Liyanage S Imindu, Santos Clarissa, Weaver Donald F
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Alzheimers Dement (N Y). 2018 Nov 13;4:628-635. doi: 10.1016/j.trci.2018.09.003. eCollection 2018.
As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial. Specifically, we observe that everyday factors such as diet, education, mental exertion, leisure participation, multilingualism, sleep, trauma, and physical activity, as well as clinical/study parameters including environment, family coaching, concurrent medications, and illnesses may serve as potent confounders, disruptors, or sources of bias to an otherwise significant drug-disease interaction. This perspective briefly summarizes the potential influence of these hidden variables on the outcomes of clinical trials and suggests strategies to abate their impact.
作为全球痴呆症的主要病因，阿尔茨海默病引发了学术界和临床界的浓厚兴趣。然而，寻找疾病修正疗法的试验绝大多数都失败了。我们认为，部分原因可能在于临床试验框架中固有干扰变量的影响。具体而言，我们观察到，饮食、教育、脑力活动、休闲参与、多语言能力、睡眠、创伤和体育活动等日常因素，以及环境、家庭指导、同时服用的药物和疾病等临床/研究参数，可能成为强大的混杂因素、干扰因素或偏差来源，影响原本显著的药物与疾病的相互作用。本文简要总结了这些隐藏变量对临床试验结果的潜在影响，并提出了减轻其影响的策略。
