Industry Review of Best Practices for Risk Management of Drug-Induced Liver Injury from Development to Real-World Use.

The relative treatment benefit of a drug for patients during development, marketing authorization review or after approval includes an assessment of the risk of drug-induced liver injury (DILI). Reported incidences of DILI range from 0.74 to 19 per 100,000, and laboratory criteria and/or clinical outcome determine the severity of DILI. At least 10% of patients who develop jaundice caused by DILI (Hy's Law cases) develop liver failure (i.e., severe DILI). A drug's liver safety profile can be assessed using Evaluation of Drug-Induced Serious Hepatotoxicity Plots. Specific recommendations for monitoring DILI in the post-marketing setting depend on characterization of the phenotype during drug development. Risk mitigation tools include additional educational mechanisms, and risk minimization measures include Elements To Assure Safe Use (ETASU) for healthcare professionals, administration sites, and patients. The overall aim of risk management is to ensure that the benefit of a particular product exceeds the risks as far as possible for the individual patient and for the target population.