针对非酒精性脂肪性肝病的新药研发目前是肝病领域的研究热点之一.然而,在开展Ⅱ/Ⅲ期临床试验时,无论是方案设计层面还是实施层面,都面临很大的挑战.由于学术界对非酒精性脂肪性肝炎组织学的确切定义尚存有争议,而且目前尚缺乏大规模长期基于非酒精性脂肪性肝病/非酒精性脂肪性肝炎临床病理学的自然史研究,因此,临床试验中研究人群的选择和界定、研究终点的选择及其真正临床价值的解释等都面临很大的挑战.而且这类临床试验中的混杂因素复杂,需在方案设计和实施层面尽可能控制,以最大程度降低对研究结论可能带来的偏倚.“,”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 addi-tion,such clinical trials often have various confounding factors,which should be controlled as much as possible in protocol design and imple-mentation,in order to minimize the bias in research conclusions.