RECENTLY, I had the opportunity to briefly meet Dr Howard Bauchner, editor-in-chief of the Journal of the American Medical Association (JAMA), who had attended the annual scientific meeting of the Australia and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG).
In the ensuing conversation, Dr Bauchner said: “I have said it privately and I will happily say it in public, the ANZICS CTG is the most effective intensive care clinical trials group in the world,” a fantastic endorsement of ANZICS from someone who is in a position to know excellence when he sees it. To which I replied, “(in that case) … come walk a little further with me, as not too far down the corridor I could also introduce you to the chair of the Australian and New Zealand College of Anaesthetists Clinical Trials Network (ANZCA CTN), and across town, the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), and I could go on and on …”.
Australia is indeed fortunate to have so many clinical trials networks actively trying to test current medical practices through investigator-led clinical trials in order to improve health care. Although curiously, these groups often fall under the radar such that a surprising number of people working in the health sector, from policy to clinical practice, are either not aware of their existence or unclear as to their role and remit. So, what are these clinical trials networks (sometimes known as “cooperative trials groups”) and what do they do?
The Australian Clinical Trials Alliance (ACTA), which links these networks around Australia, was an initiative conceived by Professor Steve Webb (a previous Chair of the ANZICS CTG) and an organisation which I am privileged to currently chair. ACTA recently conducted a survey of the existing networks in Australia – Report of the Activities and Achievements of Clinical Trials Networks in Australia 2004–2014.
There were 37 separate entities identified, of which 34 provided data to the survey. These networks covered many areas of medicine. Some were discipline-based and others disease-based. Some were independent trials organisations and some were based within professional societies, but all of them had a number of similarities. They were very often grassroots organisations including all of the relevant clinical groups involved in a particular area of medicine.
These virtual and often national networks of clinicians were collaborating to deal with key clinical questions that impacted their day-to-day practice. At various times, they may have conducted clinical trials comparing two standards of care (comparative-effectiveness research), sometimes repurposing of older drugs, sometimes high quality evaluation of novel treatments, in each case showing what works – and as importantly, what doesn’t work – building the evidence base that ultimately is crucial for high quality care.
We found that over the prior decade, these trials networks had involved over 10 000 clinical researchers, had enrolled over 1 000 000 patients in 1000 studies and had generated an investment of over $1 billion.
But more important than the metrics, the multiple publications in high profile journals like the New England Journal of Medicine, The Lancet and JAMA, and the innumerable peer-reviewed, philanthropic or commercial grants, these networks had delivered something much more tangible. The networks had improved clinical outcomes around Australia and often around the world. They were also intimately involved in the training of the next generation of academic clinicians and helped provide evidence for Australian and sometimes international regulatory or reimbursement purposes.
To illustrate the impact of this work, consider the winner of the 2016 ACTA Trial of the Year award announced by the federal Minister for Health on International Clinical Trials Day in 2016. The winning trial, known as the PPROMT Trial, was conducted by the Interdisciplinary Maternal Perinatal Australasian Collaborative Trials (IMPACT) Network and first published in The Lancet. It investigated whether pregnant women who had ruptured their membranes before term should have immediate delivery to avoid the risk of infection or continue to term. Before this trial, practices across the world varied with good arguments justifying each of the two practices (immediate v expectant management).
The trial, led from Australia, randomised 1839 women in 65 centres in 11 countries to either immediate delivery or expectant management. There was no difference in the incidence of newborn infections between babies born to women in the two groups. However, babies born to women managed expectantly had a decreased risk of respiratory disease and a decreased need for respiratory support compared with those delivered immediately. They also spent fewer days in a special care baby unit and fewer days in hospital. Women managed expectantly had a lower incidence of delivery by caesarean section. This landmark trial showed that, in the absence of a clear clinical indication, there is no benefit for mothers or babies in immediate delivery after a pre-labour, pre-term rupture of the membranes between 34 weeks and term gestation. Here is research that mattered, not just to all Australians, but to women all over the world.
The four other clinical trials networks that were finalists in this award have also played a very important role in changing practice for the relevant population. These studies further illustrate the strength and scope of these pivotal trials groups in the Australian health care landscape.
- The EXTEND-IA Trial conducted by the Australasian Stroke Trials Network was designed to evaluate a novel, minimally invasive technique called “endovascular clot retrieval” to remove large clots in the brain after stroke. It found that 71% of patients treated with the new technique regained functional independence within 3 months of their stroke, compared with only 40% who received standard clot-dissolving therapy alone. The results of this trial are set to revolutionise the way we treat ischemic stroke in the future.
- The SOFT Trial conducted by the Australia and New Zealand Breast Cancer Trials Group recruited 3066 women in Australia and across the world. It showed that treatment with oestrogen suppression may reduce the risk of the most common form of breast cancer in young women recurring by almost half – a globally significant result for women with hormone-receptor-positive breast cancer.
- The EPO-TBI Trial was conducted by the ANZICS CTG in 29 intensive care units in seven countries. It was one of the largest ever to be conducted in traumatic brain injury. The trial found that erythropoietin improved mortality in patients who had suffered such trauma. This is the first trial to show a benefit attributable to a pharmacological intervention in this patient population, and represents a major step forward in reducing the devastating burden of such injuries.
- The AVERT trial, also conducted by the Australasian Stroke Trials Network, recruited over 2000 patients and is the largest stroke rehabilitation trial ever undertaken globally. The trial showed that very early rehabilitation after stroke is not necessarily beneficial for patients providing evidence that “more is not always better”, and is set to have a major impact on stroke rehabilitation across the world.
- Finally, the AVOID Trial conducted by Ambulance Victoria and Monash University tested the belief, entrenched for over 100 years, that supplemental oxygen administered to patients with suspected heart attack as an initial first aid therapeutic measure by paramedics, doctors and nurses provides a benefit to patients. The trial found that supplemental oxygen in patients experiencing heart attack with initial normal oxygen levels, did not only not relieve their pain or minimise heart damage but rather increased the frequency of heart injury and dangerous cardiac rhythms. The results of the AVOID Trial have led to a dramatic change in practice for all care providers of patients with heart attack both in Australia and around the world.
The outstanding achievements of Australia’s clinical trials networks to date, only a small percentage of which have been illustrated by the trials that were contenders for the ACTA Trial of the Year award for 2016, demonstrate the enormous benefits to patients achieved by these groups.
Through addressing key clinical priorities and unanswered clinical questions, thereby building the evidence base on which high quality care is founded, while challenging existing approaches for which the evidence is lacking, the clinical trials network model illustrates the benefits of embedding research into routine health care. It should come as no surprise then that the Medical Research Future Fund strategic manifesto (Australian Medical Research and Innovation Priorities 2016–2018) has wisely identified infrastructure support for clinical trials networks as key national infrastructure.
On 19 May 2017, ACTA with many other groups, including the National Health and Medical Research Council, MTP Connect and Medicines Australia, will celebrate International Clinical Trials Day (officially occurring on 20 May). Once again, we will announce the ACTA Trial of the Year award. We do not know who the winner will be yet, but there is one thing we can be certain of, another Australian clinical trials network will have brought their members together to deal with a clinically important question to improve the health of Australians. The ceremonies on International Clinical Trials Day will help highlight the importance of Australia’s clinical trial networks to a sustainable health system, an approach to health care in which Australia leads the world – one for which we can all be justifiably proud.
Professor John Zalcberg is the Tony Charlton chair of Oncology at Alfred Health, and the head of the Cancer Research Program at the Monash University School of Public Health and Preventive Medicine
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