NHMRC Clinical Trials Centre 2022 Highlights

12/12/22

The NHMRC Clinical Trials Centre (CTC) continued to grow and celebrate multiple milestones in 2022. By December, we had over 100 active trials including 11 that began recruiting this year and 15 in start up.

• 104 active trials (15 start-up, 52 recruiting, 37 follow-up)
• 3,900 participants recruited
• 260 peer-reviewed publications
• 260 staff

 

RESEARCH HIGHLIGHTS

There have been many research achievements during the last year of which we are particularly proud. Highlights include several studies that have the potential to change policy and practice around the world.

• The Five year follow up results for the prostate cancer study ENZAMET, a collaboration between ANZUP and the CTC, were presented at ASCO in June. The trial found that enzalutamide, added to standard treatment, improved survival by 30% in people with advanced, hormone-sensitive prostate cancer compared to standard treatment alone.
• The SHERLOCK study led by TOGA and the CTC was activated in September. Lung cancer has the lowest survival rate of any cancer in Australia, and 15% of all lung cancer has a mutation called KRAS G12C. The SHERLOCK trial is testing a novel treatment combination to target this mutation. SHERLOCK moved rapidly from concept pitch to study activation within 11 months, reflecting the strong support for the study.
• The Neonatal study iSEARCH opened to recruitment in 2021 and has become the fastest recruiting perinatal/neonatal trial at the CTC to date due to excellent engagement of the site teams. This study is investigating the use of the oral drug sildenafil to see if it can safely avert the risks of contraction-induced hypoxia in labour. In 2022, 810 participants were randomised to study treatment and recruitment reached over 1,000 in December, with an average of 62 participants recruited per month across eight open sites.
• Using 30-years of data from youth with Type 1 diabetes, the diabetes and vascular medicine group built a means to personalise eye screening intervals, with a free on-line calculator. For adults with Type 2 diabetes, using FIELD data, the team validated risk calculators for sight-threatening retinopathy, and published a new calculator that considers fenofibrate’s protection.
• The Cholesterol Treatment Trialists’ Collaboration (CTT), a joint initiative between the CTC and Oxford Population Health, found that statin therapies are not the cause of muscle pain in over 90% of those who experience symptoms. Researchers gathered data from 23 large-scale randomised studies including information from almost 155,000 individuals. They used this information to assess the effect of statin treatments on the frequency of muscle-related symptoms across many different types of patients. These results provide important reassurance to the many people taking statins which are proven to protect against new heart attacks and strokes.
• Over 38,000 GPs in Australia now have access to a Medicare Benefits Schedule rebate (item 11607) to measure their patients' blood pressure with suspected hypertension accurately. The CTC's Health Technology Assessment team assessed the cost-effectiveness of the more accurate, Ambulatory Blood Pressure Monitoring (ABPM) versus Clinic Blood Pressure Monitoring and Home Blood Pressure Monitoring, instrumental in providing evidence to the Department of Health, Medical Service Advisory Committee (MSAC). The consultation with the MSAC was vital as it led the federal government to fund ABPM for diagnosing hypertension in the primary care setting and potentially improving the health of many Australians.
• Up to 50% of clinical trials are never published, leading to publication bias and research waste. Trial registries can provide access to unpublished results and facilitate collaboration amongst researchers working on similar research questions. In 2022, the CTC Evidence Integration team developed comprehensive methods on how to search clinical trial registries and published a guidance paper in the prestigious British Medical Journal. In less than 6 months, the guidance paper has already been read >10,000 times and received an Altmetric score of >200. The team is frequently consulted by researchers internationally for advice.

 

COVID-19 RESEARCH

We continued to call on our leading status as a clinical trials research centre to help address the COVID-19 pandemic and currently have six trials in this area.

• The CLARITY study settled a clinically controversial area and demonstrated that patients receiving a widely available treatment to protect kidney and heart function, can continue these during the COVID pandemic. At the beginning of the COVID-19 pandemic it wasn’t clear whether these agents would help or worsen COVID-19 outcomes. The CLARITY study, representing a collaboration between the CTC, the University of Sydney, The George Institute for Global Health (India) and a consortium of Australian and Indian clinicians investigated the low cost, widely available treatment, renin angiotensin receptor blockers (ARBs), to treat people with severe cases of COVID-19. Results were published in BMJ in November and showed that angiotensin receptor blockers (ARBs) do not improve outcomes in patients hospitalised with mild COVID-19 but similarly that there was no overall signal of harm over the 28 days of treatment.
• The BEAT-COVID study, in partnership with Royal Prince Alfred Virtual Hospital, continued to recruit participants in 2022. This platform trial provides a purpose built framework for COVID-19 treatments that will rapidly and efficiently establish the evidence base required to prevent hospitalisation and deaths.
• The international adaptive platform trial REMAP CAP aims to evaluate the effect of a range of interventions for patients admitted to ICU for respiratory distress associated with Community Acquired Pneumonia (CAP) or COVID-19. In 2022, CTC led the expansion of trial delivery in NSW, opening seven new sites and recruiting 193 participants.
• CTC researchers led a study that looked at health-related quality of life (HRQL) of Australians during the COVID-19 pandemic. Australians reported poorer HRQL relative to a pre-pandemic sample. Risk factors for poor HRQL outcomes included greater negative pandemic-related impacts, poorer compliance attitudes, and younger age.

 

INNOVATION IN TRIALS

A key focus for CTC in 2022 and beyond is to look at ways to improve the science and delivery of trials, generating evidence in efficient ways to maximise learnings.

• The COVID-19 studies CLARITY and CLARITY 2.0 used eMR sources, embedded trial procedures and an innovative adaptive sample size design to ensure high quality evidence was generated efficiently and effectively. Furthermore, the BEAT-COVID study is purpose built for the capacity to assess multiple treatments across diverse domains of therapeutic care within the same trial infrastructure. This provides the most efficient structure for evidence generation in this setting.
• The RESOLVE study looks at the level of dialysate sodium being used in dialysis machines around the world. With a target recruitment of over 400 dialysis units and over 50,000 people, a pragmatic and flexible protocol is needed. While the core components of the study are managed centrally, the study is operationalised in individual countries based on local practice. Data collection involves a mix of registry data, linkage to administrative data and purpose-built electronic data capture systems, with a core dataset that is required across all countries. To ensure success for such a large study, an incredible amount of collaboration is required. Currently, sites are randomised in Australia, India, China, Canada, Germany, and Malaysia, with further sites coming on board in the UK and more countries planned for 2023.
• EVIDENCE is a world first cardiovascular study in collaboration with Sydney Local Health District assessing the impact of two existing transfer options for patients who have experienced an out of hospital cardiac arrest: expedited transfer versus non-expedited transfer from scene to hospital. The study uses OHCA registry GPS data for optimum distribution of ECPR hospitals to capture >80%, >90% and >99% of eligible arrests. It is the first spatial modelling of cardiac arrests in NSW. Since opening in July 2021, the study has enrolled 921 participants, 75% of its 1,220 target. A systematic review of the expedited and standard arms is in preparation.
• The BEAT-Calci study aims to generate evidence on a range of interventions within the setting of a rare and devastating called calciphylaxis. BEAT-Calci is an adaptive platform, designed address the vast array of barriers to evidence generation in this space. These adaptations include the ability to 1. evaluate multiple interventions simultaneously and sequentially, 2. adjust the ratio of participants randomised to each treatment groups based on accumulating data, 3. "rescue" randomisation to allow for more precision care in the face of non-response to treatment, and 4. make decisions on stopping components study at multiple planned analyses points via an adaptive sample size for efficiency of evidence generation, all within the same trial infrastructure.

 

NEW INITIATIVES

2022 saw the success of two new initiatives to support the development of new or early-stage collaborative research across the CTC and The University of Sydney.

• The recipients of our inaugural Innovation in Clinical Trials Program were announced with each investigator receiving $50,000 of in-kind support for the development of their research across the CTC and University of Sydney. Research projects include: digital nutrition interventions for people with chronic kidney disease by Dr Jessica Dawson at the CTC; the environmental impact of healthcare by Dr Mbathio Dieng at the CTC; optimising referrals for knee arthroscopy for osteoarthritis by Dr Jillian Eyles at the Kolling Institute, and enhancing eHealth engagement by Dr Louise Thornton at the Matilda Centre.
• The Future Leader Research Fellowship Program also completed a successful first year. This initiative allows us to support the careers of talented Early and Mid-Career Researchers. The 2022 recipients were Dr Bradley de Vries and Dr Himanshu Popat who are both working on neonatal research studies.
• We established the Equity Diversity and Inclusion in Trials team (EDIT) as part of our commitment to designing and delivering inclusive research. The focus of this group is to address any barriers to participation and increase the diversity of populations in terms of age, ethnicity, nationality, gender, sexuality, disability, and other sociocultural coordinates, within our research. An initial focus has been on removing barriers to trial participation for LGBTQIA+ people, with the group expanding focus onto people of cultural and linguistic diverse backgrounds. Key learnings were presented and shared with the clinical trials community at the International Clinical Trials Methodology Conference in October.

 

SENIOR APPOINTMENTS

Finally, we were delighted to welcome four new senior appointments to the CTC in 2022. Rebecca Osborne joined in June as Chief Operating Officer bringing invaluable experience from commercial and academic scientific research organisations in Australia, Canada, and the USA. Professor Rob Sanders also joined in June as Critical Care Lead. Rob's research focusses on optimizing outcomes from perioperative and critical care, especially centred on delirium and cognition. Dr Katharina Bell has accepted a position as Ophthalmology Lead and will be joining us in January 2023. Katharina is an ophthalmologist and Clinician-Scientist interested in translational research approaches in ophthalmology. Professor David Beard has also accepted a position as Surgical and Complex Interventions Lead. David is currently based at Oxford University and will begin transitioning his major focus of activities over the next year.

 

THANK YOU TO OUR COLLABORATORS AND TEAM

The trials and achievements outlined above demonstrate our effort to advance the boundaries of care and treatment, with the wellbeing of trial participants front of mind. These and other successes would not be possible without our collaborators, and most of all, without the efforts of our outstanding team of dedicated, committed, enthusiastic trial staff with their shared vision of making a difference.

We have every confidence that the CTC, with such an outstanding team of researchers working in partnership with key collaborators, will continue to make a profound impact on future practice and health.