概化理论
临床试验
肌萎缩侧索硬化
医学
人口
临床研究设计
重症监护医学
心理学
物理医学与康复
疾病
病理
发展心理学
环境卫生
作者
Jeremy M. Shefner,Richard Bedlack,Jinsy Andrews,James Berry,Robert Bowser,Robert H. Brown,Jonathan D. Glass,Nicholas J. Maragakis,Timothy M. Miller,Jeffrey D. Rothstein,Merit Cudkowicz
出处
期刊:JAMA Neurology
[American Medical Association]
日期:2022-12-01
卷期号:79 (12): 1312-1312
被引量:13
标识
DOI:10.1001/jamaneurol.2022.3282
摘要
Clinical trial activity in amyotrophic lateral sclerosis (ALS) is dramatically increasing; as a result, trial modifications have been introduced to improve efficiency, outcome measures have been reassessed, and considerable discussion about the level of data necessary to advance a drug to approval has occurred. This review discusses what recent pivotal studies can teach the community about these topics.By restricting inclusion and exclusion criteria, recent trials have enrolled populations distinct from previous studies. This has led to efficacy signals being observed in studies that are smaller and shorter than was thought feasible previously. However, such trials raise questions about generalizability of results. Small trials with equivocal clinical results also raise questions about the data necessary to lead to regulatory approval. The ALS Functional Rating Scale-Revised remains the most commonly used primary outcome measure; this review discusses innovations in its use. Blood neurofilament levels can predict prognosis in ALS and may be a sensitive indicator of biologic effect; current knowledge does not yet support its use as a primary outcome.It is now possible to use specific inclusion criteria to recruit a homogeneous patient population progressing at a specific rate; this will likely impact trials in the future. Generalizability of results on limited populations remains a concern. Although clinical outcomes remain the most appropriate primary outcome measures, fluid markers reflecting biologically important processes will assume more importance as more is learned about the association between such markers and clinical end points. The benefit of use of analytic strategies, such as responder analyses, is still uncertain.
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