Clinical research and the medical research future fund

Process

It is probably unnecessary to state that any scheme of this magnitude and strategic importance should be open, transparent, competitive and meritocratic based on evaluation via peer review. Medical researchers expect these ‘gold standard’ processes, and we have been assured thus far that this will be the case for the MRFF.

Long-term sustainable growth in the sector

The pressures on the health system continue. To respond to this pressure, we need a vibrant system of data collection, analysis and discovery, buttressed by growth in workforce capacity and skill in the sector. With this mix of knowledge and people, we will be able to redress this pending economic burden to create positive and cost-effective changes. The health system needs to respond to changing demographics and events, and we must have a matching level of research capability – this in turn is contingent on stable and predictable funding support.

The principal source of medical and health-related research support currently falls to the National Health and Medical Research Council (NHMRC). Disturbingly, NHMRC grant success rates, which are the foundation of infrastructure and personnel support, have declined in the region from 25% to 14% and risk slipping further. This is creating near-impenetrable barriers, inhibiting the next generation of clinical scientists from engaging in funded clinical research and planning a career across both medicine and science. Funding insecurity also discourages the risk-taking culture that is a critical ingredient for breakthrough science, leading to applications focused more on notionally safe, low-risk and ‘in-the-box ideas’, as opposed to the high-risk ‘out-of-the-box thinking’ that promises truly transformational opportunities.

While there are practical boundary issues between the MRFF and the NHMRC’s current funding streams supported by the Medical Research Endowment Account (MREA), collectively these could work towards supporting 25% of research proposals in any given year by working together. This percentage ensures rigorous evaluation, predictability and sustainability.

We are not expecting the MRFF to replace the MREA’s key role of project and people support. Rather, we presume both funding bodies will work cooperatively to ensure maximum benefit of the discoveries that the NHMRC rigorously identifies, ensuring that funding feeds into better health outcomes and commercial opportunities. If this partnership operates well, the current returns of 3:1 for every dollar spent on medical research back to the economy should be even greater. Indeed, it is reasonable to expect that health savings will be more rapidly identified and implemented if the NHMRC and MRFF cooperate with shared goals and complementary strategies.

Such a level of funding success responds to the need to invest in tomorrow’s biomedical workforce and ensures sustainability. In parallel, it will support the development of the next generation of outstanding physician-scientists and basic researchers. Other priorities need to be part of this plan. These include initiatives to manage growing student debt, creating solutions to recruit and retain workforce who work across hospitals, universities and medical research institutes, along with increasing the diversity of our biomedical workforce. The MRFF also needs to strengthen research streams that lag behind relative to the burden of disease – mental health being an exemplar. We need to broaden graduate education to include translational science, entrepreneurship, business leadership and technology development. Commentary around the MRFF would suggest that these will be important to the future measures of its success.

Whatever the model(s), we have to move to a more stable and certain place. For instance, linking the research budget to a fixed percentage of gross domestic product (GDP) (~0.3%) would show that Australia’s’ genuine commitment to biomedical research is unshakable and apolitical. Alternatively, 3.0% of the health budget spend would address this funding uncertainty. We need to benchmark medical research against the economy broadly and certainly against the health system itself. There are numerous international precedents for this model.

Capture the economic benefit of biomedical research

Australia has exited the mining boom; traditional manufacturing is in decline and is unlikely to be sustainable vehicles for long-term economic growth. By contrast, medical device and pharmaceutical manufacturing are examples where there is economic growth and opportunity. Technology, in particular biotechnology and health research, are areas where Australia has a significant competitive advantage over many countries and which could feasibly be an engine of future growth as we transition to a post-industrial future. Other nations to our north, especially China, have bet on this. However, we have arguably been poor at communicating the economic and social benefits of investment in this sector. We need to better explain how research has transformed health care and lives. Several economic analyses by Deloitte Access Economics and others have nailed these economic and social returns, but we have not achieved the traction that might have been expected. It remains necessary to advocate prioritising biomedical research as strongly as key environmental issues that threaten our future.

Promote a long-term investment view of biomedical research

It is necessary to take a very long-term view of the potential of this sector while noting that both the general public and politicians are supportive of investment in this domain. As not all diseases will have cures around the corner or ever, we will need evidence-based approaches to achieve wellbeing while managing the chronic conditions that are the major contributors of morbidity and mortality in our society. To attain these outcomes, we need to continue to invest in new fundamental knowledge and discovery about human physiology and pathophysiology and ensure our basic scientists are well supported and invigorated to work in teams with clinical researchers. We need to feed the research discovery pipeline with outcomes that can lead to translation and implementation.

Developing shared resources for leverage

A key opportunity that the MRFF affords is to create platforms and resources capable of supporting a diversity of research endeavours across multiple fields. Medical research increasingly needs huge data sets, specimen banks and costly infrastructure whose implementation and dissemination can be synergized by public investment. Models currently exist to share these resources between disciplines and projects. Sharing also drives collaboration and cross-pollination of innovative ideas.

There are shared determinants of many disorders, especially in the domain of lifestyle and environmental factors that drive seemingly diverse disorders, including diabetes, cardiovascular disorders, common mental disorders, osteoarthritis and cancers. At present, many therapeutic and preventative interventions are siloed. Cross-disciplinary approaches and shared solutions with wide buy-in have the capacity to have far greater impact, especially in the domain of public health and preventive medicine. Many major discoveries lie at the intersection of seemingly disparate disciplines, and intellectual cross-pollination is likely to be essential to solve the complex health problems that form the bulk of the burden of disease currently. Consequently, it will be important for funding structures to recognise and reflect this reality. The MRFF is ideally suited to stepping into this important role.

Prioritise health promotion and disease prevention

Prevention is highly cost-effective. Inefficient, expensive interventions should not be incentivized at the expense of prevention. Health care systems that embrace prevention, promotion and health maintenance are most likely to bend the cost curve of health care. Acquisition of environmental and genetic information that predicts risk of diverse diseases is a cornerstone of precision medicine and disease prevention.

We need to recognise that many of the major gains in health have been in the domains of prevention and promotion. This is true across many disorders from cardiovascular disease to cancer to sudden infant death syndrome. It is also clear that such solutions will have to occur, at least in part, in the public health space and will need to be driven by public policy and funding. The path now established to tackle tobacco use is likely to be an exemplar of what is going to be needed to reduce the burden of the common, non-communicable disorders, with nutrition arguably the next threshold. The barriers to implementation in this space are not necessarily due to evidence but rather infrastructure and processes that the MRFF might consider to support.

Revise regulatory processes, especially regarding nutraceutical agents and repurposing

Success arising from MRFF initiatives would be aided by process refinements in the regulatory sector. These could feasibly include streamlining the approval process for drugs and devices through priority review, breakthrough therapy, accelerated approval and fast track. While researchers might be frustrated by many of these processes, patients and their carers are more strident and remain desperate for more rapid implementation. It would be useful if clinical trial approvals for investigator-initiated trials could be simplified. The need to build evidence for benefit or indeed identifying harm has human and economic implications across the health sector. This is especially evident in the nutraceutical and complementary sectors where greater commitment to the provision of scientific evidence is lagging or perhaps not even sought and where evidence-based regulation is urgently needed. Other potentially fruitful avenues could include informatics-based approaches to identify new indications for established drugs. Finally, expanding trial access for patients could further attract commercial partners by shortening clinical trial duration while enhancing enrolment and trial enrichment.

How could the MRFF achieve these aims?

A first point to emphasise is that resourcing should reflect the burden of disease in the society, both disability and mortality. Psychiatric disorders would be exemplars of disorders heading the list of causes of disability at a population level, but lagging in research support. We also need to better embed research within clinical care – there are islands of excellence, but in general this is not widespread across Australia. We also need to structure systems such that they enable links to biotech and pharma. There are examples of how one could usefully embed industry into the research both locally and abroad.

There are a variety of structural models that could be used to boost research. One could support classic programmes, projects or fellowships where there is the greatest need – but there are deliberate MRFF/NHMRC areas of focus that would have to be accommodated. The MRFF is ideally placed to complement the NHMRC portfolio and other international discoveries to improve health. An expanded network of advanced health and research translation centres would be a viable structure to deliver these goals. By way of example, a virtual health institute across the country would need to be targeted at specific identified priority areas that meet major public health needs; interdisciplinary, multi-centre, cross-pollination supporting structures would be preferred. Another option is large-scale government-led initiatives in critical areas of health burden where there is evidence of cause but significant challenges to implementation of the necessary health system changes. The USA BRAIN and Precision Medicine initiatives offer examples of how this might look.

The MRFF design implies that it will support and enable implementation and commercialisation of evidence-based research within the health sector. This is fantastic news for the health sector and indeed, Australia. We are hearing that the MRFF might consider building infrastructure (not buildings) that has a sound business case with ensured self-sustainability and flexibility. Government is looking for returns which in some cases might be achievable in a short space of time. It also appears to accept long-term plans that promise bigger health returns in the future. With the very recent announcement of radical restructure of the NHMRC funding schemes, the opportunities to maximally align and enhance these MRFF goals are ideally timed and essential.

There is, however, one large caveat. The pipeline of research discovery depends on a sustained research capacity that the MREA/NHMRC has until recently supported. The last 5 years of funding stasis for the MREA/NHMRC is a genuine threat to the potential impact of the research sector and hence the MRFF. Medical researchers are being lost from the sector in unprecedented numbers and promising young researchers are being blocked from entry just at the point where the workforce capacity had reached a critical and effective mass. The MRFF and the MREA represent the entrance ramps of a future bridge to a better, more responsive and sustainable health system which Australia will be proud of.