Stroke for stroke in the clinic

At first glance, Professor Geoffrey Donnan's perspective on all things clinically excellent is impressively broad. His titles are many including director of neurology at Austin Health, director of the National Stroke Research Institute (NSRI), and, in his spare time, president of the World Stroke Organisation.

For the CRX conference, however, Donnan will be wearing his hat as co-chair, with Professor Sam Berkovic, of the Centre of Clinical Research Excellence (CCRE) in Neurosciences, which was established in 2003 and is based at the Austin Health Repatriation campus in Melbourne's Heidelberg, administered through the University of Melbourne.

The centre offers a model for multi-disciplinary clinical research into stroke, epilepsy and other neurological disorders. It is headed by a team of four chief investigators under the leadership of Donnan and Berkovic.

At the conference, Donnan will detail what he, as a clinician, considers necessary for overcoming the obstacles to clinical research excellence.

Donnan has a list of 'must haves' for those wishing to undertake successful clinical research, drawn from both his own highly successful career spanning almost 30 years as a neurologist and researcher, and from his wealth of experience as a leading contributor to the field of stroke research and management in Australia and internationally.

The first two necessities for even starting research, according to Donnan, are a spirit of enquiry and the environment in which that enquiry can be expressed.

"If you have an enquiring mind and you are a clinician, then you are continually confronted with areas of evidence gap and constantly wanting to plan clinical research projects to fill those gaps," he says.

This is where the second point about environment becomes important: as he puts it diplomatically, "clinical research is not always actively encouraged in all clinical centres."

When Donnan started out at the Austin Hospital he most definitely had the spirit of enquiry, but unfortunately had to confront the appalling resources everyone else experienced in those days.

However, Donnan says he and his colleagues were lucky in that research was always supported well at the Austin.

"I think we were able to overcome the resource gap by building research protocols into the clinical management program, and we took small steps from there.

"We subsequently set up the National Stroke Research Institute, about 14 years ago, but still our resources were not great and we had to depend on our own abilities to expand the program."

Another must, he says, is the ability to create the time to do clinical research. This may sound obvious, but according to Donnan, it is not.

"Clinicians could easily be overwhelmed by their clinical duties, so those who want to pursue research have to be very good at multi-tasking and time management. Next, a successful researcher has to ask the right questions.

"This applies of course to research of any type but it is very easy in our research to undertake studies that generate uninteresting results of little clinical significance or use."

The major questions that the CCRE is addressing now in the stroke program largely revolve around defining the ischaemic penumbra - in simple terms this represents the therapeutic time window for intervention, or that portion of the ischemic brain following stroke that can potentially be salvaged by timely intervention.

"The clinical definition of this remains unclear and difficult, and Donnan names it as one of the most important issues facing clinical researchers as far as acute interventions for stroke are concerned.

"We know that we have this potentially reversible tissue: the duration for which it survives is uncertain."

At any one time, the NSRI may be conducting or involved in up to 30 trials. These vary from mega-trials of 20 000 patients to highly selected small trials on 100 or less patients.

"Some of these investigating the ischaemic penumbra have been ongoing for many years. Along the same lines, Donnan has an interest in the effectiveness of different neuroimaging techniques to hopefully unravel the duration available in a given patient for therapies and how effective they are likely to be. These techniques include magnetic resonance (MR) and positron emission tomography (PET) imaging.

Show me the money

Donnan will also discuss team building and output quantification, dry topics certainly but hugely important. Then, it's onto everyone's favourite topic - funding availability, or to be more accurate, the lack thereof.

Donnan sees the funding shortfall as the major obstacle to clinical research excellence in Australia. On this topic, his professional passion becomes clearly apparent and he does not mince words. "The funding level for clinical trials in Australia is still a disgrace and totally inadequate, and I say this as often as I possibly can."

Trials in Australia are funded through a variety of sources. The NHMRC is a major contributor, specifically through the CCRE program, and Donnan says it is doing the best it can within a limited budget. "We really need to build up further and better ways of generating research funds," he says.

Donnan has served for many years as an assessor and advisor to clinical networks and research centres in other countries, and this has made him realise just how inadequate the situation is in Australia. He cites Canada and the UK as countries with excellent clinical research networks and programs operating.

"Although the CCREs are a very good start, it is a drop in the bucket compared to what they are doing overseas. The level of funding is definitely an obstacle to the levels of clinical research we could be doing, especially for investigator-driven trials. "We have good networks and organisational structures established in the stroke field that help to conduct all the clinical trials, through networks such as Neuroscience Trials Australia and the Australian Stroke Trials Network.

"However, we simply need to put much more money in to address those evidence gaps. It would ultimately save us money and of course reduce morbid events."