A safety monitoring procedure for a clinical drug development program, with application to the assessment of a novel COX-2 inhibitor.

Formal safety monitoring procedures are well-developed for use in individual clinical trials and provide valuable guidance to Independent Data Monitoring Committees (IDMCs). Less has been written about procedures for use over the whole of a drug development program. It is becoming common for a single IDMC to be appointed for a whole series of studies involving a single compound. While each study will have its own goals in terms of efficacy, safety, or both, there is the potential for all of them to contribute to an emerging picture of safety. Indeed, an IDMC overseeing several studies will need to integrate the data coming from each and a formal pre-defined approach can be a valuable aid. Formal procedures are especially relevant in situations where one or two undesirable events are recognized from the outset as being of particular concern. In some cases this might be death, and in the example discussed here it is a cardiovascular event of the type that has been found to be related to certain COX-2 inhibitors. In this paper a design proposal for a safety monitoring procedure for use by an IDMC during the development of a new COX-2 inhibitor will be described.