Search

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. (C) 2020 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

BACKGROUND: Improving diversity in clinical trials is essential in order to produce generalizable results. Although the importance of representation has become increasingly recognized, identifying strategies to approach this work remains elusive. This article reviews the proceedings of a multi-stakeholder conference about the current state of diversity in clinical trials and outlines actionable steps for improvement. METHODS: Conference attendees included representatives from the United States Food and Drug Administration (FDA), National Institutes of Health (NIH), practicing clinical investigators, pharmaceutical and device companies, community-based organizations, data analytics companies, and patient advocacy groups. At this virtual event, attendees were asked to consider key questions around best practices for engagement of underrepresented populations. RESULTS: Community engagement is an integral part of recruitment and retention of underrepresented groups. Decentralization of sites and use of digital tools can enhance the accessibility of clinical research. Finally, improving representation among investigators and clinical research staff may translate to diverse clinical trial participants. CONCLUSION: Improving diversity in clinical trials is an ethical and scientific imperative, which requires a multifaceted approach.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.