Wesnes K A
Cognitive Drug Research Ltd, Reading, UK.
Dialogues Clin Neurosci. 2000 Sep;2(3):183-202. doi: 10.31887/DCNS.2000.2.3/kwesnes.
This paper reviews the value and utility of measuring cognitive function in the development of new medicines by reference to the most widely used automated system in clinical research. Evidence is presented from phase 1 to 3 of the nature and quality of the information that can be obtained by applying the Cognitive Drug Research computerized assessment system to ongoing clinical trials. Valuable evidence can be obtained even in the first trial in which a novel compound is administered to man. One application of such testing is to ensure that novel compounds are relatively free from cognition-impairing properties, particularly in relation to competitor products. Another is to ensure that unwanted interactions with alcohol and other medications do not occur, or, if they do, to put them in context. In many patient populations, cognitive dysfunction occurs as a result of the disease process, and newer medicines which can treat the symptoms of the disease without further impairing function can often reveal benefits as the disease-induced cognitive dysfunction is reduced. Another major application is to identify benefits for compounds designed to enhance cognitive function. Such effects can be sought in typical phase 1 trials, or a scopolamine model of the core deficits of Alzheimer's disease can be used to screen potential antidernentia drugs. Ultimately, of course, such effects can be demonstrated using properly validated and highly sensitive automated procedures in the target populations. The data presented demonstrate that the concept of independently assessing a variety of cognitive functions is crucial in helping differentiate drugs, types of dementia, and different illnesses. Such information offers a unique insight into how the alterations to various cognitive functions will manifest themselves in everyday behavior. This reveals a major limitation of scales that yield a single score, because such limited information does not permit anything but a quantitative interpretation; and the concept of "more" cognitive function or "less" is manifestly inappropriate for something as complex and diverse as the interplay between cognitive function and human behavior. Finally, the next generations of cognitive testing are described. Testing via the telephone has just been introduced and will have dramatic effects on the logistics of conducting cognitive testing in large patient trials. Testing via the Internet is not far off either, and will come fully into play as the proportion of homes connected to the Internet increases in Europe and North America. There are no sound reasons for not wishing to include cognitive function testing in the development protocol of any novel medicine.
本文通过参考临床研究中使用最广泛的自动化系统，综述了在新药研发中测量认知功能的价值和效用。文中呈现了将认知药物研究计算机化评估系统应用于正在进行的临床试验所能获得的信息的性质和质量，涵盖了从1期到3期的证据。即使在首次给人体施用新型化合物的试验中，也能获得有价值的证据。这种测试的一个应用是确保新型化合物相对没有损害认知的特性，特别是相对于竞争产品而言。另一个应用是确保不会发生与酒精和其他药物的不良相互作用，或者如果发生了，要将其置于背景中。在许多患者群体中，认知功能障碍是疾病进程的结果，能够治疗疾病症状而不进一步损害功能的新药，往往会随着疾病引起的认知功能障碍的减轻而显现出益处。另一个主要应用是识别旨在增强认知功能的化合物的益处。这种效果可以在典型的1期试验中寻找，或者可以使用东莨菪碱诱导的阿尔茨海默病核心缺陷模型来筛选潜在的抗痴呆药物。当然，最终可以在目标人群中使用经过适当验证且高度敏感的自动化程序来证明这种效果。所呈现的数据表明，独立评估多种认知功能的概念对于区分药物、痴呆类型和不同疾病至关重要。此类信息为各种认知功能的改变将如何在日常行为中表现提供了独特的见解。这揭示了产生单一分数的量表的一个主要局限性，因为如此有限的信息除了进行定量解释外，不允许有其他任何解释；而“更多”或“更少”认知功能的概念对于像认知功能与人类行为之间相互作用这样复杂多样的事物显然是不合适的。最后，描述了下一代认知测试。通过电话进行测试刚刚被引入，并且将对在大型患者试验中进行认知测试的后勤工作产生巨大影响。通过互联网进行测试也不远了，并且随着欧洲和北美的家庭接入互联网的比例增加，它将充分发挥作用。没有充分的理由不希望在任何新药的研发方案中纳入认知功能测试。
