title: New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials.
abstract: BACKGROUND
  As 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.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton Street Stop C0800, Austin, TX, 78712, USA. nishant3115@gmail.com.|NeuroTexas Institute Research Foundation, St. David's HealthCare, 1015 E. 32nd Street Suite 404, Austin, TX, 78705, USA. nishant3115@gmail.com.
authors.forename: Nishant
authors.initials: N
authors.lastname: Verma
authors.affiliation: Department of Educational Psychology, The University of Texas at Austin, 1 University Station D5800, Austin, TX, 78712, USA. tberetvas@austin.utexas.edu.
authors.forename: S Natasha
authors.initials: SN
authors.lastname: Beretvas
authors.affiliation: Nantz National Alzheimer Center, Houston Methodist Neurological Institute, 6560 Fannin Street, Houston, TX, 77030, USA. bpascual@houstonmethodist.org.
authors.forename: Belen
authors.initials: B
authors.lastname: Pascual
authors.affiliation: Nantz National Alzheimer Center, Houston Methodist Neurological Institute, 6560 Fannin Street, Houston, TX, 77030, USA. jcmasdeu@houstonmethodist.org.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Masdeu
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton Street Stop C0800, Austin, TX, 78712, USA. mia.markey@utexas.edu.|Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street FCT14.50000, Houston, TX, 77030, USA. mia.markey@utexas.edu.
authors.forename: Mia K
authors.initials: MK
authors.lastname: Markey
mesh_terms: D022126:Access to Information; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000523:psychology; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D005260:Female; D006801:Humans; D020407:Internet; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011594:Psychometrics; D012680:Sensitivity and Specificity; D013997:Time Factors