Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science
Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science
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DOI：
10.1002/hep.29607
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发表时间：
2018-05-01
期刊：
影响因子：
13.5
通讯作者：
Sanyal, Arun J.
中科院分区：
文献类型：
--
作者：
Siddiqui, Mohammad Shadab;Harrison, Stephen A.;Sanyal, Arun J.
非酒精性脂肪性肝炎（NASH）是肝脏相关发病率和死亡率的重要原因。目前还没有批准的治疗方法，由于NASH患者相关疾病参数的定义不一致，临床试验的结果难以比较。该疾病的自然病程尚未得到严格表征，特别是关于基础肥胖、2型糖尿病和其他合并症的贡献以及为这些合并症提供的治疗。对汇总数据进行分析的努力受到不同研究中用于定义疾病状态的异质性病例定义的限制。该领域仍然存在一个未满足的主要需求，即为干预性试验的人群制定标准化定义。这些定义预计将影响临床试验终点的构建方式。肝脏论坛是一个多方利益相关者的努力，包括美国和欧洲的监管机构，学术研究人员，专业和患者代表组织以及行业，通过开发潜在的解决方案来促进NASH的治疗开发。肝脏论坛成立了病例定义工作组，以从监管科学的角度评估NASH临床试验中纳入人群的病例定义的有效性。在这些分析的基础上，提出了具体建议，指出了案例定义的长处和短处，沿着指出了需要进一步研究的知识差距。（肝病学2018;67：2001-2012）
Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001-2012)