Preparing for reform: Updated clinical trials guidance ahead of 2026 changes

The UK’s clinical trials framework is undergoing a major transformation. Already, streamlined processes are seeing the time it takes to approve clinical trials in the UK cut from an average of 91 to just 41 days. With further changes approved and set to take effect on 28 April 2026, both the Medicines and Healthcare products Regulatory Agency (MHRA) and the Health Research Authority (HRA) have published updated guidance to support sponsors and other stakeholders through the transition.

These reforms (discussed here) mark a significant overhaul, aligning with post-Brexit ambitions to create a more agile, proportionate, and innovation-friendly regulatory environment. The guidance—some of which remains in draft form—offers practical steps for implementation and insight into the regulators’ direction of travel.

MHRA Guidance:

Revised Approval Pathways

The guidance introduces clearer criteria for notifiable trials (those that may proceed without full regulatory review) and those requiring formal approval. This aims to reduce regulatory burden for low-risk studies while maintaining robust oversight for more complex or novel interventions.

Route A and Route B Modifications

A new dual-track system for trial modifications reflects the risk-proportionate ethos of the reforms:

• Route A covers minor modifications that do not materially affect participant safety, or the reliability or robustness of the data generated in the trial. These can be submitted with minimal documentation and are subject to expedited review
• Route B applies to substantial modifications, which may impact safety or scientific validity. 

This new system replaces the previous amendment model and is designed to improve regulatory agility, especially for trials needing rapid adaptation.

In Vitro Diagnostic Devices (IVDs)

The new guidance clarifies how IVDs are assessed within the clinical trial framework. This is particularly relevant for trials involving companion diagnostics or biomarker-driven therapies, which are increasingly common in precision medicine.

HRA Guidance:

Ethical and Operational Alignment

While the MHRA focuses on regulatory authorisation and safety, the HRA’s guidance complements this by addressing ethical oversight and transparency:

• terminology is now aligned with international standards and clarifies the level of review required for each type of modification. Note that “amendment” has been replaced with “modification”, categorised as “substantial”, “important detail”, or “minor”
• sponsors must register trials publicly and publish results—now embedded in UK law 
• roles for Research Ethics Committees (RECs) are clarified, with streamlined review pathways and adjustments to the quorum rules
• new provisions allow simplified consent procedures for low-risk trials. This is intended to reduce barriers to participation while maintaining informed decision-making, particularly in pragmatic or observational studies
• pharmacovigilance reporting obligations are updated to align with international standards. Sponsors will need to follow enhanced procedures for reporting adverse events, ensuring timely identification and response to safety signals across all clinical trials.

Planning for Transition

Early planning is recommended to avoid disruption. Sponsors may want to start reviewing their trial portfolios and internal processes now, including:

• auditing existing trials: identifying studies that may require transition or re-submission.
• updating SOPs and templates: reflect new terminology, consent models, and transparency obligations.
• engaging early with regulators: leverage combined review pathways and seek clarification where needed.
• monitoring further guidance: additional updates are expected in early 2026, particularly around Good Clinical Practice and non-CTIMP (Clinical Trial of an Investigational Medicinal Product) trials.

Interested in more?

The emphasis on proportionality, clarity, and innovation is welcome, but the transitional period will require careful navigation. For sponsors planning new trials or modifying existing ones, early engagement with the MHRA and HRA—and proactive planning—will be key to ensuring compliance and continuity.

Mills & Reeve’s life sciences team is tracking developments and advising clients on how best to prepare for the 2026 implementation, please get in touch with your local Mills & Reeve contact if you are interested in finding out more.