologic mechanisms

underlying adverse events. Insufficient information from case reports & case

series. 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

- Higher standard of safety.

- Vaccines are generally healthy.

- Lower risk tolerance= Need to search for a rare reaction

- 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 VACCINES SAFETY

There are two methods of monitoring vaccines:

1. Pre-licensure2. Post-licensure

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PRE-LICENSURE MONITORING

Vaccines like other pharmaceutical products, undergo extensive safety and efficacy evaluations in the laboratory.

Pre-licensure studies are carried out on : - Animals - Humans

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If the vaccine is shown to be safe and effective in Phase- III, the manufacturer

applies for a license from the FDA.

The FDA licenses the vaccine itself and licenses the manufacturing plant where

the vaccine will be made.

During the application, FDA reviews:

1. The clinical trials results2. Product labeling3. The manufacturing plant4. The manufacturing protocol

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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

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VAERS

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VAERS ADR REPORTING FORM

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CASUAL LINK BETWEEN ADE AND VACCINE

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ADE CLASSIFICATIONS

Adverse events following vaccination can be classified by:

• Frequency (Common, Rare)

• Extent(Local, Systemic)

• Severity(Hospitalization, Disability

and Death)

• Causality and Preventability

(Intrinsic to vaccine, faulty

production or faulty

administration)

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CLASSIFICATION

Adverse events are divided after vaccinations into:

1. Vaccine-induced

2. Vaccine-potentiated

3. Programmatic error

4. Coincidental

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1. Vaccine-induced

Due to intrinsic characteristic of the vaccine preparation & individual

response of the vaccine, these events would not have occurred without

vaccination.

E.g., vaccine-associated paralytic poliomyelitis after oral polio vaccine.

2. Vaccine-potentiated

Would have occurred anyway, but were precipitated by the vaccination.

E.g., first febrile seizure in a predisposed child.

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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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.

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.

Vaccine safety surveillance systems: Examine multiple exposures (e.g., different vaccine antigens,

manufacturers, lot numbers) and multiple disease outcomes. Monitor both previously known and previously unknown adverse

events .

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2. ASSESSMENT OF CAUSALITY Vaccine-specific clinical syndrome. e.g.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:

1. Previous general experience with vaccine

Duration of licensure Number of vaccinees, whether similar events have been observed

among other vaccinees or nonvaccinees

2. Alternative etiologies.3. Individual characteristic of the vaccinees that may increase

the risk of the adverse event.4. Timing of events.5. Characteristic of the event (e.g., laboratory findings)6. Re-challenge.

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3. EXPOSURE Misclassification of exposure status occur if there is

poor documentation of vaccinations. Increases in number of licensed vaccines Relative lack of combination vaccines

Leads to vaccination history misclassifications.

4. OUTCOME • Events being assessed are frequently extremely rare (e.g., encephalopathy, GBS). • So identifying cases for interpretation of study findings is a major challenge.• Many adverse events caused by vaccines are poorly defined clinical syndromes.(e.g., encephalopathy,GBS)• The poor understanding & lack of diagnostic tools for these syndromes limits clinical & epidemiologic studies of these illnesses.

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5. ANALYSES, CONFOUNDING & BIAS

Since vaccines can lead to series of outcomes, cohort studies can be considered.

In this adverse events & 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 effects.

Once a vaccine is licensed, it is unethical to withhold the vaccine in subsequent randomized trials as a means to minimize confounding 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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AD HOC EPIDEMIOLOGIC STUDIES Ad hoc epidemiologic studies are employed to assess

signals of potential adverse events caused by :

Spontaneous reporting systems

Medical literature

Other mechanisms.

Cohort, case–control studies : used to gather information to measure or compare risks of an adverse event following vaccination with risk in the absence of vaccination.

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AUTOMATED LARGE-LINKED DATABASES

Automated large-linked databases provide a more cost-effective and flexible framework.

Ad hoc epidemiologic studies is needed in settings without automated large-linked databases or where the power of the automated large-linked databases may be inadequate to answer a question in a timely manner.

Eg: VSD by CDC

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VACCINE SAFETY DATALINK(VDC)

In 1990, CDC established the Vaccine Safety Datalink (CDC) project to improve scientific understanding of vaccine safety.

This project involves partnerships with 10 large managed care organizations(MCOs) to monitor vaccine safety.

Each participating organization gathers data on vaccination (vaccine type, date of vaccination) , medical outcomes(outpatients visits, inpatients visits, urgent care visits), birth data and census data.

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THANK YOU!!!


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