ISPOR 22nd Annual International Meeting
Boston, MA, USA
May, 2017
MO3
Neurological Disorders-all
Patient-Reported Outcomes & Patient Preference Studies (PRO)
Patient-Reported Outcomes (PRO)
MODELLING ALZHEIMER’S DISEASE PROGRESSION USING A MULTIVARIATE MODEL FOR THE ASSOCIATED OUTCOMES OF COGNITION, BEHAVIOR AND FUNCTIONING: DATA FROM THE ICTUS STUDY
Saunders O1, Asseburg C2, O'Reilly K3, Sly IE1, Lee D1
1BresMed, Sheffield, UK, 2The Swedish Institute for Health Economics (IHE), Lund, Sweden, 3Otsuka Pharmaceutical Europe Ltd, Wexham, UK
OBJECTIVES:  The ICTUS study provides longitudinal data on markers of Alzheimer’s disease (AD); ADAS-cog, NPI, ADL and IADL questionnaires measuring cognitive, behavioural and functional decline, respectively. Available literature indicates that it is important that models predicting AD progression account for the joint evolution of decline. The objective of this project was to develop a model to understand AD progression using ICTUS study data. METHODS: AD progression was studied in the subset of European ICTUS patients (n=982/N=1375) treated with AChE inhibitors with biannual follow-up over 2 years. A multivariate linear growth model was fitted including fixed and random covariates for years since baseline for each marker, allowing the rate of change for each marker to vary for each patient. The multivariate model structure allowed quantification of the correlation between the rate of decline across markers. The model also included baseline and time-dependent covariates, including baseline age, MMSE and concurrent treatment. Exploratory modelling revealed implausible covariate estimates and unsatisfactory residual diagnostics for NPI. NPI was therefore removed as an outcome and included as a baseline covariate. RESULTS:  The model showed a strong multivariate relationship between the rate of change in cognition and functioning. There was a strong positive correlation in the in the rate of decline of ADL and IADL (rho=0.65) and a strong negative correlation between the rate of decline of ADAS-cog and ADL and ADAS-cog and IADL (rho=-0.70 and -0.55, respectively). ADAS-cog showed an annual increase of 4.55 [95%: 4.15,4.94; p<0.001], ADL a decrease of -0.49 [-0.54,-0.44; p<0.001] and IADL a decrease of -0.87 [-0.95,-0.79; p<0.001]. CONCLUSIONS:  This study demonstrates the strength of correlation between cognition and function; providing an example of how to account for this within predictions. Whilst behaviour is also considered a conceptually important marker for AD progression; within this study it was not feasible to model all four markers simultaneously.