The Placebo Group Simulation Approach (PGSA): Predicting Decline in Patients

 
   Lead Investigator:    Rene Spiegel
   Institution      :    Memory Clinic, Geriatric University Hospital
   E-Mail           :    rene.spiegel@unibas.ch
   Proposal ID      :    109


   Publications:


1  Berres M,  Kukull WA , Miserez AR, Monsch AU,  Monsell SE , Spiegel R
   A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA). Application to MCI data from the NACC database
   Journal Article  J Prev Alzheimers Dis,1:99-109,2014,PMC4268776

   PUBLISHED



2  Berres M, Monsch AU, Spiegel R
   Putting the PGSA to the test: Rates of progression to dementia in five studies with MCI patients
   2017   Abstract  CTAD Meeting, Boston , 

   ACCEPTED



3  Spiegel R
   Modeling the Course of AD: Contributions to Better Clinical Trials
   2012   Abstract  J Nutr Health Aging   811-812   , 

   PUBLISHED



4  Spiegel R
   It really works! Confirmation of the ADNI-based Placebo Group Simulation Approach with NACC data
   Abstract  Alzheimers Dement,7:e64,2011,

   PUBLISHED



5  Spiegel R, Berres M, Miserez AR, Monsch AU
   The Placebo Group Simulation Approach (PGSA): An Alternative Study Design for Clinical Trials in Patients with Prodromal AD
   2011   Abstract  CTAD Conference, San Diego November 3-5 , 

   ACCEPTED



6  Spiegel R, Berres M, Monsch A, Miserez A,  Kukull WA
   Validating the Placebo Group Simulation Approach (PGSA), an Alternative Study Design for Preventive Trials in Prodromal AD Patients
   Abstract  Alzheimers Dement,10:P859,2014,

   PUBLISHED



7  Spiegel R, Monsch AU, Berres M
   Validation Studies with the Placebo Group Simulation Approach (PGSA) in Different MCI Datasets
   Abstract  Alzheimers Dement,13:P1141,2017,

   PUBLISHED





   Proposal Description:
   Abstract:  Aim: To forecast, based on mathematical models, endpoints and disease  trajectories of pre-symptomatic AD patient groups.  Background: Novel compounds with potential to attenuate or stop the progression of Alzheimer disease (AD) from its pre-symptomatic stages to dementia are being or will soon be tested in man. The conventional study design is the randomized, placebo-controlled clinical trial (RCCT), which implies that a high proportion of patients will receive placebo treatment for 18 months or longer. We and others consider it ethically problematic to expose patients with pre-symptomatic AD, who by definition run a high risk of developing dementia, to extended placebo treatment. In an attempt to realize an ethically acceptable  and scientifically sound alternative to RCCT designs, we have developed  mathematical models to reliably forecast clinically relevant endpoints and disease trajectories of pre-symptomatic AD patient groups. Our models make use of anamnestic, biological and neuropsychological measures that are routinely established at baseline of every study. Model-based forecasted endpoints and trajectories constitute the background - the ???simulated placebo group??? -against which potential drug effects can be contrasted. Our current models, which were presented at several international AD-meetings and have been submitted for publication, are based on data from the ADNI database with a focus on MCI subjects. At this stage we wish to validate our models by making use of new, independent data sets. The NACC datasets are expected to bring our efforts a large step ahead.