Studies of vaccine safety (Pharmacoepidemiology) V PharmD


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Studies of vaccine safety (Pharmacoepidemiology) V PharmD

  2. 2. SELECTED SPECIAL APPLICATIONS OF PHARMACOEPIDEMIOLOGY 1. Studies of vaccine safety 2. Pharmacoepidemiology and risk management 3. Drug induced birth defects.
  4. 4. 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
  5. 5. 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 selflimited, some vaccines have been associated with rare but serious health effects.
  6. 6.   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.
  7. 7. 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.
  8. 8. METHODS OF MONITORING VACCINES SAFETY  There are two methods of monitoring vaccines: 1. Pre-licensure 2. Post-licensure
  9. 9. 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
  10. 10. 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. 2. 3. 4. The clinical trials results Product labeling The manufacturing plant The manufacturing protocol
  11. 11. 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
  12. 12. VAERS
  15. 15. 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)
  16. 16. CLASSIFICATION Adverse events are divided after vaccinations into: 1. Vaccine-induced 2. Vaccine-potentiated 3. Programmatic error 4. Coincidental
  17. 17. 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.
  18. 18. METHODOLOGIC PROBLEMS 1. Signal Detection 2. Assessment Of Causality 3. Exposure 4. Outcome 5. Analyses, Confounding & Bias
  19. 19. 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 .
  20. 20. 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.
  21. 21. 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.
  22. 22. 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.
  23. 23. AD HOC EPIDEMIOLOGIC STUDIES  Ad hoc epidemiologic studies are employed to assess signals of potential adverse events caused by :   Medical literature   Spontaneous reporting systems 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.
  24. 24. AUTOMATED LARGE-LINKED DATABASES    Automated large-linked databases provide a more costeffective 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
  25. 25. 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.
  26. 26. THANK YOU!!!