known to occur in the absence of vaccine exposure, or that generally have unknown causes or mechanisms of development are also inherently difficult to investigate. Under these circumstances, epidemiologic studies offer important advantages over clinical experience and intuition, although these limiting characteristics affect epidemiologic studies also.
When the great majority of the population is exposed, as is generally true for pertussis and rubella vaccines, comparisons between exposed and nonexposed persons become clouded. This is due to the potential for selective factors against vaccination to confound the relation between immunization status and the occurrence of adverse events. For example, a decreased relative risk of SIDS has been observed in several studies in the time period immediately following DPT immunization. Although a protective effect of vaccine cannot be ruled out, it is more plausible that children who are not immunized by the recommended age are at increased risk for SIDS because of other factors, such as socioeconomic status, that are associated with both delaying immunization and SIDS (see Chapter 5). Other aspects of vaccine exposure, such as changes in vaccine formulation, single versus multiple occasions of administration, and the age pattern of administration also bear on interpretation of the evidence.
What would it mean to say that a vaccine causes one or another type of adverse event? It would not mean that exposure invariably produces the adverse event, nor that all cases of the event were due to the vaccine. Such complete correspondence between exposures and events is by far the exception in public health and does not occur in the present context, or the present review would not be required.
In general matters of health and disease, different causal explanations may apply even to a single disease. For example, the question of what causes typical cases of a particular disease is quite distinct from the question of what causes epidemic outbreaks of that disease. The answers are also distinct, in that the first might be a specific microorganism and exposure conditions of the individual case, whereas the second could entail complex ecologic and social factors suddenly favoring the widespread transmission of the microorganism. Clearly, different senses of ''cause" are implied in these two questions. Although each of these questions concerns the causation of disease, the answers require different types of evidence. This example suggests the importance of stating clearly the questions about causation to be answered.
In the present review, the committee has been concerned with causal questions of three kinds. The first of these questions about exposure to pertussis or rubella vaccine is, in general, can it cause the specified adverse