Most Clinical Studies Do Not Report FDA Recommendations For Endpoints In NAFLD/NASH

Abstract

PURPOSE: The aim of this study was to analyze whether clinical studies using exercise as an intervention strategy for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) report Food and Drug Administration (FDA) recommendations for endpoints. METHODS: All studies targeting NAFLD/NASH available on the clinical trials platform (CTP) from the National Library of Medicine (NLM) were analyzed. However, only relevant clinical studies using exercise as an intervention strategy were included. FDA recommends the following endpoints for interventions targeting NAFLD/NASH: (i) resolution of steatohepatitis and no worsening of liver fibrosis; or (ii) improvement in liver fibrosis and no worsening of steatohepatitis; or (iii) resolution of steatohepatitis and improvement in liver fibrosis greater than or equal to one stage. RESULTS: We identified 49 of 916 studies, but removed one that was duplicated, four that conducted a diet intervention, and two others involving either lifestyle modification or exercise training with liraglutide or pioglitazone and berberine. Further selection yielded 42 studies in which researchers enrolled 1886 (or planned to enroll 6365) adults and older adults (N: 23, 56%) from both sexes (N: 36, 89%). Interventions were predominantly characterized by aerobic exercise (N: 25, 61%) performed for 45.8 ± 23.0 minutes per day and 4.1 ± 2.5 days per week for 17.7 ± 28.9 weeks. Participants were randomly assigned (N: 28, 68%) in parallel designs (N: 32, 78%) with open label (N: 34, 83%) or double masking methods (N: 4, 10%). FDA recommends double-blind, placebo-controlled clinical trials for at least 48 to 72 weeks. Most studies (N: 26, 63%) described techniques to analyze steatosis and fibrosis recommended by FDA, but did not explore their criteria, while others (N: 14, 34%) did not follow recommendations; only one study (2%) fulfilled FDA criteria. Studies also satisfied only half of the items regarding objectives and methods proposed by the CONSORT checklist. For example, they neither described methods used to generate random assignments nor described how sample size was calculated. CONCLUSIONS: Most clinical studies do not report FDA recommendations for endpoints in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.