Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials
Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials
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DOI：
10.1136/jnnp-2013-306865
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发表时间：
2015-01-01
影响因子：
11
通讯作者：
Al-Chalabi, Ammar
中科院分区：
文献类型：
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作者：
Balendra, Rubika;Jones, Ashley;Al-Chalabi, Ammar
目的：临床分期在致命性神经退行性疾病肌萎缩侧索硬化症中的应用将对优化未来的治疗试验具有价值。我们的目的是使用以前的临床试验数据，以确定患者花费在每个四个阶段的时间长度，其范围和过渡模式到后续stages.Methods使用数据库从两个多中心的临床试验，患者回顾性分期通过试验过程。在每个阶段，我们评估患者是否进展到早期，连续或晚期或死亡。在每个阶段的持续时间前进展到后期stage.Results有725例患者进行了计算。没有患者进入早期阶段。更多的1、2和3期患者进展到连续期，而不是跳过一个阶段。59.3%的1期患者进展至2期，54.0%的2期患者进展至3期，42.3%的3期患者进展至4期，47.0%的4期患者进展至死亡。阶段2至4之间的过渡时间的中位数为3至7个月。讨论我们使用试验数据表明，阶段之间的过渡时间很短。使用阶段持续时间作为终点可能会缩短试验持续时间。我们已经在这个系统中显示了表面有效性，因为大多数患者通过连续的阶段进展，并且没有恢复到早期阶段。此外，我们已经证明该系统在人群中是可靠的，因此具有内容效度。
Objectives The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages.Methods Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated.Results There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4.Discussion We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.