2018 MacDiarmid Medal: Medical testing on your virtual clone

Historically there have been two modes for testing the effectiveness of treatments: in-vitro testing using tissue culture and in-vivo testing on live subjects. But now, there is a third way of testing. Called ‘in-silico’ or ‘virtual’ patients, it uses computer models of patients’ physiology to predict what the outcome of a treatment will be.

Professor Geoff Chase from the University of Canterbury’s Department of Mechanical Engineering has enabled the development of virtual patients through developing highly accurate, clinically relevant metabolic system models which, when used with clinical data, create in-silico virtual patient ‘clones’. Virtual patients enable the rapid, safe optimisation and personalisation of drug treatment.

Geoff’s models of physiological function could be said to apply Einstein’s philosophy that things should be as simple as possible, but no simpler. The models have a minimal number of parameters to adjust to capture patient-specific physiological measurements and response to care in a clinical setting. Capturing key characteristics in this way enables accurate virtual patients and the ability to test therapeutic strategies in real-time at the bedside.

Geoff has worked closely with clinicians over a long period, in particular Dr Geoff Shaw, a Senior Specialist in Intensive Care Medicine at Christchurch Hospital. This work has led to the formation of the international eTIME (engineering, Technology and Innovation in Medicine) consortia that includes several universities and 12 hospitals in Europe that can test protocols for diagnosing, monitoring and optimally treating patients with metabolic disorders.

His work has led to the development of two protocols for blood sugar (glycemic control) in adult intensive-care patients called SPRINT and STAR, which are being used in New Zealand, Hungary, Belgium, and other countries.

For SPRINT, the first 20,000 hours of clinical results matched within 1-2% the predictions from 20,000 hours of virtual trials using virtual patients, proving the ‘effectively perfect’ validity of the model. Similar results were obtained before the introduction of the STAR protocol, which directly uses these virtual patients to provide personalised care.

The SPRINT and STAR protocols have been the standard of care in Christchurch since August 2005, and are thought to have saved ~350 lives and $6-12M at Christchurch Hospital alone over 12 years. They provide a novel ‘risk-based’ insulin dosing methodology that is unique in the world to improve patient safety and outcomes. These models have helped create methods for earlier, accurate diagnosis of type-2 diabetes. Finally, a protocol called STAR-GRYPHON has also been developed for use in neonatal intensive care units (NICUs), and is the standard of care in Christchurch, and part of a large clinical trial in New Zealand’s other NICUs.

In addition to his work to develop blood glucose control protocols, Geoff has developed world-leading models for respiratory and cardiovascular systems, including, in 2018, a first virtual patient model for mechanical ventilation. His model-based CURE Soft system circulatory resuscitation in the ICU is currently under testing in large randomised trials in New Zealand and Malaysia, for mechanical ventilation in respiratory failure, a leading cause of ICU admission, stay, and cost.

As Dr Shaw summarised: “In working on these protocols, our greatest resource is not the fantastic systems and devices developed by our University of Canterbury colleagues, but the relationship our intensive care service has created with Geoff and others over the last 18 years. The devices and systems are great, but it’s the people that really have an impact.”

The medal selection committee said Professor Chase’s modelling methods and their foundation science are world leading in accuracy and the corresponding treatment protocols are proving effective and easy to implement in intensive care units around the world. “His work is saving lives and bringing us that much closer to the ideal of personalised medicine in an intensive care setting.”

In receiving the medal, Geoff said: “I’ve never been hugely worried about the science as long as we could find new ways to make patient care easier and better. In this regard, it’s fantastic to have this research recognised by Royal Society Te Apārangi.”

Geoff was elected a Fellow of the Royal Society of New Zealand in 2010, a Fellow of the Institute of Professional Engineers New Zealand in 2012 and a Fellow of the American Society of Mechanical Engineers in 2014. He received the University of Canterbury Research Medal in 2017 and was the university’s inaugural Distinguished Professor in 2013. In 2016 he received the Health Research Council of New Zealand’s Senior Researcher Award. The SPRINT Glycaemic Control in Critical Care research project was the Supreme Overall Winner of the 2006 NZ Health Innovation Awards.  In 2018 the CHYLD project he is involved with that studies the relationship between a baby’s blood glucose concentration at birth and later development was awarded a University of Auckland Research Excellence Award.

MacDiarmid Medal:

For outstanding scientific research that demonstrates the potential for application for human benefit.

Citation:

To J.Geoffrey Chase for his innovative engineering and transitional research based on unique model-based ‘virtual patients’, which has saved lives and reduced costs in New Zealand and Europe, and created a template for engineering-based solutions to significant healthcare problems confronting the world.