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Accounting for the Placebo Effect and Optimizing Outcomes in Clinical Trials of Nonalcoholic Steatohepatitis (NASH)

  • Fatty Liver Disease (V Ajmera, Section Editor)
  • Published:
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Abstract

Purpose of Review

Understand the placebo effect and optimize the design of nonalcoholic fatty liver disease (NAFLD) clinical trials.

Recent Findings

The placebo effect on histologic outcomes and liver fat on MRI-based imaging has been assessed in a systematic review and meta-analysis, and three phase 3 studies have been reported. The placebo effect on improvement in the main histologic outcome was present in ~ 25% of the patients. The placebo effect on components of the NAFLD activity index in trials using the magnetic resonance imaging proton density fat fraction and magnetic resonance spectroscopy as outcomes also was reported. In this review, we discuss factors that led to placebo effects in the reported studies and suggest measures to ameliorate the effects in future NASH trials.

Summary

The significant placebo response in NASH clinical trials is evidence that investigators should consider this effect in estimating sample size and designing future clinical trials.

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Author information

Author notes

  1. Nabil Noureddin and Ma Ai Thanda Han contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, University of Nevada, Las Vegas, NV, USA

    Nabil Noureddin

  2. Division of Gastroenterology, Mayo Clinic, Rochester, MN, USA

    Ma Ai Thanda Han

  3. Texas Liver Institute, University of Texas Health San Antonio (UTHSA), San Antonio, USA

    Naim Alkhouri

  4. Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, 8900 Beverly Blvd, Suite 250, Los Angeles, CA, 90048, USA

    Mazen Noureddin

Authors
  1. Nabil Noureddin
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  4. Mazen Noureddin
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Corresponding author

Correspondence to Mazen Noureddin.

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Conflict of Interest

MN has been on the advisory board for Gilead, Intercept, Pfizer, Novartis, Blade, EchoSens North America, OWL, and Abbott; MN has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire and Zydus; MN is a minor shareholder or has stocks in Anaetos and Viking.

NA reports grants and other from Intercept, grants from Genfit, grants from Galmed, grants from Madrigal, grants and other from Allergen, grants and other from Gilead, during the conduct of the study.

All other authors declare no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Noureddin, N., Han, M.A.T., Alkhouri, N. et al. Accounting for the Placebo Effect and Optimizing Outcomes in Clinical Trials of Nonalcoholic Steatohepatitis (NASH). Curr Hepatology Rep 19, 63–69 (2020). https://doi.org/10.1007/s11901-020-00505-1

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  • DOI: https://doi.org/10.1007/s11901-020-00505-1

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