The following HTML text is provided to enhance online
readability. Many aspects of typography translate only awkwardly to HTML.
Please use the page image
as the authoritative form to ensure accuracy.
Immunization Safety Review: Hepatitis B Vaccine and Demyelinating Neurological Disorders
Assessments begin from a position of neutrality regarding the specific vaccine safety hypothesis under review. That is, there is no presumption that a specific vaccine (or vaccine component) does or does not cause the adverse event in question. The weight of the available clinical and epidemiological evidence determines whether it is possible to shift from that neutral position to a finding for causality (“the evidence favors acceptance of a causal relationship”) or away from causality (“the evidence favors rejection of a causal relationship”). The committee does not conclude that the vaccine does not cause the adverse event merely if the evidence is inadequate to support causality. Instead, it maintains a neutral position, concluding that the “evidence is inadequate to accept or reject a causal relationship.”
Although no firm rules establish the amount of evidence or the quality of the evidence required to support a specific category of causality conclusion, the committee uses standard epidemiological criteria to guide its decisions. The most definitive category is “establishes causality,” which is reserved for those relationships where the causal link is unequivocal, as with the oral polio vaccine and vaccine-associated paralytic polio. The next category, “favors acceptance” of a causal relationship, reflects evidence that is strong and generally convincing, although not firm enough to be described as unequivocal or established. “Favors rejection” is the strongest category in the negative direction. The category of “establishes no causal relationship” is not used because it is virtually impossible to prove the absence of a relationship with the same surety that is possible in establishing its presence. If the evidence is not reasonably convincing either in support of or against causality, the category “inadequate to accept or reject a causal relationship” is used. Evidence that is sparse, conflicting, of weak quality, or just suggestive either towards or away from causality falls into this category. The category of “no evidence” is reserved for those cases in which there is a complete absence of clinical or epidemiological evidence.
The sources of evidence considered by the committee in its scientific assessment of causality include epidemiological and clinical studies. Epidemiological studies carry the most weight in a causality assessment. Case reports and case series are generally inadequate by themselves to establish causality.
The committee’s scientific assessment includes biological mechanisms, for which it has established three general categories of evidence on biological mechanisms:
Theory only: A reasonable mechanism can be hypothesized that is commensurate with scientific knowledge and that does not contradict known physical and biological principles, but it has not been demonstrated in whole or in part in humans or in model systems. Postulated mechanisms by which a vaccine might cause a specific adverse event but for which no coherent theory ex-