Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons

J Hepatol. 2023 Feb;78(2):442-447. doi: 10.1016/j.jhep.2022.09.021. Epub 2022 Oct 8.

Abstract

Non-alcoholic fatty liver disease is a condition that affects 25% of the population. Non-alcoholic steatohepatitis (NASH) is a progressive form of the disease that can lead to severe complications such as cirrhosis and hepatocellular carcinoma. Despite its high prevalence, no drugs are currently approved for the treatment of NASH. The drug development pipeline in NASH is very active, yet most assets do not progress to phase III trials and those that do reach phase III often fail to achieve the endpoints necessary for approval by regulatory agencies. Amongst other reasons, the methodological and operational features of traditional clinical trials in NASH might impede optimal drug development. In this regard, platform trials might be an attractive complement or alternative to conventional clinical trials. Platform trials use a master protocol which enables evaluation of multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. Through Bayesian interim analyses, these trials allow for early exit of drugs from the trial based on success or futility, while providing participants better chances of receiving active compounds through adaptive randomisation. Overall, platform trials represent an alternative for patients, pharmaceutical companies, and clinicians in the quest to accelerate the approval of pharmacologic treatments for NASH.

Keywords: Non-alcoholic steatohepatitis; drug development; master protocols; non-alcoholic fatty liver disease; non-invasive biomarkers; platform trials.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Fibrosis
  • Humans
  • Liver Cirrhosis / complications
  • Liver Neoplasms* / complications
  • Non-alcoholic Fatty Liver Disease* / complications