The Melbourne EpiCentre is a collaborative research centre of the University of Melbourne and Melbourne Health embedded within the Royal Melbourne Hospital. It is an academic centre of excellence with research, education, health care quality and safety, and organisation-improvement agenda. The goal of the centre is to promote and run high quality clinical, non-clinical and biostatistical methodological studies, both locally and internationally.
Melbourne EpiCentre is a National Collaborative Research Infrastructure Strategy (NCRIS) funded facility, with expertise in the planning, design, data management, statistical and clinical reporting of clinical trials, conforming to FDA requirements and industry standards. The EpiCentre is leading several early and late phase clinical trials and clinical epidemiological projects with large primary and ambulatory care databases from the US and UK. The EpiCentre also provides study design, data management and biostatistical support for diverse research groups across the University and Melbourne Health, as well as providing analytical support for data relating to health care services quality and safety.
The EpiCentre is headed by Professor Sanjoy Paul.
Research engagement of the EpiCentre includes:
Clinical study design
Consulting services in various aspects of study design including: identification and choice of primary and secondary outcomes, protocol development, comparative power analyses, and statistical analysis approaches
Clinical database development and management
The EpiCentre complies with all FDA requirements and industry standards for all clinical data management, including compliance with 21 CFR Part 11. Key aspects include: development of electronic case report form (eCRF), development and management of electronic study database, web-hosting of database, training of project research staff and randomisation services.
Biostatistical / clinical reporting
The EpiCentre offers high level expertise in the development and management of Charter for Data Safety and Monitoring Committees, development of statistical analysis plans for safety and efficacy reporting, statistical analyses and statistical and clinical reporting. The EpiCentre actively participates in research manuscript development with research collaborators.
Multi-national prospective pharmacokinetic study, improving antibiotic dosing in renal replacement therapy for the five most commonly prescribed antibiotics Piperacillin-Tazobactam, Meropenem, Vancomycin and Imipenem and Linezolid at selected sites.
SMARRT Study: An NHMRC-funded multi-national, prospective, pharmacokinetic study aimed at developing optimised antibiotic dosing guidelines for ICU patients with life-threatening infections.
Study design: Multi-national prospective pharmacokinetic study.
In collaboration with: Dr Jason Roberts of the Burns, Trauma & Critical Care Research Centre, Royal Brisbane & Women’s Hospital, QLD.
Registration ID: ACTRN12613000241730
Publications: Roberts JA, Gordon YSC, Joynt GM, Paul SK, …, Lipman J. Sampling antibiotics in renal replacement therapy (SMARRT): an observational pharmacokinetic study in critically ill patients. BMC Infectious Diseases; 2016; 16:103.
TCZ Phase III
A phase III randomized study of humanized anti-IL-6 receptor antibody Tocilizumab (TCZ) to prevent development of acute graft versus host disease (GVHD) post HLA-matched allogeneic haematopoietic progenitor cell transplantation (HPCT).
TCZ Phase III: The aim is to determine the efficacy of anti-IL-6 receptor monoclonal antibody in preventing the development of grade II-IV acute GVHD in patients with acute leukaemia or myelodysplasia receiving HLA (A, B, C, DR) - matched allogeneic HPCT after myeloablative or reduced intensity conditioning.
Study design: Randomized (1:1 ratio) placebo controlled phase III double-blinded study design.
In collaboration with: Royal Brisbane & Women’s Hospital and QIMR Berghofer Medical Research Institute. Supported by NHMRC and Roche.
Principal Investigators: A/Prof. Glen Kennedy (RBWH), Prof. Geoff Hill (QIMR Berghofer), Prof. Sanjoy Paul (Melbourne EpiCentre).
Registration ID: ACTRN12614000266662
WBV for Osteoporosis Trial
A double-blinded, block-randomised, placebo-controlled clinical trial investigating the effects of low intensity whole body vibration (LWBV) on risk factors for hip fracture in post-menopausal women.
WBV for Osteoporosis Trial: This NHMRC-funded clinical trial aims to determine if low intensity whole body vibration can reduce risk for hip fracture in postmenopausal women with low bone mass, either acting alone or in combination with osteoporosis medications. Whole body vibration is a novel and appealing therapy with promising outcomes for bone from pilot trials. It is hypothesised that the combination of vibration and osteoporosis drugs will enhance the effects of both.
Study design: Randomized (1:1 ratio) placebo controlled phase III double-blinded study design.
In collaboration with: A/Prof. Belinda Beck, Centre for Musculoskeletal Research, Griffith University, Gold Coast, QLD.
Registration ID: ACTRN12615000848505
A prospective randomised single-blinded clinical trial in a community setting will evaluate the outcome of foot orthoses compared to hip strengthening exercises in people with patellofemoral pain.
FOHX Trial: The Foot Orthosis versus Hip eXercises (FOHX) trial: Predicting success in patellofemoral pain patients. : Does mid-foot mobility predict success to intervention with foot orthoses? The aim is to compare foot orthoses to hip exercises in people with patellofemoral pain.
Study design: A Phase 2/3, single-blinded, randomised controlled trial
In collaboration with: Prof. Bill Vicenzino, School of Health and Rehabilitation Sciences, University of Queensland.
Registration ID: ACTRN12614000260628
Phase 3 Trial in Diabetes
Double blind, randomized controlled multicentre clinical trial on efficacy and safety of "Zhongyi" Xiaoke Wan for diabetes mellitus.
Phase III Trial in Diabetes: Treatment of diabetes mellitus with Traditional Chinese Medicine has a long history. The aim of this study is to establish the safety and efficacy of traditional Chinese medicine combined with glibenclamide to treat type 2 diabetes.
Study design: Double blind, randomized and controlled multicentre clinical trial.
In collaboration with: Prof. Linong Ji, Peking University People’s Hospital, Beijing, China.
Registration ID: ChiCTR-TRC-08000074 (WHO International Clinical Trials Registry)
Publications: Ji L, Tong X, Wang H, et al. Efficacy and safety of traditional chinese medicine for diabetes: A double-blind, randomised, controlled trial. PLos ONE 2013; 8(2): e56703.
Telehealth in RACF Trial
In new residents in long term care facilities, does a telehealth service providing geriatric consultation, compared to usual care, improve health outcomes?
Telehealth Trial: This NHMRC-funded pragmatic randomised controlled trial aims to examine the effectiveness of telehealth to reduce utilisation of external health services by aged care residents in long term care.
Study design: A pragmatic controlled trial. The intervention is facility based.
In collaboration with: Dr Melinda Martin-Khan and Prof. Leonard Gray of the Centre for Research in Geriatric Medicine, School of Medicine, University of Queensland.
Registration ID: ACTRN12614000913673
The Beijing Pre-diabetes Reversion Programme (BPRP) is a 3-year follow-up randomised controlled clinical trial in subjects with pre-diabetes.
BPRP Trial: BPRP trial is conducted in China to evaluate whether life-style modification alone, treatment with pioglitazone alone, or combination of these two interventions could revert pre-diabetic state to normo-glycaemic state over 3 years of follow-up in 2000 subjects in China.
Study Design: Phase 3 2×2 factorial design
In collaboration with: In collaboration with Prof. Linong Ji and Dr. Yingying Luo of Peking University.
Registration ID: ChiCTR-PRC-06000005
BLING II Trial
A Phase IIb randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients (BLING II).
BLINGII Trial: The aim of this NHMRC-funded, phase II randomised controlled trial is to compare the effect of two approaches to the administration of beta-lactam antibiotics (continuous infusion vs standard intermittent bolus dosing) in critically ill patients with severe sepsis who are managed in the Intensive Care Unit. Completed 2014.
Study design: Phase II, double blind, randomized and controlled multicentre clinical trial
In collaboration with: Prof. Jeffrey Lipman and Dr Joel Dulhunty of the Burns, Trauma & Critical Care Research Centre, Royal Brisbane & Women’s Hospital, QLD.
Registration ID: ACTRN12612000138886
- Dulhunty JM, Roberts JA, Davis JS et al. A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis: The BLING II study. Critical Care and Resuscitation 2013; 15(3): 179-185
Current Clinical Epidemiology Research
In collaboration with Imperial College London, the University of Leicester UK, Amylin Pharmaceuticals and Novo Nordisk, Prof. Paul leads a research program to evaluate the long-term effects of glycaemic and other risk factors on cardiovascular and mortality risks in patients with diabetes. This also includes the evaluation of drug specific clinical inertia in patients with diabetes and the association with vascular risks and mortality. The research program is based on the longitudinal electronic medical records of approximately 2.5 million patients with type 2 diabetes and non-diabetic controls, registered in the UK and US primary / ambulatory care databases, from 1990 to present.
Therapeutic inertia & risk burden in type 2 diabetes
With funding support from Novo Nordisk and AstraZeneca, the Melbourne EpiCentre is leading a research project to evaluate the therapeutic inertia and risk burden in patients with type 2 diabetes at population level. These studies are based on primary care and ambulatory care large population level databases from UK and USA. The initial findings have already gained international attention, with the first study reporting the consequences of delay in intensification of treatment for glycaemic control on cardiovascular risk recently published in Cardiovascular Diabetology (2015, 14:100; 3,715 accesses since published online in August 2015).
Obesity paradox in type 2 diabetes
Professor Paul is leading a NHMRC funded large comparative retrospective longitudinal case-control study to understand the possible reasons behind this observed “obesity paradox” in patients with T2DM. This study is based on half-a-million subjects with complete clinical, prescription, medical and event history data from 1990 to 2014, with a median follow-up period of 10 years. The initial findings were published in Diabetes Obesity & Metabolism 2014; 16(4): 317-312.
Pathophysiology of glycaemic and cardiovascular risk factors in diabetes
In collaboration with Imperial College London, the University of Leicester UK, Amylin Pharmaceuticals, Novo Nordisk and AstraZeneca, Prof Paul is leading a research program to evaluate the long-term effects of glycaemic and other risk factors on cardiovascular and mortality risks in patients with diabetes. This also includes the evaluation of drug specific clinical inertia in patients with diabetes and the association with vascular risks and mortality. This program of studies is based on the longitudinal electronic data on about 2.5 million patients with diabetes and non-diabetic controls, from primary care and ambulatory care databases of UK and USA. The initial exploratory study has been published and presented at several international conferences, and a number of papers in this field have been published.
Hypoglycaemia and its consequences
In collaboration with Novo Nordisk, Amylin Pharmaceuticals and University of Leicester, Prof Paul is leading a research project to evaluate the risk factors associated with mild-moderate and severe hypoglycaemia, and the long-term consequences of hypoglycaemia. The first real-world based study evaluating the cardiovascular consequences of hypoglycaemia in both type 1 and type 2 diabetes patients was published in Diabetes Care (2015; 38(2): 316-322). The possible risk factors associated with hypoglycaemia differentiated between patients treated with insulin and incretin-based therapies was published in Journal of Diabetes (2015; 7:60-7).
Development of early warning systems for Hypoglycaemia
With the prestigious Queensland Government’s Smart Futures Co-Investment Fund grant, Prof. Paul is developing methodologies and techniques to analyse continuously monitored blood glucose levels in patients with diabetes, with the aim of developing a system to warn patients about incipient hypoglycaemia or hyperglycaemia. This study has a high translational value. This study has a high translational value, and the initial methodological exploration has been published recently in a statistical research journal.
Evaluation of cardio-metabolic effects of Incretin-based therapies in type 2 diabete
The Melbourne EpiCentre is leading a major research project with program grant from Amylin Pharmaceuticals LLC, and AstraZeneca, USA, to evaluate the cardio-metabolic effects of GLP-1 receptor agonists. The initial findings from this study have already gained attention from the international research community with considerable media coverage, and I was invited at international clinical conferences to present the initial findings. The first study on the possible association of treatment with GLP1 RA Exenatide with cardiovascular risk, in comparison to treatment with insulin, has been published in Cardiovascular Diabetology 2015; 14:10. doi: 10.1186/s12933-015-0178-3.
Current health services research
Strategies for Relatives (START) Online:
A mixed methods evaluation of START online, a program to reduce depression and anxiety in carers of people with dementia.
START Online is an 8-week program of education, relaxation training and counselling for carers of people living with dementia. Developed in the UK, the program was shown to be effective in reducing the rates of depression and anxiety in carers. This project will adapt the existing program for the Australian context and be the first to test this approach via video-conferencing technology, enabling access to carers living in remote areas. Funded by the State Trustees and Melbourne Ageing Research Collaboration (MARC).
In collaboration with: The Melbourne Ageing Research Collaboration (MARC).
Preventing Avoidable Hospital Admissions for People with Dementia
This project aims to identify the primary reasons that people with dementia present to hospital emergency departments and draw on the experiences and needs of carers and clinical staff to develop resources for carers. The resources aim to provide carers with support in making decisions about health care needs. Data collection will commence in early 2017 at Melbourne Health, Austin Health, and Northern Health sites. Funded by the State Trustees and Melbourne Ageing Research Collaboration (MARC).
In collaboration with: The Melbourne Ageing Research Collaboration (MARC).
Use of Analgesia among Hip Fracture Patients with Dementia compared to Patients who are Cognitively Intact
The aim of this study was to document pain assessment and management of hip fracture in patients with dementia compared with those who were cognitively normal at a large metropolitan hospital in Melbourne, Australia.
In collaboration with: Associate Professor Dina LoGiudice, Department of Aged Care, Royal Melbourne Hospital and University of Melbourne and Dr Mizhgan Fatima, Royal Melbourne Hospital.
Improving Palliative care Education and Training Using Simulation in Dementia (IMPETUS-D)
This study will evaluate the effectiveness of IMPETUS-D an online simulated training program with follow up mentoring for staff working across the Residential Aged Care (RACF) sector. As the RACF workforce is diverse, fragmented and involves shift work, training programs must be engaging and easily accessible. IMPETUS-D is an innovative model which aims at providing high quality care for people with dementia at the end of life and to reduce acute healthcare utilisation; including visits to the emergency department and hospital admissions.
A cluster randomised controlled trial design will be used to evaluate whether the IMPETUS-D program improves staff knowledge and confidence to deliver palliative care within the facility, enhances consumer satisfaction with palliative care, and reduces the proportion of residents needing to be transferred to an acute hospital for palliative care.
Associate Professor Kwang Lim, Clinical Director of Medicine and Aged Care, Melbourne Health is leading the project.
This project is a partnership between Melbourne Health, Allity Aged Care, University of Melbourne, Monash University, Deakin University and Monash Health.
Current Methodological Research
Methodological and applied studies in the design and conduct of pharmaco-epidemiological studies with large longitudinal electronic health records from primary care data
Methodological studies in Biostatistics and Epidemiology
The Melbourne EpiCentre is leading methodological and applied research projects in collaboration with the University of Minnesota, USA, and the Imperial College London, to develop robust approaches to design pharmaco-epidemiological studies and conduct analyses with large longitudinal electronic health records from primary care systems. The methodological projects include (1) development and evaluation of robust designs to conduct pharmaco-epidemiological studies, (2) missing data imputation problems under different strategic conditions, and (3) robust approaches to conduct long-term risk analyses with drug exposure in real-world scenario.
Background: Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction (MI) and post-MI fatality compared with the general population. In a previous study examining post-MI treatment in RA compared with controls we noted that a higher proportion of the RA patients had experienced MI following a surgical procedure.
Long-term anti-epileptic drug (AED) therapy is associated with increased fracture risk. This study tested whether substituting the newer AED levetiracetam has less adverse effects on bone than older AEDs. An open-label randomized comparative trial.
Background: Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection.
Current funding and grants
Paul S. Translating Health Discovery (THD) NCRIS 2016 Funding Program, 2016-17.
Paul S. Effect of weight change and its interactions with glycaemic control and blood pressure on cardiovascular and mortality risks in patients with type 2 diabetes – A Part of Programme of Clinical Epidemiological Studies. AstraZeneca Investigator Initiated Research Grant. 2016-18.
Roberts JR, Lipman J, Peake S, Turnidge J, Slavin M, Hopkins P, Bulitta J, Paul S (Chief Investigator), de Waele J, Joynt G. Centre for Redefining antibiotic use to reduce resistance and prolong the lives of antibiotics (REDUCE). NHMRC Centre of Research Excellence, 2016-20.
Beck B, Rubin C, Paul S (Chief Investigator), Forwood M. Whole body vibration for osteoporosis: Shaking up our treatment options. NHMRC Project Grant, 2015-19.
Paul S, Atherton J. Evaluation of the association of old and new anti-diabetes drugs with the risk of heart failure in patients with type 2 diabetes. RBWH Foundation, 2016-17.
Paul S (Lead Chief Investigator), Shaw J, Majeed A, Khunti K, Klein K. Evaluation of the obesity paradox in diabetes: A longitudinal case-control study of half a million patients. NHMRC Project Grant, 2014-17.
Roberts JA, Lipman J, Peake S, Roberts MS, Paul S (Chief Investigator), Turnidge J. Robust antibiotic dosing for critically ill patients receiving renal replacement therapy. NHMRC Project Grant (Roberts J et al.), 2013-16.
Paul S (Principal Statistician / Investigator). Telehealth in residential aged care facilities: a pragmatic randomized control trial. NHMRC Project Grant (Gray L et al.), 2013-17.
The Dementia Care Pathway for use in acute hospitals: development, implementation and evaluation funded by the Victorian Department of Health & Melbourne Health $330,000. Commenced 1/2014.
Strategies for Relatives (START) Online. State Trustees and MARC funded $60,000. Commenced 7/2016.
Preventing Avoidable Hospital Admissions for People with Dementia. State Trustees and MARC funded $60,000. Commenced 5/2016.
Imperial College London, UK
University of Oxford, UK
University of Leicester, UK
University of North Carolina, USA
University of Minnesota, USA
Bristol-Myers Squibb: Amylin Pharmaceuticals, USA
Novo Nordisk A/S, Denmark
Chinese Academy of Sciences, China
Peking University, China
Guangzhou Zhongyi Pharmaceutical Co. Ltd., China
Agilent Technologies Inc., USA
Collaborations within Australia
Therapeutic Innovation Australia – Queensland Node
Melbourne Ageing Research Collaboration
Burns, Trauma and Critical Care Research Centre, University of Queensland
Centre for Clinical Research, University of Queensland
Centre for Research in Geriatric Medicine, University of Queensland
National Ageing Research Institute
Diamantina Institute, University of Queensland
School of Health and Rehabilitation Sciences, University of Queensland
School of Allied Health Sciences, Griffith University
Baker IDI Heart & Diabetes Institute, Melbourne
OzStar Therapeutics Pty. Ltd
Diabetes and Endocrinology Department, Princess Alexandra Hospital, Queensland Health
Bone Marrow Transplant Laboratory