UK clinical trials: on the mend?
pharmafile | September 26, 2007 | Feature | Research and Development |Â Â UK, clinical trials, global, researchÂ
How clinical research is organised in the UK is essential to the success of Britain's pharma industry, and to the country's economy as a whole. But just months ago, it looked as though clinical research in the UK was in big trouble.
Pharmaceutical companies based in the UK were increasingly finding that it was easier and cheaper to run trials abroad. A key factor in this was that, for several years, health service managers had been under pressure to focus strongly on tackling waiting lists and hitting targets, which frequently meant that clinicians working for the trusts were in no position to take on new trials.
Another was the impact of the European Clinical Trials Directive introduced in 2004, which rocked the UK's competitive position in clinical research. For the first time, it regulated healthy volunteer trials, and the UK could no longer offer its long-standing advantage of light bureaucracy in this area and clinical trials began to move abroad.
Finally, the TeGenero incident last year, in which six young men became very ill after receiving an investigational biologic leukaemia drug, threatened to usher in new safety curbs which could deter or slow down even further phase I research in the UK.
It was a grim picture but much can happen in a few months, and the outlook for the UK clinical research community has changed enormously in a short time.
Perhaps the change that has been most obvious and brought more cheer to pharma than any other is the arrival of a new Prime Minister in the shape of Gordon Brown. Brown's record as Chancellor of the Exchequer strongly suggests he understands and sympathises with the needs of clinical research. It was Brown who first commissioned the Cooksey reviews of UK health research funding in March 2006, it was he who ring-fenced government spending on R&D to create a single, centrally-managed fund, and Brown, again, who endorsed the report in his pre-Budget speech to the CBI later in the year.
Taking a global perspective
It was, perhaps, the European Clinical Trials Directive and its consequences that first brought into sharp focus the increasingly difficult situation of clinical research.
Professor Graham McClelland leads the Roche Centre for Applied Clinical Development, and manages Roche's clinical pharmacology units across the world and its UK trial supplies. The role gives him a global perspective on the UK's position in the competitive world of clinical research.
"Clinical research is a very competitive area. We saw that very clearly when the European Clinical Trials Directive came in and the UK lost out heavily as its commercial advantage in this area disappeared," he explained.
"We still had the advantages of our history and healthcare provision – and the cultural advantage of the natural British curiosity, which is always trying to challenge existing beliefs – but we now had some extra bureaucracy, and a cost disadvantage compared with some of the emerging markets in the new European Union members, and also China and India, whose technical skills are now improving.
"We needed to work to maintain the UK's position. There is not much that can be done about costs in the short term, so what one had to look to was creating an environment in which the process of regulatory approval is consistent and rapid, and that the bureaucracy is kept to a minimum."
Problems across the board
Healthy subject trials are an important area of clinical research, but there were more problems right across the board.
Dr Catriona McMahon, AstraZeneca's head of clinical research in the UK affiliate, has experienced some challenges in persuading her company to come to the UK for its international trials.
"When we're working to set up a trial, the primary question my company asks is this: can the UK deliver? If I can tell them the answer is 'yes', then they'll look to see whether it can be done within a reasonable cost."
In addition to the new healthy subject trials regulations, further issues were preventing Catriona and her colleagues from saying yes to her company's question more often; one was what she regards as the traditional reticence of UK patients to take part in trials; another was the simple fact that NHS managers' priorities were elsewhere; and another was the shortage of trained nurses and clinicians.
"But what really made the government worry was the state of the skills available in the UK in terms of research nurses, physicians and surgeons. They were seeing interest in doing research starting to go downhill, and people weren't being trained to work as research professionals. We were losing a valuable skill set."
A key step forward
A key step leading to today's renaissance in UK clinical research is the emergence of the clinical research networks, beginning with the National Cancer Research Network.
The National Cancer Research Network was set up by the DH in April 2001 to provide the NHS with an infrastructure to support trials of treatments, and to integrate and support research undertaken by cancer charities with the ultimate aim of speeding up the way research translates into improved patient care.
Its activities include maintaining a research database, developing coordinated research initiatives on specific topics (such as prostate cancer or in cancer prevention) to which groups of members contribute, and helping to develop facilities and resources for research.
The new network quickly proved successful, for although research in other areas continued to decline, the NCRN was able to show that it had successfully facilitated a growing number of cancer research studies.
The result is that the NCRN has now provided the model for a range of new research networks focusing on a range of different areas: dementia, neurodegenerative disease, diabetes, medicines for children, mental health, primary care and stroke.
Established under the aegis of a central UK Clinical Research Network (UKCRN), the new networks have government funding and positive support through a central body, the UK Clinical Research Collaboration (UKCRC).
McMahon is clear that the networks are at the heart of the change." If we need a trial in the area of diabetes, for example, we can go to the Diabetes Network, who will give us some feedback on whether it is in line with UK clinical practice and whether there are suitable patients available. Then, if they adopt the trial, they will work with us to get the research centres up and running. The networks have an accountability for delivery, and UKCRN take it seriously."
One of the ways in which networks are helping is in making delivery more predictable. "What's problematic for us is when a project is unexpectedly delayed, the patients or clinic space arent really there, or, critically, there is a lack of staff. But these things could change with the help of the networks, once they are fully established."
Transparency and uniformity
Another thing that's changing is a new uniformity and transparency about the way those involved in trials work together following the widespread adoption of the Model Clinical Trial Agreement, a standardised contractual framework for commercial trials put together by the DH in partnership with UKCRN and the ABPI.
The Model Trial Agreement is now being widely adopted, says McMahon. "AstraZeneca, along with many of the other pharma companies, has said that it will work with the model clinical trials agreement without any changes, unless there is a very specific need for a change. We've really embraced it and my experience is that the model clinical trials agreement is meeting the vast majority of people's needs."
A new idea that builds on the success of the Model Clinical Trials Agreement is the possibility of a single transparent research-costing template, currently being developed by UKCRN, which will be used with all clinical trials.
Says McMahon: "It will help with contracting and negotiations, and will enhance the partnership between industry and UKCRN through transparency of costs researcher time, overheads and additional investigations or treatments etc.
Also, new metrics, which will apply across all of the networks are another project weve been working on in partnership.
"All of these things are working towards transparent delivery. If we in the UK can get a strong reputation for delivering on the promises we make, it will make a big difference."
Clinical research in the limelight
Important though they are, the clinical research networks are far from the only big change in the wind. The Cooksey Report, or A Review of UK Health Research Funding as it is properly titled, marks an even more dramatic turning point.
Cooksey was published only a few months ago, and many people both in the pharma industry and in healthcare more generally are still absorbing its implications. The main elements, however, were to bring together the research budgets of the Medical Research Council and the DH under a single Office for Strategic Coordination of Health Research (OSCHR, pronounced oscar) to set and maintain a cohesive research strategy and, crucially, to encourage a stronger partnership with the health industries and charities.
At the beginning, Cooksey looked to many as if it was about making sure the NHS was pulling together all non-commercial funding for clinical trials and managing in the best way possible. However, Cooksey and his colleagues quickly realised the importance of industry involvement in UK healthcare. The result is nothing short of revolutionary.
"One of the things that is very interesting is that one of the ambitions of OSCHR is to create a priority listing of medical need," says McMahon. "For the pharmaceutical industry, it will mean that a trial that fits in with the list of priorities and meets the quality criteria will get the OSCHR brand.
"At the moment, we haven't assessed the value of an OSCHR stamp, but we do recognise that there is real value in having a list of priorities. I would be able to say to my colleagues in AstraZeneca that we should place a particular trial in the UK because it was in one of the UK's priority areas, and that we can expect it to be supported at all levels.
"We will then be able to focus on trials we can deliver on, knowing they will go into areas where they will really make a difference to patients.
"From my company's perspective, one question is whether the areas our company works in are on their list, but with our broad portfolio, including oncology and mental health, I think our R&D strategy will fit with the priority list."
One of the points about the priority lists that most interests pharma is that they will be created through a consultation process which will include the views of pharmaceutical companies.
Is enough being done to save clinical research?
Cooksey will not lie forgotten on a shelf within a couple of years – it just isn't that kind of report. As David Cooksey himself noted in his introduction, more than 300 organisations contributed to the consultation, and each of them has demonstrated a powerful motivation to improve upon the status quo. This strong ambition to make a difference and backing that comes from the very top of government will ensure that Cooksey will remain very much in the spotlight – already it's clear that Cooksey will be remembered in 20 years.
But has enough changed to enable clinical research in the UK to maintain itself and to build on its position on a worldwide basis? Based on the passion and optimism currently to be heard from people in pharma, the answer must be yes, not least because those at the coalface of clinical research in the UK regularly report that they are meeting a new, very positive approach from the state-assisted sector to working with the pharma industry.
AstraZeneca's McMahon is clearly a figure who combines both passion and optimism in large quantities. A big difference could be made as a consequence of all of this. None of us are fooling ourselves that it's just about writing a document and sending it out to everyone. Its' about collaboration, its about partnership, and its about understanding that things often won't work in the first instance and finding ways to make it work better.
"If any of us – pharma, the charities, UKCRN, the NHS or the academics – were to pull out, it wouldn't work, but if that happens, none of us will succeed. It's not easy, and it's not without its challenges, but there's a real passion to make it work.
With his global role, Professor McClelland, takes a more international view: "The UK, perhaps more than any other country in Europe, is waking up to the strategic importance of healthcare research. There are individuals who are aware of the same thing in a number of European countries, but they're not being heard."
So, it seems that the UK has some huge potential advantages, including a new Prime Minister who has already heard and understood the message and, importantly, acted upon it.
Gavin Atkin is a freelance writer specialising in medical and pharmaceutical topics. gmatkin@gmail.com
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