New scoring methodology improves the sensitivity of the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials

• DOI: 10.1186/s13195-015-0151-0
• Publication Date: 2015-10-20T08:57:31Z
• Authors: Nishant Verma; S. Natasha Beretvas; Belen Pascual; Joseph C. Masdeu; Mia K. Markey
• Keywords: Male; Clinical Trials as Topic; Internet; Time Factors; Psychometrics; Cognitive Neuroscience; Research; Clinical Neurology; Neuropsychological Tests; Sensitivity and Specificity; Access to Information; 03 medical and health sciences; 0302 clinical medicine; Neurology; Alzheimer Disease; Humans; Computer Simulation; Female; Longitudinal Studies

AbstractIntroductionAs currently used, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer’s disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity.MethodsUsing item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect.ResultsThe ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect.ConclusionsThe proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer’s disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.