Hepatotoxicity in the Review of Clinical Safety Data

Abstract

In recent years, several postauthorization drugs were withdrawn or forced to issue major labeling warnings after major adverse events were reported to be associated with their use. As a result, considerable efforts have been made to improve the assessment of safety data generated from clinical trials to reduce these remedial events. Concerns about the drugs' hepatotoxicity are a major reason leading to these types of postauthorization actions. Measures to effectively predict warning signs of drugs that are hepatotoxic before they are authorized are being diligently pursued. The authors present their thoughts regarding the issues frequently encountered in the safety review of clinical hepatic data. Although these comments may not hold true for all types of data collected, and are not made on behalf of all regulatory agencies, it is hoped that these scientific discussions can help improve the safety review and, therefore, reduce postauthorization events that lead to irreversible liver damage.