Developing Methods of Precision Medicine in the Psychological Treatment of Depression. Medical Studies, PhD (GW4 BioMed MRC DTP)

Supervisory team:
Professor David Richards, University of Exeter Medical School
Professor Rod Taylor, University of Exeter Medical School
Dr David Kessler, University of Bristol
Dr Fiona Warren, University of Exeter Medical School

Project description:
You will develop new precision medicine statistical techniques and models to help clinicians prescribe different psychological treatments for depression. Models will predict clinical outcomes from patient and therapy characteristics. This translational project will develop your statistical, health services research and clinical trials expertise.

This project will:
a) review, develop and apply novel algorithmic approaches, including PAI, to prescribing psychological therapies for depression;
b) review and develop clinical trials designs to prepare trials of precision medicine in depression.

It is driven by meta-analyses that show little difference between approaches, all achieving barely moderate effect sizes (g = 0.4). However, retrospective trial analyses by DeRubeis at Penn State Uni., USA, have demonstrated the possibility of calculating a precision medicine prescriptive algorithm – the Patient Advantage Index (PAI) – to differentiate and predict patient response to different treatments, with the potential to double effect sizes and recovery rates by allocating patients to treatments based on PAI scores.

We envisage four work stages:
1. A review of the prescriptive value of different statistical approaches to precision medicine and the evidence for their clinical application.
2. Developing methods identified in (1) further, using our NIHR HTA COBRA trial dataset (n=440) to test their predictive utility.
3. Refinement of PAI and other models through an individual patient data (IPD) meta-analysis to obtain PAI’s and other predictive algorithms from other available trial datasets of several thousand patients on psychological therapy for depression.
4. Production of recommendations for the design of the next generation of clinical trials using precision medicine approaches for psychological therapies in depression.

Significance, originality, feasibility and degree of challenge:
This studentship will for the first time internationally apply precision medicine approaches to psychological therapy datasets and prepare the ground for prospective randomised clinical trials of prescriptive approaches; we have access to multiple psychological therapy trial datasets and are already collaborating with the DeRubeis lab; the work uses novel statistical techniques and is challenging per se and in its application across multiple datasets with multiple treatment comparisons.

Research training:
We describe this in detail in section 11 (masters level taught courses, co-location of trials and statistics expertise and international and national experience placements).

Added-value features:
The student will be required to work across multiple disciplinary boundaries (e.g. evidence synthesis research, medical statistics, psychological therapies) with the IHR and Bristol centres offering multiple opportunities for collaboration.

Strategy for knowledge transfer:
Implementation science is central to our groups’ culture. Richards’ work has directly influenced the care of over 3m people (REF impact case study rated 4*outstanding). The student will have access to IHR and Bristol research groups including operational and behaviour change research into the effectiveness, cost effectiveness and implementation of health interventions for NIHR, NICE and national policy makers.

To apply for this project, please complete the application form at https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-dtp-student-2019 by 5pm Friday 23 November 2018.