As the UK negotiates its exit from the EU, Emma Cave considers the implications for the implementation of the new Clinical Trials Regulation, likely to come into operation in 2018. The key regulatory challenge is to enhance the competitiveness of UK clinical trials without compromising ethical integrity.

The EU Clinical Trials Directive 2001/20/EC sets out rules on the conduct of clinical trials on medicinal products for human use. Each member state was required to comply with the Clinical Trials Directive, but inconsistencies added layers of costly bureaucracy to an already complex set of requirements. Applications to carry out clinical trials in Europe fell by 25% between 2007 and 2011 as the EU became decreasingly attractive to scientists. [1,2]

The much maligned Clinical Trials Directive has been referred to as a reason for leaving the EU. [3] Upon exit from the EU, the UK would be able to amend the regulations giving the Clinical Trials Directive force. Visions were presented of Britain as a world leader in healthcare research, finally free of the shackles of the EU Directive. [4] But using the Clinical Trials Directive as an argument for leaving the EU was disingenuous given its imminent replacement by a new EU Regulation 536/2014. Unlike directives, regulations have direct effect and do not require member states to enact national legislation to bring them into force. Regulation 536/2014 harmonises clinical trials regulation across Europe, and initiates a proportionate approvals process.

The Clinical Trials Regulation is scheduled to come into operation by October 2018. It is therefore likely to be captured by the Great Repeal Bill, which will set out a process for converting EU law into UK law. However, the transfer will not be seamless. The Clinical Trials Regulation assumes a web of integrated principles of EU law, many of which will be rejected when the UK exits the EU. It sets out remedies that might not be available at national level and relationships with EU authorities that may no longer exist. Clearly, the terms of the Clinical Trials Regulation will need to be modified for national application in light of the fact that the UK is no longer a member state.

Theresa May has promised that post Brexit: “Parliament will be free—subject to international agreements and treaties with other countries and the EU on matters such as trade—to amend, repeal, and improve any law it chooses.” [5] But any advantages that might flow from derogating from the Clinical Trials Regulation must be balanced with the advantages of harmonisation. Exacerbating the differences between the UK and the rest of Europe has the potential to lead to isolationism. [6] It could also limit the effectiveness of European and global health initiatives, such as pandemic responsiveness and the fight against antimicrobial resistance.

The Clinical Trials Regulation rebalances the rights, safety, dignity, and wellbeing of research participants and the efficiency, reliability, and robustness of the data generated. The aim “to foster innovation and simplify the clinical trial application process, in particular for multistate trials,” is secondary to protecting the interests of research participants.

Critics of the Clinical Trials Regulation fall into two broad categories. There are those who still think that the bureaucratic processes designed to protect research participants impede good research. They focus less on the provisions of the regulation and more on the limitations of the new regime to iron out inconsistencies. [7] Others argue that the Clinical Trials Regulation swings too far in favour of facilitating research, thereby exposing trial participants to unacceptable levels of risk. Shaw and Townend argue that a simultaneous approval of science and ethics will reduce bureaucracy, but hamper ethics committees. [8] Westra argues that assessing risk “in comparison with the standard treatment of the subjects’ condition” raises the possibility of exploiting vulnerable research participants. [9] Where the standard treatment poses substantial risk, there is the potential to exceed the levels of risk set out in international guidance, such as the Declaration of Helsinki.

Lobbying during draft stages resulted in amendments that met many of industry’s concerns. [10] Provisions to further deregulate or facilitate research risks the strong reputation of the UK for high ethical standards. For these reasons, Britain is likely to support the implementation of the Clinical Trials Regulation.

Emma Cave is a professor of healthcare law at Durham University.

Competing interests: None declared.

[1] NHS European Office. The new EU Clinical Trials Regulation. 5 January 2017. Available at http://www.nhsconfed.org/regions-and-eu/nhs-european-office/influencing-eu-policy/clinical-trials

[2] Science and Technology Committee. EU Regulation of the Life Sciences (June 2016), Conclusion para 6. Available at http://www.publications.parliament.uk/pa/cm201617/cmselect/cmsctech/158/15807.htm#_idTextAnchor035

[3] Gove M. EU Referendum: Michael Gove Explains why Britain Should Leave the EU. The Telegraph. 20 February 2016. Available at http://www.telegraph.co.uk/news/newstopics/eureferendum/12166345/European-referendum-Michael-Gove-explains-why-Britain-should-leave-the-EU.html

[4] Dalgleish A. Brexit means we can Revive Clinical Trials Killed by the EU. The Telegraph 7 October 2016. Available at http://www.telegraph.co.uk/news/2016/10/07/brexit-means-we-can-revive-clinical-trials-killed-by-the-eu/

[5] Prime Minister: Britain After Brexit: A Vision of a Global Britain. Available at http://press.conservatives.com/post/151239411635/prime-minister-britain-after-brexit-a-vision-of

[6] Gulland A. What comes next after Brexit vote, scientists ask. BMJ 2016;353:i3558. Available at http://www.bmj.com/content/353/bmj.i3558

[7] Lepola P, Needham A, Mendum J, et al. Informed consent for paediatric clinical trials in Europe. Arch Dis Child. 25 May 25 2016. Available at https://www.ncbi.nlm.nih.gov/pubmed/27226526

[8] Shaw D , Townend D. Division and discord in the Clinical Trials Regulation. J Med Ethics doi:10.1136/medethics-2016-103422. Available at http://jme.bmj.com/content/early/2016/07/22/medethics-2016-103422

[9] Westra AE. Ambiguous articles in new EU Regulation may lead to exploitation of vulnerable research subjects. J Med Ethics 2016;42:189-191. Available at http://jme.bmj.com/content/42/3/189.info

[10] Zanon E. Momentous changes to EU rules will finally unleash the NHS’s clinical research potential. 6 October 2014. NHS Confederation Blog. Available at http://www.nhsconfed.org/blog/2014/10/momentous-changes-to-eu-rules-unleash-nhs-clinical-research-potential