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Semin Liver Dis 2021; 41(03): 277-284
DOI: 10.1055/s-0041-1723030
Review Article

Assessing Toxicity in Drug Trials in Liver Disease

Morris Sherman
1   Research Administration, University Health Network, Toronto, Canada
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Abstract

Since the early trials in viral hepatitis, more and more new drugs are being tested for use in various liver diseases. Since drug hepatotoxicity is a major cause of drugs under investigation not making it to market, the assessment of drug-induced liver injury in clinical trials of new drugs is crucial. This review will focus on the systems that are used to assess drug-induced liver injury in clinical trials and will discuss how some of these criteria are inappropriate or inaccurate in this function together with suggestions for improvement.

Keywords

clinical trials - drug-induced liver injury - adverse event


Publication History

Article published online:
08 March 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Regev A. Drug-induced liver injury and drug development: industry perspective. Semin Liver Dis 2014; 34 (02) 227-239
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 McKenzie R, Fried MW, Sallie R. et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995; 333 (17) 1099-1105
    CrossrefPubMedGoogle Scholar
  • 3 Chang CY, Schiano TD. Review article: drug hepatotoxicity. Aliment Pharmacol Ther 2007; 25 (10) 1135-1151
    CrossrefPubMedGoogle Scholar
  • 4 Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity from immune checkpoint inhibitors: a systematic review and management recommendation. Hepatology 2020; 72 (01) 315-329
    CrossrefPubMedGoogle Scholar
  • 5 Rooks JB, Ory HW, Ishak KG. et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. JAMA 1979; 242 (07) 644-648
    CrossrefPubMedGoogle Scholar
  • 6 Hayashi PH. Overview of causality assessment in drug-induced liver injury. Clin Liver Dis (Hoboken) 2017; 9 (02) 29-33
    CrossrefPubMedGoogle Scholar
  • 7 Rockey DC, Seeff LB, Rochon J. et al; US Drug-Induced Liver Injury Network. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel-UCLAF causality assessment method. Hepatology 2010; 51 (06) 2117-2126
    CrossrefPubMedGoogle Scholar
  • 8 United States Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER): Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation, Final, July 2009.
  • 9 National Cancer Institute Division of Cancer Treatment and Diagnosis. Cancer Therapy Evaluation Program. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm . Accessed December 16, 2020
    Google Scholar
  • 10 International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). www.MedDRA.org. Accessed December 16, 2020
    Google Scholar
  • 11 Council for International Organizations of Medical Sciences. https://cioms.ch/wp-content/uploads/2017/01/Mgment_Safety_Info.pdf. Accessed December 16, 2020
  • 12 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (02) 228-247
    CrossrefPubMedGoogle Scholar
  • 13 Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981; 47 (01) 207-214
    CrossrefPubMedGoogle Scholar
  • 14 De Martin E, Michot JM, Papouin B. et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol 2018; 68 (06) 1181-1190
    CrossrefPubMedGoogle Scholar