S3‐02‐02: Prevention trials

not available. S3-01-02 IS THERE A NEED FOR LARGER PREVENTION TRIALS? Laura Fratiglioni, Aging Research Center, Karolinska Institutet & Stockholm University, Stockholm, Sweden. Contact e-mail: laura. fratiglioni@ki.se Abstract not available. S3-01-03 EXPERIENTIAL AND PSYCHOSOCIAL RISK FACTORS FOR DEMENTIAnot available. S3-01-03 EXPERIENTIAL AND PSYCHOSOCIAL RISK FACTORS FOR DEMENTIA David A. Bennett, Rush University Medical Center, Chicago, IL, USA. Contact e-mail: David_A_Bennett@rush.edu Abstract not available.not available. S3-01-04 IS IT TIME TO GO BEYOND RANDOMIZED CONTROLLED TRIALS? Kaarin J. Anstey, Centre for Research on Ageing, Health and Wellbeing, Dementia Collaborative Research Centre, Research School of Population Health, The Australian National University, Canberra, Australia. Contact e-mail: kaarin.anstey@anu.edu.au Abstract not available.not available. TUESDAY, JULY 21, 2015 SYMPOSIA S3-02 NOVELTRIAL DESIGN S3-02-01 QUANTIFYING THE PLACEBO EFFECT THROUGH MODELING AND SIMULATION Klaus Romero, Kaori Ito, Brian Corrigan, Richard J. Anziano, Jon Neville, Diane Stephenson, Richard Lalonde, CAMD AD Modeling and Simulation Team, Coalition Against Major Diseases, Critical Path Institute, Tucson, AZ, USA; Pfizer, Groton, CT, USA; Critical Path Institute, Tucson, AZ, USA. Contact e-mail: kromero@c-path.org Background:Understanding the magnitude, duration and variability of the placebo effect in longitudinal Alzheimer’s disease (AD) studies is critical in order to optimally design clinical trials and interpret their results. Standardized and integrated data, along with literature data, provide a platform to develop quantitative models for the placebo effect. Methods:The placebo response component from an FDA/EMA-endorsed drug-disease-trial model for AD, developed from ADNI, CAMD and the literature, is used to illustrate disease progression in the control groups from various case studies. Results: The case studies show how the varying placebo response in control arms has an impact in understanding the magnitude of drug effect in clinical trials. Relevant covariates like baseline disease severity are important factors to take into account when comparing outcomes between groups. Study duration, sample size and study design are important factors to consider when interpreting a trial’s results. These case studies show that failures in late-stage studies are not likely due to insufficient cognitive decline in the control groups. Conclusions: Meta-analytic approaches that integrate all available relevant data provide a quantitative understanding of placebo effect, disease progression and potential interpretation of treatment effects, which offers a useful tool to optimize trial design and interpretation. S3-02-02 PREVENTION TRIALS CraigW. Ritchie, EPAD Consortium,University of Edinburgh, Edinburgh, United Kingdom. Contact e-mail: craig.ritchie@ed.ac.uk Background:An ever-increasing understanding of neurodegenerative disease processes preceding dementia coupled to a lack of success in developing disease modifying drugs for this condition have driven a need to undertake secondary prevention trials differently. To address this problem, a significant public-private partnership was developed by the European IMI (Innovative Medicines Initiative). Through this award, the EPAD (European Prevention of Alzheimer’s Dementia) Project was established. Methods:EPAD will draw together 24,000 subjects from existing cohorts and registers in Europe to then enter Podium Presentations: Tuesday, July 21, 2015 P211 6,000 of these subjects into the EPAD Longitudinal Cohort Study (LCS). This cohort will provide a trial ready cohort, provide data for pre-clinical disease models and risk stratification as well as run-in data of the highest quality for analyses of an intervention’s efficacy in the EPAD Proof-of-Concept trial. This adaptive trial will involve 1,500 subjects at any one time and be constructed to allow testing of drugs concurrently and in combination against a shared placebo group. Results: The Consortium has 36 partners working across 8 Work Plans. The final protocol for the EPAD-LCS will be delivered in Autumn 2015. Keymethodological elements of this protocol in terms of subject selection, outcome measures and recruitment will be presented. Conclusions: In 2016 EPAD will provide an environment for the optimal testing of interventions at the PoC stage of development. The EPADLCS is a critical element within the platform. The EPADConsortium is alsoworking with other IMI projects (EMIF and AETIONOMY) as part of the IMI-AD Platform and with the GAP Initiative to share knowledge, ideas and approaches for the secondary prevention of Alzheimer’s dementia. S3-02-03 RATIONALLY ITERATING NOVELTRIALS Table 1 Autopsied Ma