Changes in the global markets have led to a funding crisis, with investors looking for companies to advance products further along in development than ever before. This has made it harder for companies, especially the smaller start-ups, to access sources of financial support and investment. They are, therefore, looking for cost-effective locations that allow them to move quickly and efficiently to proof of concept in humans, because the results may clinch an important partnership or financing deal.
This stage of development is known as translational medicine — the translation of basic research from a lead molecule to a drug candidate in proof of concept trials in humans. “A wider definition is moving from an idea in a lab to the actual drug or diagnostic given to the patient,” says Geoff Davison, Ph.D., director of Bionow, the cluster support group for the northwest of England’s biotechnology, pharmaceutical, and healthcare industry.
“In translational medicine, speed and the mitigation of risk are key parameters,” says Scott Kozak, VP of life sciences at the U.S.-based North of England Inward Investment Agency. “A large percentage of drug candidates fail at the early clinical stages, and a well-constructed, efficient phase I trial can take much of the risk out of drug development by making the go/no-go decision much clearer. It can also make the difference between success and bankruptcy for a company that has enough financing for only one key trial, by avoiding expensive pitfalls at the regulatory stage.”
Why the United Kingdom?
What can the United Kingdom do to provide a service to these companies? The UK government has made some significant investments in order to make the country a highly efficient location for clinical trials. “The Department of Health [DOH] saw that it was missing an opportunity and responded by investing in infrastructure and health research in order to capitalize on the NHS [National Health Service] asset base and attract biomedical industry R&D,” explains Davison. This involved the improvement of access for companies to patients, staff, and infrastructure within the NHS, through clinical research networks and streamlining processes.
The National Institute for Health Research Clinical Research Network Coordinating Centre (NIHR CRN CC) has created population- and disease-specific research networks, including:
- National Cancer Research Network (NCRN)
- Diabetes Research Network (DRN)
- Dementias and Neurodegenerative Disease Research Network (DeNDRoN)
- Medicines for Children Research Network (MCRN)
- Stroke Research Network (SRN)
- Mental Health Research Network (MHRN).
As an example (especially important as trials in children are now required for drug approval in Europe and the United States), the MCRN treats approximately 6 million children at over 100 NHS pediatric sites in England.
“The UK population is an ideal one for clinical trials,” says Davison. “The population is socially and ethnically very diverse, and its disease incidence reflects that of the United States and the rest of Europe. The NHS has patient records for each individual, kept from the beginning of the NHS in 1948, and the population is very stable, which helps retention in clinical trials. As well as providing companies with single-entry points for specific populations, the networks provide sites with dedicated resources and research staff and have adopted standardized agreements and costing processes. The networks will also make regulatory submissions for certain studies.”
These standardized processes and protocols will make the process of conducting clinical trials in the United Kingdom more efficient. The government also has worked to smooth out the process of ethics. Previously, in order to conduct clinical trials, companies needed to apply individually to the ethics committee at each study site, and each ethics approval could take up to three months.
The government recognized that this was a bottleneck and created IRAS (Integrated Research Approval System), a single point of entry for permissions and approvals for health research from all the relevant review bodies, including the Gene Therapy Advisory Committee (GTAC), the Medicines and Healthcare products Regulatory Agency (MHRA), and the NRES (National Research Ethics Service) and NHS Research Ethics Committees.
“It’s a Web-based system and allows you to enter the data just once, instead of duplicating all the paperwork for each site. It really has speeded things up — MHRA approval for a healthy volunteer phase I study now takes, on average, less than 13 days, which compares favorably with the United States,” explains John Illingworth, managing director at the UK-based CRO Clinical Development and Support Services (CDSS). “Instead of having to wait for an ethics committee meeting at the relevant site, the submission is allocated to the next meeting anywhere in the country.”
In 2004, the EU put in place the Clinical Trials Directive, which requires approval of all phase I clinical trials. At the time, this caused around a 50% fall in the number of clinical trials conducted in the United Kingdom. However, numbers of trials returned to predirective levels within 12 months. This prompt recovery reflects the quality of, and confidence in, clinical trials in the United Kingdom, supported by the MHRA’s decision to put guaranteed timelines on its clinical trial approval process.
A Cost-Effective Destination
In the current economic downturn, companies are struggling, looking to cut costs everywhere, including in clinical trials. To do this, they may look to countries with low labor costs like India and China. “While these countries are set up well for large phase III trials and have access to huge treatment-naïve populations, for phase I and II trials companies need to be able to rely on the academic structure and historical knowledge base that the United Kingdom can supply,” says Illingworth.
Kozak adds, “The United Kingdom presents a very cost-effective solution for translational research, particularly the lower-cost regions in the north of England. Because companies conducting phase I and II clinical trials really can’t afford to take unnecessary risks, setting up in a region known for academic rigor, high-quality research, and clinical efficiency makes a lot of sense. This is worth so much more than the simple dollar amount.”
A Commitment To Biomedical Research
The United Kingdom has an excellent history of biomedical research. It has a well-established pool of talented researchers and health professionals, with UK scientists having won more than 70 Nobel Prizes. Five of the top 20 pharmaceuticals in the world were developed in the United Kingdom, and 35% of Europe’s biopharmaceutical clinical trials take place in the United Kingdom.
In April 2007, the DOH announced £45 million (about $66 million) of funding to create 12 new specialist biomedical research centers across the country, including two in the northwest of England, in Liverpool and Manchester, and one in the northeast, based in Newcastle. These units will focus on translational research and are located at existing research centers nominated as specialist units based on their quality of research and selected by an international panel of experts.
“These centers are the best in class for biomedical research, and all benefit from being in very close proximity to clinical researchers and patients in leading teaching hospitals, as well as bioscience clusters. These clusters, such as those in London, Cambridge, and the northeast, will support innovation arising from the early-stage research,” says Kozak. According to the UKTI (UK Trade & Investment), the DOH has committed to spending more than £1 billion on health research between 2010 and 2011, with Higher Education Funding Councils investing £620 million in the same period.
“The government has made a good start,” says Davison. “It is committed to bringing the United Kingdom back into the game, translating potential therapeutics and devices into successful products, and is looking at the processes on an ongoing basis.”
Lord Darzi, parliamentary undersecretary of state at the DOH, has conducted a review of the NHS known as “High Quality Care for All.” “The outcomes of this report will drive the adoption of new therapeutics, diagnostics, and devices, as will the legal obligation on UK health authorities to innovate,” explains Kozak. “With the ongoing support of the government to provide streamlined processes and solid infrastructure and access to world-class researchers and motivated patients, this level of innovation will continue to make the United Kingdom the location of choice for translational medicine.”