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athy, or thrombocytopenia, and between the currently used rubella vaccine (RA 27/3) and radiculoneuritis and other neuropathies or thrombocytopenic purpura;

· that the evidence does not indicate a causal relation between DPT vaccine and infantile spasms, hypsarrythmia, Reye syndrome, or SIDS;

· that the evidence is consistent with a causal relation between DPT vaccine and acute encephalopathy and shock and "unusual shock-like state," and between RA 27/3 rubella vaccine and chronic arthritis; and

· that the evidence indicates a causal relation between DPT vaccine and anaphylaxis, between the pertussis component of DPT vaccine and protracted, inconsolable crying, and between RA 27/3 rubella vaccine and acute arthritis.1

RESEARCH NEEDS

In the course of its review, the committee encountered many gaps and limitations in knowledge bearing directly and indirectly on the safety of vaccines. These include inadequate understanding of the biologic mechanisms underlying adverse events following natural infection or immunization, insufficient or inconsistent information from case reports and case series, inadequate size or length of follow-up of many population-based epidemiologic studies, and limited capacity of existing surveillance systems of vaccine injury to provide persuasive evidence of causation. The committee found few experimental studies published in relation to the number of epidemiologic studies published. Clearly, if research capacity and accomplishment in these areas are not improved, future reviews of vaccine safety will be similarly handicapped.

With respect to pertussis and rubella vaccines, careful review is needed to identify what sorts of questions might be best answered by further investigations and which kinds of studies could be carried out economically. The availability and introduction of new forms of pertussis vaccine, for example, could offer valuable opportunities for comparison of vaccine safety as well as efficacy. The committee's experience points to fresh possibilities and to the need for such a review.

1The available evidence is consistent with a causal relation, but, on balance, is more persuasive than that in the previous bullet.