About the Project
The MRC Hubs for Trials Methodology Research (HTMR) Network has one non-clinical studentship available for early 2018 entry. Below is a description one project which can be applied for. Please contact the named supervisor in advance of submitting your application.
Hub: MRC Biostatistics Unit University of Cambridge
Please see our website for further details, guidance and application form.
https://www.methodologyhubs.mrc.ac.uk/about/phd-studentships/
Background to the project
Within a clinical trial it is common to make longitudinal observations of biomarkers (and other covariates). If the primary outcome is concerned with a change in the longitudinal biomarker we could consider assessing the time until a change-point occurs in the longitudinal process, that is, when the long-term behaviour of the biomarker changes abruptly. A change-point is an identifiable shift in the long-run biomarker level at an individual level, only some individuals may have a change-point and the time when this occurs will vary by person. This is a non-linear longitudinal model of the biomarker and is appropriate when the trajectory of the biomarker over time is of interest as a clinical outcome, rather than simply the overall change.
For example, monitoring cognition in older individuals, there is a distinct rapid decline in cognitive ability linked with dementia and other cognitive impairments, beyond the normal age-related decline. Rather than assessing a treatment’s effect on preventing a change in cognition, another outcome would be to delay the change to so-called rapid decline. A treatment might fail to prevent rapid decline, but could delay the time until onset of rapid decline; to test this involves analysing the time to the change-point (between normal and rapid decline of cognition). The estimation of the change-point in cognitive decline is well established in the cognition literature, using the Mini-Mental State Exam (MMSE), but there is little research on designs with the time to a change-point as the outcome.
What the studentship will encompass
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.
Detail of supervision
The main supervisor will be Simon White and Adrian Mander will co-supervise. The supervisors and student will have weekly or fortnightly meetings.
Deadline: 8 January 2018 at 4pm (GMT)
General enquires [Email Address Removed]
Supervisor Dr Simon White [Email Address Removed]
Funding Notes
Stipend of £17,726 per year
Due to funding restrictions only home/EU applicants are eligible for funding through this programme. Eligibility and residence requirements must be met. Candidates are advised to review the RCUK/MRC studentship documentation for full details.
http://www.rcuk.ac.uk/documents/documents/termsconditionstraininggrants-pdf/