'Phase II and III trial simulators: Using mathematical, computational and
statistical techniques to simulate trial design for new products in the 
   Lead Investigator:    Emma Lawrence
   Institution      :    Imperial College London
   E-Mail           :    e.lawrance@imperial.ac.uk
   Proposal ID      :    743


   Publications:


1  Evans S, McRae-McKee K, Ower A, Hadjichrysanthou C, Wong MM, Wolf F, Anderson RM
   Rates of progression between diagnostic groups towards Alzheimer's disease: Comparison between cohort studies
   Abstract  Alzheimers Dement,13:P351,2017,

   PUBLISHED



2  Hadjichrysanthou C, McRae-McKee K, Evans S, Wong M, Wolf F, Anderson RM
   Potential Factors Associated with Cognitive Improvement of Individuals Diagnosed with Mild Cognitive Impairment or Dementia in Longitudinal Studies
   Journal Article  J Alzheimers Dis,66:587-600,2018,PMC6218131

   PUBLISHED





   Proposal Description:
   The overall aim is the development of a clinical trial simulator for use in the   design of phase II and III clinical trials of novel therapies for the             prevention or slowing of AD onset.                                                1) We have begun by conducting a systematic review of the literature on the       changes in neuropathology and cognition throughout the course of disease. The     epidemiological data identified will be utilised in the model development.        2) An exploratory analysis will be performed to dissect the relationship          between various biomarkers and clinical measures of progression (cognitive        function scores and imaging) given the following co-variates:                     - Genetics                                                                        - Sex                                                                             - Age of onset.                                                                   3) Data will also be analysed to characterise the variance between individuals    and groups.                                                                       4) Data will be used to estimate transition probabilities in the Markov chain     model.                                                                            6) Selected models and the estimates of the parameters will then be used within   the clinical trial simulator, in order to simulate disease progression under      different assumptions, for example, following the administration of               prophylactic treatments.                                                          This will be a descriptive study and there is no hypothesis to be tested.