MHRA: what we're doing to cement the UK's position as a world leader in clinical research

Marking International Clinical Trials Day, we bring you a special Q&A with Andrea Manfrin (pictured above), Deputy Director of Clinical Trials from the UK's Medicines and Healthcare products Regulatory Agency (MHRA).

As the USA grapples with its regulatory offering under the new administration, the MHRA is set to deliver the biggest overhaul of clinical trial reform in over 20 years. What spurred this reform and what will it offer?

The MHRA’s response to the COVID-19 pandemic demonstrated what an agile, flexible regulator can accomplish. But it also taught us that we should not get complacent about resilience. While the pandemic initially resulted in a sharp decline in approvals for non-COVID clinical trials, it then led to a huge surge as UK researchers sought to build on the success of COVID research, contributing to a backlog of clinical trial applications at the agency. 

We eliminated this backlog quickly in 2023, and all trials have been assessed in statutory timeframes since then. But we want to go further as an agency in our work cementing the UK as one of the best places in the world to do research.

So, we’ve taken advantage of the opportunities to create our own sovereign framework and are undertaking a total overhaul of clinical trials regulation – the biggest in over 20 years – which will see a plethora of changes introduced, addressing the research sector’s need for a more efficient, streamlined and adaptable regulatory framework for clinical trials. This will include cutting duplication and unnecessary delays, improving transparency, making the regulations more risk-proportionate and of course putting patient safety first.

These changes, which are being implemented with support from partners including the Health Research Authority, will take effect in April 2026 to allow industry time to prepare.

Your first ever analysis of the UK clinical trial landscape shows the UK is a world leader in clinical research but that there are still major gaps. What is the MHRA doing to address these?

This study is the first of its kind, conducted by the MHRA in collaboration with the University of Liverpool. It helps provide a snapshot of the clinical trial initial submission landscape in the UK, which is an important baseline for policymakers and other stakeholders. By identifying where disparities exist, we can better target future action to deliver fairer, more effective care.

The UK is a research powerhouse driven by innovation. The study shows this, with one in eight trials testing treatments in humans for the first time.

It also shows that cancer trials dominate, making up nearly a third of all studies, but other major diseases lag behind. Heart disease, which we know is the world’s biggest killer, receives just 5.2% of research focus. Trials for conditions such as chronic pain, respiratory conditions and mental health disorders were among the least common, despite their major impact on public health.

It also gives us important insights into participant demographics, with there being a notable imbalance in the proportion of male-only trials (6.1%) vs female-only trials (3.7%). Pregnant and breastfeeding women are especially underrepresented, featuring in just 1.1% and 0.6% of trials respectively.

Increasing diversity in clinical trials is a priority for us at the MHRA, and we’re working closely with sponsors, researchers, ethics committees and global regulators to promote trial designs that better reflect the populations who will ultimately use these medicines.  

We also support the future uptake of preclinical evidence using computer model simulations to enable safer participation of underrepresented groups, including pregnant and breastfeeding women, including through the UK Centre of Excellence on In-Silico Regulatory Science and Innovation.

Why should Sponsors set up trials in the UK?

We’ve published guidance on how to avoid common application errors, which is definitely worth Sponsors reading before they submit an application to us to set up a trial in the UK.

We commonly see quite small issues, like submitting under the wrong submission category, that can have significant impacts on timelines.

If Sponsors are unsure of something or have questions about their trial, we encourage them to engage with us early.

In 2023, Lord O’Shaughnessy did an independent review into the commercial clinical trials landscape in the UK and made a number of recommendations for improvement. What have you done to address these?

We’ve made significant strides in addressing the recommendations in Lord O’Shaughnessy’s report.

We eliminated our backlog in clinical trial applications in 2023, and all trials have been assessed in statutory timeframes since then. In fact, Combined Reviews with the Health Research Authority are now taking place in 40 days on average - that’s 20 days quicker than the 60-day timeline.

To help improve the predictability of decision making in applications for clinical trials, marketing authorizations and variations to existing approvals, we also now publish performance data for these key areas on our website on a monthly basis.

In addition, we’ve been producing great guidance that supports and promotes innovative trials. In fact, we launched a consultation on the third phase of our guidance on the use of real-world data in clinical trials today [20 May]– this time about the use of RWD in external control arms to support regulatory decisions. This has the potential to accelerate approval timelines, address ethical concerns and increase the feasibility of conducting trials for rare diseases.

You’ve made great strides in getting clinical trials set up quicker – how do you ensure this does not come at the expense of patient safety?

Our risk-proportionate approach, which we started implementing in September 2023, centres around patient safety – no compromises are made on that. Our overhaul of the regulations isn’t designed to cut corners, but rather to remove or streamline non-value adding or lower risk assessment.

It’s important to note that all clinical trials we approve, including those that are approved via our Notification Scheme, will also require review by a Research Ethics Committee.

Quality assurance checks will be in place and Good Clinical Practice Standards will apply to all trials.

What are you most excited about in the next year?

There is a lot to be excited about!

Obviously, we have our substantial reforms, which we will be phasing in over the coming months, backed by updated guidance and ongoing engagement with trial sponsors and researchers.

We’ve also seen some exciting developments in the use of Large Language Models to support our review of applications. After a successful proof-of-concept, we deployed LLM to support assessors during the clinical trial application reviews, and also to support training of new assessors. This has shown that it could speed up some parts of our review from three hours to just 35 seconds.

There are so many other things too – we’re looking to offer enhanced advice and support to Sponsors submitting applications involving the life cycle of investigational medicinal products. More on this to follow…

As the government pushes forward the development of the Life Sciences Sector Plan and the 10 Year Health Plan, all this exciting work at the agency comes at a crucial time.