Recommendations for standardized nomenclature and definitions of viral response in trials of hepatitis C virus investigational agents

Authors

  • Heiner Wedemeyer,

    1. Hannover Medical School, Hannover, Germany
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  • Donald M. Jensen,

    1. University of Chicago Medical Center, Chicago, IL
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  • Eliot Godofsky,

    1. Bach and Godofsky, Bradenton, FL
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  • Nina Mani,

    1. Forum for Collaborative HIV Research, University of California, Berkeley, School of Public Health, Washington, DC
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  • Jean-Michel Pawlotsky,

    1. National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor, University of Paris-Est, Créteil, France
    2. INSERM U955, Créteil, France
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  • Veronica Miller,

    Corresponding author
    1. Forum for Collaborative HIV Research, University of California, Berkeley, School of Public Health, Washington, DC
    • Forum for Collaborative HIV Research, University of California, Berkeley, 1608 Rhode Island Avenue NW, Suite 212; Washington DC 20036

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    • Fax: 202-872-4316

  • on behalf of the Definitions/Nomenclature Working Group* of the HCV DrAG (HCV Drug Development Advisory Group), under the auspices of the Forum for Collaborative HIV Research


  • Potential conflicts of interest: Dr. Miller is the director, and Dr. Mani a project manager of the Forum for Collaborative HIV Research which receives unrestricted funds from pharmaceutical and diagnostic industries. Prof. Pawlotsky has received research grants from Roche and Gilead, and has served as an advisor for Abbott, Achillion, Anadys, Biotica, Boehringer-Ingelheim, Bristol-Myers Squibb, DebioPharm, Gen-Probe, Gilead, Glaxo-SmithKline, Idenix, Inhibitex, Janssen, Madaus-Rottapharm, Sanofi-Aventis, Schering-Plough/Merck, Novartis, Pfizer, Roche, Vertex and Virco. Dr. Jensen has received research grants from Abbott, Boehringer-Ingelheim, Genentech/Roche, Pharmasett and Tibotec, and served as an advisor to Abbott, Boehringer-Ingelheim, Genentech, Globeimmune, Merck, Pharmasett, Roche, and Vertex. Dr. Wedemeyer has received grants and honoraria for speaking and consulting for Roche, Abbott, Merck, Novartis, Gilead, BMS, and Transgene. Dr. Godofsky has served as consultant/advisory board member for Merck, lectures for Vertex, and receives research funding from Vertex, Merck, Novartis, Roche, Abbott, Gilead, Glaxo SmithKline, Idenix, and Human Genome Sciences.

  • Funding for the HCV DrAG from the following companies is gratefully acknowledged: Abbott Laboratories, Abbott Molecular, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biocartis, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, DDL Diagnostic Laboratory, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intermune, Merck & Co., Monogram Biosciences, Novartis, Pharmasset, Inc., Pfizer, Inc., Roche, Roche Molecular Systems, Tibotec Therapeutics, Vertex Pharmaceuticals and Virco.

Abstract

Outdated virological response terms used at key trial timepoints in clinical trials with first-generation direct-acting antivirals plus pegylated interferon and ribavirin have failed to keep pace with hepatitis C virus (HCV) drug development. A more intuitive and flexible nomenclature capable of adapting to continuing advances in HCV drug development is needed. Assistance in standardization of the field was provided by members of the Hepatitis C Virus Drug Development Advisory Group, a project of the Forum for Collaborative HIV Research with participation from the American Association for the Study of Liver Diseases, European Association for the of the liver, and the Infectious Diseases Society of America. Our proposed descriptive, virological response nomenclature for key decision points in trials (with and without lead-in treatment) is based on an assay-specified lower limit of quantitation cutoff. This allows responses to be categorized as either quantifiable or unquantifiable HCV RNA, with unquantifiable responses further divided based on whether target HCV RNA was detected or not detected. The unified reporting recommendations will facilitate interpretation of results across clinical trials and validation of new response-guided timepoints. As time-critical treatment parameters are shortened in HCV trials, the proposed nomenclature will greatly simplify and facilitate future adaptations of virological response terms. Our proposed nomenclature will also be helpful in developing treatment guidelines for use in clinical practice. (HEPATOLOGY 2012;56:2398–2403)

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