Pharmacoepidemiology in pre-approval clinical trial safety monitoring

Applications of pharmacoepidemiology to the pre-approval safety monitoring of investigational drugs are examined and compared with the post-approval applications. Pre-approval epidemiologic assessments of drug safety can complement clinical assessments of rare, serious adverse events occurring in open label uncontrolled clinical trials. Applications include retrospective identification of patient risk factors for adverse drug events and incidence comparisons based on historical controls. While similar in concept to applications of pharmacoepidemiology in the analyses of uncontrolled open label post-marketing surveillance studies, answers are often needed in days rather than weeks and the emphasis is on whether human studies can continue. Advance planning of historical data sources is essential as is an effective clinical trial data management system. Implications for methodologic research and for drug development are discussed.