Clinical endpoints and adaptive clinical trials in precirrhotic nonalcoholic steatohepatitis: Facilitating development approaches for an emerging epidemic.
Clinical endpoints and adaptive clinical trials in precirrhotic nonalcoholic steatohepatitis: Facilitating development approaches for an emerging epidemic.
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DOI：
10.1002/hep4.1079
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发表时间：
2017-09
影响因子：
5.1
通讯作者：
Sanyal A
中科院分区：
文献类型：
--
作者：
Filozof C;Chow SC;Dimick-Santos L;Chen YF;Williams RN;Goldstein BJ;Sanyal A
由于非酒精性脂肪性肝炎（NASH）及其相关健康负担的患病率不断增加，因此非常需要为患有这种疾病的患者制定治疗策略。不幸的是，其漫长而无症状的自然史，疾病进展的不确定性，大多数患者未被诊断的事实，以及对连续肝活检的要求，为临床开发带来了巨大的挑战。适应性设计方法越来越多地用于临床研究，因为它们提供了识别研究中试验治疗临床获益的潜在信号的灵活性和效率，并在不破坏试验有效性或完整性的情况下进行及时的预先计划的调整。鉴于NASH中未满足的医疗需求较高且缺乏经验证的替代终点，使用适应性设计方法似乎是合理的。此外，由于愿意进行多次肝活检的患者数量有限，并且需要长期暴露以评估对结局的影响，连续无缝自适应设计可能会减少总体样本量，同时允许患者在每个阶段后继续。在这里，我们回顾了战略框架，包括潜在的替代终点以及统计和后勤方法，可以考虑将适应性设计应用于NASH临床试验，以促进药物开发，满足日益增长的医疗需求。（Hepatology Communications 2017;1：577-585）
Due to the increasing prevalence of nonalcoholic steatohepatitis (NASH) and its associated health burden, there is a high need to develop therapeutic strategies for patients with this disease. Unfortunately, its long and asymptomatic natural history, the uncertainties about disease progression, the fact that most patients are undiagnosed, and the requirement for sequential liver biopsies create substantial challenges for clinical development. Adaptive design methods are increasingly used in clinical research as they provide the flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation and make prompt preplanned adaptations without undermining the validity or integrity of the trial. Given the high unmet medical need and the lack of validated surrogate endpoints in NASH, the use of adaptive design methods appears reasonable. Furthermore, due to the limited number of patients willing to have multiple liver biopsies and the need for long‐term exposure to assess an impact in outcomes, a continuous seamless adaptive design may reduce the overall sample size while allowing patients to continue after each one of the phases. Here, we review strategic frameworks that include potential surrogate endpoints as well as statistical and logistical approaches that could be considered for applying adaptive designs to clinical trials in NASH with the goal of facilitating drug development for this growing medical need. (Hepatology Communications 2017;1:577–585)
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影响因子：
5.1
作者：
Pagadala MR;McCullough AJ
通讯作者：
McCullough AJ
非酒精性脂肪肝病患者的纤维化无创评估。
影响因子：
2.8
作者：
Buzzetti E;Lombardi R;De Luca L;Tsochatzis EA
通讯作者：
Tsochatzis EA
DOI：
10.1002/hep.28677
发表时间：
2016-12
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Setiawan VW;Stram DO;Porcel J;Lu SC;Le Marchand L;Noureddin M
通讯作者：
Noureddin M
影响因子：
3.2
作者：
Chow, Shein-Chung;Tu, Yi-Hsuan
通讯作者：
Tu, Yi-Hsuan
DOI：
10.1002/hep.27678
发表时间：
2015-04
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sanyal AJ;Friedman SL;McCullough AJ;Dimick-Santos L;American Association for the Study of Liver Diseases;United States Food and Drug Administration
通讯作者：
United States Food and Drug Administration