Postmarketing Surveillance of Drug-Induced Liver Injury
Background Most clinical trials that support approval are not adequately powered to detect rare adverse reactions (e.g., drug-induced liver injury, Stevens–Johnson syndrome, and others) that may emerge under real-world use of a drug. The US Food and Drug Administration (FDA) and other global drug regulatory bodies conduct postmarketing surveillance for these types of adverse events.
FDA Methods FDA’s Center for Drug Evaluation and Research (CDER)—Division of Pharmacovigilance (DPV) is devoted to postmarketing adverse event surveillance for drug-induced liver injury (DILI) and other adverse events. DPV predominantly relies on clinical assessment of spontaneous reports submitted to the FDA Adverse Event Reporting System (FAERS) and published case reports to assess for DILI in the postmarketing setting. DPV uses criteria established by the Drug-Induced Liver Injury Network (DILIN), and others, to assess cases for causality and severity. In the past, the FDA has collaborated with professional groups with an interest in DILI to improve the quality of case reports. DPV also uses disproportionality and reporting rate analyses to detect and assess potential safety signals. Additionally, DPV collaborates with CDER epidemiologists who conduct analyses to refine DILI signals that emerge from surveillance.
Conclusion DILI continues to be a significant concern for marketed drugs and a leading cause of drug withdrawal from the worldwide market. Because events such as DILI are rare, systems such as those described in this chapter are important components of postmarketing surveillance, which is designed to recognize liver injury that may have gone undetected in a clinical development program for a drug.
Key wordsDrug-induced liver injury Postmarket Surveillance Epidemiology Drug safety Causality assessment Hepatotoxicity Drug toxicity Adverse event
The views expressed are those of the authors and do not necessarily represent the position of, nor imply endorsement from, the US Food and Drug Administration or the US Government.
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