Lecture 6: Intro to vaccine safety Flashcards
How many Vaccines, Doses and antigens will a child receive before 18?
36 vaccines, over a 100 doses and a lot of antigens as well.
Possible explanations for the fear of vaccines
1) unfortunate events
2) uncommon but severe events (swine flu)
3) unfounded safety concerns (autism, SIDS cancer)
4) experience of one adverse event leading to fear of another
Importance of Vaccine Safety
1) Higher standard safety expected of vaccines
2) Lower risk tolerance = search for rare reactions (but rare event studies are costly and less likely to be definitive)
Vaccine + Disease statistics
As the number of vaccines as gone up, the total number of diseases has gone down. However, when there is a period of loss of confidence in vaccines, outbreak of disease goes up, until resumption of confidence, then disease goes back down until eradication.
Methods of monitoring immunization safety
Pre-licensure evaluation and post-licensure evaluation
Pre-licensure Evaluation
Clinical trials (from phase 2 and 3 to larger clinical trials which detect attributable risk > 1/10,000)--> they also evaluate number/timing of doses, concomitant administration, strains, formulations, etc. -Brighton Collaboration (established to standardize case definitions for adverse event, reduce misclassification and increase comparability)
Post-licensure Evaluation
- Passive surveillance (VAERS)
- Post-licensure LST
- epidemiologic studies with linked dbs
VAERS (Vaccine adverse event reporting system)
-passive surveillance spontaneous reporting system which reports clinically significant adverse events, narrative descriptions, patients, parents, HCPs, 30,000 reports per annum.
Strengths of VAERS (Vaccine adverse event reporting system)
- identify first safety data for new vaccines
- rates calculation of dose distribution
- covers ENTIRE US population
Challenges of VAERS (Vaccine adverse event reporting system)
- Underrreporting
- Biased reporting (due to changes in reporting efficiency and vaccine coverage)
- Case data only (no denominator)
- Quality of diagnostic information
Necessity for Big data
It is costly and inefficient to assess single events/outcomes in single data sources (VAERS), So, we need databases that can link medical outcomes with immunization records (ex. Vaccine safety Datalink (VSD), PRISM,)
Vaccine safety Datalink (VSD)–background
- CDC collaborates with 8 HMOs for this
- 10 million members (3% of US Pop)
- Each partner prepares standardized data files to link to death and immunization registries and some files are updated weekly
Vaccine safety Datalink (VSD)–priorities
- evaluate safety of newly licensed vaccines
- evaluate safety of new vaccine recommendations for existing ones
- evaluate clinical disorders after immunizations
- assess vaccine safety in special high risk populations
- develop and evaluate methodologies for vaccine safety assessment
PRISM (Post-licensure rapid immunization safety monitoring)
- developed by FDA to support sentinel
- N= 100 million
Benefits of VSD/PRISM
- Large
- well-defined (geographically diverse populations)
- access to EMR for review
- Comparison groups available
- Rapid (real time data available)
Challenges of VSD/PRISM
- VSD less diverse than PRISM and may not represent low SES
- difficult to assess mild AEs
- difficult to control some confounders
- high vaccine coverage
Self Control Methods
- rationale is that there is a lot of between person confounding when doing observational studies comparing vaccinated and unvaccinated (different types of ppl)
- so within the same individual, a risk window is compared to a control window (this automatically adjusts for between confounding, but only for confounders that do not vary over time)
Self Control Designs
- Case-Crossover
- Self-Controlled Case series (SCCS)
- Self-Controlled Risk Interval (SCRI)
Case-Crossover
- acute event and transient exposure
- case window and control window for each person = exposed or unexposed
Self-Controlled Case series (SCCS)
- Study population has cases (exposed) identified during a predefined observation period
- Compare rate of outcome at different times relative to exposure
- IRR = incidence rate of outcome within each risk interval divided by incidence rate of outcomes outside of risk interval
Self-Controlled Risk Interval (SCRI)
- only vaccinated cohort (cases and non-cases)
- consider it like a traditional cohort study where the same person contributes to both risk and control intervals
- Research q: Outcome more common in period X (risk window) following vaccination compared to period Y (control window)
Common features of these studies
- Risk intervals
- Control intervals from same person
- count events in each interval
- condition analysis on the patient
- best for acute onset events
- automatically adjusts for between person confounding
- must take into account time-varying confounders
- approximate RR well
Taking care of time varying confounders
Adjust in model or choose risk and control intervals close to one another in short duration
-examples of these confounders are: Age, Concomitant vaccines
