The European Clinical Trials Directive (EUCTD) has been a contentious issue across the UK’s medical research community since its introduction in 2004. Promising to bring a unified system of approvals and standards of clinical practice to the UK and across Europe, the directive has at best fallen short on delivering these promises and at worst created a system which makes conducting research so slow, complex, and expensive that it simply doesn’t get done.
Recognising that a reform would have to take place, the European Commission has been consulting and developing its position on this issue since 2008. Following two recent public consultations, we are expecting to see the draft proposals for a revision published in July 2012.
What are the main issues?
A robust clinical trials system is important to the future of medical research in the UK and Europe. The main goal of regulation is to promote patient safety and confidence in medical research. What the clinical trials directive tried to do was to provide a uniform system of approvals and regulations across the EU which would have allowed large multinational trials to progress with greater ease. Unfortunately, too many arrangements brought in under the directive have led to unnecessary duplication of regulatory activities, without enhancing patient safety. The key problems the research community has with the directive in its current form are:
- The wide scope for interpretation of the legislation has led to inconsistencies in its adoption in different member states. This has led to disparities of approval times between member states and has meant that the bureaucracy associated with running a multinational trial has got much worse.
- Overall, research has shown that the CTD has increased administrative costs with more research team staff required to file applications and a longer wait for approvals.
- The lack of proportionality and inflexibility on the definition of what should be classified as a trial has meant that smaller, lower impact studies could not be conducted by research teams with limited resources.
In April, the UK government released its growth review which acknowledged that “gold plating” European legislation was a particular issue in this country. The review stated that UK authorities had enacted the directive to the letter of the law rather than creating the flexibility in its legislation that other countries have achieved.
Since the introduction of the clinical trials directive to the UK in 2004 the UK’s share of clinical trials has plummeted globally from 6% to 2% in 2008. As a percentage of European trials, the UK share of trials has declined from 46% to 24%. While we cannot conclude that these sharp falls are solely a result of changes to regulation, the issues of over-regulation do nothing to increase the UK’s attractiveness as the destination to perform clinical research.
What are we advocating?
We want to reduce the time it takes to gain approval to undertake a clinical trial and the administrative costs involved. Not only that, but reducing the complexity of clinical trials is important to freeing up the time of researchers to do the main job, looking after research subjects and collecting data. This is possible to achieve not by reducing the standards set by regulations but through reducing duplication of work and unnecessary delays by regulators while also drafting legislation with clear language to make it straightforward for researchers to set up and run their trials.
There is a growing consensus within the medical research community about what needs to be done to reform the clinical trials directive to make it suitable for research. The five key asks are:
- Adopting a proportionate approach: The revision of the directive should address the lack of proportionality across all aspects of clinical trial regulation – including clinical trial assessment, authorisation, and monitoring. Unfortunately this may be one of the most challenging aspects to introduce into the revision of the clinical trials directive as the commission has not laid out proposals on how this may be achieved.
- Streamlined authorisation and assessment of clinical trials. The proposal of an optional EU portal to submit multi-country assessments would certainly be welcome if it demonstrates a reduction in cost and approval times.
- Clarity in scope and definitions of the directive. Currently, there are significant issues in the way that the directive is applied over different member states. There is evidence that national regulators are making excessive requirements of researchers which are not within the scope of the directive.
- Simplified approval and monitoring requirements. Under the current directive, researchers are required to submit reports on adverse reactions occurring during clinical trials to several regulatory bodies, which creates an unnecessary duplication. The creation of hundreds of adverse reaction reports is not only bureaucratic but creates an issue in identifying important safety issues when they do arise.
- Co-sponsorship: Through the experience of our non-commercial clinical trials units, we have found benefit from the current UK regulatory approach that allows allocation of the sponsors’ responsibilities between two or more institutions (co-sponsors) or joint responsibility shared by institutions. We support this approach and would value recognition of these models throughout the EU.
The medical research community will continue to engage with the EU on ways to improve the clinical trials directive ahead of the first draft publication in July 2012. We also have support from government following its commitment in the plan for growth to “influence the commission to bring forward soundly based proposals to reduce regulatory burdens in the European Clinical Trials Directive.”
It’s essential that European institutions and governments take action against the over-regulation of clinical trials, to ensure that patients and the public can continue to reap the benefits from the world class research taking place throughout the UK and Europe. CR-UK has led on producing a joint statement co-signed by top medical research organisations across Europe calling for the Directive’s revision.
The long timeline for the revision of the directive to eventually be implemented onto UK statute books, has led the research community to identify several measures that can be made nationally to quickly alleviate some of the issues arising under the current policy. This includes implementing the changes recommended in the recent Academy of Medical Sciences review of the governance and regulation of medical research. The government announced that it was ready to be a leader in “proportionate regulation” – a move that could increase UK researchers’ ability to conduct clinical research significantly.
Clinical trials are conducted ultimately to benefit patients by developing new techniques and therapeutics. What we need to see is regulation that protects participants through the clinical trials process but also gives researchers the freedom and flexibility to advance scientific knowledge and understanding.
Peter Johnson is the chief clinician, Cancer Research UK
Competing interests: PJ had support from Cancer Research UK for the submitted work; PJ acted as a paid consultant to Boehringer-Ingleheim, Pfizer and Millennium-Takeda, and received financial support for research from Janssen-Cilag in the previous 3 years.