Pericàs Juan M, Tacke Frank, Anstee Quentin M, Di Prospero Nicholas A, Kjær Mette Skalshøj, Mesenbrink Peter, Koenig Franz, Genescà Joan, Ratziu Vlad
Liver Unit, Internal Medicine Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute for Research (VHIR), Universitat Autònoma de Barcelona, Centros de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
J Hepatol. 2023 Feb;78(2):442-447. doi: 10.1016/j.jhep.2022.09.021. Epub 2022 Oct 8.
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.
非酒精性脂肪性肝病是一种影响25%人口的疾病。非酒精性脂肪性肝炎（NASH）是该疾病的一种进行性形式，可导致诸如肝硬化和肝细胞癌等严重并发症。尽管其患病率很高，但目前尚无药物被批准用于治疗NASH。NASH的药物研发进程非常活跃，但大多数项目未能进入III期试验，而那些进入III期的项目往往也未能达到监管机构批准所需的终点。除其他原因外，NASH传统临床试验的方法学和操作特点可能会阻碍最佳药物研发。在这方面，平台试验可能是传统临床试验的一个有吸引力的补充或替代方案。平台试验使用一个主方案，该方案能够通过一个单一的、共享的对照臂同时或相继评估多种研究用药品。通过贝叶斯中期分析，这些试验允许根据药物的成功或无效情况提前将其从试验中撤出，同时通过适应性随机化使参与者有更好的机会接受活性化合物。总体而言，平台试验为患者、制药公司和临床医生在寻求加速NASH药物治疗的批准方面提供了一种替代方案。
