Canevelli Marco, Trebbastoni Alessandro, Quarata Federica, D'Antonio Fabrizia, Cesari Matteo, de Lena Carlo, Bruno Giuseppe
Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Front Neurol. 2017 Nov 27;8:628. doi: 10.3389/fneur.2017.00628. eCollection 2017.
To date, the external validity of randomized controlled trials (RCTs) on Alzheimer's disease (AD) has been assessed only considering monodimensional variables. Nevertheless, looking at isolated and single characteristics cannot guarantee a sufficient level of appreciation of the AD patients' complexity. The only way to understand whether the two worlds (i.e., research and clinics) deal with the same type of patients is to adopt multidimensional approaches more holistically reflecting the biological age of the individual. In the present study, we compared measures of frailty/biological aging [assessed by a Frailty Index (FI)] of a sample of patients with AD resulted eligible and subsequently included in phase III RCTs compared to patients referring to the same clinical service, but not considered for inclusion. The "RCT sample" and the "real world sample" were found to be statistically similar for all the considered sociodemographic and clinical variables. Nevertheless, the "real world sample" was found to be significantly frailer compared to the "RCT sample," as indicated by higher FI scores [0.28 (SD 0.1) vs. 0.17 (SD 0.1); < 0.001, respectively]. Moreover, when assessing the relationship between FI and age, we found that the correlation was almost null in the "RCT sample" (Spearman's = 0.01; = 0.98), while it was statistically significant in the "real world sample" ( = 0.49; = 0.02). The application of too rigid designs may result in the poor representativeness of RCT samples. It may even imply the study of a condition biologically different from that observed in the "real world." The adoption of multidimensional measures capable to capture the individual's biological age may facilitate evaluating the external validity of clinical studies, implicitly improving the interpretation of the results and their translation in the clinical arena.
迄今为止，关于阿尔茨海默病（AD）的随机对照试验（RCT）的外部有效性仅在考虑单维变量的情况下进行了评估。然而，仅着眼于孤立的单一特征并不能保证对AD患者的复杂性有足够程度的认识。了解这两个领域（即研究和临床）所处理的患者类型是否相同的唯一方法是采用更全面地反映个体生物学年龄的多维方法。在本研究中，我们比较了符合条件并随后纳入III期RCT的AD患者样本的衰弱/生物衰老指标[通过衰弱指数（FI）评估]，并与来自同一临床服务但未被考虑纳入的患者进行比较。对于所有考虑的社会人口统计学和临床变量，“RCT样本”和“现实世界样本”在统计学上相似。然而，“现实世界样本”被发现比“RCT样本”明显更衰弱，如更高的FI分数所示[分别为0.28（标准差0.1）对0.17（标准差0.1）；P < 0.001]。此外，在评估FI与年龄之间的关系时，我们发现“RCT样本”中的相关性几乎为零（斯皮尔曼相关系数 = 0.01；P = 0.98），而在“现实世界样本”中具有统计学意义（相关系数 = 0.49；P = 0.02）。采用过于严格的设计可能导致RCT样本的代表性不足。这甚至可能意味着研究的是一种与“现实世界”中观察到的生物学状况不同的情况。采用能够捕捉个体生物学年龄的多维测量方法可能有助于评估临床研究的外部有效性，从而含蓄地改善结果的解释及其在临床领域的转化。
