Perspectives on the design and analysis of prelicensure trials: Bridging the gap to postlicensure studies

Recently, there has been growing concern regarding vaccine safety. Vaccines have led to the eradication of many serious diseases. Accordingly, there i s less familiarity with the consequences of diseases and increasing concern with potential rare adverse events. The availability of clinical informati on systems within health maintenance organizations makes assessment of safe ty in larger cohorts, with power to assess rare adverse events, possible. H owever, no trial, no matter how large, can rule out all possible adverse ev ents. There will always be the possibility that a rarer adverse event-just beyond the power of detection of a given trial-may occur. It is proposed th at prelicensure trials in 10,000-40,000 children are now feasible. However, it will be necessary to develop an analytic continuum in which prelicensur e studies are followed up with postmarketing assessments. Accordingly, the rapid identification of intussusception as a complication of rotavirus vacc ination should not be seen as a failure of prelicensure studies but rather as a positive example of an effective integrated safety assessment program.