Beers Erna, Moerkerken Dineke C, Leufkens Hubert G M, Egberts Toine C G, Jansen Paul A F
Department of Geriatric Medicine, University Medical Center, Utrecht, The Netherlands; Expertise Centre Pharmacotherapy in Old Persons, University Medical Center, Utrecht, The Netherlands.
J Am Geriatr Soc. 2014 Oct;62(10):1883-90. doi: 10.1111/jgs.13067. Epub 2014 Oct 3.
To investigate the inclusion of older people in clinical trials of recently authorized medicines, evaluating adherence to the 20-year-old International Conference of Harmonisation (ICH) guideline on geriatrics (E7).
Observational.
European public assessment reports, published clinical trials, World Health Organization International Clinical Trials Registry Platform.
Individuals aged 65 and older and 75 and older.
Number and proportion of randomized participants and all exclusion criteria of studies involving diseases characteristically associated with aging (venous thromboembolism, osteoporosis, atrial fibrillation) and diseases not unique to older adults (type 2 diabetes mellitus, depression, bipolar disorder, epilepsy).
In 114 Phase II and III trials of 12 medicines, 43.1% of participants were aged 65 and older, and 16.1% were aged 75 and older. In trials involving diseases characteristically associated with ageing, 57% were aged 65 and older; 22% were aged 75 and older. In trials involving diseases not unique to old age, 9% were aged 65 and older, and 1% were aged 75 and older. Upper age limits were applied in 30.7% of the trials; the frequency did not differ between larger (sample size ≥ 500) and smaller trials (P = .36), although it was significantly lower in trials involving diseases characteristically associated with aging (18.0%) than in trials of diseases not unique to old age (45.3%; P = .002). Age-sensitive exclusion criteria, based on comorbidity (75.4%), concomitant medication (71.9%), and other criteria correlated with age (60.5%) were applied more frequently in larger trials (P < .02).
Studies of diseases not uniquely associated with old age included an unacceptably low proportion of older people, contrary to the recommendations of the ICH E7 guideline. Although the proportion of older participants in trials of diseases characteristically associated with aging was appropriate for certain medicines, the use of age-sensitive exclusion criteria limits the representativeness of the trial population for daily practice.
调查近期获批药物临床试验中老年人的纳入情况，评估对已有20年历史的国际协调会议（ICH）老年医学指南（E7）的遵循情况。
观察性研究。
欧洲公共评估报告、已发表的临床试验、世界卫生组织国际临床试验注册平台。
65岁及以上和75岁及以上的个体。
随机参与者的数量和比例，以及涉及与衰老典型相关疾病（静脉血栓栓塞、骨质疏松症、心房颤动）和非老年人特有的疾病（2型糖尿病、抑郁症、双相情感障碍、癫痫）的研究的所有排除标准。
在12种药物的114项II期和III期试验中，43.1%的参与者年龄在65岁及以上，16.1%的参与者年龄在75岁及以上。在涉及与衰老典型相关疾病的试验中，57%的参与者年龄在65岁及以上；22%的参与者年龄在75岁及以上。在涉及非老年人特有的疾病的试验中，9%的参与者年龄在65岁及以上，1%的参与者年龄在75岁及以上。30.7%的试验设置了年龄上限；大型试验（样本量≥500）和小型试验之间的频率没有差异（P = 0.36），尽管在涉及与衰老典型相关疾病的试验中（18.0%）该频率显著低于非老年人特有的疾病的试验（45.3%；P = 0.002）。基于合并症（75.4%）、合并用药（71.9%）和其他与年龄相关标准（60.5%）的年龄敏感性排除标准在大型试验中应用更为频繁（P < 0.02）。
与非老年人特有的疾病相关的研究纳入的老年人比例低到不可接受，这与ICH E7指南的建议相悖。虽然在涉及与衰老典型相关疾病的试验中，老年参与者的比例对于某些药物来说是合适的，但使用年龄敏感性排除标准限制了试验人群在日常实践中的代表性。
