Can genomics enhance care and quality of life in psychosis? Investigating the cost-effectiveness of pharmacogenomics in mental health.

John Grace QC PhD Scholarship 2018: Division of Psychiatry, University College London

Supervisors: Prof Elvira Bramon, Dr Barbara Barrett

Summary:

More than 20 medications have been shown to be effective in treating psychosis. However, these medications can cause side effects, causing patients to stop taking them. Genetic differences can influence the way patients respond to their medicine, but these genetic differences are not usually considered by doctors when they prescribe medications. It is possible that genetic testing could improve the way we adjust the dose of these medications to help reduce side effects. Pharmacogenetic testing is not used in UK mental health due to insufficient evidence of its benefits and of its cost-effectiveness, thus, this project involves running the first UK clinical trial offering a pharmacogenomic personalised intervention for psychosis and an investigation of the cost-effectiveness of pharmacogenomics in mental health. This study will provide much needed evidence for a new NHS pharmacogenomics service currently under development by Genomics England, in which supervisor Prof Elvira Bramon is collaborating.

Study Aims:

To investigate if genetics-guided antipsychotic treatment improves quality of life and other clinical outcomes.
Does genetics help to reduce polypharmacy and adverse drug reactions?
Is the genetics intervention cost-effective compared to treatment as usual?
Investigate the acceptability of using genetics to inform treatment amongst patients and clinicians.

Start Date: September 2021

Research Student: Noushin Saadullah Khani

Hello, my name is Noushin and I am starting a multidisciplinary PhD covering mental health, pharmacogenomics and health economics at University College London in September 2021 funded by Mental Health Research UK and the Economic and Social Research Council (UBEL Doctoral Training Programme).

I completed an Integrated Master’s degree in Biochemistry at the University of Surrey, where I developed a passion for genomics. My Master’s research project investigated the causal relationship between adiponectin and diabetes (type II diabetes and gestational diabetes) using genetic variants as instrumental variables in a Mendelian randomisation analysis. My research interests include understanding how genetic variation impacts the drug response and genetics-guided therapy for psychosis.

I am thrilled to have the opportunity to carry out this project and I would like to express my gratitude to Mental Health Research UK for co-funding this project.

Progress Report year 2, 2023

I began the second year of my PhD by completing a Mendelian randomization analysis to examine whether there is a causal relationship between schizophrenia and cardiometabolic traits, such as blood lipids (LDL, HDL, triglycerides, and total cholesterol), glycaemic traits (fasting insulin, fasting glucose, and HbA1c levels) and anthropometric traits (BMI, WHR). I have published this piece of research in Frontiers Genetics and have presented it at the World Congress of Psychiatric Genetics (WCPG) 2022 conference in Florence, Italy.

I have since then completed a systematic review and meta-analysis to investigate whether genetic testing in individuals to guide prescribing and dosing for antipsychotic treatment improves clinical and economic outcomes. The implementation of this testing in clinical practise could optimise antipsychotic treatment by preventing adverse drug reactions, improving treatment adherence, and potentially relieving a major cost-burden on the healthcare system. I am now working towards publishing this research and will be presenting it at the WCPG 2023 conference in Montreal, Canada.

Alongside the academic research I have been working on, I have been a postgraduate teaching assistant at UCL and have provided support in online and face-to-face practical sessions in statistics and programming (R/Stata). I have also assisted with marking for several modules for MSc and undergraduate courses.

In June 2023, I passed my MPhil to PhD upgrade. I completed a 10,000-word upgrade report, a presentation to the Neuroscience department outlining the work I have completed so far, and an upgrade viva.

My plans for the future include undergoing health economics training to develop a health economic decision model. Adverse events related to the intake of antipsychotic medication include chronic conditions, such as type II diabetes and cardiovascular disease. Thus, I am interested in investigating the long-term economic and clinical impacts of using the genetic tests to guide prescribing for antipsychotics using this model.

Progress Report year 1, 2022

Training and professional development

Over the past year, I have focused on improving my quantitative, programming and analytical skills. Thus, I have undertaken modules from the MSc Social Research Methods course, including:

Introduction to Regression Analysis
Advanced Quantitative Methods
Using Stata Efficiently and Effectively
Introduction to Systematic Review Design and Planning

I have also attended Inkpath short courses:

Statistics for Researchers: Scientific Method, Probability and Statistics
A Quick Introduction to UNIX

I have also been interested in developing my data science and machine learning knowledge in the context of health and disease. Thus, I have attended practicals from the Computational Genetics in Healthcare module from the MSc Health Data Science course. These training opportunities will allow me to utilise cutting edge techniques in my PhD research.

Clinical trial coordination and management

I have contributed to the coordination and management of the Genetics to Personalise Antipsychotic Treatment (G-PAT) study. This experience has allowed me to develop my knowledge of clinical trial operations. I have presented to various research and clinical teams to promote the study and gain further support for our research. I have contributed to the setting up, initiating and monitoring of multiple sites across England and liaising with their research and clinical teams during this process and have been responding to their queries about the study. I have also been involved in the participant recruitment process by visiting one of our sites, Camden and Islington NHS Foundation Trust, and discussing the study with potential participants. I have become familiarised with information governance software such as Data Safe Haven and data collection and entry platforms, such as REDCap and have used it to build an electronic questionnaire for participants. In the next few months, I will be helping to deliver the trial intervention.

Schizophrenia research and analysis

Individuals with a diagnosis of schizophrenia are known to be at high risk of poor physical-health outcomes due to cardiovascular disease, diabetes, and obesity. The reasons for these physical health complications are complex. Despite well-documented cardiometabolic side effects of certain antipsychotic drugs, schizophrenia may have an independent effect. I have conducted a Mendelian randomization analysis to examine whether there is a causal relationship between schizophrenia and cardiometabolic traits, such as blood lipids (LDL, HDL, triglycerides, and total cholesterol), glycaemic traits (fasting insulin, fasting glucose, and HbA1c levels) and BMI. This research will be presented as a poster in the World Congress of Psychiatric Genetics in September 2022.