About the Project
Predicting the time to onset of Alzheimer’s disease is challenging, but predictions will help to identify patients at risk and help to identify patients that may benefit from new developments in care and treatment. Building a robust prediction model requires incorporating multiple biomarkers with variable selection, possibly model selection, and validation of predictions. The last decade has seen an increase in high quality and large scale neuorimaging being included within studies that are suitable for building Alzheimer’s risk prediction models. However imaging data present substantial challenges, not least the large dimensionality of the data and how to apply dimension reduction or variable selection approaches, such as region of interest derived measures or voxel-based reduction methods like independent component analysis. Further, there are typically multiple imaging modalities available such as structural Magnetic Resonance Imaging (MRI), functional MRI, resting-state MRI, and Positron Emission Tomography (PET); how to incorporate multiple highly correlated high dimensional biomarkers with potentially repeated measures over time is the focus of this project.
The MRC Biostatistics Unit is a partner in the Medical Research Council (MRC) Dementia Platform UK (DPUK) Consortium, this study includes participants with longitudinal observations and multiple imaging modalities. The project will use data from the DPUK to investigate methodological issues on using imaging modalities within risk prediction models, whether selection into imaging sub-studies could influence findings and the problem of high-dimensional imaging as a biomarker in a risk model.
The ultimate aim of the project is to create a novel adaptive design that adapts the number and interval of observations for each individual and to demonstrate whether this leads to an increased power to detect a treatment affect, within a biomarker with change-point(s), which could lead to changes in clinical practice.
The MRC Biostatistics Unit is a partner in the European Prevention of Alzheimer’s Dementia (EPAD) Consortium, this study includes a longitudinal cohort from which participants will be recruited into trials. The EPAD study, as well as historical cognition studies (using, for example the MMSE), will be used to assess novel designs developed during the project. The project will investigate alternate methods for analysing time to change-point type trials, such as assessing the proportion that have changed after a fixed interval or inferring the time of the change-point using regularly timed observations, and compare the power and efficiency of these designs to the adaptive design. Within the context of EPAD, there is the additional issue of designing trials within longitudinal cohort studies that will need to be incorporated into the trial design. The focus of the project is to investigate adaptive sampling of individuals. Adapting the observation interval and number will minimise the number of observations on each individual, thus leading to a more efficient design for each participant and overall reducing the number of observations required. The project will investigate the power, efficiency and bias of the adaptive design compared to the alternate methods.
Funding Notes
The MRC Biostatistics Unit offers at least 6 fulltime PhDs funded by the Medical Research Council or NIHR for commencement in April 2019 or October 2019.
Academic and Residence eligibility criteria apply.
More details are available at
(https://www.mrc-bsu.cam.ac.uk/training/phd/ )
In order to be formally considered all applicants must also complete a University of Cambridge application form- full details can be found here (https://www.mrc-bsu.cam.ac.uk/training/phd/ )
However informal enquiries are welcome to [Email Address Removed]
Projects will remain open until the studentships are filled but priority will be given to applications received by the 3rd January 2019