PhD Studentship

QIMR

Ph. D. Studentship in Clinical Biostatistics & Clinical Epidemiology

The Clinical Trials and Biostatistics Unit of the QIMR Berghofer Medical Research Institute is pleased to offer two international collaboration-based Ph. D. projects in Clinical Biostatistics & Epidemiology. These positions are open to Australian & international candidates.

Project #1

Project Title:
Exploring the Cardiometabolic Effects of Treatment with GLP-1R Agonists in Type 2 Diabetes Patients

International Collaborators:
Bristol Myers Squibb and Amylin Pharmaceuticals

Project Description:

Lifestyle modifications in conjunction with anti-diabetes medications can produce near-normal blood glucose concentrations in patients with type 2 diabetes mellitus (T2DM). As these patients have increased cardiovascular morbidity and mortality, treatment strategies should also address the cardiovascular aspects of the disease, including body weight, blood pressure (BP) and lipids. Since the prevalence of these abnormalities is increasingly secondary to poor diet and sedentary lifestyles and because most patients with T2DM are overweight/obese, clinicians are encouraged to help patients reduce body weight while correcting hyperglycaemia by selecting treatment options that improve both parameters. synthetic GLP-1 receptor agonists (GLP-1R agonists) represent promising new areas of research and therapeutics in the struggle not only against T2DM but also against the cardiovascular morbidity and mortality associated with T2DM. Two approved and marketed GLP-1R agonists are "exenatide" and "liraglutide". these drugs have demonstrated their ability to significantly reduce the glucose level and body weight, and maintain lower rate of hypoglycaemia, compared to existing oral anti-diabetes drugs (OADs) and insulin.

Although some extra-glycaemic effects (including chronotropic and hypertensive effects) of GLP-1R agonists have been observed in higher-animal models and human studies, little is understood about the background mechanism of cardiometabolic effects of this class of drug. Also the long-term cardiovascular effect of GLP-1 receptor activation in humans is not yet known.

Combining patient-level data from several randomized clinical trials (n~2400) comparing the safety and efficacy of GLP-1R agonists with other anti-diabetes treatments, and also using a large population level clinical and event data (n~1million), the aims of this study are to:

1. Determine the possible effects and clinical significance of glucose control and weight loss longitudinally on blood pressure, pulse pressure and heart rate in patients treated with GLP-1R agonists;
2. Explore the long-term effects of weight loss and glycemic control longitudinally on cardiovascular events in patients treated with GLP-1R agonist, compared with other anti-diabetes treatments;
3. Evaluate the individual and interactive effects of longitudinal changes in various risk factors on the incidence and rate of hypoglycaemia - compared between GLP-1R agonists and other anti-diabetes treatments;
4. Explore the long-term effects of treatment with GLP-1R agonists on lipid profiles, and to determine if there exists any interaction of early weight reduction and glycemic control on lipid profile.

Person Specification:

B. Sc. or M. Sc. in Statistics or Clinical Epidemiology with strong Statistical background - with strong methodological background and programming ability, with some research experience;

Interest in clinical research, especially in diabetes and metabolic diseases;

Strong motivation to conduct independent research in the field of clinical biostatistics;

Excellent programming knowledge with software, e.g. R & SAS;

Ability to work independently and take responsibility of a programme of work;

Excellent written communication skills.

Contact:

Interested applicants may contact Prof. Sanjoy Paul, the Head of Clinical Trials and Biostatistics Unit and the Principal Investigator in this project - Email: sanjoy.paul@qimrberghofer.edu.au .

Project #2

Project Title:
Evaluation of the Obesity Paradox in Diabetes: A Longitudinal Case-control Study of Half a Million Patients

International Collaborators:
Imperial College London; UK and University of Leicester, UK

Project Description:

Being overweight or obese is a risk factor for developing type 2 diabetes (T2DM). However, a recent studies have reported increased mortality risk associated with normal body weight in people with incident diabetes compared to those who are overweight or obese. This "obesity paradox", in which being overweight appears to be protective against mortality risk, is new in diabetes and the possible mechanisms behind this phenomenon are not yet explored. In general populations, however, a recent meta-analysis has reinforced the fact that compared to normal weight, obesity was associated with significantly higher all-cause mortality. This leads to the challenge of exploring the optimum adult body weight that best advances health, minimizes the risk of chronic disease like diabetes, and promotes longevity. This question has recently engaged the interest of the clinical investigators and public health professionals, since weight loss is so frequently a focus of management of T2DM. A comparative long-term longitudinal study of patients with newly diagnosed T2DM and non-diabetic controls is the best way to address this question of the obesity paradox. The consequences of answering this question have profound health and socio-economic implications for individuals and the population as a whole.

We propose to conduct a large comparative retrospective longitudinal case-control study to understand the possible reasons behind this observed "obesity paradox" in patients with T2DM. Specific aims are:

1. What is the relation between baseline body mass index (BMI) with cardiovascular risk, death due to cardiovascular diseases, death due to non-cardiovascular diseases and all-cause mortality (ACM) in those with and without incident T2DM after accounting for:
a. All comorbidities, including the pre-existing cardiovascular and non-cardiovascular disease burden;
b. Weight trajectory prior to index date - allowing account to be made for those already losing weight because of serious comorbidities.
2. Are there specific causes of death that could explain the increased mortality in individuals with normal weight (BMI: 18.5-25 kg/m2)?
3. Does the BMI trajectory over time after diagnosis explain the association of baseline BMI with vascular risks and mortality?
4. Are there any long-term interactions of cardiovascular (blood pressure, lipids) and glycaemic risk factors (e.g. glucose levels measured by HbA1c and hypoglycaemia) with body weight that modify the risks?

Person Specification:

B. Sc. or M. Sc. in Statistics or Clinical Epidemiology with strong Statistical background - with strong methodological background and programming ability, with some research experience;

Interest in clinical research, especially in diabetes and metabolic diseases;

Strong motivation to conduct independent research in the field of clinical biostatistics;

Excellent programming knowledge with software, e.g. R & SAS;

Ability to work independently and take responsibility of a programme of work;