tion, individual case reports and case series were relied upon, provided that the nature and timing of the adverse event following vaccine administration and the absence of likely alternative etiologic candidates were such that a reasonable certainty of causality could be inferred (as described above) from one or more case reports. The presence or absence of demonstrated biologic plausibility was also considered in weighing the overall balance of evidence for and against a causal relation. In the absence of convincing case reports or epidemiologic studies, however, the mere demonstration of biologic plausibility was felt to constitute insufficient evidence to accept or reject a causal relation.

Acceptance and rejection of a causal relation between any exposure and outcome are inherently asymmetric. Very strong evidence in favor of such a causal relation can be said to establish a causal relation, although 100 percent ''proof,'' in the mathematical sense, is never possible. It is almost never possible, however, to be as sure about rejecting such a causal relation because even the largest population-based epidemiologic studies have insufficient statistical power to detect extremely rare causes of an outcome (e.g., an excess risk of 1 per 1 million population). Hence, the categories in which the committee has summarized the evidence for causality (see below) reflect this essential asymmetry.

Despite the committee's attempts at objectivity, the interpretation of scientific evidence always retains at least some subjective elements. Use of such "objective" standards as P values, confidence intervals, and relative risks may convey a false sense that such judgments are entirely objective. However, judgments about potential sources of bias, although based on sound scientific principles, cannot usually be quantitated. This is true even for the scientific "gold standard" in evaluating causal relations, the randomized clinical trial.

For each vaccine-adverse event association under consideration, the committee started from a neutral position, presuming neither the presence nor the absence of a causal relation between the vaccines and the adverse events under consideration. Each category of evidence was then assessed and weighted (as described above) to arrive at an overall judgment as to whether the balance of evidence favored acceptance or rejection of a causal relation between the vaccine and the adverse event. To enhance scientific accountability, the committee's judgment of causality for each vaccine-adverse event association considered is accompanied by an explanation of the evidentiary basis for that judgment.


The committee attempted to build on the methods and procedures used by the Committee to Review the Adverse Consequences of Pertussis and

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