Pharmacoepidemiology

Pharmacoepidemiology

1. Definition, scope, and rationale

• Pharmacoepidemiology is the application of epidemiologic methods and reasoning to the study of the use of, and the effects (beneficial and adverse) of, drugs in large human populations — i.e. the population-level study of drug exposures and outcomes using observational designs and routinely-collected real-world data (G&G 14e Ch.8, pp.149–51).
• It is the methodological engine of post-marketing drug safety: signals raised by spontaneous reports are refined and quantified by observational pharmacoepidemiologic studies before regulatory action (G&G 14e Ch.8, pp.148–49).
• The discipline arose from the recognition that rare but serious adverse drug reactions (ADRs) are usually identified only after a drug is in widespread clinical use — the thalidomide–phocomelia catastrophe (>10,000 affected children, 1957–61) being the founding example that drove national post-marketing surveillance systems worldwide (G&G 14e Ch.8, p.145).
• Three principles underpin the modern (life-cycle) view of drug safety that pharmacoepidemiology serves (G&G 14e Ch.8, p.145):
  • Safety and efficacy are not fixed at approval — they must be reassessed across the drug's life cycle.
  • Post-marketing safety is driven not only by rare ADRs but, often more importantly, by increased risk of common events not initially recognised as ADRs (e.g. myocardial infarction with rofecoxib).
  • Effective risk-mitigation strategies can keep drugs with serious adverse effects usefully on the market (e.g. thalidomide for multiple myeloma).
• KDT frames the same observational toolkit (cohort and case-control studies) within clinical pharmacology and drug research, defining them as observational studies "in which no intervention for the sake of the study is done" used "primarily to discover uncommon adverse effects that may be missed during formal therapeutic trials" (KDT 8e Ch.5, pp.86–87).
• Relation to pharmacovigilance: pharmacovigilance is defined by WHO (2002) as "the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems" (KDT 8e Ch.6, p.93). Pharmacoepidemiology supplies the quantitative, population-based methods (cohort/case-control studies, prescription-event monitoring, record-linkage, signal detection) that pharmacovigilance uses to move from anecdotal signal to measured association (KDT 8e Ch.6, p.93; G&G 14e Ch.8, p.149).