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independent assessment of the committee's conclusions, the
committee wishes to make the process of its evaluation as explicit
The adverse events under consideration by the committee are, in
most instances, rare in the exposed population. They also are known
to occur in the absence of vaccination, are clinically ill-defined,
and are generally of unknown causation in the general population.
The exposurespertussis and rubella vaccinationsare very
widespread in the population, so that the absence of exposure may
itself require an explanation in the interpretation of comparative
studies. These and other features raise a number of difficulties
both in the investigation and in the evaluation of the resulting
The committee considered causal questions of three kinds in
connection with adverse events that have been reported to occur
after administration of pertussis or rubella vaccine. The first of
these questions about exposure to pertussis or rubella vaccine is,
in general, can it cause the specified adverse condition?
For example, can rubella vaccine cause chronic arthritis? If the
conclusion is affirmative, a second question becomes pertinent:
How frequently does it cause that condition? Or, how frequently
is arthritis a result of rubella vaccination? The third question,
which applies to a particular instance or case of an adverse event,
is did it cause that specific event? Or, did rubella vaccine
cause this particular individual to develop arthritis? The
committee has undertaken its evaluation from a neutral posture,
presuming neither the existence nor the absence of association
between these vaccines and the events under consideration.
The identification and acquisition of the relevant evidence were
major tasks of the committee throughout the course of its work. The
preponderance of this material comprised either reports of
controlled, observational epidemiologic studies (case-comparison or
cohort studies) or uncontrolled case reports or case series. There
was no experimental evidence, whether in humans or animals, that
clearly proved or disproved a causal relation. Each study or report
reviewed by the committee was first assessed individually and then,
as appropriate, incorporated into the collective results that
underlie the committee's conclusions.
Both quantitative and qualitative approaches to integration of
the evidence were utilized. Formal meta-analysis was applied when
it was feasible and appropriate. All of the studies were assessed
insofar as possible with respect to the roles of error, bias,
confounding, and chance in producing the observed results. Several
considerations bearing on the inference that an association may
reflect a true causal relation were also included in the
committee's evaluation of the overall body of evidence pertaining
to each type of adverse event under review. These included the
strength of association, temporal relation between exposure and
event, consistency of results between studies, specificity of the
relation between exposure and event, and biologic plausibility of
such a relation.