title: Liver safety assessment in special populations (hepatitis B, C, and oncology trials).
abstract: The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral therapies with reduced side effects. Without clearer guidelines, questions regarding liver safety may become a major factor in regulatory approval and ultimately physician uptake of the new treatments. The lack of consensus in defining stopping rules based on serum alanine aminotransferase (ALT) levels underscores the need for precompetitive data sharing to improve our understanding of DILI in these populations and to allow evidence-based rather than empirical definition of stopping rules. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland, gerd.kullak@usz.ch.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: Michael
authors.initials: M
authors.lastname: Merz
authors.forename: Louis
authors.initials: L
authors.lastname: Griffel
authors.forename: Neil
authors.initials: N
authors.lastname: Kaplowitz
authors.forename: Paul B
authors.initials: PB
authors.lastname: Watkins
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000209:etiology; D002986:Clinical Trials as Topic / Q000379:methods*; D015195:Drug Design; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D018570:Risk Assessment / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration