The countdown to March 29 2019 is happening, when the United Kingdom is scheduled to withdraw from the European Union – with or without a new deal. We know that Brexit will impact on clinical trial activities, with some observers projecting dire consequences, while others believe it poses a new opportunity for UK research.
Background to Brexit
In 2016, the UK held a referendum to decide whether to leave or remain in the EU. The population voted to leave by 51.9% to 48.1% and the UK is now scheduled to exit the EU on March 29th.
What’s not yet known is whether the UK will leave the EU with a newly negotiated trading relationship or without any such deal at all. Much has been made during these deal negotiations of issues related to food supplies, the border between Ireland and Northern Ireland, and the free movement of people. But one of the other greatest uncertainties is the impact of Brexit on the availability of medicines and the conduct of collaborative research – in particular, clinical trials.
The UK is a unique landscape for clinical trials
The UK is a global leader in clinical research and an attractive setting for clinical trials to take place, thanks to its unique National Health Service (NHS) and the significant research activity and expertise embedded within it.
Worryingly, a recent report found that the number of clinical trials taking place in the UK has already fallen by more than 25%, from an average of 806 between 2009 and 2016 to just 597 in 2017. The BBC also reported that one drug company planned to suspend clinical trial activities in the UK because of concerns about how medicines will be approved after Brexit, and doubt over whether the European Medicines Agency would accept data generated in the UK.
Most of the headlines paint a pessimistic picture, or at the very least an uncertain future, pertaining to three key aspects of clinical trials:
- Trial recruitment
The UK has one of the highest trial participant rates in the world – around 9 in 10 UK patients say they would be willing to participate in a trial if they were diagnosed with a condition. Patients in the UK and Europe currently benefit from the UK’s participation in EU trials, and this is particularly important for improving access and patient recruitment in trials for rare diseases and trials involving children. Losing the UK as an attractive environment for clinical research would not only affect UK patients, but would deny access to an enthusiastic pool of trial participants embedded in an integrated research and care environment.
- Changing regulations
Under the current EU membership, the UK is integrated in the EU Medicines Regulatory Network (EMRN), including the European Medicines Agency (EMA). However, if there’s no deal, the UK’s participation in the European regulatory network would cease and the Medicines and Healthcare products Regulatory Agency (MHRA) would take on its functions for medicines on the UK market.
Clinical trials are already managed nationally in the UK by the MHRA, with requirements and procedures set out in the Medicines for Human Use (Clinical Trials) Regulations 2004 (2004 Regulations). These will remain in force if the UK exits the EU without a deal, but will be modified using powers under the EU (Withdrawal) Act (EUWA) to make sure they still work in the UK after exit.
The new EU Clinical Trials Regulation (CTR) 536/2014 is intended to further integrate clinical trial processes and requirements, but will not be in force in the EU at the time that the UK exits, and so will not pass into UK law. The MHRA has pledged to align where possible with the CTR, but there is concern that two parts of the regulations – participation in the EMA’s single-assessment model and shared use of a centralized IT portal for tracking trial progress – cannot be implemented outside of the EU bloc.
Read more on the MHRA’s stance on leaving the EU without a deal.
“Whether you think regulations are good or bad, you need to be part of the system. Otherwise, who would pay attention to the UK, and what value would it be except to us?”‘Future of Clinical Trials after Brexit’ Final Report - School of International Futures and Cancer Research UK
- Drug supply
One of the major concerns for the life sciences industry and patients alike is the continuity of supply of medicines to the UK. Indeed, when charity Cancer Research UK recently published a report looking at the impact of different Brexit models on clinical research, one of its key recommendations was that “the UK and EU should work to ensure that trade barriers do not impact the availability or movement of new and existing licensed medicines.”
One of the problem areas relates to the rules on batch testing of medicines that ensure medicines comply with GMP and can be sold or supplied in the UK. The MHRA has published guidance on this issue, which states that the UK will continue to accept batch testing of human medicines carried out in EU countries, other EEA countries, and those third countries with which the EU has a Mutual Recognition Agreement (MRA).
What about the opportunities?
Although Brexit raises concerns, some have suggested it is just the opportunity the UK needs to elevate its status as a location for clinical research. Potential positive shifts could include centralizing ethics review processes, contracting, and more relaxed rules around contacting potential participants during recruitment, according to the Association of Clinical Research Organizations (ACRO). It’s hoped that these measures would go some way to “counterbalance some of the likely disincentives for clinical research in the UK after Brexit”.
Indeed, others have said that this is a time for optimism and potentially a time when the UK can “shake off unnecessary bureaucratic restraints and showcase its excellence in both research and medicine.” The integrated way that medicine is practiced in the UK and the highly connected nature of [the UK’s] systems potentially offers an appealing environment for more complex trials – such as CAR-T Cell therapies, immuno-therapeutics, or those requiring long-term patient follow-up.
Whatever the outcome of Brexit, there are a lot of uncertainties on the road ahead of March 29th and beyond. This is an evolving situation, and clinical trial sponsors and associated partners should be prepared for a variety of scenarios due to the probability of one outcome or another currently changing day-by-day.