adverse events, events not previously reported in the medical literature or demonstrated in epidemiologic studies?

The committee encourages the consideration of a more active system. Such a system might follow a representative sample of new vaccine recipients rather than the population at large. Alternatively, a randomly selected subgroup of serious adverse events reported to VAERS might be investigated fully. This latter approach suffers the inevitable limitations of retrospective review. It may be necessary to retain some broad-based passive reporting system to serve an early-warning function for unpredicted adverse events.

The committee found that a judgment regarding causality was often limited by the absence of background data for the occurrence of the pathologic condition (the putative adverse event) in apparently normal individuals not recently exposed to the vaccine. Regional or national disease registries could be established for those rare but serious conditions suspected of sometimes being caused by one or more licensed vaccines, for example, GBS, transverse myelitis, optic neuritis, and Stevens-Johnson syndrome. Such disease registries, if reasonably complete, would provide information about the descriptive epidemiology of these conditions, including age-, sex-, and race-specific background incidence rates. This information would facilitate the performance of case-control studies and other attempts to investigate vaccines as potential causes of the disorders.

The committee believes that future clinical trials of vaccines licensed or under development should study the serious adverse events examined by the present committee and its predecessor committee. Although any single trial may be too small to detect an effect of vaccine on rare adverse events, meta-analyses of several large trials may provide useful information. Meta-analysis could also be used to improve the statistical power of case-control studies to detect rare sequelae of vaccine administration.

With the existence of the large databases that have recently been established for defined populations, cohort studies become a feasible and desirable epidemiologic method of detecting the adverse effects of vaccines. Cohort studies would also permit the follow-up of patients exposed to specific vaccine types or batches that are suspected (e.g., on the basis of case reports) of being associated with a pathologic condition. Here, too, meta-analyses of cohort studies from different settings and different databases may permit identification of effects not detectable within individual studies.

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