Are You Ready for the Entry into Force of the UK’s New Clinical Trials Regime?

On 28 April 2026, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 will enter into force, representing the most significant overhaul of UK clinical trials regime in more than two decades. Its goal is to create a modern, streamlined regulatory environment that maintains high standards of participant safety while accelerating access to innovative treatments.

The reforms were principally prompted by the UK government’s broader policy to enhance the competitiveness of clinical research and support the vibrant life sciences sector. Developments during Brexit and the COVID-19 pandemic highlighted the need for greater flexibility and efficiency in clinical trial processes. Feedback from a public consultation in 2022, and Lord O’Shaughnessy’s independent review into the UK’s commercial clinical trial ecosystem, helped shape the reforms. Both Houses of the UK Parliament broadly welcomed the changes, highlighting their potential to accelerate patient access to innovative treatments, support the NHS, and boost the UK’s life sciences sector. Practical concerns were raised about ensuring adequate resources for regulators and research ethics committees (REC), maintaining consistency in risk assessments, and protecting commercial confidentiality. Overall, these changes aim to make the UK one of the best places in the world to conduct clinical research, with a patient-centred, innovation-friendly, and globally competitive regime.

Key Overarching Reforms

The new UK clinical trials regime introduces a streamlined, risk-based approval process that will enable faster approvals for low-risk trials; consolidates regulatory and ethics reviews into a single application; and mandates greater transparency through trial registration and result publication with the aim of strengthening public trust in clinical research. These reforms are designed to accelerate access to innovative treatments while maintaining high standards of participant safety. Entities involved in clinical trials should prepare for updated requirements and ongoing enhancements to the regulatory landscape.

Core Features of the New Legislative Framework

Approvals

• Combined review. Since early 2022, all UK clinical trials of investigational medicinal products have undergone a combined review by the Medicines and Healthcare products Regulatory Agency (MHRA) and the UK Research Ethics Services, in collaboration with the Health Research Authority (HRA) via a single application covering both the clinical trial authorisation and REC opinion. This process, now enshrined in legislation, requires authorities to complete their assessment and make a decision within 30 days of validation.
• Notifiable trials. Low-risk trials—those posing no significant safety concerns, such as studies using authorised medicines within their approved indications and dosages—are eligible for automatic authorisation. If the MHRA does not respond within 14 days of the validation of an application, the trial is deemed approved. Sponsors will receive a combined outcome when the REC opinion is issued within 30 days.

Modifications

• Route A substantial modifications. Under the new regime, substantial amendments are now known as “substantial modifications,” classified as route A or B. Route A covers changes likely to significantly impact participant safety, rights, or data integrity, and requires formal MHRA and REC assessment within 35 days of validation.
• Route B substantial modifications. Route B substantial modifications are those posing no new significant safety concerns and include (A) changes already approved in the EU/EEA or U.S. for trials not involving first-in-human investigational medicinal products (IMPs); (B) defined protocol changes, such as altering the primary objective or endpoint measurement; and (C) updates to the investigator’s brochure or product characteristics, where such updates were not driven by safety concerns. These will be subject to automatic approval by the MHRA, with REC approval issued within 35 days of validation if needed.
• Modifications of important details. Non-substantial amendments are now known as “modifications of important details” and include changes that do not significantly impact participants’ safety or rights (e.g. a change of sponsor). These modifications simply require notification to the MHRA via the online portal.
• Minor modifications. Minor modifications can be made at any time without notifying the MHRA or REC. The sponsor must keep records of any minor modifications made and, if requested, mention them in the next substantial modification submission.

Safety reporting

• Development safety update reports. Under the new regime, the sponsor must submit its annual development safety update report (DSUR) to the MHRA only. Relative to the previous regime, the DSUR now focuses more on signal-management and the documentation of safety actions.
• Urgent safety measures. Immediate action upon the identification of an urgent safety issue is still permitted. The sponsor now has seven days, instead of three, to notify the MHRA of any urgent safety measures taken.

Research transparency

• Registration of clinical trials. Previously, clinical trial registration was only required as a condition of a favourable REC opinion, with no legislative mandate for public database registration. The new regime requires sponsors to register clinical trials in a public registry within 90 days of approval or when the first participant is recruited.
• Summary of results. Sponsors must publish trial results in the public registry within 12 months of completion and provide participants with a lay summary. Deadlines may be deferred for justified reasons, such as commercial confidentiality.

Next steps

Ahead of the new regime entering into force, the MHRA has published detailed guidance on its clinical trials hub. All entities involved in clinical trials are advised to review these requirements and update their SOPs, training, and monitoring processes accordingly.

Ongoing initiatives will continue to refine the UK clinical trials landscape, including new guidance on EU GMP Annex 13 for IMPs, in silico trials, AI tools, and international collaboration. The HRA is replacing the Integrated Research Application System with the Plan and Manage Health and Care Research platform, which will streamline all aspects of clinical trial administration and is expected to launch next year.

If you have any questions regarding the new regime, please contact any member of Ropes & Gray’s life sciences regulatory and compliance practice or your usual Ropes & Gray advisor.