Clinical trials are the key components of modern health research, undertaken by both pharmaceutical companies and the NHS to develop new treatments. They are defined as ‘any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes’ (WTO, link). Clinical trials in the UK and across Europe are vital for our health care, but have been seriously undermined by EU law. New research by Change Britain shows:

  • EU regulation has had a disastrous impact on clinical trials in the UK – the number of commercial clinical trials fell dramatically following the introduction of the Clinical Trials Directive (CTD) and has never risen above its 2005 level.

  • The cost of the CTD to the NHS can be put at nearly £250 million since 2009 in added red tape costs.

  • This slowdown in medical research has likely contributed to up to 5,000 deaths between 2004 and 2013.

Commenting, Change Britain Chair and former Labour health minister Gisela Stuart said:

‘In delaying lifesaving medical research, this disastrous EU ruling has cost both lives and money.

‘It is just one more example of the meddling nature of the Brussels bureaucracy. Eurocrats should not be making decisions which have such a devastating effect on our health service.

‘Outside the EU’s single market we can stop these damaging EU regulations and spend the billions we send to Brussels each year on our priorities like the NHS.’

Notes to Editors

Both the 2001 ‘Clinical Trials Directive’ (Directive 2001/20/EC, link) and the ‘Good Clinical Practice Directive’ (Directive 2005/28/EC, link), were implemented to govern clinical trials across Europe. The 2001 Directive was incorporated into UK law books via The Medicines for Human Use (Clinical Trials) Regulations 2004 (link) while the 2005 Directive was incorporated into UK law via The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (link). The CTD came into force in the UK on 1 May 2004.

These EU laws created serious problems for UK clinical trials

In 2000, the EU claimed that its new Clinical Trials Directive (CTD) would ‘reduce delay in the commencement of a trial’ and ‘will promote the conduct of such trials in the European Union’ (European Parliament, September 2000, link). In fact, the European Commission has subsequently admitted ‘Directive 2001/20/EC has… led to a decline in clinical trial activity in the EU’ (European Commission, July 2012, link). Cancer Research UK has described how the regulation – which demands that all treatments are treated the same, regardless of whether they are new or established – caused serious problems: ‘The original Directive had a ‘one size fits all’ approach, focusing mainly on the development of new drugs. It failed to recognise that most trials undertaken by charities and academia involve existing medicines… As one of the largest funders of clinical research in the UK, Cancer Research UK suffered disproportionately under the Directive: many of our trials took longer to start or were prevented from going ahead’ (Cancer Research UK, link).

Since coming into force, the number of clinical trial applications received in the UK has declined dramatically and, while there has been some recovery since 2010, the number of commercial trials still remains significantly below the 2005 level.

Commercial Clinical Trial Applications received by the Medicines and Healthcare products Regulatory Agency

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

912

829

899

873

772

711

713

728

759

760

842

Source: HM Government, link

This is not unique to the UK – between 2007 and 2011, applications for clinical trials fell by 25% across the EU – equivalent to the 21% drop denoted in the table above (European Commission, July 2012, link). It is widely accepted that the CTD is responsible for this. The House of Commons Science and Technology Committee, who stated ‘at least part of the decline in UK trial activity is the result of the Clinical Trials Directive, which, since its adoption… has imposed a significant burden on anyone wanting to conduct a clinical trial within the European Union’ (House of Commons, September 2013, link). Morris Brown, professor of clinical pharmacology at Cambridge University also criticised the directive, saying that it resulted in a huge increase in bureaucracy and delayed trails (Daily Telegraph, August 2010, link). According to Cancer Research, between 2003 (before the Directive) and 2007 (following the Directive) the time to set up a study increased by 65% and the staffing requirements increased by 75% (Cancer Research UK, February 2013, link)

This has generated large costs for the NHS

According to academic studies of the impact of the CTD on the UK, ‘the EUCTD has resulted in a doubling of the cost of running non-commercial… clinical trials in the UK’ (Hearn & Sullivan, 2007, link). This is similar to the European Commission’s own calculations, which has found that ‘for non-commercial sponsors, the increase in administrative requirements due to the Directive 2001/20/EC has led to a 98% increase in administrative costs’ (European Commission, July 2016, link).

This has generated considerable costs for the NHS, which conducts a lot of its own clinical trials via the National Institute of Health Research (NIHR). According to its own documents, ‘NIHR spends a large proportion of its research programme budget on clinical trials’ (NIHR, link). Unfortunately, NIHR does not reveal exactly how much it spends on clinical trials each year, however, it is possible to break down NIHR’s research spending by different programmes. This allows us to approximate how much it spends on clinical trials, as we can focus on the programmes where the main focus is clinical trials:

NIHR spend on clinical trials 2009-2015

£ millions

2009/10

2010/11

2011/12

2012/13

2013/14

2014/15

Total

Health Technology Assessment (used to ‘support response-mode clinical trials to investigate issues that are directly relevant to clinical practice in the NHS, link)

40.7

49.7

48.5

60.4

65.8

74.2

339.3

Programme Grants for Applied Research (link)

29

38

67

Invention for Innovation (used for ‘support[ing] research and development of medical devices, active implantable devices and in vitro diagnostic devices… including the clinical development of laboratory-validated technologies or interventions, link)

8.8

12.9

10.8

11.3

10

12.4

66.2

Health Innovation Challenge Fund (provides a ‘funding scheme to accelerate the clinical application of projects’, link)

2.4

2.5

6.6

6.9

7.9

26.3

Total

78.5

103

61.8

78.3

82.7

94.5

498.8

With a final figure of £498.8m, we can use the European Commission’s own calculation that the CTD increased costs by 98% to calculate that £246.8m of this figure had to be spent on administration costs. This is likely a significant underestimation of the amount NIHR spends on clinical trial research, as it doesn’t count infrastructure spending which often helps compliment clinical trials costs – e.g. via the Experimental Cancer Medicine Centres.

Experts believe that this delay has resulted in deaths

Experts have linked the problem in research to the raising number of cancer-related deaths. Angus Dalgleish, Professor of Oncology at St George’s, University of London, has said that ‘Academic-led studies (like mine) were degraded or destroyed [by the directive], resulting in thousands of unnecessary deaths’ (Daily Telegraph, October 2016, link). Rory Collins, professor of epidemiology and medicine at Oxford University, told a briefing organised by the Science Media Centre on the threat to clinical trials, claiming that the Directive has ‘hugely increased bureaucratic burden… It’s killing people. I believe that’s a fact’ (BJM, 2009, link).

It is difficult to link mortality with specific developments in research. But what is clear is that – since the CTD came into force in the UK in 2004, the number of people who suffered avoidable neoplasm (abnormal growths, particularly cancers) deaths plateaued, having been falling dramatically in previous years, and subsequently increased. An indicative number of people whose deaths were affected by the failure to develop new clinical cures can be seen by comparing the actual number of avoidable deaths due to neoplasms to the ‘line of best fit’ for the declining rate before 2004 (i.e. what the rate would have been had the trend before 2004 continued). The difference between the actual number of deaths, and the projected pre-2004 rate is 5,000 (see graph below).

Source: ONS, link (NB, 2001 is the earliest year figures are available)

NB, this is ‘avoidable’ mortality, a definition which inter alia includes it being reasonable to expect deaths to be avoided through good quality health care, even after the condition has developed.

The situation is unlikely to improve

The Directive was repealed on 28 May 2016 by Parliament and Council Regulation 2014/536/EU of 16 April 2014 on clinical trials on medicinal products for human use, which centralises the regulation of clinical trials to an even greater extent, and is considerably longer than the Directive. The new regulation is nearly seven times the CTD’s length (EUR-Lex, 2014, link). It seems unlikely that this will reduce the regulatory burden that the CTD created.