Navigating the new landscape: 2026 Clinical Trial Regulations changes and contract review requirements

The UK clinical trials regulatory framework has now completed its largest reform in decades. As the Health Research Authority (HRA) and the Medicines & Healthcare products Regulatory Agency (MHRA) each continue to release guidance, stakeholders should now have greater clarity on the changes, what to expect, and how to ensure a smooth transition to implementation.

Following a 12-month transition period, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (SI 2025/538) (CTR 2025) officially came into effect on 28 April 2026. The amendments to the existing Medicines for Human Use (Clinical Trials) Regulations 2004 were approved last year after a three-year-long period of extensive public consultation and stakeholder engagement. In the lead-up to the official transition date, the HRA has been disseminating guidance and a countdown webinar on the key changes and how they will impact the running of clinical trials of investigational medicinal products (CTIMPs) in the UK, and the MHRA has further released detailed guidance on applying for and conducting clinical trials in the UK after 28 April 2026.

This article looks at the key changes introduced and signposts affected stakeholders to some of the relevant resources to aid understanding of, and preparation for, the new regulatory framework. There are a variety of key themes to the changes including greater transparency, changes to informed consent requirements, streamlined approval processes and stronger expectations around diversity and public involvement, which will impact all those involved with applying for, managing, and conducting CTIMPs in the UK, from sponsors, participants and ethics committees to health care professionals.

It will also require the detailed review of contracts with sites, CROs, contract manufacturers, and all associated support organisations to ensure that the new requirements are adequately reflected in those agreements.

The government has emphasised its overarching aim of boosting the attractiveness of running safe, high-quality and efficient clinical trials in the UK. The ambition to see the time from application to first participant cut to 150 days was exceeded last year, with time reduced to 122 days, and the time for the combined review average is now 41 days.

In the past year, something of a positive trend can already be seen as clinical trial applications rose by 9% between January and November 2025 compared with the same period in the previous year, while trials involving healthy volunteers rose by 16% and those being run in the UK for the first time increased by 7%. Notably, there is also a significant increase (75%) in sponsors and innovators seeking scientific advice meetings early-on to ensure they get the trial design right first time, and speed up approval.

Transparency

Transparency in clinical research ensures that participants’ contributions are respected, underpinning ethical accountability. The open sharing of results strengthens scientific integrity and fosters public confidence in clinical trials. Yet, longstanding concerns persist, particularly around selective reporting and the lack of meaningful feedback to trial participants, which have historically undermined confidence in the research process. The CTR 2025 directly confronts these issues, placing transparency at the forefront of sponsor’s responsibilities.

Pursuant to the updated regulations, sponsors now must:

  • register all CTIMPs on a public registry on the earlier of the enrolment of the first participant, or 90 calendar days from the trial receiving approval;
  • publish a summary of their results within 12 months of the global end of the trial, regardless of the outcome; and
  • offer participants a lay summary of the results.

The precise detail concerning each mandated change has now been released by the HRA and MHRA, and the HRA has published a useful blog post summarising the position and any transitional arrangements.

Streamlined approval process

The CTR 2025 makes some amendments to the Combined Review process which allows sponsors and research teams to submit one application via the Integrated Research Application System (IRAS), which is simultaneously reviewed by the MHRA (for regulatory approval) and a research ethics committee (REC) (for ethical review). Although the process itself is not changed under the CTR 2025, sponsors now have a set timeframe of 60 days to respond to requests for further information from either the MHRA or the REC, rather than the clock-stop approach used previously.

Importantly, there are a number of other schemes in the CTR 2025 aimed at streamlining the approval process including:

  • Automatic authorisation for certain ‘notifiable’ low-risk trials, such as for IMPs which have already received regulatory approval in the US or EU and are not first-in-human trials. Full guidance and inclusion/exclusion criteria can be found here.

Updates to Good Clinical Practice (GCP) requirements

Under the CTR 2025, GCP requirements become more closely aligned with those of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 GCP guidelines as it becomes a legal requirement to adhere to the principles (but not the full guidance) of ICH E6 GCP as it is updated from time to time.

These principles are complemented by three UK-specific principles: one requiring compliance with the Declaration of Helsinki, a second relating to adequate insurance provision, and the third requiring the investigator and sponsor to have due regard to all relevant guidance with respect to commencing and conducting a clinical trial, including, notably the annexes to ICH E6 GCP.

For trials that started before 28 April 2026, regulators will expect sponsors to document the impact assessment of the GCP updates on the trial, noting also that ongoing compliance with GCP is required from the CTR implementation date.

Informed consent

One of the most crucial components to any clinical trial is obtaining clear and informed consent from participants to their involvement in the trial. While this principal remains firmly embedded in the new framework, the CTR 2025 does enable simplified arrangements for seeking and evidencing consent in low intervention CTIMPS, provided certain criteria are met.

Sponsors may, for example, request that investigators show potential clinical trial participants a video to explain the study as part of a preliminary appointment, ensure that they have the opportunity to ask further questions from a member of the trial recruiting team, and then evidence consent via digital records of a subsequent explicit consent discussion.

Consent must nevertheless remain freely obtained, informed, explicit and prospective, it cannot be waived or assumed, and any simplified arrangements for consent must be documented as part of the trial protocol and approved by the REC.

Inclusion and diversity

The participant-centric focus is also visible from a diversity and inclusion perspective. In response to public demands for more equitable research, the HRA and MHRA have developed a set of questions and guidance to assist sponsors in drafting an inclusion and diversity plan for clinical trials and investigations. While not mandatory, this initiative is a best practice approach which aims to ensure sponsors have considered the demographic of trial participants by developing a plan based on the following four questions:

  1. Who is affected by the disease or condition being studied?
  2. Do the aims/design of the research mean that the findings will be generalisable to the groups identified in question 1?
  3. What are the recruitment goals for the population identified in question 1?
  4. What is the plan of action to recruit and retain the proposed study population?

Sponsors are now encouraged to proactively consider how they will recruit and retain diverse participants, embedding representative participation into trial design. The change reflects the UK’s commitment to improving data quality and the generalisability of clinical trial results. The HRA has been piloting the latest draft of inclusion and diversity guidance and questions, and an update and next steps are anticipated to be published this year.

Revised definition of ‘health care professional’

This definition is expanded to include a broad range of non-medically trained professionals that can now be involved as investigators in clinical trials with appropriate medical oversight where tasks such as prescribing, determining eligibility, and assessing adverse events are delegated to ensure patient safety and trial validity.

This guidance reflects ‘a broader recognition of professional competencies across healthcare disciplines’ and the amends allow for clinical trials to be managed at site by the most appropriate and qualified persons for the role, which reflects the updating and modernisation of clinical research in the UK being implemented by the CTR 2025.

Research ethics committees (RECs)

The requirement for the composition of the RECs under the CTR 2025 is now changed to require at least five members, consisting of a layperson (with no formal clinical research or healthcare qualifications) and an appointed chairperson. The members of the REC must have collective expertise in scientific, medical, and ethical aspects of clinical trials. These updates aim to strengthen the role of RECs, aligning their constitution and operation with international standards, including GCP.

Trial Master File retention

A further change to address ethical stewardship of patient data is to the archiving period for trial master files. The prior five-year requirement has been extended to 25 years, ensuring that the data is retained and stored for the purpose of audit and bettering long-term analysis. The responsible use of clinical trial data over time demonstrates the commitment to respecting participants’ contributions and ensuring their data serves research purposes beyond the conclusion of the trial, whether the results were a clinical success or not.

Safety measures for clinical trials

Certain pharmacovigilance and safety reporting procedures are also updated, and this applies to all current CTIMPS, whether or not submitted before 28 April 2026.

The key changes are:

  • All suspected unexpected serious adverse reactions (SUSARs) and annual safety reports must be reported to the MHRA alone (even if submitted via Combined Review). Ethical issues will then be passed on separately to the REC if necessary.
  • The notice period for reporting urgent safety measures (USMs) has been extended from three to seven days, though the process for doing so remains the same (via IRAS if all relevant trials were submitted via Combined Review, or if not, to the REC by email.)

Stronger enforcement provisions

The CTR 2025 has introduced a number of new offences targeting non-compliance with certain core principles of the regulations, including:

  • breaches of the notification scheme;
  • failures in record-keeping for serious adverse events and reactions; and
  • non-compliance with transparency requirements.

In addition clinical trial approvals will now lapse if there is no recruitment within two years of clinical trial commencement.

New requirements for non-investigational medicinal products (NIMPs)

There is a particular new focus on regulating the use of non-investigational medicinal products in clinical trials. NIMPs are medicinal products to be used in a clinical trial as described in the protocol, but not as an investigational medicinal product. Examples include the provision of traditional standard of care medicines as a combination therapy with the IMP in oncology clinical trials.

The CTR 2025 adds requirements for the dossier to document the NIMPs’ quality, submitted as part of the regulatory approval application, how they are manufactured in accordance with good manufacturing practice (GMP), and how they should be labelled.

As the majority of NIMPs are expected to be authorised, unmodified medicinal products, they should in most cases be labelled in accordance with the existing UK requirements for prescribed medicines dispensed by pharmacies set out in part 13 of the Human Medicines Regulations 2012 with the required addition of references to the clinical trial, details of the sponsor, and contact persons for the trial.

Concluding remarks

The CTR 2025 mark a transformative moment for health research in the UK, placing patients at the heart of trial design and delivery. The reforms aim to ensure that trials are safer, more inclusive and better aligned with public health needs.

These updates also reinforce the UK’s position as a global leader in clinical innovation. With streamlined approvals and alignment with international standards, the UK is creating an environment that supports faster, more efficient research while maintaining rigorous ethical standards.

Although this article has not covered all of the detail contained in the CTR 2025, it is clear from the details set out above that all new contracts and existing contracts with sites, CROs, and any associated support organisations related to clinical trials will need careful review to ensure they comply with the CTR 2025.

  • CRO contracts should focus on compliance with the new obligations, including for safety reporting and record keeping, and TMF archiving requirements.
  • Agreements with manufacturers will need to ensure labelling compliance, including for any NIMPs.
  • Site contracts may need to be modified to allow for the broader definition of a health care professional and the associated additional requirements for safety and trial oversight.

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