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HealthHatchery, a scalable program for healthcare innovation Personalised approach to limit adverse reactions to medicines New Digital Health lab addressing health challenges
FOREWORD We are so pleased to publish Issue 18 of INSPIRE focusing on the critical bridge between basic and clinical research – translational research. How pertinent in light of the world’s focus on a COVID-19 vaccine – the greater community can now appreciate the importance of the process and the challenges it faces across the pipeline.
he past few decades h ave b r o u g h t e n o r m o u s breakthroughs in the fundamental knowledge necessary to understanding, preventing, diagnosing, and treating many diseases and Australia has an excellent global reputation in this area. However, our ability to translate these new discoveries into both clinical and non-clinical outcomes is lagging behind the relative pace of discovery. There remains a formidable list of diseases for which there are no cures or even meaningful treatment
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options. T he fact is that many basic discoveries barely get to start the journey down the therapeutic development pipeline. Fascinating observations and creative insights often get lost in translation because they lack funding, incentives, and technical expertise to advance. This translational gap is often referred to as the “Valley of Death.” We know that an enormously high number of research projects fail before they ever get tested in humans and so few make it to clinical trials. There is genuine concern about getting more and bet te r tre atme nts to patients sooner and the success of
the translation from laboratory bench to patient bedside depends on the joint efforts of funders, academic institutions, non-profit foundations, and the pharmaceutical and biotechnology industries. Research Australia advocates for collaboration in so many areas of health and medical research and innovation and translation is also a team spor t. The translational journey from a basic discovery to a demonstrated improvement in public health requires a team of scientists and clinicians with wide-ranging expertise. We advocate for innovative collaborations across traditionally separate scientific disciplines and organisations, including government agencies, academia, industry and non-profit patient and philanthropic organisations. Collaboration in commerialisation is showcased in SPHERE’s article. They are leading a collaborative, evide nce -based approach to optimise the commercialisation of healthcare innovations partnering with Maridulu Budyari Gumal, national and international consortiums to
launch HealthHatchery. It is a unique collaboration which facilitates and funds the development of promising ideas arising from unmet clinical needs. I was interested to read about the Burnet Institute’s designing of the CD4 point-of-care test, and it was encouraging to see the WHO’s endorsement validating their overall approach to making diagnostics that can have a global impact. QUT shares how a Personalised approach can limit adverse reactions to medicines. Their researchers are extending their genomic capability and collaborating with industry which bodes well for strong outcomes and I was delighted to read how the National Breast Cancer Foundation is collaborating with their fellow members, CSL, UNSW Sydney developing life-changing technology that is being recognised and translated into real-world impact by making cell manufacture affordable with a microbioreactor. Last but by no means least, I take this opportunity to thank our outgoing Chair Chris Chapman for his unfailing leadership over the past four years. Chris brought a lawyer’s finely tuned
questioning technique to always cut through to the heart of the matter, especially impressive given the complexity of our sector. We look forward to seeing him as part of our illustrious alumni and we welcome Research Australia Director Associate Professor Annette Schmiede into the role for 2021 – it is going be a great year! For now, on behalf of the Research Australia Board and team, we wish
you a healthy and safe holiday season and I look forward to celebrating and sharing your incredible work next year.
Nadia Levin CEO & Managing Director
AWARD CATEGORIES Peter Wills Medal Advocacy Award Griffith University Discovery Award Frontiers Award Sponsored by ANU Data Innovation Award Sponsored by Bupa Health Foundation Philanthropy Award Health Services Award Sponsored by the NSW Government
Thank you to our 2020 Award Sponsors 2020 | INSPIRE 018 3
Australian Health & Medical Research & Innovation
WHO Endorses Burnet Hiv Diagnostic
Using evidence to inform guidelines
06 26 A growing appetite for new Eating Disorder solutions FLINDERS UNIVERSITY
44 Science at Warp Speed PRAXIS AUSTRALIA
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30 Banking on the genetics of PRADER-WILLI and Angelman syndromes to improve individual outcomes MURDOCH CHILDREN’S RESEARCH INSTITUTE
46 Personalised approach to limit adverse reactions to medicines QUEENSLAND UNIVERSITY OF TECHNOLOGY
34 Arming Australian clinicians with the latest evidence from around the globe AUSTRALIAN CLINICAL TRIALS ALLIANCE
50 ‘Where tomorrow’s health becomes reality’ SPHERE
Publisher Research Australia Ltd Art Direction Matthew Ware p +61 403 844 763 or e email@example.com For Advertising enquiries please contact the Research Australia office on p 02 9295 8546 or e firstname.lastname@example.org researchaustralia.org INSPIRE ONLINE issuu.com/researchaustralia
Flinders new digital health lab addresses health challenges
Towards a More Specific and Safer Treatment for Autoimmune Vasculitis
Preventing neurodegeneration after stroke
Tipping the scales on cell and gene therapy
INSPIRE is a publication of Research Australia Ltd ABN 28 095 324 379 384 Victoria Street Darlinghurst NSW 2010 Who canMy submit articles? CHRISTOPHE KEREBEL Twitter : @chriskere My Twitter : @chriskere CHRISTOPHE KEREBEL Any current member of Research Australia who would like to share a relevant story that affects their organisation including, philanthropic donations and their outcomes, research findings, and any other related health and medical research topic that affects the Australian population. Submission guidelines & deadlines For information regarding how to submit and publishing deadlines visit the Research Australia website. Disclaimer The opinions expressed in INSPIRE do not necessarily represent the views of Research Australia. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted by Research Australia for omissions, typographical or inaccuracies that may have taken place after publication. All rights reserved. The editorial material published in INSPIRE is copyright. No part of the editorial contents may be reproduced or copied in any form without the prior permission from Research Australia. ÂŠ Research Australia 2020.
THE LAST WORD
Attacking the fortress on more than one front
Time for action: towards a research ecosystem inclusive of people from CALD backgrounds
Refocusing medical research on publicprivate partnership
UNIVERSITY OF WOLLONGONG
AUSTRALIAN CLINICAL TRIALS ALLIANCE
AWARDS UPDATE: Finalists announced July 2021 Award ceremony late 2021 Four Seasons Hotel Sydney
Research Australia proudly hosts its health and medical research and innovation Awards each year. The support given to these Awards this year through sponsorship and nominations has been incredible and we are extremely grateful. Our program is a year long event culminating in the exciting gala dinner where the winners are announced. Due to the pandemic our event will be extended further as the Gala dinner will take place later 2021. We’re excited that this will allow us to showcase the work of all our nominees in the lead up. Finalists will be announced in July and the winners, as per tradition, on 6 INSPIRE 018 | 2020
the night, which gathers members of parliament, sector leaders, key influencers and our members from across the entire health and medical research pipeline. This will be our 18th annual Awards but it also marks the 40th Anniversary of GSK's Award for Research Excellence which has been presented at our event for many years now. In the lead up to the announcement of the Award finalists we’ll be featuring all the nominations as well as the various Awards alumni. We are pleased to begin with the GSK Award for Research Excellence.
The Bupa Health Foundation partners with health and medical researchers to address the health needs of the Australian community. Our approach to partnering includes investing in research that improves health through changes to policy practice and behaviour; collaborating with researchers across the academic, industry and healthcare sectors; advocating for those who are improving health and developing the capabilities, skills and networks of the health and medical research community. The Bupa Health Foundation is one of Australiaâ&#x20AC;&#x2122;s leading foundations dedicated to health, investing over $33 million since 2005.
Find out more at bupa.com.au/foundation
GSK Award for Research Excellence Whilst the 2020 winners of Research Australia's seven Award categories will be announced in 2021, GSK has awarded their 2020 winner and will also be awarding a 2021 winner. Both will be acknowledged and celebrated at our Gala Dinner next year.
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2020 Winner - Professor Mark Febbraio
he GSK Award for Research Excellence (ARE) is one of the most prestigious and longstanding awards available to the Australian medical r e s e a r ch communit y. S ince 19 8 0, the awa r d recognises outstanding achievements in medical research focused on improving human health. In 2020, GSK Australia is proud to celebrate 40 years of the Award for Research Excellence and support for Australian research that helps to improve outcomes for patients both here in Australia and around the world. GSK Australia has awarded almost $3 million* to support Australian research and innovation through 40 years of the GSK Award for Research Excellence. Among the previous recipients of the GSK Award for Research Excellence are some of Australia’s most noted scientific researchers, including Professor Tony Basten (1980), Dr Bruce Kemp (1993), Professor Kathryn North (2011) and Professors Georgina Long and Richard Scolyer (2018).
and Molecular Metabolism Laborator y within the Drug Discovery Program at the Monash Institute of Pharmaceutical Science. Professor Febbraio’s research is pioneering the development of a new potential treatment for obesity, type 2 diabetes, and muscle mass loss. He and his team synthesized a protein (called IC7Fc), which has the potential to treat metabolic diseases that are known to be protected by exercise, by improving glucose metabolism and preventing weight gain. The team is now preparing for phase one clinical trials to determine the application of this discovery in addressing currently unmet treatment needs. The $80,000 prize that comes with the GSK ARE will support this next stage of the research. Professor Febbraio said that being the 40th winner of the GSK ARE is a great honour, and an achievement that belongs to his entire team.
* 2019 value calculated from the respective yearly grant by adjusting for inflation. We are delighted to announce the winner of this year’s Award, Professor Mark Febbraio, Head of the Cellular 2020 | INSPIRE 018 9
THE WORLD DESPERATELY NEEDS SCIENCE AND TECHNOLOGY TO PROVIDE THE PATH FORWARD FOR ALL OF US LIVING CREATURES. GSK Award for Research Excellence makes a difference
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1991 Winner - Emeritus Professor Alan Trounson CHRISTOPHE KEREBEL
resently, we are suffering immensely from a lethal virus pandemic brought on by human over-population, rapid and efficient mobility of humans and ineffective global political leadership. A lack of real global partnership to address these challenges through management of health and climate stability is a threat to our survival. The COVID-19 pandemic and its consequences have long been predicted by scientists. Population pressures enable a rogue virus with high infectivity to disperse rapidly. The mobility provided by air travel ensures its rapid dissemination through global populations. Unfortunately, a widespread lack of regard or understanding of science has made this tragedy lethal. Short-term funding has severely handicapped the vaccine research needed to be prepared for this event. This is why the GSK Award for Research Excellence (ARE), and initiatives like it, make an important contribution by recognising medical advances driven by scientific excellence. The multiplier effect of the Award has enhanced the scientific recognition and the productivity of special scientific minds. We need to hope that these advances will receive the wider community and political recognition needed to help us address the incredible challenges we presently face. My own career led from my early interests in animal reproduction to my involvement in the human In Vitro Fertilisation (IVF) and associated technologies. My work in these areas was recognised by the GSK ARE which I won in 1991.
My Twitter : @chriskere
will be welcomed by the entire global community. Meanwhile, I retain my strong attachment to animals, particularly endangered species, through my work with the Institute for Breeding Rare and Endangered African Mammals (IBREAM). I also continue my connection to delivery of IVF, focussing on helping resource challenged communities through the Low-Cost IVF Clinical Program, presently centred in Harare, Zimbabwe. When asked about over-population and IVF, my response is “educate communities about reproduction” and this has had a knock-on effect, which is limiting family size across couples in the population of reproductive age. Another issue that concerns me is the cost of technological advances in medicine. They can be large, threatening equality of adoption. It doesn’t have to be so. A case in point is the Low-Cost IVF Clinical Program. Medical economics needs a new paradigm, one where the costs can be absorbed by the benefits through offsetting the cost of keeping patients well and out of medical and social care. Finally, we – professors, doctors and researchers – in the medical research field need to continue the dialogue of medical benefits and true advances in health care with the community. In particular, we must ensure that we continue to support greater understanding around the key role of science, and become partners with political leaders to ensure that we are able to deliver developments in science and technology to the global community. Our work helps keep us all safe for the future.
My interests moved to human embryonic stem cells as a consequence of study of human embryos. This was an incredible development that has bolstered a massive interest in regenerative medicine across many diseases and injuries. As a result of my research, I had the privilege to lead the Australian Stem Cell Centre and the California Institute of Regenerative Medicine, with the support of Prime Minister John Howard and Governor Arnold Schwarzenegger. In these positions, I was able to help drive a medical revolution in cell biology and cell therapy. Since winning the ARE, I’ve been involved in numerous projects using stem cells in regenerative medicine. Currently, I am using these experiences to develop new immune stem cell therapies for cancer, along with my colleagues at Cartherics, Monash University and the Hudson Institute of Medical Research. We are also targeting cells infected with pathological viruses such as those associated with COVID-19 and HIV. The opportunity to work with like-minded scientists around the world on major diseases and conditions is very special. I’m confident that the technology, which is evolving rapidly,
Author: Emeritus Professor Alan Trounson, MSc PhD LLD Hon Dr FRCOG FRANZCOG FATSE FAHMS Distinguished Scientist, Hudson Institute Emeritus Professor, Monash University CEO, Cartherics Pty Ltd
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HEALTH ECONOMICS ROUNDTABLE The Research Australia Health Economics Roundtable was established in 2017 as a forum for connecting health economists from within Research Australia’s membership with the broader research community and government. The group exists as a forum for collaboration, comment and research and was established to play a key and unique role in driving research-based evidence for health policy and program development.
Tom Walley CBE – HMRI
Research Australia’s sixth Health Economics Roundtable held on 16 September 2020 explored the impact of COVID-19 on medical researchers and assessed the economic case for health system reform in a postpandemic Australia. The Roundtable chaired by Research Australia Chair, Associate Professor Annette Schmiede, heard from Professor Tom Walley CBE the Director of the Hunter Medical Research Institute, Martin Bowles AO PSM the National CEO of Calvary Health Care Australia and Jennifer Doggett an editor at Croakey and former chair of the Australian Healthcare Reform Alliance.
Martin Bowles AO PSM – Calvary healthcare
The speakers and Research Australia’s CEO and Managing Director, Nadia Levin hosted working groups which discussed finding better ways to fund Australian health and medical research, the economic case for virtual care, and overdue reforms to the health system.
Jennifer Doggett – Croakey
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My Twitter : @chriskere CHRISTOPHE KEREBEL
UNIVERSITY ROUNDTABLE The Research Australia University Roundtable met for the last time in 2020 on 11 December. Presenters to the Roundtable included Professor Frank Wagner, currently Dean: Industry and Enterprise, University of South Australia, but previously Head of Strategic R&D Management at Fraunhofer Institute for Industrial Engineering IAO. Professor Wagner provided a brief explanation of the origins of the Fraunhofer Institutes and an overview of their structure, including the shared model and services. A presentation by Alison Verhoeven, Chief Executive of the Australian Healthcare and Hospitals Association described some of the challenges to undertaking research in Australia’s hospitals and the health system more broadly. This included a lack of understanding by funding bodies of the prerequisites for research in health settings, inadequate funding for research, and the challenges of balancing the time demands of research and clinical responsibilities. Alison shared some ideas for how to overcome current problems. Better recognition of the strategic place of health services in the research funding process and the design of programs is key. Consolidating funding processes across the Commonwealth and increasing
compatibility between ARC, NHMRC and MRFF programs would also be helpful. Dr Chris Nave, CEO Brandon Capital Partners Limited, provided the last presentation of the day. Chris started with an explanation of the origins of Brandon Capital Partners and the role it plays in the commercialisation of health and medical research in Australia. Chris explained how MRCF has progressed since its inception in 2007 and now has a large portfolio of investments at various stages of the commercialisation pipeline. Chris also provided a number of comments from the perspective of an investor dealing with research organisations and the research communit y and emphasised the need to overcome fragmentation. More standardisation in some areas, particularly around research agreements, would be beneficial. This was the last Roundtable chaired by Professor Shitij Kapur, as he is returning to the UK at the end of the year, to become the next President and Principal of King’s College London. Nadia thanked him on behalf of all present for his leadership of the Roundtable this year and wished him all the best for the future. The Research Australia Board is responsible for appointing a new Chair of the Roundtable, and this will be considered in the near future.
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ENDORSES BURNET HIV DIAGNOSTIC WHO offers highest level of regulatory approval for Burnetdeveloped point-of-care HIV test. Commercial and manufacturing partner Omega Diagnostics sees significant orders and interest from African, Latin American and Asian countries.
Burnet Institute-designed rapid point-of-care test for HIV has been accepted for the World Health Organization’s (WHO) list of prequalified in vitro diagnostics.
“In many countries around half of the patients who are diagnosed each year with HIV for the first time will actually need a range of other interventions, which they would miss out on if they didn’t have the CD4 test,” he said.
The VISITECT® CD4 Advanced Disease Test, developed by Burnet’s Global Health Diagnostics Group and c o m m e r c i a l i s e d a n d m a n u f a c t u r e d by O m e g a Diagnostics, was listed after WHO auditors found it effective at measuring a patient’s CD4 T cell count to assess whether urgent interventions are required in a patient diagnosed with advanced HIV.
SIMPLE AND ROBUST
Burnet Deputy Director, Associate Professor David Anderson said WHO prequalification, the highest level of regulatory approval for a product of its type, meant aid agencies delivering HIV services in low-to-middle income countries could use the test to put more people onto the appropriate HIV treatment sooner. “If you’re very sick with HIV before you get diagnosed, just going on some antivirals is not enough,” he said. The low-cost and portable test, which functions in a similar manner to a pregnancy test, provides a visual reading of whether a patient’s CD4 T cell count in their blood is below 200/μL, meaning their immune system has been compromised.
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Associate Professor Anderson said simplicity and robustness were key principles in designing the CD4 point-of-care test, and it was encouraging to see the WHO’s endorsement of these principles. “It validates Burnet’s overall approach to making diagnostics that can have a global impact: something as complicated and important as CD4 testing can be made into something as simple as a pregnancy test that you can read by eye,” he said. The technology and philosophy behind the CD4 test was being applied to other point-of-care tests currently in development for other diseases, including COVID-19 and sepsis.
We’re applying those principles in the same manner: making them work in the simplest possible way in any setting,” Associate Professor Anderson said.
My Twitter : @chriskere CHRISTOPHE KEREBEL
He reaffirmed that working with good partners, including Omega Diagnostics, which has commercialised and manufactured the VISITECT® CD4 Advanced Disease Test, as well as strong collaborations with Rush University and Duke University in the USA, showed Burnet’s diagnostics team could make a lasting impact on global health. Omega Diagnostics has attracted significant orders and interest from African, Latin American and Asian countries for the test.
PR China (ALT1 test, plasma separator, and others); and Axxin Ltd, Melbourne (instruments and design capability). They also work closely with international partners, and with other working groups across Burnet, to progress R&D on new diagnostics in malaria, hepatitis C, tuberculosis and other diseases.
“I am very excited about it. It will make a huge difference to the ability to get the most value out of the interventions available for HIV,” Associate Professor Anderson said.
OTHER DISEASES, INTERNATIONAL COLLABORATION
The Burnet Global Health Diagnostics Development Group laboratory has been active in the development of rapid, point-of-care tests for diagnosis of a number of infectious diseases, most recently in tests for improved patient management in the case of HIV and AIDS, viral hepatitis and liver disease, and other conditions in Africa and other resource-poor settings. The group works closely with Industry partners to achieve commercially available and sustainable diagnostic solutions, including Omega Diagnostics, UK (CD4 tests); Burnet spinoff, Nanjing BioPoint Diagnostic Technology Co. Ltd.,
Authors: Associate Professor Anderson trained in microbiology and molecular virology at the University of Melbourne and Fairfield Hospital/ Burnet Institute. His work has focused on understanding the structure and assembly of hepatitis viruses, and the use of this information to design better diagnostics, vaccines and antiviral therapies for control of major viral infections in humans. He has been active in translation of research into practical outcomes through commercial ventures and academic collaborations and is an inventor on 10 patent families. 2020 | INSPIRE 018 15
USING EVIDENCE TO INFORM GUIDELINES Supporting clinicians in finding the balance between COVID-19 risk-minimisation and a familycentred approach to end-of-life care in critical care
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My Twitter : @chriskere CHRISTOPHE KEREBEL
ust like many other countries, the Australian h e a l t h c a r e sy s te m h a s b e e n i m m e n s e l y challenged in responding to the coronavirus (COVID-19) pandemic. Whilst Australian public health and infection prevention and control measures, designed to contain and minimise the spread of COVID-19, have been successful relative to other countries, sadly, more than 800 Australians lost their lives to the disease.
Early data examining the transmission mechanisms and pathogenicity of SARS-CoV2 and infection rates from China, Italy and the USA provided evidence of the potential impact of a surge in admission due to COVID-19 on hospital resources. These data and WHO guidelines1 were used to guide Australia’s preparations and response, particularly for how health services would manage an imminent and significant increase in critical care admissions for people diagnosed with COVID-19. Substantial preparations were necessary to accurately measure current ICU bed and ventilator capacity, surge capacity, and address resource sustainability, in particular, personal protective equipment. But ICU is not just about beds, ventilators and personal protective equipment. Given that international COVID-19 data showed that in excess of 60% of patients who required mechanical ventilation died2, the intent of ICU care is not only to help patients survive acute threats to their health through the use of life-sustaining treatments, but also to provide highquality end-of-life care.
CARING FOR THE FAMILY
Critical care nurses are highly skilled and provide expert person-centred care to the sickest of patients, including at the end of life. Prior to COVID-19, in addition to managing a critically ill patient’s ongoing clinical needs, nursing care also extended to care of the family through advocacy, facilitating sensitive communication 3 and providing bedside education and support, including after a patient death4. The infection prevention and control measures put in place to minimise transmission of COVID-19 however, have meant that family members of patients who are SARS-CoV 2 positive and those with other lifethreatening diagnoses, are not permitted to visit in critical care settings. Significant mainstream and social media attention has highlighted the distress for families who are unable to visit the dying person. What is known is that family members want to hold vigil, and show their love and respect for the dying person. Staying close, observing and protecting is important to family members. When family visits are restricted, family members miss out on receiving immediate emotional 2020 | INSPIRE 018 17
support and are at greater risk of complicated grief 5. Nurses may also experience job dissatisfaction and moral distress associated with not being able to support family members. Whilst the rationale for restricted visits is understood, it also raised the question as to whether it would be possible to facilitate family visits for dying patients in the ICU, while also aligning with public health and IPC recommendations and guidelines. To that end, a position statement was developed, that synthesised existing evidence related to end-of-life care and family visits in Australian critical care settings, with emerging international COVID-19 research data, and public health and infection prevention and control guidelines for COVID-19 to develop a set of recommended practice guidelines for use by critical care nurses. 18â&#x20AC;&#x192; INSPIRE 018 | 2020
The position statement6 includes eleven evidence-based practice recommendations aimed at supporting and facilitating family visits in Australian critical care units, where ICU staff, resources and individual factors permit. The practice recommendations commence with factors to consider prior to facilitating a family visit such as assessing a family memberâ&#x20AC;&#x2122;s health and risk of COVID-19, and environmental considerations and limitations. Recommendations for how to manage the family visit including the timing of the visit, clothing recommendations, and how to prepare them for what they may see and do when entering the unit are also provided. According to the evidence, recommendations are also provided for family use of personal protective equipment with support from a suitably qualified clinician to don and doff the personal protective equipment safely.
My Twitter : @chriskere CHRISTOPHE KEREBEL
The recommendations also include facilitating privacy and time alone with the dying person, to allow the family member to say farewell. The recommendations conclude with describing hygiene, travel and laundering requirements for the family member, the importance of providing immediate emotional support at the cessation of the visit, and referral to additional services for ongoing support.
In recognition of the importance of developing an evidence-based solution that acknowledges the importance of family presence at the end of life, the position statement was jointly endorsed by the Australian College of Critical Care Nurses and Australasian College for Infection Prevention and Control and promoted nationally to members of each professional group. Whilst these evidence-based practice recommendations were developed to address an immediate need associated with the COVID-19 pandemic, it is possible they may also be relevant to future public health emergencies with the aim of protecting family-centred care and addressing the needs of patients, families and clinicians in times of challenge.
Author: Dr Stéphane Bouchoucha is a fellow and a Director of the Australasian College for Infection Prevention and Control. Stephane’s research programme in infection prevention and control has a focus on psychosocial factors affecting guideline adherence in contexts such as antimicrobial resistance and staff and patient safety. Deakin University
You may view the position statement here 1. World Health Organization. Infection Prevention and Control During Health Care When COVID-19 is Suspected. Interim Guidance. Geneva: WHO, 2020 https://www.who.int/publications/i/ item/10665-331495. 2. Yang X, Yu Y, Xu J, Shu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Resp Med. In Press 10.1016/S2213-2600(20)30079-5. https://doi. org/10.1016/S2213-2600(20)30079-5 3. Brooks LA, Bloomer MJ, Manias E. Culturally sensitive communication at the end-of-life in the intensive care unit: A systematic review. Australian Critical Care. 2019;32:516-23 10.1016/j.aucc.2018.07.003 4. Coombs M, Parker R, Ranse K, Endacott R, et al. An integrative review of how families are prepared for, and supported during withdrawal of life-sustaining treatment in intensive care. Journal of Advanced Nursing. 2017;73(1):39-55 10.1111/jan.13097. 5. Wallace CL, Wladkowski SP, Gibson A, White P. Grief during the COVID-19 pandemic: considerations for palliative care providers. J Pain Symptom Manage. 2020 10.1016/j.jpainsymman.2020.04.012. http://www.sciencedirect.com/science/article/pii/ S0885392420302074 6. Bloomer MJ, Bouchoucha S. Australian College of Critical Care Nurses and Australasian College for Infection Prevention and Control position statement on facilitating next-of-kin presence for patients dying from coronavirus disease 2019 (COVID-19) in the intensive care unit. Australian Critical Care. in press 10.1016/j. aucc.2020.07.002. https://doi.org/10.1016/j.aucc.2020.07.002
Author: Associate Professor Melissa Bloomer is internationally-known for her program of research focusing on end-of-life and palliative care in hospital settings. With a clinical background as a registered nurse, her work specifically focuses on end-of-life care planning and decisionmaking, clinician preparedness for supporting dying patients, family involvement and care participation. Melissa was named as Postdoctoral Researcher of 2020 by the European Association for Palliative Care in recognition for her research bridging the gap between critical care and specialist palliative care. Deakin University
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FLINDERS NEW DIGITAL HEALTH LAB ADDRESSES HEALTH CHALLENGES In partnership with Cisco Systems and part of the Flinders University of Digital Health Research Centre, the Digital Health Design Lab (DHDL) was launched in February 2020 by Professor Trish Williams. This lab brings together some of the best minds in healthcare, industry and academia to create practical digital health solutions to some of society’s most pressing health challenges.
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My Twitter : @chriskere CHRISTOPHE KEREBEL
ollaboration and innovation are core to the Lab’s mission: using science, technology and people to bring to life a world of possibilities in digital health. We take a systems perspective, dr awing on year s of industr y and healthcare experience in data and design thinking to understand the unique environment of healthcare settings and create solutions which integrate seamlessly into their workflows. We build a community of practice: drawing together healthcare and healthcare innovation leaders nationally and internationally to deepen insights, facilitate the identification of gaps in knowledge and to enable fast, impactful progress. Our areas of focus : ● We under take applied innovation projects with stakeholders in the health system to create new techniques, understandings, collaborations and initiatives in the task of health transformation. ● We publish research that shares insights and knowledge in digital health, explores new topics and knowledge and informs broader theory, public policy, debate and practice. ● We host research seminars and events which showcase and communicate insights and facilitate collaboration.
RECENT PROJECTS :
● DIGITAL HOSPITAL SAFE WIRELESS: A standardsd r i v e n f r a m e w o r k f o r s a f e w i -f i d e s i g n a n d implementation in hospitals. ● INFRASTRUCTURE MATURITY ASSESSMENT: An international benchmark for the technology capabilities required to support increasing sophistication in healthcare delivery. ● INFRASTRUCTURE INFORMATION EXPERIENCE FRAMEWORK: A method to create a positive impact on the patient and clinical experience whilst supporting operational outcomes. ● CAMPUS MENTAL WELLNESS IOT FRAMEWORK: For enhancement of student wellbeing. ● DIGITAL HEALTH SYMPOSIA: Bringing together international experts in digital health and medical devices to network, share knowledge, and discuss issues and trends. ● VIRTUAL CARE WHITEPAPER : Reimagining a better healthcare system through virtual care. 2020 | INSPIRE 018 21
JOINING THE DOTS
We aim to join the dots between technology, people and process; bringing individuals a step closer to more effective, personalised and precise healthcare. We undertake innovative collaborations and experimental research with a variet y of stakeholders applying computation design, digital foot-printing, experience mapping, proof-of-value and prototyping. We generate applied and actionable knowledge and we share our digital health insights and knowledge through publications and white papers informing theory, public policy and practice. By enabling healthcare professionals to quickly connect 22â&#x20AC;&#x192; INSPIRE 018 | 2020
with patient information and gain new insights into their treatment progress and overall health, the field of digital health has great potential to improve patient outcomes and empower individuals to better manage their health. But we are still a long way from the vision of truly transformative information-enabled care. The interoperability and security challenges of digital health are real: from integrating new and legacy systems, multiple organisations, individuals and workflows; to the evershifting threat of cyber security. Despite years of progress we still struggle to bridge the gaps between technology, people and process. Our mission is to join the dots.
My Twitter : @chriskere CHRISTOPHE KEREBEL
To provide the missing parts of the puzzle by finding opportunities for people, data and devices to work together better, and by mining data for information which can be put to work in a useful way. At the end of the day, we want to bring humans a step closer to more effective, personalised and precise healthcare.
A UNIQUE COMBINATION
It took an unusual combination of expertise, passions and experience to create the Digital Health Design Lab. We are drawn together by our commitment to answering the central question of digital health: how information and technology can support people to deliver better healthcare.
Our human-centred approach gives us a deep understanding of how people and healthcare systems work; and gives meaning and context to our vision of optimising care delivery by better connecting people with information, systems and each other. The Lab’s team has real-life experience in the field of digital health. Our unique ability to bridge the gap between academia, healthcare and industry has given us a proven track record of tangible, practical outcomes in a clinical context. And because we approach problems from a systems perspective, grounded in design thinking, we are able to create integrated solutions as well as new applications for existing ones. Our Lab’s unique combination of expertise, real-life experience, and industry relationships puts us at the heart of industry, policy, academia, international standards, and frontline users – all of which need to be connected in order to achieve true digital health transformation. We collaborate with healthcare, industry and academics to inspire and enable them to see new solutions to today’s digital health problems.¸
Professor Trish Williams
Author: Professor Trish Williams, Professor in Digital Health Systems Flinders University
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TOWARDS A MORE SPECIFIC AND SAFER TREATMENT FOR AUTOIMMUNE VASCULITIS Novel Immune Cell Therapy for Autoimmune Vasculitis
nti-myeloperoxidase vasculitis (MPO-AAV) is a life-threatening disease which causes severe inflammation and damage of small blood vessels, mainly in the kidney. It leads to significant morbidity and mortality. In Australia, its incidence is similar to that of multiple sclerosis and it costs our health system hundreds of millions of dollars/year. It equally affects men and women, mainly over 50, but it also affects young adults and children. MPO-A AV is caused by autoimmunity to MPO, an abundant protein found inside our most common white 24â&#x20AC;&#x192; INSPIRE 018 | 2020
blood cell, the neutrophil. Current treatments for MPOAAV are partially effective, non-specific and toxic. The first line of therapy still consists of high doses of immunosuppressive drugs, cor ticosteroids and cyclophosphamide, which were first introduced in the 1960s. They induce remission in 70-90% of patients, but the incidence of dialysis or death at 5 years is still high (30%). 1 in 3 patients also relapse while being treated. The main problem with these therapies is that they work by suppressing the entire immune system. This leaves
patients highly vulnerable to serious infections and Generating cancer. They also cause other serious side effects such as cardiovascular problems, depression and diabetes. Of all patient deaths, an alarming 70% are caused by drugrelated side effects, mostly infections. CHRISTOPHE KEREBEL Hence, there is an urgent need for more specific, safer therapies. Ideally, such therapies would induce antigenspecific immunosuppression, i.e. they would inhibit only anti-MPO autoimmunity, while leaving our protective immunity against pathogens and cancers intact.
A NEW APPROACH
Specialised immune cells called tolerogenic dendritic cells (DCs) can deliver antigen-specific immunosuppression and are therefore an appealing therapy for autoimmune disease. Autologous tolerogenic DCs have been shown to be effective in animal models of various diseases. Importantly, several phase I clinical trials have proven their feasibility and safety in patients. Therefore, these inhibitory cells (by presenting MPO) have the potential to turn off only autoimmunity to MPO which causes vasculitis, without affecting the rest of the immune system. This would stop or reverse kidney damage caused by vasculitis, with negligible adverse effects. In our recent study (Odobasic et al, J Am Soc Nephrol, 2019), we innovatively took a leap away from standard, non-specific approaches to treat MPO-AAV. We used an animal model of this disease, which we uniquely established several years ago and which closely resembles human disease. In this model, we showed for the first time that injecting MPO-presenting tolerogenic DCs can specifically turn off only anti-MPO autoimmunity and thus vasculitis, without affecting immune responses against other proteins.
& Using Autologous MPO-presenting Toler KEREBELpatients as a therapyCHRISTOPHE in MPO-AAV My Twitter : @chriskere CHRISTOPHE KEREBEL
MPO-presenting Tolerogenic DCs
Incubate with human MPO (2 hours)
Culture for 6 days (with GM-CSF + IL-4 and NFkB inhibitor)
tolerogenic DCs in humanised mice (mice with human immune cells) to show that these cells can specifically turn off pathogenic human autoimmunity to MPO in vivo. These studies will likely lead to a first-ever clinical trial of tolerogenic DCs in MPO-AAV which we hope to start at Monash Health.
The DCs were made tolerogenic by pre-treatment with an inhibitor of NFkB, a major pro-inflammatory pathway in DCs. Importantly, the DCs were also treated with MPO, so they can present it and therefore turn off only MPOspecific T cells which cause MPO-AAV. In addition, we showed that the DCs suppressed anti-MPO autoimmunity and vasculitis by inducing immunosuppressive cells called regulatory T cells in the recipient animals. The importance of this work was shown by the fact that it was immediately featured as a Research Highlight in the prestigious international journal, Nat Rev Nephrol (15, 662; 2019). Therefore, tolerogenic DCs could potentially be a new, effective and much safer treatment for MPO-AAV. This therapy could provide immense benefit to patients and improve their quality of life by reducing their complications and death which are currently experienced with the standard, non-specific, harmful therapies. In fact, by turning off autoimmunity to MPO, the primary cause of vasculitis, these cells could virtually provide a ‘cure’ for this devastating disease.
Future work involves collecting blood cells from MPOAAV patients to show that patients’ own tolerogenic dendritic cells can turn off their autoimmunity to MPO in vitro. We also plan to use human MPO-presenting
Dr. Dragana Odobasic
Author: Dr. Dragana Odobasic is a Research Fellow and an Emerging Leader in the Department of Medicine, Centre for Inflammatory Diseases, Monash University. Her main research focus is to find safer treatments for autoimmune kidney disease. She is currently testing various cell therapies including tolerogenic DCs, regulatory T cells and stem cells.
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A GROWING APPETITE FOR NEW EATING DISORDER SOLUTIONS
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Research combing through a myriad clinical, genetic and environmental factors is bringing order to the life-threatening chaos of disordered eating.
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roblems attached to eating disorders reach far Importantly, this is a real-world trial of MBS payments and CHRISTOPHE KEREBEL My Twitter : @chriskere other supports for clinicians required to change primary care beyond affected individuals. They ultimately CHRISTOPHE KEREBEL become family concerns, which is why evidence- responses to people with eating disorders. The research based research into eating disorder interventions results – both emerging and final – will be used to influence must be informed by partnerships between patients, state, territory and Commonwealth government policy. carers, health professionals and researchers if they The Blackbird Initiative contributes to a personalised are to lead to tangible improvements.. medicine approach, using individual profiles to fit indicated Eating disorders mainly emerge over adolescence and treatments and adjuncts. For this to succeed, we must are often dismissed at first as “a phase” – a trajectory ask new and more specific questions. What’s the genetic that usually turns from wanting to lose a bit of weight, profile? What’s the personality profile? What are the to developing strict rules around healthy eating, to particular risk factors? What sensible additions to the goodnot wanting to eat with the family, and by that time the enough treatment would be very effective for this individual? changes should be ringing alarm bells. Having worked as a clinician to address eating disorders for 30 years, I know it’s important at this stage for families to seek help as early as possible for an eating disorder. These situations need to be closely monitored because problems can develop quick ly, especially if the individuals are in a peer group that’s particularly critical of appearance and they’re being bullied or teased about appearance through the sometimes toxic world of social media, particularly platforms like Instagram that feature many images of idealised bodies.
MANY FACTORS AT WORK
While interventions like cognitive behaviour therapy help 50% of people with bulimia nervosa to recover, and around 30% of people with anorexia nervosa, we need to extensively comb through clinical, genetic and environmental factors to improve outcomes. This is the focus of the Blackbird Research Initiative. We seek to gain a better understanding of genetic and epi-genetic pathways that may suggest novel adjunct interventions, and we are evaluating and disseminating forms of online therapy that young people and their carers find accessible and compelling. We are developing models for early intervention with primary health care settings such as headspace, and evaluating the rollout of eating disorder treatments by nonspecialist clinicians.
We seek to empower consumers seeking private therapy for an eating disorder under new expanded Medicare items, to locate the best option for them. This work needs to be underwritten by a commitment to involve more people with lived experience in co-designed research.ˮ Applied focus is evident in our partnership with the Sunshine Coast Eating Disorders Access Trial, administered by Butterfly. This Federally funded translation project is evaluating the rollout of the provision of Eating Disorder treatment by clinicians not already working in this area. The analysis will identify what issues need to be sorted before wider rollout of such therapies, in response to the expanded Medicare funding that commenced last November.
MORE THAN A DISORDER OF YOUNG WOMEN
This is challenging because eating disorders are not just a disorder of young women. It is rising steeply in men, who can often experience a severe course with the illness if they get anorexia nervosa as a teenager, resulting in high co-occurrence of obsessive/compulsive traits and perfectionism. Gender identity challenges lead to increased risk for the development of eating disorders. Women in their forties and fifties are another group vulnerable to disordered eating, with about 15% struggling with this at any one time. Engaging people in interventions can be difficult because of ambivalence about disordered eating. While people might not like aspects of disordered eating, such as binge-eating and vomiting, they don’t want to gain weight, or they want to continue losing weight – a value highly endorsed by society generally. Change is also difficult because eating disorders are highly comorbid with other conditions, such as anxiety disorders (50%), mood disorders (40%), self-harm (40%) and substance use (10%). Devastatingly, people with an eating disorder have a mortality rate 12 times higher than people without an eating disorder. Unless treated successfully, a person’s struggles with an eating disorder can be lifelong if not life-ending. Our research indicates 15% of Australian teenage girls will be diagnosed with an eating disorder before they turn 19. The COVID-19 era has seen an alarming increase in demand for eating disorders services, especially from young people, with wait lists extending across all services. There is an urgency and immediate need for the type of applied research that Blackbird champions. My passionate vision is for a future where all young people can live a life free of mental illness and embrace all the possibilities that life has to offer. Author: Professor Tracey Wade, Mathew Flinders Distinguished Professor in Psychology at Flinders University, and Director of the Blackbird Research Initiative. From January 2021, Professor Wade will commence as Director of Órama Institute for Mental Health and Wellbeing at Flinders University. 2020 | INSPIRE 018 29
BANKING ON THE GENETICS OF PRADER-WILLI AND ANGELMAN SYNDROMES TO IMPROVE INDIVIDUAL OUTCOMES
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Possible triggers have been identified for debilitating symptoms of rare diseases including Prader-Willi and Angelman syndromes. The discovery, along with Australia’s first biobank specifically for chromosome 15 disorders, could lead to more effective and personalised therapies.
ew research, and a philanthropically funded biobank for Prader-Willi, Angelman and other chromosome 15 associated syndromes, could help develop personalised therapies for associated mental illness, autism features and motor issues. Those with Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) have few treatment options for possible complications including motor issues, autism and mental illnesses such as psychosis. PWS and AS affect 1 in 15,000 people. PWS is a leading cause of life-threatening obesity, while AS is associated with potentially severe seizures. Both can cause intellectual and behavioural challenges. Apar t from growth hormone, the only Prader-Willi Syndrome treatments are for individual symptoms. Angelman Syndrome only has symptom therapies such as anti-seizure medication and physical, communication and behaviour therapy. Murdoch Children’s Research Institute (MCRI) experts collaborated with the University of Kansas Medical Center (KU Medical Center) to examine the expression of key genes, such as UBE3A, in white blood cells which form part of the immune system. Published in Translational Psychiatry, the new study found that functional changes to UBE3A in white blood cells are associated with social and communication difficulties and autism features in PWS, and impairment of fine motor and language skills in AS. These are paradigm shifting findings, as previously researchers thought that the function of genes in nerve cells was responsible for the key clinical features. The findings from this study are important because they suggest that other cells regulating inflammatory pathways may contribute to key clinical features in PWS and AS.
Senior author, MCRI Diagnosis and Development Laboratory head Associate Professor David Godler, said that immune system cell changes had been linked to mental health issues in other disorders, including autism. This study now also implicates them in chromosome 15-related conditions, which could lead to future studies and new treatments to control immune cell function, predict the type and severity of symptoms and assess the effectiveness of new treatments as they are developed.
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UNCOVERING THE ROLE OF THE IMMUNE SYSTEM
“The immune system plays an important role in ensuring that nerve cells in the brain function properly through cells called glial cells,” Associate Professor Godler said. “These cells are closely related to white cells found in blood. Our findings suggest that this interaction between cells of the immune system and nerve cells in the brain also contributes to key symptoms in PWS and AS, where changes in immune cells outside of the brain reflect processes in the brain.” The rare disease natural history was performed on 58 individuals with chromosome 15 imprinting disorders and 20 typically developing controls. Australian study clinical lead, paediatrician and clinical genetics specialist Professor David Amor said, “What we’re really trying to do is look in great detail at the biology, coupled with the psychology features and the behavioural features, to see if we can use those insights on the translational pathway to effective, individualised treatment.” “For a child that has significant obsessions or behavioural 32 INSPIRE 018 | 2020
disturbance or autism, even if we can improve those by 20 per cent, that translates into a substantial improvement in quality of life both for the child and for the family.” Project psychologist Dr Emma Baker said psychiatric and behavioural issues associated with these conditions, such as emotional outbursts, communication issues, and restrictive and repetitive behaviours, were “quite challenging”. “This can really interfere with how an individual with Prader-Willi engages with the world,” Dr Baker said. “One of the big issues for children with Angelman syndrome is their motor difficulties and we did find associations between these genes and fine motor skills. If you can improve motor skills, you can improve engagement and learning.” The project involved international experts from the University of Kansas Medical Centre and was funded by US-based Foundation for Prader-Willi Research (FPWR) and Foundation for Angelman Syndrome Therapeutics (FAST), and now has FPWR funding to examine brain tissue. FPWR Director of Research Programs Dr Theresa Strong
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said novel insights the study had uncovered laid the groundwork for exploring new therapeutic approaches for some of the most challenging aspects of PWS. “Autism features, behavioural problems and mental illness can have profound impacts on the individual with PWS and their family,” Dr Strong said.
“We hope that this important resource will be widely used by other researchers to more efficiently move the field forward, with the ultimate goal of finding new treatments or repurposing old ones that would improve the lives of thousands of children and their families around the world.”
Such projects will also benefit from Australia’s first biobank for rare genetic diseases caused by changes to genes on chromosome 15, which MCRI recently launched with Prader-Willi Research Foundation Australia (PWRFA) and FAST Australia. Associate Professor Godler said the biobank would facilitate research in Australia and internationally by other researchers, building on the important findings reported in this study. “We have answered a couple of key questions, but now there are another thousand questions that follow,” he said. “Rather than contacting 100 patients 100 times by 100 researchers to collect the same data and biological samples to answer different question, we will do this once and make it available to others through the biobank.”
Authors: Associate Professor David Godler is a Medical Research Future Fund (MRFF) Next Generation Clinical Researchers Program – Career Development Fellow, group leader at MCRI, and a Principal Fellow (honorary) at the Department of Paediatrics, University of Melbourne. Professor David Amor is a Clinical Geneticist and Galli Chair of Developmental Medicine at the University of Melbourne, and group leader at MCRI. Dr Emma Baker is a provisional psychologist and post-doctoral research officer at the Murdoch Children’s Research Institute.
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ARMING AUSTR CLINICIANS WI LATEST EVIDE AROUND THE G In late March, as lockdown restrictions were rolling out around the country, a diverse coalition of representative health bodies came together to focus on clinical care for Australians with COVID-19. A first of its kind, the National COVID-19 Clinical Evidence Taskforce was established to provide a trusted voice of cross-disciplinary evidence-based consensus in a time of great uncertainty.
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RALIAN ITH THE ENCE FROM GLOBE
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lmost eight months on, the Taskforce now includes over 200 leading experts from 32 national peak health organisations across primary, acute and critical care. The Taskforce team works around the clock to analyse global research findings, summarise the latest evidence and inform easily accessible ‘living’ COVID-19 Clinical Guidelines. Typically, guidelines such as these are updated every 3-5 years, but in a world-first approach these COVID ‘living’ guidelines are updated with the latest research every week. This up-to-the minute approach accelerates the translation of the latest research into practice and provides Australia’s frontline health workers with a trusted single source of evidence-based guidance so they can provide the best possible care for people with COVID-19.
THE ONGOING DATA DELUGE: TRACKING GLOBAL COVID RESEARCH IN REAL TIME
A key challenge for anyone involved in the response to the COVID-19 pandemic is keeping up with the sheer volume of research being published; over 26,000 studies have been published and 2,000 randomised trials registered to date and these numbers keep climbing every week. To continuously monitor and translate this research, the Taskforce employs a dynamic model that uses continuous evidence surveillance systems to identify relevant studies as soon as results are made available. Evidence teams rapidly incorporate these data into summaries and present 36 INSPIRE 018 | 2020
these to 9 expert guideline panels that meet weekly to update specific, patient-focused recommendations. The need for this kind of near-real time or ‘living’ evidence has never been more critical, given the high levels of uncertainty around treatments, the rapid emergence of new research, and the conflicting and often controversial claims made in daily media coverage.
Against this challenging backdrop, the Taskforce continues to arm Australian clinicians with the up-to-date evidence and trusted advice they need. This approach is also providing a realworld demonstration of how living guidelines can transform what has traditionally been a fragmented, slow and expensive process into one that is responsive, collaborative, efficient and rigorous. ‘LIVING’ GUIDELINES BASED ON NEARREAL TIME, TRUSTED EVIDENCE
The ‘living evidence’ model was pioneered in Australia by the Australian Living Evidence Consortium in partnership with Cochrane (one of the world’s most trusted health evidence providers). First tested in frontier projects maintaining living national stroke and diabetes guidelines,
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this model is now being deployed in the rapidly evolving response to the COVID-19 pandemic. To date the Taskforce has published 88 recommendations covering treatment for adults, adolescents, children, pregnant women, older people and people receiving palliative care, including the use of dexamethasone, remdesivir and the controversial drug hydroxychloroquine. An additional advantage of this dynamic model is the ability to continually identify and respond to frontline clinicians’ current questions and concerns. These can be submitted by clinicians through the Taskforce website and are used to shape the priorities and work of the Taskforce panels. As such, a ‘living evidence’ approach allows a dynamic two-way partnership between the Taskforce guideline panels and their clinician colleagues.
LOOKING AHEAD: THE CHALLENGES OF INFECTION PREVENTION AND CONTROL
With most lockdown restrictions now lifted and numbers of COVID cases low across Australia, prevention of future outbreaks has become a central focus for policymakers and clinicians. To this end, in late September Health Minister Greg Hunt announced a new partnership between the Taskforce and the Australian Government’s Infection Control Expert Group (ICEG) with the aim of providing living guidelines on specific infection control issues that are critical to the ongoing response of Australia’s health system to the pandemic.
This partnership brings together Australia’s leading infection control practitioners and the Taskforce’s multidisciplinary experts to review the latest evidence and make consensus recommendations on infection prevention and control. This represents a significant broadening of scope for the Taskforce, and is one of the many significant areas that has challenged Australia’s ability to navigate this global health crisis. But as the Taskforce continues to demonstrate, Australia’s leading researchers, health experts and peak health organisations have the unity of purpose and experise to deliver the guidance frontline health workers continue to need throughout the COVID-19 pandemic.
Author: Rhiannon Tate is the Director of Strategy and Engagement for the National COVID-19 Clinical Evidence Taskforce and the National Development Coordinator for the Australian Living Evidence Consortium. She has over a decade of experience in strategic development and leadership of major national and international research collaborations, including as Chief Executive Officer of the Australian Clinical Trials Alliance which she helped to establish in 2014.
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PREVENTING NEURODEGENERATION AFTER STROKE Stroke is a leading cause of death and disability worldwide. Ischemic stroke accounts for more than 85% of the stroke cases in people >50 years old. Stroke is characterised as a focal neurological deficit that results from a disruption of blood flow and subsequent neuronal death in that area of the brain. Current acute stroke treatment is focused on interventions to prevent mortality, minimise acute brain damage and /or resultant neurological disability.
schemic stroke also trigger s secondar y neurodegenerative injury pathways in the brain, resulting in debilitating comorbidities including chronic fatigue, spasticity, mood disturbances, c o g n i t i ve d e c l i n e a n d p o s t- s t r o ke - e p i l e p sy. Unfortunately, current treatments are not able to prevent these debilitating comorbidities. To date, the pathophysiological mechanisms that underlie these long-term neurodegenerative consequences remain unknown; however they hold promise as potential targets for therapeutic intervention to improve the long-term health outcomes for individuals following stroke. 38â&#x20AC;&#x192; INSPIRE 018 | 2020
As the prevalence and enormous socioeconomic burden of these chronic consequences is huge, it is imperative that experimental research studies are performed as the first step to identify the underlying mechanisms, as well as develop targeted therapeutic interventions, followed by proof of concept and translational studies. Dr Pablo Casillas-Espinosa is a NHMRC Peter Doherty Early Career Research Fellow from the department of Neuroscience Monash University and Alfred Health, in Melbourne, Australia. Dr Casillas-Espinosaâ&#x20AC;&#x2122;s team is using multi-omics approaches to understand the pathophysiological mechanisms that lead to the
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development of epilepsy after traumatic brain injury and stroke. Using the same multi-omics approach, the team is investigating novel targets for drug development and repurposing in dif ferent brain conditions. Dr Casillas-Espinos a’s late st wor k is inve stigating hyperphosphorylated tau (also known as h-tau) as a promising novel mechanism of neurodegeneration after ischemic stroke, and further as a biomarker of strokerelated comorbidities (e.g. epilepsy, motor and cognitive problems).
H-TAU AND NEURODEGENERATION
Group, Department of Neuroscience) and Professor Terence O’Brien (Head of the Central Clinical School, Monash University) has shown that treatment with sodium selenate potently reduces h-tau and improves outcomes of traumatic brain injury, dementia and epilepsy. Given the pathophysiological overlap between these brain conditions and ischemic stroke, h-tau may also be a central mediator of the long-term neurodegenerative consequences of ischemic stroke. Moreover, sodium selenate has great promise as a “game changer” in treatment that prevents neurodegeneration after ischemic stroke and generates improvement of the devastating comorbidities associated with ischemic stroke.
The microtubule associated protein tau is key to microtubule stability and axonal transport within neuronal cells. Hyperphosphorylation of tau causes this protein to dissociate from microtubules creating aggregates of protein, reducing neuronal stability and promoting neurodegeneration. H-tau is observed across a wide range of neurodegenerative diseases including traumatic brain injury, epilepsy, Alzheimer’s Disease and other dementias. Dr Casillas-Espinosa’s team in collaboration with Drs Lucy Vivash and Bianca Jupp from the Department of Neuroscience at Monash University, has shown a world-first using tau tracer PET imaging of tau levels in the brain of rats following experimental stroke using the middle cerebral artery occlusion (MCAO) model. This has been accomplished by using the novel tracer preclinical imaging facility at the Alfred Translational Research Precinct, a node of the Monash Biomedical Imaging. This work provides important proof of concept for the utility of this tracer to study the role of tau in rodent models of neurological and neuropsychiatric disease, as well as test new therapeutics targeting this protein.
CAN THE H-TAU NEURODEGENERATIVE AFTERMATH BE PREVENTED?
Sodium selenate is a novel and unique oxidised form of selenium that activates PP2A/PR55 phosphatase (the main tau phosphatase) and also decreases h-tau. Work from Dr Casillas-Espinosa, Associate Professor Sandy Shultz (Principal Investigator, Monash Trauma
Author: Dr Pablo M. Casillas-Espinosa is a NHMRC Peter Doherty Early Career Fellow in the Department of Neuroscience, Central Clinical School at Monash University and Alfred Health in Melbourne, Australia.
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TIPPING THE S ON CELL AND G MAKING THERAPY: MANUFA
Chief Investigator Robert Nordon and the Development Team; from left to right: Dr Jingjing (Jane) Li, Osmond Lao, Dr Kajal Chaudry, Dr Liyuan Wang. 40â&#x20AC;&#x192; INSPIRE 018 | 2020
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Cell therapy is the introduction of cells into a patient’s body to grow, replace or repair damaged tissue or as a treatment for cancer.
G CELL ACTURE DABLE WITH A T BIOREACTOR
he intersection with gene therapy occurs when cells carrying a genetic mutation are collected from a patient, genetically modified to correct the defect and then returned to the same patient. In 1990, 4-year-old Ashanti DeSilva was treated by gene therapy for ADA-SCID, a severe combined immune deficiency caused by homozygous mutation of the gene encoding adenosine deaminase. Although only partially effective, that event is widely accepted as the world’s first successful human gene therapy trial.
Since then, gene therapy has been somewhat slow to progress with the confidence of biopharmaceutical companies and investors waxing and waning as problems arising from the negative impact of the 1995 NIH report on investment in gene therapy1, adverse events and concerns around durability have taken their toll2. The successful registration of Glybera in 2012 to treat a rare lipoprotein lipase deficiency played a large part in rebuilding that momentum, leading to the current position where nine cell and gene therapy (C&GT) products are now approved by the FDA and 362 novel C&GTs are in clinical development by biopharmaceutical companies in the U.S. alone3.
EFFECTIVE BUT EXPENSIVE
However, the health economics is one of the major obstacles facing widespread introduction of these transformative technologies into clinical use. A report issued by the Institute for Clinical and Economic Review concluded that the $850,000 price tag for Luxturna, a treatment for retinal disease, was 2- to 4-fold above costeffectiveness standards4. The market price in the US for FDA-approved C&GTs for refractory B-Cell leukaemia and lymphoma, $US475,000 Kymriah (Novartis) and $US373,000 Yescarta (Gilead) is well beyond healthcare budgets in Europe and Australia.
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The Australian government has allocated funding for only 50 Kymriah treatments each year. The large number of C&GT products in development represents a threat to the health insurance systems around the world. If pricing remains the same, payers may refuse to support reimbursement and investors could fail to see their expected returns5. To offer C&GT at more affordable prices without disincentivising biopharmaceutical companies or investors, it will be necessary to dramatically reduce the cost of C&GT manufacture6.
REDUCING THE COST
The price tag of C&GT is critically dependent on the manufacturing cost of the genetically modified cells, which in turn, is critically related to the cost of goods, such as viral vectors and culture media, facilities such as clean rooms, capital costs including automated cell processing systems and personnel trained in good manufacturing practice. Estimates indicate labour costs constitute 70% of the total6. Part of the answer lies in the development of low-cost, highefficiency, automated cell processing devices that minimise these costs. While automated cell processing devices are already in use, they are large footprint machines that require highly skilled staff to run and involve complicated multi-step procedures.Dr Robert Nordon and his team from UNSW’s Faculty of Engineering are tackling these problems and have developed microfluidic technology for miniaturising and simplifying the therapeutic cell manufacturing process. Building on an existing collaboration with CSL, the team recently expanded to include Genesys Electronics Design and were successfully awarded a 3-year CRC-P grant with a total project budget of $9M including $6M in cash to develop their microbioreactor7.
CSL aims for the microbioreactor to be focused on enduser needs and support the technology’s development. CSL is a global leader in biotechnology and one of the largest companies in Australia. Cell and gene therapy development is an area in which CSL is expanding its capabilities, having recently acquired a number of biotherapeutic technologies for the treatment of diseases such as sickle cell disease and β-thalassemia. Dr Anthony Stowers, Senior Vice President Recombinant Product Development at CSL, welcomed the grant, saying,
gene therapies hold great promise in providing lasting and even curative treatments for conditions that are currently incurable. However, as an emerging field, they are difficult and expensive to make. We are very pleased to be able to support this program by providing our expertise in cell biology and manufacturing in the hope that a fast, reliable and efficient instrument will be delivered to support better outcomes for people with serious medical conditions.” This project supports the strategic priorities of Genesys, which has been to increase its focus on the development of high-reliability devices such as those used in medical industries. A few years ago, Genesys attained ISO 13485 certification for the design of active medical devices – those with software and electronics. This new project will take the company beyond design to become a certified manufacturer of medical devices.
UNSW Deputy Vice-Chancellor (Acting) of Enterprise Professor Eliathamby Ambikairajah said: “It is exceptional partnerships like this that brings UNSW closer to our vision of improving quality of life for people in Australia and around the world. We are delighted to see our life-changing technology being recognised and translated into real-world impact. The grant is a testament to the extraordinary work being done throughout the University and in conjunction with our partners. UNSW looks forward to continuing the relationship with Genesys and CSL, and seeing the positive impacts the new platform will have on society.”
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Author: Stephen Palmer PhD, Senior Business Development Manager, Life Sciences Knowledge Exchange, Division of Enterprise, UNSW Sydney
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SCIENCE AT WARP SPEED THE RAPID RESEARCH TRANSLATION AND COVID-19 We often hear that biomedical innovation and research translation is slow, sometimes taking decades for an idea to translate into practice.
ar ious explanations ar e of fer ed for this slowness, including resource limitations, cultural barriers, and the need for reflection and critique inherent in the scientific method itself. Research is also slowed by the governance processes that demand that criteria be met before research projects are funded and technologies are registered, funded, and made accessible to patients. The COVID-19 pandemic, the worst public health crisis in a century, has changed the world in profound ways and led to significant shifts in our social, political, economic, and scientific priorities. It has meant that the usual nonlinear pathways of evidence creation that informs practice and policy have been disrupted and significantly sped up.
SCIENCE AT WARP SPEED
In late October, the World Health Organisation recorded over 2 million new cases and close to 40,000 new deaths from COVID-19 in a single week – making it clear that the COVID-19 pandemic has not begun to abate and in many parts of the globe it is resurging or accelerating. In response to the COVID-19 pandemic, there has been a rapid growth in research focused on developing vaccines and therapies. The most recent landscape update reveals 44 INSPIRE 018 | 2020
that at least 44 vaccine candidates are at various stages of clinical evaluation, progressing through development phases at speeds previously not realised. On the surface, this appears to be a good thing and there are justified calls for this pace and momentum to be maintained. But, like “warp speed” (a science fiction notion, specifically because matter cannot travel faster than light without distorting into infinite mass), there might be a maximum pace at which science can “travel” before it distorts and its harms begin to consistently outweigh its benefits. A myriad of events, such as the retraction of the Surgisphere hydroxychloroquine study by the Lancet and the New England Journal of Medicine in June of this year, President Trump’s efforts to fast track Emergency Use Access approvals and the increasing use of off-label therapies for patients with COVID-19 raise the question of what, if anything, might be lost when research is sped up.
GOVERNING AND PROMOTING SCIENCE AT WARP SPEED
While there are excellent reasons for conducting, reviewing, and translating research rapidly during epidemics, there are also serious risks associated with doing so. The potential damage caused by not ensuring
effective governance of research during epidemics may be immense and result in injury to millions of people, useful drugs and devices might be abandoned, and irrational and ineffective healthcare might proliferate. CHRISTOPHE KEREBEL So, how do we facilitate rapid research, while still ensuring research quality, safety and integrity are maintained?
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Some possible solutions include: ● independent scientific review panels to review research prior to it commencing, during its conduct, and prior to publication (including rejecting research which would not meet basic quality standards in non-emergency times or research that is not of the utmost priority during an emergency, establishing standards for review of emerging technologies or methodologies, and making sure that competing interests are identified and managed); ● establishing or repurposing dedicated research facilities that specialize in and can coordinate rapid research and its governance (and providing the resources needed for all bona fide researchers to be able to access these facilities); ● establishing processes by which data both for and from rapid research can be widely shared and collectively critiqued; and ● increasing the resources available to the agencies charged with rapidly making sense of the results of research and with making decisions under pressure about registration, funding, and clinical practice guidelines so that they can put in place the necessary scientific review and conflict of interest management processes. With such mechanisms in place (and adequately resourced) it should be quite possible to both speed up science and remain attentive to scientific quality and integrity. At the same time, we need to have a sensible discussion to determine how much quality people are willing to sacrifice in the name of speed. This is not the first time that science and research translation has been sped up with problematic effects, and we will undoubtedly need to speed science up again, many times in the future.
Author: Melanie Gentgall, Chief Executive Officer, Praxis Australia 2020 | INSPIRE 018 45
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PERSONALISED APPROACH TO LIMIT ADVERSE REACTIONS TO MEDICINES QUT researchers are analysing genomes for more than 2000 Queensland people each year, diagnosing cancer, identifying mutations, predicting how the disease will behave and how patients will best respond to treatment.
ow the researchers are extending their genomic capability and collaborating with industry to provide a personalised approach that limits adverse reactions to medications.
Senior bioinformatician Associate Professor Paul Leo and Advance Queensland Industry Research Fellow Dr Jonathon Ellis aim to integrate pharmacogenomics testing into clinical care, involving the screening for variants in a person’s DNA. Pharmacogenetic variants are known to play a major role in increasing the risk of adverse drug reactions (ADRs) and in the varying individual response to many medications.
Sequencing manager Lisa Anderson
Associate Professor Leo leads research at the Australian Translational Genomics Centre (ATGC), using nextgeneration sequencing to diagnose cancer for hospital patients within Brisbane’s Metro South Hospital and Health Service (MSHHS), as well as rare and heritable diseases. 2020 | INSPIRE 018 47
The ATGC’s laboratories are at the Translational Research Institute, adjacent to Brisbane’s Princess Alexandra Hospital (PAH), to enable collaboration with clinicians. A $700,000 grant from the Australian Department of Industry, Innovation and Science facilitates a collaboration with partners Illumina Inc, a US company manufacturing systems that analyse genetic variation and biological function; and Biocomputing Platforms, a Finnish genomic technology company. The collaboration is developing a test that uses a patient’s individual genomic profile to optimise drug doses and avoid ADRs. The pharmacogenomics service will initially be offered to PAH patients.
what the clinical significance and recommendation in regards to that variant is.’ ADRs are a major cause of disease and death globally, with statistics showing they are responsible for about 5 per cent of hospital admissions and occur during 6 to 15 per cent of hospital stays. The likelihood of ADRs increases with age and number of medications being taken. Elderly patients are more likely to have ADRs, are on more medications, and are more likely to respond poorly if they have an ADR. Subsequently, elderly patients are particularly likely to benefit from pharmacogenomics testing.
Assisting with the implementation is Dr Chris Morris, the PAH Director of Clinical Pharmacology and chair of the Drugs and Therapeutics Committee. He is also a member of the PAH Adverse Drug Reactions Subcommittee.
In about 30 per cent of adverse reactions, pharmacogenomic variants af fect the ef ficacy of medicines, suggesting that 30 per cent of ADR-related admissions may be predictable—and thus preventable— using pharmacogenomics.
‘When clinicians wish to prescribe any future medication,’ Associate Professor Leo says, ‘for patients that have had testing performed they will be able to check whether the patient has any relevant pharmacogenomic variant – and
Associate Professor Leo says the ATGC’s genomics approaches will enable pharmacogenetic profiling for individual patients, optimising doses for therapeutics and preventing ineffective medication being prescribed. ‘That
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will be of particular relevance in organ transplantation, antibiotic therapy and where patients are prescribed more than one medication,’ he says. ‘The pharmacogenomics ser vice will enable implementation of pre-emptive genetic testing at low cost. The information will be available to inform clinicians of the risk of ADRs and the correct dose to use for many common medications, with the test result and its interpretation available prior to the medicine being prescribed.’ Better personalisation of medication dosages for patients will mean they have fewer side effects while still gaining the full benefit of the medication, Associate Professor Leo says. ‘Conversely, placing patients on a higher dose, when appropriate and safe, means that they will benefit from a medication that may otherwise be ineffective—while also incurring a cost for no benefit.’ P e r s o n a l i s a t i o n r e s u l t i n g f r o m t h e AT G C ’s pharmacogenomics service will also provide significant time and cost savings to the health system. ADRs are estimated to cost Australian hospitals $1.2 billion annually. With the suggestion that about 30 per cent of admissions are predictable and preventable, savings of $360 million per year are possible. The ATGC will also work with Biocomputing Platforms to build a new database of pharmacogenomic variants using publicly available clinical and genomic data. Associate Professor Paul Leo
Ahead of the ser vice implementation, the ATGC will need to pass stringent accreditation tests for pharmacogenomics. The National Association of Testing Authorities (NATA) assesses laboratories for performance of tests and analysis against International Standards Organisation requirements. ‘The ATGC is NATA accredited for the cancer genomics service. Having a NATA-accredited pharmacogenomics facility would also enable other non-pharmacogenomics services using similar technologies to be offered, such as genetic risk testing for common heritable diseases including diabetes, arthritis, cardiovascular and mental health diseases,’ Associate Professor Leo says. ‘In those instances, early intervention improves prognosis and genomic risk testing has now been shown to have strong diagnostic performance.’
Author: Erik de Wit, Communications Program Coordinator, Institute of Health and Biomedical Innovation, Queensland University of Technology
2020 | INSPIRE 018 49
‘WHERE TOMORROW’S HEALTH BECOMES REALITY’ Successful healthcare innovation will drive future economic and social opportunities, while building a knowledgebased workforce that will be innovative, responsive and resilient to future challenges in health.
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aridulu Budyari Gumal, The Sydney Partnership for Health, Education, Research a nd Ente r pr is e (S PHER E ) is le ading a collaborative, evidence-based approach to optimise the commercialisation of healthcare innovations. We have partnered with national and international consortiums to learn and leverage for greater impact to launch HealthHatchery, a scalable program for healthcare innovation that is fit-for-purpose for the Australian innovation ecosystem. HealthHatchery draws focus on the early stages of innovation management and is strategically complementary to the existing innovation ecosystem. SPHERE’s HealthHatchery, where tomorrow’s health becomes reality, operates to source, facilitate and fund the development of innovative healthcare technologies. We aim to improve healthcare outcomes through innovation and build prosperity in the Australian health and medical technology sector. Australian entrepreneurs have access to a thriving innovation ecosystem with an abundance of accelerators, incubators, training programs and collaboration hubs spread across the country and intersecting numerous industries. This innovation ecosystem is further buttressed by competitive funding opportunities and business development programs that support the growth and development of local enterprise. Essentially, we have the foundations to develop a thriving innovation epicentre right here in Australia. However, despite the breadth of opportunity and resources, Australia is currently in an innovation stalemate. We are not benefiting from the considerable investment in innovation and entrepreneurship when it comes to translation and commercialisation outcomes. There is an undisputed need to optimise our innovation pathways and improve commercialisation outcomes. HealthHatchery can lead an intervention to challenge the status quo of healthcare innovation and the development and commercialisation of novel medical technologies. SPHERE’s HealthHatchery provides a systematic pathway for the development and commercialisation of novel medical technologies that arise from unmet clinical needs. HealthHatchery draws focus on the early stages of innovation management to validate the commercial feasibility of innovations. This ensures we focus resources on the development of innovations that address a global healthcare market need. This is paramount for successful commercialisation of novel medical technologies. 2020 | INSPIRE 018 51
Facilitate & Fund
Healthcare: Clinical practice + experi
Academia: Technical knowledge + R
Industry: Business acumen + Market kn
HealthHatchery representatives will network throughout health to find innovators. The innovators, our HealthHatchery catalysts, will identify unmet clinical needs and help develop ideas for innovative solutions.
WHAT DO WE DO DIFFERENTLY?
● H ealthHatchery is focused on unmet clinical need identified through clinical experience. The root cause for innovation failures is in consequence to the development of products and solutions that do not meet a healthcare market need. HealthHatchery is problem led and facilitates the validation (market and impact) of the unmet clinical need (the problem) prior to inventing the solution (the innovation). Significantly, there is no other healthcare innovation framework in Australia that is embedded within the healthcare services. This unique attribute enables HealthHatchery to source unmet clinical needs from clinicians, who have identified the unmet clinical need through clinical experience. ● H ealthHatcher y builds collaboration; integrated interdisciplinary, cross-institutional teams that have the capability to navigate and understand the global 52 INSPIRE 018 | 2020
Identify Unmet Clinical Need
Identify Unmet Clinical Need:
We aim to capture unmet needs that are identified through clinical experience and are of a magnitude that will deliver health and economic impacts for our patients and communities. Demonstration of a comprehensive understanding of the clinical unmet need is required to progress through the HealthHatchery innovation pathway.
Inventing sustainable solutions starts with identifying stakeholder needs, assessing standards of care, and developing protectable prototypes. Solutions must meet the diverse requirements of those who use, choose and pay for new healthcare products and services.
healthcare market while focusing on impact and outcomes that improve good health and wellbeing. HealthHatchery appreciates the complex domains (clinical, technology, regulatory business/market) that need to be addressed to successfully commercialise novel medical technologies. We use the human capital from across the SPHERE partnership to build diverse project teams. Furthermore, a key feature of HealthHatchery is the facilitation of projects by experts from the health and medical technology sector. ● H ealthHatchery deploys competitive pump-prime funding grants to progress projects through the HealthHatchery Idea Navigation Framework. This funding is used for activities that support the commercial feasibility of the projects to help them advance forward along the healthcare innovation development pathway towards successful commercialisation.
Innovation Ecosystem Partnering CHRISTOPHE KEREBEL
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Industry Partner Licence
Proof of Concept Start-up
Further Incubation Proof of Concept:
PoC activities cover relevant technical and clinical issues as well as identifying pathways to regulatory approval, reimbursement payment and commercial success: Development of prototypes to demonstrate the feasibility and functionality of your innovation. Complete initial testing to demonstrate that the finished product or service is likely to meet stakeholder needs.
Enter into the existing innovation ecosystem either with further incubation, licencing the innovation, spin-out and start-up companies or continued development with an industry partner. Continued Long-Term Support + Facilitation Pathway to SPHERE partner health service infrastructure for trials, testing and adoption of new healthcare products and services.
● HealthHatchery was developed using the conceptual framework of the CIMIT (Consortia for Improving Medicine with Innovation and Technology) model for healthcare innovation. CIMIT originated in Boston in 1998 and is a network of medical and academic institutions partnering with industry and government. CIMIT’s Healthcare Innovation Cycle is a highly successful model for accelerating the translation of healthcare innovations, with proven impact and evidence of success. Between 1998-2014, CIMIT leveraged over $1 billion USD in follow on funding and commercial investment on the back of a $69 milliondollar investment in 545 projects. Our vision is to build collaboration, lead innovation and build a prosperous Australia. Together we can innovate to shape competitive industries and companies, promote collaborative education and knowledge institutions and
HealthHatchery’s Idea Navigation Framework provides a systematic pathway for promising ideas to flourish. We aim to improve health outcomes through innovation and build prosperity in the Australian health and medical technology sector.
deliver impact through the development of healthcare innovation led enterprise. We aim to use healthcare innovation to build a fair and inclusive society with a healthy, high quality of life.
Author: Helena Malinowska has worked across the healthcare, research and industry sectors for over 10 years and brings a dynamic mix of skills to her role as Manager Strategic Programs at Maridulu Budyari Gumal SPHERE. Driven by a passion for healthcare innovation she has worked to establish HealthHatchery with a vision to improve the health and economic outcomes for our patients, communities and SPHERE partners.
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ATTACKING THE FORTRESS ON MORE THAN ONE FRONT: MULTI-ACTION ANTIBIOTICS FOR CHRONIC LUNG INFECTIONS IN CYSTIC FIBROSIS
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My Twitter : @chriskere CHRISTOPHE KEREBEL
Cystic fibrosis (CF) is a common genetic condition affecting 100,000 individuals worldwide and 3500 within Australia. People with CF produce an abnormal amount of thick, sticky mucus within their lungs, which tends to trap bacteria and provide a haven for infection.
hile this and other challenges of CF are largely treatable these days with exhaustive lifestyle interventions and modern medicine, years of regular antibiotic treatments eventually cause drug-resistant Pseudomonas aeruginosa infections to take hold in the lungs of people with CF. Once established, these notorious infections are extremely difficult to eradicate because of P. aeruginosa’s penchant for communal living in biofilms. By living within a protective self-produced gummy biofilm matrix, the bacterial cells are shielded from the action of antibiotics and the host’s immune system. As a result, P. aeruginosa chronic lung infections are highly resistant to antibiotics and greatly reduce the quality of life and lifeexpectancy in adults living with CF. Researchers from the University of Wollongong, Nanyang Technological University (NTU, Singapore) and the University of Southampton (UK) have been working together to develop an innovative new class of multiaction antibiotics (nitric oxide cephalosporins; C3Ds) as treatments for P. aeruginosa CF lung infections. “For the past 11 years, we have been tweaking the molecular mechanism of how C3Ds can launch a multipronged attack on P. aeruginosa biofilms. When the C3D molecules reach biofilm infection sites, such as in the CF lung, they are designed to react with the normal bacterial target of cephalosporins and kill the cells. Nothing new there – that’s how all cephalosporin-type antibiotics work. However, our NO-cephalosporins are unique in that they are triggered by this reaction to concurrently release nitric oxide (NO), which then tricks bacteria into dispersing from biofilms. These dispersed cells are more exposed and vulnerable to the antibiotic and immune defences,” says lead investigator Professor Mike Kelso from UOW. ”The NO-mediated surprise attack is the real kicker as the liberated bacteria are upwards of 1000x more sensitive to antibiotics than their biofilm cousins, which potentially allows for easier clearance of the infection,” he adds.
“We refer to C3Ds as ‘All-in-One’ antibiotics because of their dual-action in both killing P. aeruginosa cells and dispersing biofilms.”
NO NOT AN OVERNIGHT SUCCESS
The UOW/NTU/Southampton collaboration dates back to 2006, when researchers at the University of New South Wales in the lab of Prof. Staffan Kjelleberg were the first to report that low concentrations of NO can trigger dispersion of P. aeruginosa biofilms. Scott Rice and Jeremy Webb, both postdocs at the time at UNSW and key contributors to the NO discovery, later moved to NTU and Southampton. Then, as a new medicinal chemistry academic at UOW in 2008, Prof Kelso having read the 2006 UNSW paper, hatched the idea for C3Ds and reached out to the Kjelleberg group. With early funding from the NHMRC (2009-2011), the collaboration was able to demonstrate the promise of the compounds and in 2015 they received major funding from Cystic Fibrosis Australia to advance the technology. “Our work with Cystic Fibrosis Australia really sounded the arrival of C3Ds as possible treatments for P. aeruginosa lung infections in CF. We’re very excited about the compounds and recently we started discussions with the US Cystic Fibrosis Foundation about funding for further proof-of-concept work. If all goes well, we’ll be looking to establish an antibiotics start-up company within about 2 years,” say Prof Kelso. “That will surely be an exciting new adventure.”
Author: Professor Michael Kelso, Illawarra Health and Medical Research Institute University of Wollongong. Faculty of Science, Medicine and Health, School of Chemistry and Molecular Bioscience
2020 | INSPIRE 018 55
TIME FOR ACTION: TOWARDS A RESEARCH ECOSYSTEM INCLUSIVE OF PEOPLE FROM CALD BACKGROUNDS Translating research into better health outcomes for all means ensuring equitable access and representation of people from many different backgrounds in the research process.
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ne group t ypically underrepresented in healthcare and research is people from culturally and linguistically diverse (CALD) backgrounds, defined in Australia as people born overseas, in countries other than those classified by the Australian Bureau of Statistics (ABS) as ‘mainly English-speaking countries’. In 2016, 28% of the Australian population was overseasborn and an additional 21% had at least one overseasborn parent1. Despite CALD Australians making up almost a third of the population they are often excluded from clinical research conducted within Australia. For example Low and colleagues (2019) conducted a search of the Australian New Zealand Clinical Trials Registry (ANZCTR),
CHRISTOPHE My and Twittercurrent : @chriskere and the government website ClinicalTrials.gov, and found KEREBEL ● E nvironmental scan of the status CHRISTOPHE KEREBEL that 44.7% of currently registered active dementia clinical initiatives to improve clinical trial awareness and access trials in Australia excluded patients not fluent in English2. of CALD populations nationally and internationally (accessible here)
ENSURING EQUITABLE ACCESS
In Australia, significant efforts are underway to ensure equitable access to clinical research. The Australian Commission on Safety and Quality in Healthcare has begun work to implement the National Clinical Trials Governance Framework (the Framework) and embed clinical trials into routine hospital care. The Framework recommends the provision of resourcing to allow consumers from different demographic locations and culturally diverse backgrounds to participate in all available clinical trials within and across health service organisations. The Australian Clinical Trials Alliance (ACTA) is committed to improving clinical trial awareness, involvement, and access, with and for people from CALD backgrounds within Australia. We recognise the reciprocal benefits to both research and CALD communities that can be achieved through collaboration and partnership. Participants in research should reflect the diversity of our society and culture. Evidence generated from more representative investigator-led trials has the potential to be more generalisable and relevant to the broader Australian population. To advance this issue, ACTA formed a national working group to lead the ‘clinical trial diversity: CALD project’. It engaged consumers from diverse CALD backgrounds, p e a k b o d i e s re p re s e nti n g eth n i c c o m m u n i ti e s, researchers, and policymakers to par ticipate in a workshop and together develop a National position statement.
● A ‘clinical trials awareness education session for CALD consumers’ was held to help prepare consumers participating in a national workshop to be informed about clinical trials. ● A National clinical trial diversity - CALD workshop: bringing together a diverse group of stakeholders from CALD backgrounds and the research sector to identify key principles that could drive action or recommendations to improve clinical trial awareness, involvement and access of people from CALD backgrounds (access the report here).
ACTA’S CALD ACCESS POSITION STATEMENT
The ACTA position statement can be accessed here. The aim of the position statement is to advocate for change and action to improve clinical trial (research) awareness, involvement, and access with and for people from CALD backgrounds. ACTA is committed to the development of a several actionable position statements aiming to advance and foster a fair and equitable research ecosystem, enabling improved health outcomes, with and for all people across Australia. The first position statement makes a start with a call to action, encouraging the research sector to be more inclusive of people from CALD backgrounds. ACTA gratefully acknowledges operational funding from the Australian Government’s Medical Research Future Fund.
Several activities were conducted over a 12-month period that led to the development of the position statement. These included: ● E ngagement and relationship-building with key sector stakeholders to discuss and progress the issue, contributing as relevant to ongoing sector projects to enhance clinical trial diversity for people from CALD backgrounds. ● P reliminar y mapping of Australian diversit y initiatives seeking to improve clinical research pa r ti cipati o n w i th a nd fo r p e o pl e f ro m CA L D backgrounds (refer to ACTA workshop report accessible here). Author: Nicola Straiton, Project Manager Australian Clinical Trials Alliance (ACTA) 1. Australian Bureau of Statistics. Cultural diversity in Australia, census article; 2016 (accessed here https://www.abs.gov.au/). 2. Low, L., Barcenilla-Wong, A., and Brijinath, B. Including ethnic and cultural diversity in dementia research, Medical Journal of Australia 2019; https://doi.org/10.5694/mja2.50353
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THE LAST WORD Refocusing medical research on publicprivate partnership We don’t do this because its easy, we do it because its hard.
his is the answer given by AbbVie’s global CEO Rick Gonzalez whenever he is asked why we invest so much primary research for hard to treat diseases when the risk is so high? Why not just invest when the hard work is done?
The review had noted the vital role that R&D plays in economic growth and job creation and one of the Finding treatments for the most serious diseases key recommendations was an additional presents a challenge like no other and while this tax offset of up to 20 per cent on has always been the case, in the last half century, collaborative R&D expenses for larger organisations in both the public and private sector companies.” had a tendency to want to go it alone. Well perhaps untill now… Finding vaccines, treatments and tests to combat COVID-19 predicament is taking collaboration we haven’t witnessed before. And this must continue if we are to advance medicine at the rate the human race will need. This pandemic is the tip of an iceberg. Australia has had a long standing reputation as a world leader in medical research but unfortunately also one for being below average in commercilisation. As a result, we are missing out. At AbbVie we bring people together because we know that collaboration is the key to breaking barriers and exploring new frontiers in science. This emphasis on collaboration is an important part of our approach to R&D. We look for opportunities to work with external partners who share our goals for addressing serious health issues. We collaborate with hundreds of biotech companies, universities, nonprofits and government organizations to advance science every year. And we want to do more of this but we need support and yes this includes tax incentives. The assessment of the Australia’s R&D Tax Incentive in 2016 was summed up by then Innovation and Science Australia Chair, Bill Ferris, Chief Scientist, Alan Finkel, and now former Secretar y to the Treasur y, John Fraser as “Good but not great.”
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It also suggested the government consider doubling the $100 million cap per company per year because the existing limit reduced the scope of large R&D-intensive companies to support local innovation. The changes to the R&D ta x incentive recently announced in the budget are a welcome step, but much more could be done. The idea that Australia lags other leading nations in fostering public-private partnerships isn’t a new concept. But as we look to rebuild our economy in the wake of the COVID-19 pandemic, it’s worth revisiting because both sides of the equation have much to gain from greater collaboration with each other. Our economy has now entered its first recession in almost 30 years, unemployment rates are unusually high, and the Federal Government has committed more than $260 billion to support businesses and consumers through this period of uncertainty. Universities have been badly impacted, mainly because they rely so heavily on revenues generated through international students. The government has responded with initiatives designed to increase domestic enrolments and protect teaching jobs. But this reallocation of resources and the ongoing travel bans will be felt most acutely in university research labs across the country.
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Ferris, Finkel and Fraser also had a theory on why Australia had relatively low rates of collaboration. They felt it was partly reflective of Australia being a small but open economy with a tendency to adapt rather than produce frontier technology. Other factors include the allocation of intellectual property rights, differences in timing and capacity, mismatched capabilities, and the sharing of risks and rewards. But the lack of financial incentives is undoubtedly the largest barrier to public-private R&D partnerships.
Australian academics face relentless pressure to deliver research outcomes, in the form of publications. The absence of established pathways to commercialisation means that they are forced sell promising intellectual property very early, before the full value of their intellectual property is clear.” The Medical Research Future Fund is an important source of funding for academic research, but it does not directly address the need for a stronger bridge to commercialisation. With respect to medical research and medicines, any scheme must bring together unlikely partners in the search for the next life-saving treatment.
products, such as clinical development, is characterised by capital intensity, high levels of risk and complex regulatory oversight. As such, it is a natural place for industry to contribute, translating early collaborative research success into the next generation of life changing products. At AbbVie, we maintain state-of-the-art research and development centers in some of the most productive innovation hubs across the world. This puts us at the heart of cuttingedge research to move the best ideas forward faster. Australia’s relatively low COVID-19 infection rates and economic resilience have made it a more attractive destination for multinationals like AbbVie looking for R&D locations. So there’s never b e e n a b et te r ti m e fo r government to drive greater collaboration between large companies and publicly funded research organisations.
Author: Chris Stemple, General Manager, AbbVie ANZ
Industry support accelerates the pace of primary research through capital injections and offers access to markets. This dramatically increases the speed at which new treatments are made available to those who need them. The ‘last mile’ of commercial development for med tech 2020 | INSPIRE 018 59