Clinical trials of investigational new drugs for nonalcoholic steatohepatitis:challenges in design and practice

Research and development of investigational new drugs for nonalcoholic fatty liver disease is now a research hotspot in the field of liver disease. However, there are still great challenges in protocol design and implementation in phase II/III clinical trials. Since there are still controversies over the exact histological definition of nonalcoholic steatohepatitis in the academic world and a lack of long-term large-scale studies on the natural history and clinical pathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, we still face a lot of challenges in the selection and definition of study population, selection of study endpoints, and interpretation of true clinical value. In addition, such clinical trials often have various confounding factors, which should be controlled as much as possible in protocol design and implementation, in order to minimize the bias in research conclusions.