Clinical Impact of Adverse Event Reporting

All reports from health professionals (direct reports) and specific reports from manufacturers are individually reviewed by an FDA health professional safety evaluator, with particular attention to all reported serious adverse events that are not in the labeling in the case of pharmaceuticals⁽⁴⁴⁾. All other reports are entered into the database for use in aggregate analysis. In focused evaluation of adverse events, the postmarketing surveillance database is searched for other reports, and further steps such as literature searches and use of medical product utilization databases may be taken.

Based on careful review of spontaneous reports, the FDA can initiate various actions, including a "Dear Health Professional" letter or Safety Alert; labeling, name or packaging change(s); conducting further epidemiologic investigations; requesting manufacturer-sponsored postmarketing studies; conducting inspections of manufacturers' facilities/records; or working with a manufacturer regarding possible withdrawal of a medical product from the market.

Four clinical synopses^(44-55) provided by each of the four participating FDA Centers that outline examples of regulatory actions based on postmarketing surveillance are presented with this article.

The clinical synopses demonstrate the step-wise process of spontaneous reports evaluation that is utilized at the FDA. In addition, these cases clearly illustrate that a single adverse event report from a health professional can often lead to an FDA action that has clinical importance.

At times signals generated by the spontaneous reporting system are of sufficient strength that further epidemiologic investigation is not necessary, a situation exemplified by the clinical synopses. However, non-epidemiologic types of studies may be indicated, such as those attempting to explain the etiology of eosinophilia-myalgia syndrome^{(50, 53, 54)}.

Should formal epidemiologic study be deemed useful in regard to an adverse event, well-validated methods can be utilized by FDA, industry, and academia in their investigations*. For example, FDA regulation of oral contraceptives has relied heavily on the findings of case-control and cohort studies⁽⁵⁶⁾.