From bench to bedside

A major funder of health research in Ireland is moving its focus away from basic research and towards the patient. CLAIRE O'CONNELLreports

HOW DO you turn scientific research into something that helps a patient? It’s a question that has received considerable attention in Ireland as our basic research in life sciences has grown.

But a new strategy announced by one of the State’s largest funders of medical research stands to boost that process of translating discoveries from bench to bedside by shifting its focus away from basic research and towards applying that knowledge.

“Make no bones about it, we are making a clear statement that we will no longer be funders of basic, biomedical research,” says Enda Connolly, chief executive of the Health Research Board, which last week launched its new strategic plan.

“So much health research can end up just being in the basic research to increase understanding, but increasingly if you are going to get the benefits you must also invest in the application and translation and how it is used, and how you actually create mechanisms for using it within your systems and care processes. That’s where you see us focusing over the next three to five years.”

The strategy is a conscious shift by the agency, which currently has investments of about €200 million across hospitals and third-level institutions, and its aim is to bolster the Republic’s health research infrastructure, according to Connolly.

“The really big gap identified was that we had an underperforming clinical and health research environment.

“Academia and industry in life sciences was not able to exploit the possibilities because they don’t have the proper access to the clinic, the patients, the knowledge that being close to the bedside delivers in new products, new services and new activities.

“That’s the huge gap that Ireland has, and that’s the gap the HRB sees itself trying to fill over coming years.”

The plan itself sets out a number of goals: driving clinical and applied biomedical research, building up our understanding of population health and how health services are delivered, developing and managing high-quality health information systems and generating evidence that can support policy-making.

But what does that mean in practice? The shift in emphasis is probably best exemplified by some of the projects selected for this year's A Picture of Healthdocument – an annual report that summarises snapshots of HRB-funded research.

This year’s crop includes the Sphere study (Secondary Prevention of Heart Disease in General Practice, www.spherestudy.com), cited as the largest non-pharmaceutical clinical trial in Ireland. Co-funded by the Irish Heart Foundation, it is working with more than 900 patients in 48 practices to improve aftercare for patients with heart disease to prevent premature death.

A Picture of Health, which is published today, also highlights research that found the 2004 ban on smoking in the workplace improved respiratory symptoms of bar workers; research on the effectiveness of interventions to prevent tooth decay in children; and findings that challenge the assumption that most terminally-ill patients want to die at home.

Connolly particularly highlights HRB-funded research on information systems and biobank management, which he sees as an important area, both for improving patient care and even linking into the economy.

“That’s the start of an area we have to invest more in to create a capacity and a capability in Ireland overall to exploit, not just in terms of our own patient care systems but also the industry and economic benefit that could accrue,” he says.

“If we could bring a number of areas together, I think we could create a competitive advantage for Ireland in what is essentially genomic database research. That will enable us not just to work with our own system, but could attract international investment as well.”

The shift away from the bench and towards the beside and community now sets the HRB very much apart from other State-funding agencies in the life sciences, such as Science Foundation Ireland.

Was the change in emphasis prompted by the McCarthy report recommendations this summer that the HRB be merged with a single stream of science funding?

No, insists Connolly, the agency’s review of its strategic direction started almost a year ago, but the changes still address Snip Nua’s concerns over issues such as potential duplication of funding activities.

“When McCarthy talks about a single agency, what he is actually saying is there needs to be a better return on investment, there needs to be a better focus on the benefits and outcomes of the investment to ensure there’s no duplication or overlapping between funding activities,” says Connolly.

“We believe we are now positioning health research and the work that we do to address those issues. Now whether that ends up being managed in a single funding agency or single overarching body is really not relevant because at the end of the day the key issue is to ensure that the health research agenda is not lost.

“We cannot exploit the opportunities economically or for our €15 billion health service, which is the biggest service business in the country, and for us not to be doing research that helps to transform that, to create different ways of caring for people that are more effective, and also be in a position where that system doesn’t participate in the economic agenda would be folly.”

Managing the blood stocks

Ensuring that enough blood is available for patients who need transfusions is a tricky balance for hospitals. Order too little and patients face delays in potentially life-saving interventions. Order too much and precious donated blood stocks can be wasted.

Recent HRB-funded work by the Transfusion Research Network has analysed how the blood supply is managed in the Republic and has helped to improve awareness of stock control in hospitals.

“Our objective was to work with hospitals to raise awareness of stock management as an issue,” says Prof Anthony Staines, chairman in health systems research at Dublin City University’s School of Nursing.

“So we spent a lot of time working with the hospitals, evaluating their data and developing a very simple model for stock management.

“There were hospitals that were ordering 20 to 30 times a week and everybody knew it was crazy, but they had to step back and change how they order, so we did quite a bit of work on ordering schedules and processes.”

Taking the time to step back and research the area, working closely with transfusion services and hospitals, was a key step towards improving the control of blood stocks, and wastage has fallen as a result, according to Staines.

Their research into risk perception also found that parents of children who require a transfusion understand the relatively small risks involved. “That hadn’t been looked at before, and we found that they had a very solid understanding of what the issues were and that surprised us – they understood the need and the potential risks, like getting an infection,” says Staines, adding that the risk of infection from the blood supply here is now very low.

Why do smoking mothers have smaller babies?

Mothers who smoke cigarettes during pregnancy tend to have smaller babies than non-smoking mothers, but how does this actually happen?

HRB-funded research at the Coombe Women’s Hospital has not only highlighted the nature of smoking-related growth restriction in the womb, but has also raised questions about a biochemical, thromboxane, that has been suspected to play a role.

Researchers Dr Carmen Regan and Dr Caoimhe Lynch used ultrasound to track the growth of the foetus at intervals in later pregnancy in 60 smokers and 60 non-smokers, and found that babies of mothers who smoked were globally smaller.

“The babies are not just thinner, but their head size is smaller,” explains Regan, a consultant lecturer in obstetrics and gynaecology, noting that studies have linked growth restriction in the womb with increased risk of heart disease and diabetes in later life.

The Coombe researchers also analysed urine samples from the mothers for levels of thromboxane, a biochemical produced by the body that causes vessels to narrow and makes blood platelets more sticky, and found unexpected results.

“When we looked at it from a statistical point of view, thromboxane was not related to foetal weight, so thromboxane is not the whole story in how small the baby is. It’s likely there’s another factor in cigarettes that is causing the babies to be globally small,” says Regan.

A separate study they carried out of babies who were severely growth restricted also challenges the suspected role of the biochemical, she adds.

“We found in the very severe growth restriction that contrary to what we would have thought, the thromboxane was quite low in the babies that were very small. So it’s possible that thromboxane has a role that is different from what we thought in growth restriction and in normal pregnancy.”

Using gene therapy in fight against cancer

Our own immune systems can be a powerful ally in fighting cancer in the body, but tumours can thwart those defences by dodging our immune radar.

Now researchers at UCC are developing an approach that uses gene therapy to make tumours more visible to the immune system.

“There is abundant evidence that the immune system is active in containment of cancer, and current research strategies aim to understand the mechanistic nature of this and to exploit it for treatment,” says Prof Gerald O’Sullivan, a consultant surgeon at Mercy University Hospital.

“There is evidence also to suggest that for many cancers, chemotherapies work best in the presence of anti-tumour immune responses.”

The Cork team has used gene therapy to treat tumours so they now produce molecules that recruit and protect the immune cells when they reach the cancer, explains O’Sullivan, director in chief of the Cork Cancer Research Centre.

“This produces powerful immune responses which are active against the disseminated cancer cells and sometimes also effective against the local cancers. Thus the strategy is to create an immune reaction to the cancer which is left after removal and prevents recurrent disease.”

The immunotherapy approach has shown promise in pre-clinical trials and clinical trials are imminent.

Protecting donors’ data

Biobanks, or repositories of donated biological samples, can be a goldmine for research if the samples are linked with clinical information about the donor patient. Well-managed biobanks can speed up the discovery process and help shed light on links between genes, diseases and how well particular patients respond to treatment.

But to protect the confidentiality of donors, patient information needs to be handled carefully, according to Jane Grimson, professor of health informatics at Trinity College Dublin.

She and Dr Geoff Bradley have led research on a HRB-funded project with the Irish Prostate Cancer Consortium to better manage biobank information across its four universities and six hospitals. They have developed a Biobank Information Management System that lets researchers search the database and identify the samples they need, explains Grimson.

“The samples are in designated freezers on the hospital sites and when the researchers want to investigate a particular group of patients, they query the database . . . and it’s transferred from the hospital site to the research site,” she says. But crucially, the patient-identifying information stays within the hospital, so researchers never see it.

Work is now under way to make the information-management system more generic so it could be applied to other biobanks, she adds, and having a safe and standardised system also opens up the possibility of linking with other biobanks internationally.

• A Picture of Health 2009 and the HRB Strategic Business Plan 2010-2014: The Future of Irish Health Researchare available to download at www.hrb.ie/ publications. To download the related Action Plan for Health Research 2009-13, also launched last week, go to www. dohc.ie/publications