The “choice destination” of clinical trials evolves hugely as economics of competing countries fluctuate and political decisions introduce new obstructions. The popularity of the UK, for instance, fell steeply in the 21st century, which epitomises some of the acting forces.
With an understanding of the factors that mold these changes, we can gain a position to predict or at least consider the changes ahead and, therefore, how to select optimal sites for clinical trials.
Weakened UK position
If we look at the UK, we see that its position on the global clinical trial stage declined by almost a quarter between 2000 and now. Its global share of patients in clinical trials fell from 6% to 1.4% between 2000 and 2006, and this was echoed by a 22% cut in the number of clinical trials performed in the UK between 2007 and 2011 (Parliament, 2013).
It is thought that this change was driven in part by the EU Clinical Trials Directive, which was adopted in 2001 (Parliament 2013b). The Clinical Trials Directive brought in significant challenges to the conduction of clinical trials within the whole European Union. This line of thinking is also supported by observations of a similar downward trend in other established EU countries.
Many academic organisations agree that the Clinical Trials Directive increased the cost and bureaucracy of conducting clinical trials, with no clear improvement in patient safety or the quality of trial results (ICR, 2013).The situation in the UK is particularly challenging because it has a difficult governance and regulatory landscape (Parliament, 2013).
The Science and Technology Committee is conducting an inquiry into clinical trials. In its third report, published in September 2013, the Committee stated that although it believes the government is aware of these problems, it has not yet delivered fully on its promises to address them.
Governance and regulation
Meanwhile, a discussion published by the Institute of Cancer Research (Emedcareers, 2013) discussed the future of the UK in clinical research. Marie Palmer, Director of the UK NHS R&D Forum, pointed out that research and development is not currently a core part of a Trust’s business in the UK and that R&D is barely accountable. If insufficient patients are recruited to a trial, for instance, there are no consequences, she said. Jackie Powell, Director, Joint Clinical Trials Office, Guy’s Hospital, pointed out that investigators are currently not driven to recruit patients into trials (Emedcareers, 2013). Marie Palmer (Director of the UK NHS R&D Forum) added that this weak motivation would continue unless the Government introduces “meaningful targets”.
UK future and global context
Dr Palmer proposed that a “cultural shift” is needed within the NHS that positions clinical trials as a business and makes trusts accountable. She said that they need to be made a “core activity” to make them a genuine priority. Allison Jeynes-Ellis (Medical and Innovation Director, ABPI) said that UK clinical trial champions are needed to really embrace them.
Across the world, other key players are improving their position. Areas including China, India, South Africa, Latin America and Eastern Europe can offer more cost-effective clinical trials, through less expensive medical staff and study sites. The quality of the clinical data from these ‘emerging regions’ may cause some uncertainty but, as can be judged by the results of numerous FDA inspections, at least the Eastern European data is on par with data originating in the established regions of US, Europe and Japan.
The Institute of Cancer Research discussion concluded that the UK will improve its position but not regain the 6% hold it had at the turn of the century. Alastair McDonald, Study Program Director, Astrazeneca, noted infrastructure is improving in emerging countries and that Astrazeneca has consequently closed sites in the UK and Sweden in favour of sites such as China.
The UK Government has an ongoing interest in clinical trials and recognises their economic importance, it claims in its response to the Science and Technology Committee Inquiry into Clinical Trials (Parliament, 2013b). Weighed against the less expensive, and increasingly proficient, options in other regions, the UK could see gradual, limited improvement in its position on the clinical trial stage.
Parliament (Sept, 2013) Science and Technology Committee Third Report: Clinical Trials: http://bit.ly/V6iVez
Parliament (2013b) Barriers to conducting trials in the UK: http://bit.ly/1mqmphu
Institute of Cancer Research (2013) Effective action needed to make the UK a more attractive location for clinical trials: http://bit.ly/1qEp8cc
Emedcareers (Sept, 2013) Do clinical trials have a future in the UK?: http://bit.ly/TsmtpX
Interesting post (‘NHS: declining UK position on the clinical trial stage’) with some encouraging statistics and information on the quality and health of clinical trials in Eastern Europe and other nations but not quite so positive for the UK. An additional, yet important, reason for decline in the attractiveness of running of running UK clinical trials has been the complexity of processes involved in obtaining the various approvals: Competent Authority (where applicable), Ethics and local NHS Trust (R&D) permissions.
However, moves are well underway by the UK’s new ‘Health Research Authority’ (HRA) to streamline all the Ethics and NHS processes with the ultimate aim – next year – of providing just one application, one assessment and one approval per study, using the already established electronic online application and submission system ‘IRAS’. The Ethics opinion has been obtained as a single national assessment and approval for some years and the NHS / R&D assessments have already been streamlined and centralised to a large extent for many studies, with the result that NHS permission times (traditionally the rate-limiting factor in study start-up!) have been falling significantly over the last four years.
A symposium (UK Clinical Research – A Professional Awareness Update) held in London on July 14th by the Clinical Contract Research Association (CCRA) highlighted these changes and “presented the United Kingdom’s approach to speeding up drug development and explained the UK’s initiatives to provide alternative and smarter ways to achieve improved data quality and patient safety in a cost-efficient manner”: Access to the presentations can be viewed here: http://www.ccra.org.uk/Meetings/20140714/Presentations.asp
Thus we do see concerted attempts to regain at least some of the lost competitiveness for attracting research and clinical trials to the UK. Ability to recruit and retain patients as quickly and easily as we see in Eastern Europe is another matter, which may also need addressing!
Brian Cary – Clinical Research Consultant