Introduction

Clinical trials regulation is about to get an overhaul in the UK. So promised the Medicines & Healthcare products Regulatory Agency (“MHRA”) which, on 21 March 2023, published details of its proposed changes to the UK clinical trials regulatory framework following a consultation in early 2022. While the proposals promise meaningful reforms, enabling the UK to “deliver a world-class sovereign regulatory environment for clinical trials” while enhancing its competitiveness as a “transformational, global regulatory leader” at the forefront of medicinal innovation, some would argue that this is simply a case of the UK playing catch-up.

The timing of the UK’s exit from the European Union meant that it was unable to benefit from the reforms to the original Clinical Trials Directive (2001/20/EC) from which current UK law (Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031)(“MHU(CT)R”)) is derived. While the EU went ahead with widespread changes to its clinical trials regime in the form of a new Clinical Trials Regulation (EU 536/2014)(“CTR”) and an innovative Clinical Trials Information System (“CTIS”) at its heart ensuring a streamlined approach to trial authorisations and lighter touch regulation for “low intervention clinical trials”, there were fears that the UK was being left behind. Indeed, it cannot have been a coincidence that the MHRA launched its consultation on proposals to reform the UK’s regulatory regime mere days before the CTR finally came into force on 31 January 2022. Which begs the question: Will the proposed reforms to the UK really enable it to climb the rankings as the world’s favoured place for clinical trial regulation, or is this simply the UK aligning lockstep with the reforms our European neighbours have already put in place?

What are the main proposals for change?

While the government has not yet put pen to paper in terms of the anticipated amends being proposed to the  MHU(CT)R, the MHRA has set out its high level proposals for legislative change and its objectives for reform. Advancing a new regulatory regime which seeks to facilitate innovation through proportionate, flexible regulation which respects and guards against medical risk and aligns to international standards of care, the MHRA’s proposals can be grouped under four broad objectives:

1. Ensuring patients and their safety are the focus of clinical trials while bringing the benefits of clinical trials to everyone. While the MHRA does not go into a lot of detail on how this will be achieved (although it is keen to emphasise that a more flexible style of regulation should not jeopardise current safety standards), it seeks to ensure a patient-centric approach is realised by publishing clear guidance on diversity in trials. By advancing measures to select trial participants from across a fully diverse group of ethnicities, ages, sex and socio-economic background, the MHRA aims to ensure clinical trial findings reflect prevalence and clinical need across the population so that more people can benefit from new treatments. Notably the MHRA discarded a previous proposal to hard-wire this diversity requirement as a legislative obligation, instead preferring guidance as a means of encouraging a diverse representation without imposing targets or arbitrary quotas.
   
   
2. Create a proportionate and flexible regulatory environment by matching an appropriate level of regulation to the degree of risk entailed, and imposing an overarching expectation on regulators to consider proportionate approaches to managing risk. This includes the creation of a “notification scheme” for trials where the risk is similar to that of standard medical care, and which will enable such trials to be notified/ approved without the need for a regulatory review (but maintaining the requirement for a favourable opinion from the Research Ethics Committee (“REC”)). It also entails the introduction of a simplified informed consent process for lower-risk trials whereby patients will receive critical information relevant to their participation, but will be supported to give their consent “in an easier way”. It is not yet clear what mechanisms will be in place to facilitate that ease of consent, nor how such streamlined approach will meet other, often more stringent, regulatory requirements around consent such as the UK GDPR. What is clear, however, is the overarching objective of the MHRA to move away from a “one size fits all” style of regulation, empowering researchers to design and conduct the most appropriate trials and so enable more innovation in the clinical trial arena.
   
   
3. Make the UK a competitive and attractive leading global destination for clinical trials by streamlining regulatory approvals and aligning to international standards wherever possible. As part of these reforms, the proposals aim to streamline the process for seeking ethics and MHRA approval through use of a single approvals process for both. This requirement is not exactly new, with a one-stop-shop process having been piloted over the last year via the Integrated Research Application System (IRAS). However, that process will now be given a legislative footing, with commitments made as to shorter timelines in concluding approvals, namely a maximum 30 calendar days for approvals with a further 10 calendar days for a decision to be granted once the regulator has received responses to any Request for Further Information (“RFI”). Where RFIs are made, Sponsors will have a maximum of 60 days to respond, with the right of a “flexible extension” (the details of which will be dealt with via MHRA guidance). The extent to which this means following EU rules to achieve alignment, so as to minimise the need for registration of UK trials on multiple registers, remains to be seen, but this issue could be particularly prevalent for any trials conducted in Northern Ireland which would be governed by EU and UK law.
   
   
4. Future-proof the regulatory environment to facilitate innovation and minimise regulatory burdens. This will be achieved through the removal of “granular and duplicative requirements” in legislation, preferring instead the use of guidance to set out more specific requirements which can, by their nature, be changed without the burdens of the usual legislative amendment processes. While the rationale for this change is no doubt welcome, the lack of granularity in legislation may give rise to uncertainty for clinical trial providers, and further detail around the level of scrutiny required for making changes to guidance will be needed. It is also unclear how this aligns with other regulatory blocks that head in the opposite direction.

How do the proposals compare with EU reforms?

There is a clear articulated ambition in the MHRA’s proposals to make the UK a leading destination for clinical trials. Less clearly articulated, but ubiquitous across the proposals, is the aim to compete with, if not surpass the EU’s own amends to clinical trial regulation. The success, or otherwise, of that aim is difficult to conclude in the absence of some of the finer detail which only the eventual legislative detail will provide. Nevertheless, there are areas where the UK’s proposals could equal, if not exceed the EU’s offerings.

For example, the UK’s single authorisation process aligns to the EU’s new CTIS which enables authorisations for clinical trials extending across different member state boundaries to be approved in one go. The shortest possible timeline for EU approvals is 60 days, while the UK is aiming at 30 days from acknowledgement of a valid application to approval or RFI. That timeline could however be significantly delayed if there are RFIs, leading to a possible 60 day (or longer, if extended) time lag plus a further 10 days for the regulator’s further response.   

Like the UK’s proposals for a “notification scheme” for low-risk clinical trials, the EU has introduced the so called “low intervention” clinical trial where: the investigational medicinal product (“IMP”) is authorised for marketing and used in accordance with that authorisation; supported by published scientific evidence on the safe use of that IMP; and additional diagnostic or monitoring procedures do not pose more than minimal additional safety risk. In such cases, the EU applies less stringent regulatory obligations, particularly with respect to mandatory insurance coverage and monitoring requirements. But the advantages of the UK’s notification scheme are conceivably greater, further streamlining the initial approvals process, and removing the need for MHRA approval of any substantial amendments to the clinical trial.

Under the EU’s CTR, there remain some fairly burdensome reporting obligations, via the EU portal, at various stages of the clinical trial, for example notifications at the start and end of the trial, a summary of the results, an annual report on safety for each IMP and a raft of safety reporting obligations, particularly around the reporting of a serious breach (which must be reported to the Member States concerned within seven days of becoming aware of the breach).

In the UK, reporting has been streamlined, but there remain various obligations for Sponsors to contend with. For example, clinical trials will need to be registered in a World Health Organisation public register before starting the trial, and a summary of clinical trial findings must be published by the Sponsor within 12 months of the end of the trial and shared with participants in a suitable format, the details and format of which will be fleshed out in guidance.

With respect to safety reporting, the UK proposes removing the requirements: for individual Suspected Unexpected Serious Adverse Reactions (“SUSARs”) to be reported to all investigators; to report SUSARs and annual safety reports to the REC in addition to the MHRA; and to include listings of serious adverse events and serious adverse reactions in annual safety reports. Rather, the MHRA plans to introduce a legislative provision allowing SUSARs to be reported in an aggregate manner and to extend the timing for written notification for urgent safety measures.

Does all of this make the UK a more attractive destination for clinical trials than the EU? It feels too early to tell, although as a mechanism for catching up with the EU, the MHRA proposals certainly seem to hit the spot. One notable difference, however, is the UK’s general objective to effectively deregulate and promote flexibility and innovation through the use of guidance to flesh out details, rather than the law. Anyone familiar with the process for making legislative amends in the EU will be aware of the significant loopholes which must be surpassed to bring any legal changes to life (the fact some 7 years passed before the finally became effective as law is perhaps demonstrative of that point). Consequently, if successful, the UK’s ambition to create a regulatory process with built-in flexibility for change could give it the edge, particularly in a world where clinical trials are progressively driven by fast-moving technological advancements and, as recent COVID-19 experience has taught us, the need for speed in obtaining approvals.

Next steps and final thoughts

There can be no doubt that having missed out on the EU’s reforms to the original clinical trial regulatory regime from which UK laws are derived, the amends proposed by the MHRA will be welcomed by clinical trial providers operating (or hoping to operate) in the UK. The UK government is keenly aware that the UK’s ability to be positioned as a competitive and globally-attractive destination for clinical trials will depend on striking a careful balance between safety and deregulation. It is therefore right that the MHRA is looking for ways in which clinical trials can be both expedited and given the freedom to innovate, without undermining patient safety or transparency obligations.

It is not yet clear whether the UK’s proposals do enough to surpass the EU’s own recent reforms and exceed the EU as a preferred destination for clinical trials. While the UK has the advantage of being a single-state territory with the scope for a conceivably simpler, and as with CTs under Covid a nimbler and more responsive regulatory landscape as a result, the fact that the EU can involve multiple member state territories via a single authorisation process will in itself be undoubtedly attractive to clinical trial providers. There are also concerns that any attempts by the UK to diverge from EU rules will cause more, rather than less, administrative burdens for clinical trial providers, particularly for trials extending across both the UK and the EU which will need to manage the administrate burdens arising from both regimes.

The MHRA has addressed these concerns head on, stating that the UK’s alignment with the Good Clinical Practice principles of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“ICH”) will ensure a level of global interoperability which ought to streamline the process for cross-jurisdictional trials. How that will play out at a practical level however remains to be seen, and with no timeline yet announced for when the UK’s draft legislation will be published, this remains a watching brief.