UK clinical trials regulation undergoes its biggest overhaul in 20 years

The most significant overhaul of UK clinical trials regulation in 20 years takes effect on 28 April. Developed by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Health Research Authority (HRA) and implemented through the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025, the new framework represents a fundamental shift in how clinical research is regulated in the UK.

The new regulations introduce a more transparent regime intended to protect trial participants and reduce unnecessary red tape to make the UK one of the most attractive destinations in the world for clinical research and investment, as envisaged in the government's 10-year health plan for England and life sciences sector plan.

The regulations make changes to existing definitions as well as introducing new ones to modernise the regime and ensure that the rules operate coherently as a whole.

Changes to existing definitions

The term "amendment" will be replaced with "modification" when describing changes to approved trials, bringing the UK into closer alignment with EU nations and the wider international research community, which already use this terminology for changes to clinical trials of investigational medicinal products.

Modifications will be categorised as "substantial modifications" (Route A and Route B), "modification of an important detail", or "minor modifications". Route A applies where MHRA assessment is required due to a likely substantial impact on participant safety, the rights of participants, or data integrity, or to address new safety concerns. Route B is an automatic approval route without MHRA assessment. Sponsors classify modifications with the support of MHRA guidance, with Route B providing accelerated timelines and no Request for Information stage.

Replacing the term "subject" with "participant" aims to recognise the voluntary nature of trial participation.

Replacing "trial site" with "trial location" recognises that trials increasingly use decentralised methods such as taking place remotely at a participant's home.

New definitions

"Non-investigational medicinal product" covers products provided as a medicinal product used or to be used in a clinical trial, but not the medicinal product which is being investigated. This means that these non-investigational medicines can be regulated in a similar way to investigational ones.

"Notifiable trials" are trials that have no significant safety concerns with the investigational medicinal products, with the sponsor having made reasonable enquiries in accordance with defined conditions. These are explained in more detail below.

"Public registry" – the new regulations impose legal requirements to register clinical trials and publish a summary of results in a publicly accessible registry.

Streamlined approvals process

One of the most significant changes for pharma sponsors is the Combined Review. Under this model, the HRA and MHRA offer a single application pathway for ethical and regulatory approval of new Clinical Trials of Investigational Medicinal Products (CTIMPs) and combined medicine and device trials.

Instead of navigating parallel systems, sponsors need only submit a single application via the Integrated Research Approvals System (IRAS). This will eliminate submission complexity, duplication and conflicting feedback and provide clearer timelines at each stage.

The HRA has published guidance on how CTIMP applications will be processed from 28 April 2026.

From 2027, a new digital service, Plan and Manage Health and Care Research, will replace IRAS to streamline applications.

New notification scheme

Alongside the Combined Review is a new notification scheme for some clinical trial initial applications and amendments. There is an option for independent submission in exceptional circumstances. The scheme, which was previously voluntary, will now be provided for by law.

These types of trials do not require MHRA assessment, reducing unnecessary red tape. A notification will suffice as relevant safety features have already been reviewed, although approval by a research and ethics committee (REC) remains mandatory.

The MHRA will process initial applications for the lowest-risk Phase 3 and 4 trials within 14 days, instead of the standard 30 days, where sponsors can demonstrate the trial meets the relevant criteria, including confirmation of no known safety issues with the medicine under investigation. Approximately 20% of UK initial clinical trial applications are expected to qualify, though applications for clinical trial amendments will not be eligible.

For commercial sponsors, qualifying a study as a "notifiable trial" is expected to accelerate timelines without reducing participant protection.

Risk-proportionate approach

The new regime embeds a risk-proportionate approach so that regulatory oversight better reflects the risk involved in a clinical trial. High-risk studies will continue to be scrutinised while lower-risk trials will benefit from more streamlined requirements.

The regulations also provide for simplified consent procedures for low-risk trials to reduce barriers to participation while maintaining informed decision-making.

They also broaden the pool of eligible healthcare professionals who can serve as an investigator. Professionals must be registered with their relevant regulator, such as the General Medical Council, and be appropriately trained to undertake that role in a clinical trial. This aims to generate opportunities for multi-disciplinary trial delivery, particularly in community or decentralised settings

Safety reporting and pharmacovigilance

One of the most practically significant changes brought about by the new framework is the reform of safety reporting obligations. The new regulations simplify safety reporting requirements for study sponsors and remove duplicate reporting requirements that do not add value to patient safety monitoring. 

Under the previous framework, Suspected Unexpected Serious Adverse Reactions (SUSARs) and annual safety reports for trials not submitted through Combined Review had to be sent to the MHRA and the REC.

From 28 April 2026, SUSARs and annual safety reports for all will only be reported to the MHRA CTIMPs (regardless of whether they were submitted via Combined Review). Where the MHRA identifies any ethical issues upon receipt of these reports, it will liaise directly with the REC. The MHRA has published guidance on how to submit SUSARs and annual safety reports.

The new rules place the onus on the sponsor to review safety signals identified during product development and inform the regulator as to how these are being managed in the context of their ongoing clinical trials. This is a more proactive model of safety oversight through which the sponsor can demonstrate the benefit-risk profile of their product throughout the trial lifecycle.

The new framework also includes an extension of the urgent safety measure (USM) notification window. From 28 April 2026, the period a sponsor has to give written notice to the REC and MHRA for a USM will be extended from three calendar days to seven calendar days. For manufacturers with complex multi-site studies, this additional time to communicate and document urgent safety decisions is practically significant.

Critically, while the new legislation offers risk-proportionate streamlined pathways for medication, any safety-related changes that impact the benefit-risk of an investigational medicinal product will still require review by the MHRA.

Binding transparency requirements

The new rules introduce binding transparency requirements that will fundamentally change how results are handled after a trial is concluded. For the first time in the UK, it will be a legal requirement to register clinical trials involving medicines in a public registry. A study must be registered before the first participant is recruited, or within 90 days of approval (whichever is earlier). 

Sponsors are also required to publish a summary of results within 12 months of trial completion and offer to share results with participants in a format they can easily understand. These requirements should be integrated into trial planning from the outset as good practice.

Good manufacturing practice

The new regulations mandate strict Good Manufacturing Practice (GMP) for investigational medicinal products including ensuring safety, quality and compliance with relevant EU law.

The MHRA also remains committed to internationally harmonised standards of Pharmaceutical Inspection Co-operation Scheme and the EU, including requirements for the Qualified Person.

Labelling

Products manufactured before 28 April 2026 can continue using existing labelling text. All new material released thereafter is expected to comply with the updated requirements.

Two-year recruitment window

The legislation sets an expectation that all CTIMPs should recruit their first participant within two years of approval, with extensions available. If there is no recruitment and no extension has been granted, the approval will lapse.

Updated model clinical trial agreements

The HRA has published updated model clinical trial agreements (mCTAs) to reflect the requirements of the new clinical trial regulations. These should be used to enter into new contracts from 28 April 2026 in England, Scotland, Wales and Northern Ireland. Previous versions will not be accepted after this date.

Notably, clause 8.5 of the new mCTA template restricts the use of another party's confidential information using AI tools without that party's prior consent. An exception applies where the sponsor or Contract Research Organisation (CRO) uses the Trial Site's confidential information within their own "Secure AI Tools". This is defined as meaning that the confidential information cannot be used to train the underlying AI model and must remain solely for use by the sponsor or CRO. Any use of the Trial Site's confidential information outside of those Secure AI Tools requires the Trial Site's consent.

The changes will affect a broad range of stakeholders, including commercial and non-commercial sponsors, contract research organisations (CROs), NHS and Health and Social Care organisations, chief investigators and applicants.

Osborne Clarke comment

The changes brought about by the new regulations seek to streamline safety reporting processes without compromising participant safety. While the new regime removes certain reporting requirements, it strengthens obligations around transparency and pharmacovigilance. This recognises that speed inherently carries risk, for example, the risk that clinical trial data is overlooked.

Trial sponsors will be responsible for maintaining robust pharmacovigilance systems to ensure continuous safety monitoring, effective risk management, and clear and ongoing communication with the MHRA.

Looking ahead, the new International Council for Harmonisation Good Clinical Practice (ICH GCP) guidelines come into force on the same date as the new UK regime. As the risk-based approach under ICH GCP E6(R3) aligns closely with the proportionality principles underpinning the new Clinical Trials Regulations, sponsors may wish to take a coordinated approach to prepare for these forthcoming changes.