1. Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials
- Author
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Avigan, Mark I, Bjornsson, Einar S, Pasanen, Markku, Cooper, Charles, Andrade, Raul J, Watkins, Paul B, Lewis, James H, Merz, Michael, and [Avigan, MI] Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, United States. [Bjornsson, ES] The National University Hospital of Iceland, Reykjavík, Iceland. [Pasanen, M] School of Pharmacy Kuopio, University of Eastern Finland, Kuopio, Finland. [Cooper, C] Becton Dickenson, Franklin Lakes, NJ, United States. [Andrade, RJ] Gastroenterology Service and Liver Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Investigación Biomédica de Málaga (IBIMA), University Hospital Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. [Watkins, PB] The Hamner-University of North Carolina Institute for Drug Safety Sciences, Research Triangle Park, NC, United States. [Watkins, PB] Schools of Medicine, Pharmacy and Public Health, University of North Carolina, Chapel Hill, NC, United States. [Lewis, JH] Georgetown University, Washington, DC, United States. [Merz, M] Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland.
- Subjects
Diseases::Digestive System Diseases::Liver Diseases::Drug-Induced Liver Injury [Medical Subject Headings] ,Enfermedad hepática Inducida por Drogas ,Health Care::Health Care Economics and Organizations::Organizations::Government::Federal Government::United States Government Agencies::United States Dept. of Health and Human Services::United States Public Health Service::United States Food and Drug Administration [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Tests, Routine [Medical Subject Headings] ,Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics [Medical Subject Headings] ,Farmacogenética ,Ensayos clínicos como asunto ,Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic [Medical Subject Headings] ,Estándares de referencia ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Weights and Measures::Reference Standards [Medical Subject Headings] ,Proteómica ,Health Care::Health Services Administration::Organization and Administration::Risk Management::Risk Assessment [Medical Subject Headings] ,Pruebas diagnósticas de rutina ,Medición de riesgo ,Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacogenetics [Medical Subject Headings] - Abstract
Journal Article; A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration. Yes
- Published
- 2014