Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, 221 85, Lund, Sweden.
Department of Clinical Chemistry and Pharmacology, Skåne University Hospital, Lund, Sweden.
Drug Saf. 2024 Jan;47(1):23-28. doi: 10.1007/s40264-023-01378-1. Epub 2023 Nov 16.
The number of reports on suspected drug-induced memory impairment submitted to the US Food and Drug Administration increased 30-fold from 2000 to 2022. Drugs are the most common cause of reversible dementia. However, there is very little research on drug-induced cognitive impairment. The aim of this study was to investigate if and how an assessment of cognitive safety was included in recent, registered, controlled, clinical drug trials.
The clinical trials registry ( www.
gov ) was searched for randomized controlled clinical trials with available study protocols. After excluding irrelevant trials such as surgical procedures, local or short-term treatment, and dietary supplements, 803 trials were included in this study. The protocols were manually reviewed for information on if, and how, cognitive safety had been assessed. Trial drugs were categorized into those targeting the central nervous system or not, as well as older and newer drugs. Methods used for the assessment of cognitive function were categorized into questionnaires, screening instruments, and neuropsychological tests. If the trial results were published, we examined whether the publication contained any data on cognitive safety that had emerged from the trial.
The start dates of the screened trials ranged from 31 July, 2009, to 4 April, 2021. Out of the 803 trials, 52 (6.5%) actively assessed cognitive safety. The remaining trials relied solely on spontaneous reporting. Of 429 trials studying a new drug, 32 (7.5%) actively assessed cognitive safety. One hundred and fifty-eight trials examined drugs intended to, or known to have, pharmacological effects on the central nervous system. Of these, 21 (13.5%) assessed cognitive safety. Most of the trials that assessed cognitive safety used either crude screening tools or questionnaires.
Cognitive safety is largely ignored by recent controlled clinical trials. This applies even to trials assessing new drugs and trials assessing central nervous system drugs. There is an urgent need for drug manufacturers, regulatory authorities, and the medical profession to address the cognitive safety of drugs.
从 2000 年到 2022 年，向美国食品和药物管理局（FDA）报告的疑似药物引起的记忆损伤的报告数量增加了 30 倍。药物是导致可逆性痴呆最常见的原因。然而，关于药物引起的认知障碍的研究很少。本研究旨在调查最近注册的对照临床试验中是否以及如何评估认知安全性。
在临床试验注册处（www.clinicaltrials.gov）中搜索了可获得研究方案的随机对照临床试验。排除了不相关的试验，如手术程序、局部或短期治疗和膳食补充剂后，本研究共纳入了 803 项试验。手动审查了方案，以获取有关认知安全性评估的信息。根据是否针对中枢神经系统以及药物的新旧，将试验药物分为两类。将用于评估认知功能的方法分为问卷、筛查工具和神经心理学测试。如果试验结果已发表，我们检查了出版物中是否包含了试验中出现的认知安全性数据。
筛选试验的开始日期为 2009 年 7 月 31 日至 2021 年 4 月 4 日。在 803 项试验中，有 52 项（6.5%）主动评估了认知安全性。其余试验仅依靠自发报告。在 429 项研究新药的试验中，有 32 项（7.5%）主动评估了认知安全性。有 158 项试验研究了旨在或已知对中枢神经系统有药理学作用的药物。在这些试验中，有 21 项（13.5%）评估了认知安全性。评估认知安全性的大多数试验使用了粗略的筛查工具或问卷。
最近的对照临床试验在很大程度上忽略了认知安全性。这甚至适用于评估新药和评估中枢神经系统药物的试验。制药商、监管机构和医学界迫切需要解决药物的认知安全性问题。
