Principles of Pharmacovigilance and Drug Regulation

This chapter aims to establish understanding of the drug regulatory activities that take place to ensure that a drug’s benefits outweigh its risks and appreciate how drug regulatory systems support safe and effective use of drugs in clinical practice. First, it discusses the series of historical events that led to the current complex drug regulatory systems. Specifically, the emergence of contemporary drug regulation and pharmacovigilance in response to drug safety crises and European and global drug regulatory harmonisation are addressed. Second, it discusses current principles of pharmacovigilance and drug regulation. Important aspects comprise pharmacovigilance as a drug lifecycle activity, risk management planning, routine pharmacovigilance activities such as periodic safety updates and additional pharmacovigilance activities such as post-authorisation safety studies, as well as post-authorisation efficacy studies and the concept of expedited regulatory pathways. Third, it discusses advanced pharmacoepidemiological approaches in drug regulatory decision-making, including contemporary approaches to signal detection, the use of multi-database observational studies, the use of external control groups to contextualise, for example, single-arm studies, and the target trial emulation approach to facilitate causal inference from observational studies. Although some sections of this chapter focus mostly on the European drug regulatory system, connections to important global activities and developments are made to put the contents in a broad perspective.