Background

Up to 50% of people with amyotrophic lateral sclerosis (ALS) experience cognitive dysfunction, whilst depression and anxiety are reported in up to 44% and 33%, respectively. These symptoms impact on quality of life, and are associated with a poorer prognosis. Historically, outcomes in clinical trials have focused on the effect of candidate drugs on physical functioning.

Methods

We reviewed the past 25 years of clinical trials of investigative medicinal products in people with ALS, since the licensing of riluzole, and extracted data on frequency and type of assessment for neuropsychiatric symptoms and cognitive impairment. Trial registry databases, including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed, were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 31/10/2019. No language restrictions were applied. Outcome measures, exclusion criteria and assessment tool used were extracted.

Results

216 trials, investigating 26,326 people with ALS, were reviewed. 35% assessed neuropsychiatric symptoms, and 22% assessed cognition, as Exclusion Criteria or Outcome Measures. 3% (n = 6) of trials assessed neuropsychiatric symptoms as a Secondary Outcome Measure, and 4% (n = 8) assessed cognition as Outcome Measures; only one trial included assessments for both cognition and neuropsychiatric symptoms as Outcome Measures. Three ALS-specific assessments were used in six trials.

Conclusions

Trials for people with ALS have neglected the importance of neuropsychiatric symptoms and cognitive impairment. Evaluation of these extra-motor features is essential to understanding the impact of candidate drugs on all symptoms of ALS.

PROPSERO registration

CRD42020175612.

中文翻译：

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对肌萎缩侧索硬化症临床试验中使用的神经精神和认知评估的系统评价。

背景

多达 50% 的肌萎缩侧索硬化症 (ALS) 患者出现认知功能障碍，而据报道，抑郁和焦虑分别高达 44% 和 33%。这些症状会影响生活质量，并与较差的预后相关。从历史上看，临床试验的结果集中在候选药物对身体机能的影响上。

方法

我们回顾了自利鲁唑获得许可以来过去 25 年对 ALS 患者进行研究性药物产品的临床试验，并提取了有关神经精神症状和认知障碍评估频率和类型的数据。试验注册数据库，包括 WHO International Trials Registry、European Clinical Trials Register、clinicaltrials.gov 和 PubMed，系统检索了在 1994 年 1 月 1 日至 2019 年 10 月 31 日期间注册、完成或发表的 II、III 或 IV 期试验. 没有语言限制。提取了使用的结果测量、排除标准和评估工具。

结果

审查了 216 项试验，调查了 26,326 名 ALS 患者。35% 评估神经精神症状，22% 评估认知，作为排除标准或结果测量。3% ( n  = 6) 的试验将神经精神症状评估为次要结果指标，4% ( n  = 8) 将认知评估为结果指标；只有一项试验包括对认知和神经精神症状的评估作为结果测量。在六项试验中使用了三项针对 ALS 的评估。

结论

针对 ALS 患者的试验忽略了神经精神症状和认知障碍的重要性。评估这些运动外特征对于了解候选药物对 ALS 的所有症状的影响至关重要。

PROPSERO 注册

CRD42020175612。