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Suitability of the Clinical Dementia Rating‐Sum of Boxes as a single primary endpoint for Alzheimer's disease trials
Author(s) -
Coley Nicola,
Andrieu Sandrine,
Jaros Mark,
Weiner Michael,
Cedarbaum Jesse,
Vellas Bruno
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.01.005
Subject(s) - clinical dementia rating , cronbach's alpha , dementia , rating scale , clinical endpoint , alzheimer's disease , cognition , clinical trial , ceiling effect , sample size determination , psychology , convergent validity , medicine , physical medicine and rehabilitation , disease , clinical psychology , psychometrics , internal consistency , psychiatry , statistics , developmental psychology , pathology , mathematics , alternative medicine
Background 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. Methods 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. Results 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. Conclusions 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.