By Deborah Borfitz

August 12, 2019 | The United Kingdom (UK) has several attributes that make it uniquely appealing to clinical trial sponsors and contract research organizations (CROs) looking to cut the cost and time of drug development. The virtues are all related to its world-class National Health Service (NHS), the largest single-payer healthcare system on the planet.

The UK government generously funds the National Institute for Health Research (NIHR) Clinical Research Network (CRN) with £300 million annually in support of clinical research, most of it for the salaries of 10,000 staff—from research nurses to clinical research practitioners and data managers—placed across 15 local CRNs that are fully operational in England, says Matt Cooper, director of business development and marketing, at the NIHR Clinical Research Network Coordinating Centre. Another chunk of funding supports 30 national specialty groups, collections of key opinion leaders in different disease areas who regularly advise on study feasibility at the pre-protocol stage.

The centerpiece is a decade-old integrated research application system (IRAS), the UK's single application gateway for regulatory, ethics, and NIHR support, Cooper says. Alongside this is the central portfolio management system (CPMS), a warehouse of intelligence on investigator performance, research capacity and disease prevalence as well as the track record of all ongoing academic studies and 75% of commercial studies coming into the UK. An important complement to the big data is live feedback from on-the-ground staff providing information CPMS never could—a lead investigator about to go on a six-month sabbatical, for example, or a study nurse who just went on maternity leave.

"Essentially, we want to make sure studies land well," says Cooper, citing the signs of success. For fiscal year 2018-2019, the NIHR recruited 870,000 UK residents into clinical trials (46,000 for industry-sponsored studies). All NHS inpatient facilities are now research-active in one form or another, with 78% engaged in commercial research. Notably, only 8%-12% of sites fail to enroll even one patient compared to a CRO-reported global non-enrolling rate of 20%-22%. Three-quarter of studies in the network recruited on time and on target, he says.

The NIHR has been advocating for sustained participation in interventional clinical trials in the NHS as part of patients' "standard" healthcare journey for several years now, based on proof that it improves the outcomes for all patients, Cooper says. Best practices and protocol-driven approaches of research teams get "diffused" across entire organizations. "It's really important for us to convince chief executives at these hospitals that research is not just a nice-to-do thing but should be part and parcel of their active care with patients because it increases the standards."

NIHR got its start in 2000 with an experiment demonstrating that running clinical trials outside of teaching hospitals improves study participation rates and equity in access to studies, says Cooper. By 2014, it had built a "true national network" for all types of research.

"A lot of countries have started to copy elements of what we do, and some have come to us about how we operate trials," says Cooper. Five years ago, NIHR helped establish the Canadian Cancer Clinical Trials Network (3CTN) based on the original UK network called the National Cancer Research Network set up by Peter Selby, a professor of cancer medicine at the University of Leeds. "Over the past six years, we grew participation of cancer patients in clinical trials from just under 3% to 20%."

Support Services

Protocol feasibility and "matchmaking for sites" are among the support services offered free of charge to study sponsors and CROs, says Cooper. The NIHR can also help them make all the right contacts prior to study startup.

Specifically, the NIHR can assist drug developers with a rundown on where studies are currently underway, the capabilities and track record of research sites, where sufficient volumes of patients in a particular therapeutic area (or clusters of individuals with a rare disease) can be found, and whether the standard of care in the control arm aligns with clinical practices in the UK. It can also provide guidance on ethical and regulatory matters or make the appropriate referral to the Health Research Authority or Medicines and Healthcare products Regulatory Agency.

It's a highly streamlined process, says Cooper. If a company is looking to place a study in non-small cell lung cancer, for example, the NIHR can say which research sites have done well on past non-small cell lung cancer studies and estimate how many patients they're likely to recruit.

Locally based staff can report on the live situation, perhaps learning that a first-pick center already has four other such studies ongoing, Cooper continues. The NIHR can suggest other top performers at places where patients aren't being as well served. "We can build a diagram showing where non-small cell carcinoma studies are happening, where the gaps are and where there are overlaps."

Similarly, for a sponsor planning to do a diabetes study, the NIHR can quickly produce heat maps of disease prevalence and then overlay where research-active diabetes clinicians are located, Cooper says. "We can see where we have good research activity compared to disease prevalence or, conversely, where we have a hot spot of diabetes but don’t have many research centers."

The CPMS houses information on thousands of hospital-based investigators affiliated with one of 246 NHS trusts, giving the NIHR a good idea of where to find new sites for industry-sponsored trials, Cooper adds. This includes, most notably, groups that have been solid performers in academic settings.

"In some [therapeutic] areas, companies keep going back to the same sites and then run out of capacity," he says, pointing to a recent rheumatology study where the sponsor handed Covance a list of 50 must-have sites. Only two of the 50 even responded to the invitation to participate. But using NIHR's research network and support services, the CRO immediately turned up 19 "ready, willing and able" sites.

Increasingly, the new research sites being identified are outside the standard hospital setting, says Cooper. These include dental offices, ambulance services (for critical care studies), schools, hospice care facilities and prisons.

38% of general practitioners in the UK are actively engaged in clinical research, he continues, recruiting more than 78,000 patients into studies last year. All 10 ambulance trusts are now actively engaged in clinical research as well.

The NIHR has particularly strong partnerships with publicly run and privately-operated hospices for palliative care, dementia and Parkinson's disease studies, he adds. A few years ago, the NIHR launched a web-based Join Dementia Research tool allowing patients and caregivers to register their interest in research. About 40,000 individuals signed up during the most recent fiscal year, of which 46% were recruited into studies.

Network of Specialists

The national specialty groups are the "go-to people" for study sponsors seeking early feedback on a study concept, sometime before the protocol is at the first-draft stage, says Cooper. Among the focus areas are diabetes, stroke, cancer, surgery, injuries and emergencies, infectious diseases and microbiology, and dementias and neurodegeneration.

Each specialty group has roughly 15 key opinion leaders able to give their "top-line thoughts" in a matter of days or to have a more in-depth conversation about the contemplated study, Cooper says. "It's a great offer used by a lot of companies." The group's national lead is sometimes brought in for face-to-face meetings with company representatives to ensure they have a good overview of what's happening in the country in terms of current trials, research capacity and patient needs.

In fields that are quite broad, such as oncology, group members keep an open communication line with subspecialty groups and key experts in different disease subtypes, Cooper says. They're also aware of who maintains a national registry for small subsets of patients with rare diseases and the referral centers where there are clusters of patients receiving care.

The specialty groups have had discernable impact on perceptions of the UK as a clinical study destination, notes Cooper. Recently, the NIHR stepped in after a UK investigator wrongly concluded that an oncology study could not be conducted in the country due to the competitive landscape. When the protocol was submitted to NIHR's online system, the consensus of three key opinion leaders was that the study would be of interest to England and several sites were identified. "The UK ended up being the top enrolling country," he says.

What's Ahead

"We're starting to look at research in public health and social care settings… in hopes of preventing disease before it effects the population," Cooper says. "Some of this is about mental health services and how we treat young and vulnerable patient groups." The NIHR also plans to start running studies in local community pharmacies within the NHS—the equivalents of those ubiquitous street-corner Walgreens in the US.

"We also want to remind companies that it's not all about big data when it comes to how sites will perform in a trial," says Cooper. "The other vital part is having on-the-the ground knowledge of their research capability to attract patients to trials, their current workload in terms of clinical research studies and their staffing capacity over the next few months or years."

Edit: An earlier version of this article suggested that NIHR Clinical Research Network was funded by the NHS. Instead the UK government funds the network. 

Editor's Note: Cooper will be presenting at the upcoming Summit for Clinical Trials Operations Executives (SCOPE) Europe, being held in Barcelona, Spain Sept. 17-18, on the study support services of NIHR specific to commercial research. Attendees can expect to hear more about how the NIHR has been making the UK an industry-friendly place to conduct clinical trials and what to expect moving forward, he says.