| 1) Lower tolerance for immunization risks: Medical intervention, including immunizations, aims to minimize the risks while maximizing the benefits. Because most immunizations are administered to healthy persons (frequently babies) to prevent illness, are commonly recommended for near-universal use, and are often legally required for school entry, the tolerance for risks is much lower than most other medical interventions (generally targeted at treating ill patients). |
| 2) Increasing maturity of National Immunization Programs (NIP): Most NIPs are maturing with high coverage and effectiveness of most commonly used immunizations, resulting in (near) elimination of their target vaccine-preventable disease (VPD) (125)but also an increased number of adverse events following immunizations (AEFI; both true reactions and temporally coincidental events). |
| 3) Limited clinical trial sample size: The inherent limits of sample size in pre-licensure clinical trials usually means rare, AEFIs are likely to be detectable only in post-licensure settings once larger populations are immunized (126); |
| 4) New vaccines and complex schedules: The biotechnology revolution triggered by our ability to sequence the genome of any microorganism has enhanced our ability to develop and introduce new vaccines (121, 122); each of whom, however, needs to be added to an already complex routine immunization schedule, thereby raising concerns in some parents about “over-immunization” of their babies (123). Furthermore, pre-licensure clinical trials often involve looking at a single vaccine and comparator control vaccine or placebo, or a minimal number of simultaneous vaccines. This is not necessarily how vaccines are administered in children in practice, where many vaccines might be co-administered. So the pre-licensure trials might not be representative of how vaccine is administered to children in practice and does not completely address the issue of simultaneous vaccination and the safety of the schedule (81). |
| 5) Evolving Parenting: Post-modern parenting aiming to make optimal informed risk-benefit decision for their own child may overemphasize perceived vaccine risks in absence of wild disease, thereby delay (“hesitate”) or increase use of exemptions to mandated immunizations (123, 124); |
| 6) Diverging risk-benefit: For vaccines that confer herd immunity, there is an inherent divergence between societal and individual risk-benefit at high vaccine coverages (127); |
| 7) Time lag between hypothesis and evidence: Hypothesis testing validation studies of rare vaccine safety associations are difficult, costly, time consuming, and can usually tackle only one or small number of AEFI's at a time. Even under optimal circumstance, months but typically years are usually needed for expert consensus to develop based on appropriately gathered scientific evidence. Therefore there is an inherent mismatch in timespan between the questions (and expectations) raised by rapid and unpredictable communications via 24/7 mass media and social network apps on cell phones and scientific process that allow vaccine safety controversies to amplify (124, 128). |
