Vaccine efficacy determination.

The "Gold standard" in vaccine testing is the randomized, placebo controlled, double-blind efficacy trial. Once a protective immune mechanism is defined, e.g., from an efficacy trial, vaccine performance can then be judged by serologic parameters. Although immunogenicity studies can provide important information, in many instances the answer has to come from efficacy trials. For rare diseases like meningococcal disease, these trials are expensive and difficult to conduct. It is therefore incumbent to learn as much as possible from each trial. Issues in pre-licensure studies include: vaccine selection, site selection, trial design, assignment to treatment and control groups, definition and surveillance for endpoints (cases, adverse reactions), identification of surrogate markers for protection, and utilization of monitoring committees.