Lecture 6: Intro to vaccine safety

Question 1

How many Vaccines, Doses and antigens will a child receive before 18?

Answer 1

36 vaccines, over a 100 doses and a lot of antigens as well.

Question 2

Possible explanations for the fear of vaccines

Answer 2

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

Question 3

Importance of Vaccine Safety

Answer 3

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)

Question 4

Vaccine + Disease statistics

Answer 4

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.

Question 5

Methods of monitoring immunization safety

Answer 5

Pre-licensure evaluation and post-licensure evaluation

Question 6

Pre-licensure Evaluation

Answer 6

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)

Question 7

Post-licensure Evaluation

Answer 7

• Passive surveillance (VAERS)
• Post-licensure LST
• epidemiologic studies with linked dbs

Question 8

VAERS (Vaccine adverse event reporting system)

Answer 8

-passive surveillance spontaneous reporting system which reports clinically significant adverse events, narrative descriptions, patients, parents, HCPs, 30,000 reports per annum.

Question 9

Strengths of VAERS (Vaccine adverse event reporting system)

Answer 9

• identify first safety data for new vaccines
• rates calculation of dose distribution
• covers ENTIRE US population

Question 10

Challenges of VAERS (Vaccine adverse event reporting system)

Answer 10

• Underrreporting
• Biased reporting (due to changes in reporting efficiency and vaccine coverage)
• Case data only (no denominator)
• Quality of diagnostic information

Question 11

Necessity for Big data

Answer 11

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,)

Question 12

Vaccine safety Datalink (VSD)–background

Answer 12

• 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

Question 13

Vaccine safety Datalink (VSD)–priorities

Answer 13

• 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

Question 14

PRISM (Post-licensure rapid immunization safety monitoring)

Answer 14

• developed by FDA to support sentinel

- N= 100 million

Question 15

Benefits of VSD/PRISM

Answer 15

• Large
• well-defined (geographically diverse populations)
• access to EMR for review
• Comparison groups available
• Rapid (real time data available)

Question 16

Challenges of VSD/PRISM

Answer 16

• VSD less diverse than PRISM and may not represent low SES
• difficult to assess mild AEs
• difficult to control some confounders
• high vaccine coverage

Question 17

Self Control Methods

Answer 17

• 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)

Question 18

Self Control Designs

Answer 18

• Case-Crossover
• Self-Controlled Case series (SCCS)
• Self-Controlled Risk Interval (SCRI)

Question 19

Case-Crossover

Answer 19

• acute event and transient exposure

- case window and control window for each person = exposed or unexposed

Question 20

Self-Controlled Case series (SCCS)

Answer 20

• 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

Question 21

Self-Controlled Risk Interval (SCRI)

Answer 21

• 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)

Question 22

Common features of these studies

Answer 22

• 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

Question 23

Taking care of time varying confounders

Answer 23

Adjust in model or choose risk and control intervals close to one another in short duration
-examples of these confounders are: Age, Concomitant vaccines