UK Clinical Trials Reform: Early Growth Indicators And Key MHRA Guidance

Growth in UK clinical trials

The UK's ambition to strengthen its position as a leading destination for global clinical research is beginning to show results. According to a recent MHRA publication, clinical trial applications submitted between January and November 2025 were 9% higher than during the same period in 2024, with particularly notable increases in:

• Trials in healthy volunteers (+16%)
• First‑in‑human studies (+5%)
• Trials being run in the UK for the first time (+7%)

The publication notes that "growth was strongest in early and innovative research, where speed and expert regulatory support can make or break decisions on where companies invest."

Sponsors are also engaging earlier with the MHRA to optimise study design and avoid downstream delays. The MHRA reported a 75% increase in scientific advice meetings over the same period, an impressive rebound following the post‑pandemic backlog.

These improvements come at a pivotal time, occurring before the UK's major forthcoming reforms to its clinical trial framework, which aim to "strengthen the UK's offer to global life sciences developers as a safe, fast place to start high‑quality clinical trials."

With regard the incoming regime, the MHRA publication emphasises that around 1 in 5 studies will move to a fast‑track notification route, enabling lower‑risk trials to begin sooner while maintaining high safety standards and allowing experts to focus on more complex, early‑phase research. A 14‑day assessment pathway for phase 1 trials will also be introduced, using a stepwise approach to restore rapid access for first‑in‑human studies. This is seen as an important factor for global developers choosing research locations.

Additionally, there will be clearer and more flexible routes for innovation. This includes greater use of early safety data from overseas studies that meet UK requirements, and new MHRA capabilities to evaluate computer‑based models, such as in‑silico trials, to predict how medicines may behave before patient testing.

Upcoming reform to UK clinical trial regulations

The UK is preparing for the most substantial update to its clinical trial rules in 20 years. The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 (the new Regulations) will introduce a more flexible and streamlined system designed to reduce administrative burden and accelerate trial start‑up. Key features include:

• A single combined review for MHRA and ethics approvals
• A risk‑proportionate notification route for lower‑risk trials
• Less prescriptive legislation supported by 'live' guidance
• A move away from "one‑size‑fits‑all" governance
• A more responsive system aligned with innovation and new trial models

For a more detailed overview of the key incoming changes, see our previous blog posts from January 2025 and April 2025.

MHRA guidance: what sponsors should note

To support implementation of the new Regulations, the MHRA has issued an extensive package of guidance. Last week, additional and updated guidance was added to the package. We highlight some key points from the guidance below.

• International Council for Harmonisation (ICH) E6(R3) Guidance and UK‑Specific Annotations

ICH E6(R3) Guidelines for Good Clinical Practice establish a unified global standard to support mutual acceptance of clinical trial data across ICH regions. The MHRA has now published UK‑specific annotations to clarify how these international standards apply in the UK.

For example, the MHRA guidance clarifies, amongst many other issues, that:

• the ICH Guidelines apply to clinical trials conducted in the UK whether or not the trial is intended to support an application for a marketing authorisation,
• while the ICH Guidelines refer to periodic review of the trial by an ethics committee (EC), there is no legal requirement for such periodic reviews of clinical trials once approved but an EC will review documentation relating to an ongoing trial in certain circumstances, such as an urgent safety measure or serious breach, and
• while the ICH Guidelines specify that suspected unexpected serious adverse reactions (SUSARs) should be reported to the Institutional Review Board/EC in accordance with applicable regulatory requirements, there is no legal requirement in the UK to report SUSARs to the investigators or EC but should be reported to the MHRA.

• Declaration of Helsinki and Clinical Trial Regulations alignment

The new Regulations require compliance with the principles of the Declaration of Helsinki (which contains the international ethical standards for medical research on humans), unless these contradict the requirements of the new Regulations. MHRA guidance explains that there are several areas of potential conflict, including where sponsors may, in specified circumstances, implement urgent safety measures without prior EC approval, which differs from the Declaration's expectations.

Further, the Declaration of Helsinki only permits the use of placebos or no intervention where: no proven intervention exists or if there exists 'compelling and sound methodological reasons' for the use of any intervention other than the best proven one and there is no risk of serious or irreversible harm. Conversely, the new Regulations are more flexible about this, provided that: the trial is scientifically sound and has approval from an EC, the risk-benefit ratio of the product is favourable and the safety of trial participants is not compromised, and that trial participants are informed that they may receive a placebo or no intervention as part of the informed consent process.

• Notifiable trials

Certain lower‑risk trials may be categorised as "notifiable", meaning they benefit from automatic authorisation where appropriate. Notifiable trials must be identified as such in the application for a clinical trial approval. The MHRA's guidance provides details on inclusion and exclusion criteria, allowing sponsors to assess whether their trial is considered notifiable. It has also published a flowchart on the application process.

A notifiable trial can still only proceed if it receives a combined decision for approval issued by the EC and the UK licensing authority. The same validation checks shall be applied as for non-notifiable trials.

• Clinical Trials that include in vitro diagnostic devices (IVDs)

The MHRA has refreshed its guidance on the requirements for IVDs, including companion diagnostics, used in clinical trials performed in Great Britain. To use an IVD in a clinical trial, IVDs must typically be UKCA‑ or CE‑marked for their intended use. Alternatively, the health institution exemption may apply to the IVD, where it is manufactured and used within the same health institution. The MHRA published updated guidance on the health institute exemption in December 2025.

In circumstances where neither of those requirements apply, the guidance sets out that an analytical performance study should be conducted prior to the use of the IVD in the clinical trial, or where a performance study has not yet been conducted, the characteristics of the IVD should be studied. On this basis, the Tabular Summary that describes the intended performance characteristics of the IVD will be accepted by the MHRA.

Notably, these requirements apply to clinical trials conducted in Great Britain, even if patient samples are analysed outside the UK, provided results inform UK patient management. The guidance does not apply to clinical trials involving IVDs conducted in Northern Ireland, where EU regulations and guidance on medical devices and IVDs apply.

On the execution of a performance study in this context, the MHRA's guidance is similar in principle to the 2022 EU guidance of the EU Commission's Medical Device Coordination Group (MDCG) on the interface between the EU clinical trial regulations and the EU IVD Regulation 2017/746 (IVDR). However, the MDCG guidance specifies that a performance study of the IVD should be ongoing in parallel with the clinical trial, and that if performance data is generated for an IVD outside of a performance study this may be insufficient for a future performance evaluation, meaning further studies may be required to generate sufficient clinical evidence

The MHRA guidance also outlines the approvals process for clinical trials which include an IVD. While the process follows the standard clinical trial approval process, additional information about the IVD must be provided, including documentation confirming the compliant use of the IVD in the trial setting.

Additionally, the MHRA has recently published guidance on the updated process which should be followed where a proposed study is both a Clinical Trial of an Investigational Medicinal Product (CTIMP) and a Clinical Investigation (CI) of a medical device. Such applications must be submitted as a "IMP+Device review application". The guidance outlines that the device application should be submitted first, with the CTIMP application to be submitted on (or after) at least 14 days to align the 'Requests for Further Information' applicant response dates. The MHRA acknowledges that the review process for such studies has been complex and the aim is to streamline the process as much as possible going forwards.

• Enforcement provisions

The MHRA has issued guidance on the expanded and clarified enforcement powers that apply under the new Regulations. Notably, the scope of provisions against which the MHRA may issue infringement notices or pursue offences has been widened. The MHRA now has the ability to issue infringement notices for the same provisions that, if breached, constitute criminal offences, enabling a more proportionate, pragmatic, and graduated approach to enforcement. The MHRA emphasises that criminal prosecution will remain a last resort, with compliance-focused interventions used first wherever possible.

For sponsors, this means more explicit accountability: any false or misleading information submitted as part of a notification of an important detail or modification request, whether to the MHRA or an EC, may trigger regulatory action. Furthermore, sponsors and any delegated organisations must ensure they fully understand and comply with all relevant guidance, as they are legally required to "have regard to" it when commencing and conducting clinical trials.

Final Thoughts

With the UK's recent growth in clinical trial activity, coupled with its ambitious regulatory overhaul and newly issued MHRA guidance, it is hoped that sponsors, both domestic and international, will gain a renewed confidence in selecting the UK as a research destination. With greater clarity, enhanced flexibility, and a modernised system designed to support innovation, the UK is positioning itself to compete strongly as a global hub for clinical trials.

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