Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum.

Lifestyle modification is the foundation of treatment recommendations for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The design of clinical trials in NASH may be impeded by the lack of a systematic approach to identify and evaluate how lifestyle changes and/or modifications influence clinical trial outcomes and associated endpoints. Furthermore, there are additional uncertainties regarding the methods that can be utilised to better characterise and quantify lifestyle variables - which can influence disease activity and alter trial endpoints - to allow for comparisons of trial outcomes across different phases of research and/or within drug-classes. This summary by the Liver Forum's Standard of Care Working Group reviews currently available clinical data, identifies the barriers and challenges associated with the standard of care in NAFLD/NASH clinical trials, defines available assessments of lifestyle changes, and proposes approaches to better understand and define the influence of diet and exercise on NASH treatment in the context of different pharmacologic interventions. The ultimate objective is to propose tangible solutions which enable investigators, sponsors, and regulatory authorities to meaningfully interpret clinical trial outcomes and the impact of lifestyle modification on such outcomes as they pertain to phase I-IV clinical trials.

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Copyright © 2020. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Conflict of interest SF: Consultancy and/or speaker for Gilead, MSD, BMS, Roche, Bayer, Aktelion, Janssen, Intercept, Genfit, Inventiva, GSK, Boehringer Ingelheim, Galmed, Genentech, Galapagos, Aligos, MedImmune, Novartis, Novo Nordisk. CF: Employee of Covance. MN: Advisory board or a speaker for Allergan, Gilead, Intercept, Pfizer, Novartis, Blade, EchoSens North America, OWL, Simply Speaking, and Abbott; Research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire and Zydus; Minor shareholder or has stocks in Anaetos and Viking. MBH: Employee of Zealand Pharma, former employee of Novo-Nordisk. JS. Consultancy AbbVie, Boehringer Ingelheim, BBN Cardio, BMS, Echosens Galamed, Genfit, Gilead Sciences, Intercept Pharmaceuticals, IQVIA, MedImmune, Novartis, Novo Nordisk, Pfizer; Research Funding: Gilead Sciences, Yakult Europe B.V.; Travel Support: Janssen; Lecture: Falk Foundation, Takeda, Merck, Norgine. MFA: Consultancy and/or speaker for BMS, Intercept, Inventiva, Novo Nordisk, Allergan, TaiwanJ, NGM Bio, Pfizer Research, Prometic. Research support from Conatus, Intercept, Allergan, Novartis, Genfit, Galmed, Galactin, Madrigal, BMS, NGM Bio, Novo Nordisk, Poxel, Durect, Inventiva, Enyo, and Enanta. All other authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details.