John Shillingford, CEO, Orsus Medical, offers insight into the implications of Brexit as Prime Minister Theresa May prepares to trigger Article 50
Whilst the UK has been a world leader in the field of medical research for many years, it became apparent post year 2000 that a change was underway. Central and Eastern Europe (CEE) were developing as attractive centres for clinical research, with a cost base in the order of 30-40 percent of UK costs with rapid patient recruitment. The questions and fears regarding data quality were soon allayed by an extensive audit both by pharmaceutical sponsor companies and regulatory authorities. So, in this region we had recruitment options that were difficult to match in either the UK or Western Europe. Companies (both pharmaceutical and CROs) recognised that they needed some western countries for their key opinion leaders and to show that data generated in the CEE region was of equivalence to that from Western Europe. However, because of cost and time reason, the UK became side-lined predominantly by Germany, Belgium, Italy, Spain and The Netherlands, who whilst they did not have the patient recruitment rates of the CEE region were cheaper with good data quality.
In 2000, the UK had the third largest share of global trials behind only the US and Germany. Between 2000 and 2006 the UK’s rating dropped to ninth. This downward trend continued to drop throughout 2007 to 2011, at which point the British Government recognized action needed to be taken to stop the decline. Over time, it was becoming clear that jobs were at risk and it was increasingly difficult for British patients to benefit from the cutting edge technology that was being tested in other jurisdictions. The Government then created the Health Research Authorities in 2011 in an effort to streamline the process of researchers getting permission to start studies by binding together the various health authority committees that were causing duplication, and costing time and money. The binding of the ethics committee with various hospital governance committees went a long way to helping this situation. But it became clear that this was not the only fix that needed to be made and in 2013 the House of Commons Science and Technology Committee started an enquiry into the industry. This was published on Sept. 17, 2013. The report clearly supported the greater use of the Health Research Authority (HRA) and gave Government commitment to supporting actions to make the UK a more attractive location for clinical trials. The report also called for greater clinical trial transparency and called for the Government to do more in this arena.
In recent years, hospitals have been recruiting professional clinical trial managers/co-ordinators, whose jobs it is to smooth the progress of a clinical project through the HRA committee or any other required group. This, along with a more standardized costing model, which is NHS approved, ensures an improvement in project cost-effectiveness. Consequently since 2013 the attractiveness of the UK and success of these organizational changes has become readily apparent by the return of more clinical research work to the UK.
Then came June 23, 2016 – Brexit. In a burst of exultation one article was published in a broadsheet indicating that the UK “will now be free of EU rules for Clinical Studies that were bureaucratically choking the Clinical Research community”. However, this so called heavy and unnecessary EU bureaucracy is no more than that required by ICH (International Committee on Harmonisation) Research Guidelines. As these are embraced around the world as the requirements to ensure patient safety and data integrity, for the UK to shake off this shackle would be simply impossible.
Much has been written regarding the effect of Brexit to clinical research in the UK. The Medicines and Healthcare Products Regulatory Agency (MHRA) has acknowledged that the European Medicines Agency (EMA) will be duty bound to leave the UK. Several EU countries have shown interest in hosting this body although no clear winner will be apparent for some time yet, but competition will be hot! The MHRA has had an enormous and effective partnership with the EMA over the last 20 years. Founded in 1995, the EMA has benefitted from its proximity to the UK Medicines Authority and currently the MHRA is the recipient of about 40 percent of the EMA assessment work as an external contractor. This work will of course go and alongside the 900 jobs at the EMA. Many of the expert assessors and related staff are expected to relocate but the ripple effect into the industry will be significant.
Experts in the MHRA have been very active in the formulating of the new EU Legislation which is bringing in the new one portal clinical trial assessment and approval system in 2018. The Regulation will harmonize the assessment and supervision processes for clinical trials throughout the EU, via an EU portal and database. The EMA will set up and maintain the portal and database, in collaboration with the member states and the European Commission. As Britain enters the Brexit negotiations, it is feared that access to this system is at risk, despite the fact the MHRA have been fundamentally involved in the framing of the legislation to bring this into effect. Non-access will reduce the attractiveness of the UK as this will necessitate a separate submission outside of the one portal system, which may be viewed as an unnecessary extra cost, given the relatively small size of the UK marketplace.
The MHRA role in driving through the new EU Medical Device Regulations, due to come into force later this year is again an indicator of just much the UK has influenced health care research in Europe. It can only be hoped that as Brexit negotiations progress, the political classes do not damage these professional relationships with UK patients becoming the poorer because of political expediency.
The UK has been a popular route for non EU countries (i.e. US) for entry into the EU of Clinical Trial Investigative Product, which needs the approval of a qualified person for entry into the EU for clinical trial purposes. Clearly this function will need to be based in an EU country and again whilst this is not a huge amount of work, for those companies involved it will be a problem to be overcome. Again there may be a ripple effect. The same will be true for the Qualified Person for Eudravigilance, with this function moving to an EU base. The interaction of the MHRA eudravigilance experts with the EU will need to be clarified and a suitable system be in place to ensure patient safety.
The status of EU citizens in the UK is an additional unknown. This unsettling environment will inevitably lead to an exodus of health and clinical research talent. This comes at a time when the UK needs their skills and will be regretted in the long term.
A recent survey of clinical trial experts both in the UK and on mainline Europe indicated two differing views. The UK respondents commented that whilst they were acknowledging the issues and difficulties, the positive thinking is that in the long run, the changes that have been put in place with HRA efficiencies and presence of research study co-ordinators in Health Authority Units/Hospitals, should be enough to maintain the attractiveness of the UK for Clinical Research. This is further boosted by acknowledgement of the standing the MHRA has had in the European Healthcare community in its work with the EMA.
The European approach appears to be more cautious. Currently work that is being placed in the UK tends to be short term (Early Phase – 1 to 2b) with an associated – wait and see attitude for longer projects. Some companies have ceased to place work altogether until the Brexit issues become clearer.Clearly the next year or so could be difficult for the Industry in the UK with uncertainty remaining the major issue. The sooner the MHRA can announce clarity of process for regulatory processes, eudravigilance and IP issues, the better. However, whilst the fear remains that the negotiations will lay in the hands of the politicians, the hope is that they will appoint negotiators from within the MHRA, who understand the huge issues at stake, both for the health care and pharmaceutical industries in the UK and ultimately of course, for the patients.