UK clinical research is being transformed
pharmafile | April 4, 2008 | Feature | Research and Development |Â Â UK, clinical trialsÂ
Politicians have been talking, reports have been published, a series of initiatives have been launched and a fist full of organisations with confusingly similar-sounding names have been created – all with the aim of making research easier and quicker, and to make better use of the opportunities both academic and commercial that the NHS offers.
Readers could be forgiven for wondering how all this expensive public activity is being translated into reality. The answer is that change is coming thick and fast, and that it's aimed squarely at the problems and opportunities identified by a report from consultants McKinsey.
The report found that the UK had well qualified researchers and an NHS structure that offered great opportunities for research – but clinical trials were dogged by a bureaucracy that slowed start-up times, and an organisational structure that meant delivery was both slow and unreliable. Both of these were major problems, particularly for the pharma industry.
The good news is that the structural and cultural changes being made are aimed squarely at cutting start up times and ensuring study delivery to target. And even at this early stage, evidence is building that this approach is beginning to pay off.
The networks
Perhaps the biggest sign of progress so far is the establishment of research networks focused on specific disease areas and, a couple of years after being assembled, the ABPI and others are reporting that the new networks are showing every sign of delivering on their promise.
Working along lines first developed by the National Cancer Research Network, the new bodies offer a means of networking that makes patient recruitment much easier. But they also provide statisticians, IT and nursing staff to support both industry and academic projects, and help to train established and new investigators to work to standardised operating procedures. And, crucially, they also performance-manage individual projects to ensure they deliver on time and on cost.
The model is an interesting one, and one that many in pharma industry research circles see as being much more akin to the approach a business would take than established NHS practice.
The longest established network, the Cancer Research Network, covers the whole of the UK from 34 centres. If a particular category of patient is required for a trial, the network will know where those patients can be sources, and where the investigators required can be found to complete the trial to target. Moreover, if a particular trial has trouble recruiting, it can quickly find additional sources of patients, and even extra investigators. It's very different from the traditional situation where the company sponsoring the trial has to try to identify another site on its own.
The network has also shown that it can make much more realistic assessments of the feasibility of particular studies than were previously possible, because they know where the patients are and have an excellent understanding of current UK clinical practice. And where a particular study protocol will not make sense in the UK context, they can also suggest alternative approaches that can be made to work.
Following the Cancer Research Network, the network approach has been extended into stroke, dementia, mental health, diabetes, medicines for children and primary care.
The Cancer Research Network is an undoubted success, but does the model work when transferred to other areas? The latest news is that commercial studies are beginning to flow from the networks. As of January, around 160 companies were in negotiations with the networks about studies, 85 of which had been formally adopted.
Another networks development expected to bring major changes to the clinical research landscape is the new Comprehensive Research Network, scheduled to open its doors in April.
The Comprehensive Research Network will follow the same model and infrastructure as the topic-centred networks, and will have the same staff and resources, but its agenda will be more general and will reflect local needs and strengths. The aim is that 25 locally-organised Comprehensive Local Research Networks will focus on delivering successful trials in clinical areas not already covered by the earlier networks, and within those clinical areas in parts of the country where the topic networks are not represented.
The Comprehensive Networks are also expected to have a particularly powerful effect in developing a much more standardised approach to running clinical trials across the UK.
It's still very early days. Staff have to be appointed and the structures have to be assembled, but on the heels of their experience with the topic networks, research insiders are optimistic the new local networks will be very effective.
Each Comprehensive Local Research Network will be led by a clinical director responsible for developing strategy and overseeing implementation, an executive and a manager responsible for human resources, finance, premises and facilities, and a broader network board representing the relevant NHS organisations, education institutions and other stakeholders in the area.
Instead of attempting to cover all the disciplines in medicine, the expectation is that each will focus on ten or twelve topic areas where they have particular expertise based at individual centres.
Start-up and delivery
The networks are designed to ensure that the trials that get started are delivered. Other key pieces of the jigsaw of reforming clinical research in the UK are aimed at enabling founders and investigators to get trials set up more quickly by streamlining the regulatory and governance processes that investigators have to go through. This effort has several strands.
The first was to develop the Model Clinical Trials Agreement, a model contract for research founders and the NHS that can eliminate much of the initial negotiating and legal wrangling that has to be completed before a study can even begin recruiting.
Previous attempts to do something similar have failed, but because the new contract was negotiated with all the relevant parties around the table, the latest model contract has much more support from the people needed to make it work. Published in 2006, it has quickly been adopted by the pharma industry and is now being used.
In Scotland, the ABPI reveals that where the contract is used without modification, the initial phases can be simplified to such an extent that trial Start-up time can be as much as halved.
Late last year, the UK Clinical Research Collaboration (UKCRC) published a three-way version of the contract for use by clinical research organisations working together with founders and the NHS.
The Research Passport
The second strand encompasses the Research Passport, which greatly simplifies the contract issues that arise where academics and other researchers work with patients within NHS organisations. Each time this happens, the investigators involved need to undergo a number of checks such as Criminal Records Bureau, occupational health checks and perhaps blood tests.
When carried out on a single occasion this can be irritating and time consuming, but probably not a major difficulty. However, in the case of a multi-centre trial with half a dozen centres, the process will have to be multiplied many times, and it quickly becomes a burden for both investigators and Trusts.
Under the Research Passport scheme, a standard set of checks are made by a lead organisation, and these are then accepted by agreement across the rest of the NHS. Originally developed in Manchester and piloted at various centres across the UK, the Passport scheme was finally launched across the UK late in 2007.
The difference with the Passport scheme can be astounding. In one case under the pre-Passport regime, a multi-centre trial involving seven research staff working across 21 sites required as many as 147 honourary contracts to be issued, and these took an average of 21 weeks to sort out. This compares with a later study that took place under the Passport scheme involving eight researchers. They needed just eight sets of checks, each were given Passports and the process was complete in just 14 days.
Independent as they are, Trusts are under no mandatory pressure to adopt the Passport scheme – but with time savings of this order on offer, it seems likely that they will be powerfully motivated to go with it.
The main challenge involved is said to have been getting university and NHS human resources departments working together, but the introduction of the Passport together with a HR resource pack covering research in the NHS has brought an important cultural change.
Permissions
Another aspect undergoing revolutionary change is obtaining permissions. These have to come from ethics committees, and the specialist regulatory authorities, covering drugs and devices, gene therapy, radioactive substances and so on.
Depending on the study, up to seven or eight permissions may be required. Traditionally investigators have had to apply to each one individually by filling out forms, and much of the information would be the same in each case.
So a key objective has been to negotiate an agreement to allow a single central computerised application system to be developed. The Integrated Research Application System (IRAS) was finally launched a few weeks ago. This currently allows investigators to work with a single online permission system for seven of the main organisations, and offers users an adaptive interface designed to ask only relevant questions. If, for example, a particular study does not involve ionising radiation, the applicant will not be asked any further questions required by the ionising radiation regulator.
Some regulators require an electronic signature that can be added online, while others still require the resulting document to be printed out and signed in ink. However, researchers are no doubt relieved that at least the information only has to be entered once!
The system is currently running in parallel with the old applications arrangements and the MHRA medicines permissions system is soon to be included, with IRAS likely to become the only available route to obtaining approvals, perhaps by mid-year.
R&D departments – the next target
Talking with the pharma industry, it's clear that these reforms all add up to a sea-change in the UK environment. Where industry figures used to complain that MHRA and ethics approvals unnecessarily slowed study start-up, these two areas have improved hugely in the past couple of years, driven by deadlines imposed by Government. However, more recently Trust R&D departments have emerged as a key cause of delays in starting trials.
Frequently the problem has been that the Trusts are innately risk-averse. Often they duplicated the scrutiny that is properly the responsibility of the specialist regulators – instead of concentrating on their remit of looking at local issues, such as whether the required patients exist in their Trust, some have even gone as far as peer-reviewing study proposals.
A better approach would be to remind the Trusts of their obligations and to make them fully aware of the checks that have been performed by the regulators. An earlier initiative in this area was the establishment by the UKCRC of an advice line providing information for Trust R&D personnel, but another result of this line of thought is the NIHR Co-ordinated System for Gaining NHS Permission (NIHR CSP) now being set up by the UK Clinical Research Network (UKCRN).
Originally known by the working title of Central Sign-Off, this process checks that the various required permissions and approvals have been given, so that the Trust R&D departments are reassured that they only need to focus on local issues – is the Trust interested in being involved in the research project, does it have the patients, and does it have the staff required?
NIHR CSP comes into operation in April this year, and while it will mean a big change for R&D offices there is good reason to hope that it will simplify their role, reduce their workload – and contribute to reducing trial start-up times.
* For more information on the McKinsey report visit http://www.ukcrn.org.uk ” TARGET=”_blank”> www.ukcrn.org.uk . The website also explains the UKCRN's structure and responsibilities.
Gavin Atkin is a freelance writer specialising in medical and pharmaceutical topics. E-mail him at: gmatkin@gmail.com
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