University of Toulouse III, France.
Alzheimers Dement. 2011 Nov;7(6):602-610.e2. doi: 10.1016/j.jalz.2011.01.005. Epub 2011 Jul 13.
Clinical measures continue to be used as primary endpoints for disease-modifying trials for Alzheimer's disease (AD). Currently, two co-primary endpoints must be specified, which measure cognitive and functional impairments. Generally, the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is one of the co-primary endpoints, but high variability in this measure results in large sample sizes. We evaluated the psychometric properties of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) to assess its suitability as a single primary endpoint as an alternative to the traditional co-primary approach.
Internal consistency, structural and convergent validity, and 2-year internal and external responsiveness of the CDR-SB were assessed in 667 very mild to moderate (global Clinical Dementia Rating, 0.5-2) AD patients from the REAL.FR (Réseau sur la Maladie d'Alzheimer Français) study.
The CDR-SB showed good internal consistency (Cronbach's alpha = 0.88), and acceptable structural (separate "cognitive" and "functional" factors) and convergent validity. Variability in mean changes over time was low, leading to excellent internal responsiveness (effect size = 1.2; standardized response mean = 1.17 at 2 years) and smaller sample sizes as compared with the ADAS-Cog. External responsiveness was acceptable when compared with "clinically meaningful" changes on the Activities of Daily Living scale but only borderline acceptable when compared with the ADAS-Cog and Instrumental Activities of Daily Living. Levels of missing data and floor/ceiling effects were low.
The CDR-SB measures cognitive and functional impairment simultaneously, and has excellent 2-year internal responsiveness. This makes it a promising candidate as a sole primary endpoint for AD trials, although more work is required to determine the clinical relevance of CDR-SB changes, and its usefulness as an endpoint at other disease stages.
临床指标仍被用作阿尔茨海默病（AD）疾病修饰试验的主要终点。目前，必须指定两个共同主要终点，以衡量认知和功能障碍。一般来说，阿尔茨海默病评估量表-认知子量表（ADAS-Cog）是共同主要终点之一，但该指标的变异性较大导致样本量较大。我们评估了临床痴呆评定量表-总盒评分（CDR-SB）的心理测量特性，以评估其作为替代传统共同主要方法的单一主要终点的适宜性。
我们评估了 667 名非常轻度至中度（全球临床痴呆评定，0.5-2）AD 患者的 CDR-SB 的内部一致性、结构和收敛效度，以及 2 年的内部和外部反应性，这些患者来自 REAL.FR（法国阿尔茨海默病网络）研究。
CDR-SB 显示出良好的内部一致性（Cronbach's alpha = 0.88），以及可接受的结构（独立的“认知”和“功能”因子）和收敛效度。随着时间的推移，平均值变化的变异性较低，导致良好的内部反应性（效应大小=1.2；标准化反应均值=1.17，2 年）和与 ADAS-Cog 相比较小的样本量。与日常生活活动量表上的“临床有意义”变化相比，外部反应性是可以接受的，但与 ADAS-Cog 和工具性日常生活活动相比，仅边缘可接受。缺失数据和地板/天花板效应的水平较低。
CDR-SB 同时衡量认知和功能障碍，具有出色的 2 年内部反应性。这使其成为 AD 试验的单一主要终点的有前途的候选者，尽管还需要更多的工作来确定 CDR-SB 变化的临床相关性及其在其他疾病阶段作为终点的有用性。
