The largest redesign of clinical trials for 20 years was implemented on the 28 April 2026 when the Medicines for Human Use (Clinical Trials) (Amendment Regulations) 2025 came into force.
These regulations make changes to the Medicines for Human Use (Clinical Trials) Regulations 2004 which remain the core rulebook for clinical trials, together with a suite of guidance from the MHRA and HRA.
What are the key changes?
The new regulatory framework introduces a more streamlined, efficient, and transparent approach to the approval and conduct of clinical trials. It aims to simplify processes, reduce unnecessary delays, and align UK requirements with international standards, while maintaining robust protections for patient safety.
A unitary application process
Comprising of a single application with co-ordinated regulatory and ethics review. Applications must be made in English through an online portal. Exceptionally, if agreed with the authority, these applications may be made separately; this may be relevant if the application is urgent but one part of it is delayed.
A streamlined notification process for low-risk trials
Notification of whether the request is valid will be given within 7 days. There will be a duty to take “all reasonable steps” to provide a substantive decision within 30 days of confirmation that the request was valid. However, these timeframes will not apply where further consultation is needed and for higher risk trials.
Ensuring research transparency
Public registration is now required in advance of the trial in addition to publication of a summary of results within 12 months of the trial’s conclusion. There will be an application process to defer this to protect commercially sensitive information or on national security grounds.
Alignment with international standards
Such as the ICH guidelines and the Declaration of Helsinki. This also includes adapting terminology to match common international frameworks.
Reduced duplicate safety reporting
Serious adverse events and reactions will be included in the safety discussion rather than the annual report.
Clinical trial regulation reforms
The MHRA has run two webinars on the lifecycle of a clinical trial under the new regulations, transparency requirements and the statutory developments.
These changes are designed to;
- streamline the application framework to ensure it is flexible and proportionate while maintaining patient safety;
- promote research transparency;
- align terminology and standards with international norms; and
- reduce duplication and unnecessary delays.
New regulatory offences
Amendments to Regulation 48 have expanded the circumstances where an infringement notice can be issued to include where there is a breach of manufacturing and labelling requirements. Similarly, new offences have been created in Regulation 49, including for;
- breach of the notification scheme;
- non-compliance with labelling criteria;
- breaches of manufacturing standards for non-investigational products, both medicinal and otherwise; and,
- failure to keep detailed records of all serious adverse events and reactions.
The maximum sentences for all these offences remain the same: a fine, two years imprisonment, or both.
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Labelling requirements
The labelling requirements for investigational medicinal products are expanded. Simultaneously, those updated requirements have been applied to non-investigational medicinal products too, with some exclusions for radiopharmaceuticals and products only used in healthcare environments.
The MHRA has issued new guidance on the requirements for each type of product. Though most cases will be the same, the exact requirements will depend on whether the product is investigational and which country the product is authorised in.
The labelling for a product can be amended by submitting a Route A substantial modification application.
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Storage of clinical trials records
The update also includes new stipulations around the storage of records, including: the sponsor must appoint a named person to have responsibility for retention of records; if the essential records are transferred to another organisation, the sponsor should record this. The new owner will take on all regulatory responsibilities for the records; the sponsor and chief investigator should keep the master file accessible and complete for twenty-five years after the conclusion of the trial (previously five years). If the data is being used for a UK marketing authorisation, the essential records must be stored for two years after the authorisation is given. Even where trials are applied for before 28 April 2026, they must still comply with these archiving rules, albeit there are some transitional provisions; and the MHRA has detailed rules on data protection. Steps must be taken to prevent damage to data from fire, flood, theft or accidental destruction, such as from errors in digitisation or transferring data to a new format.
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Compliance with international standards
The International Council for Harmonisation E6(R3)
The Guideline for Good Clinical Practice E6(R3) from the International Council for Harmonisation provides an global framework for promoting consistent quality of clinical trials. This makes reference to “applicable statutory requirements” in each country. The MHRA provides a note of the relevant provisions in the UK.
The Declaration of Helsinki
The new regulations require all trials to comply with the Declaration of Helsinki which lays down ethical principles for research with human participants. However, in several areas, this will not be straightforward due to conflicts between the declaration and the domestic regulations.
| UK regulations | Declaration of Helsinki | |
| Placebo / Non-intervention | The UK regulations are more flexible. Placebos can be used under these criteria: - approval by the Research Ethics Committee- a supportive risk-benefit assessment, and - that participants are informed they may receive a placebo | The declaration’s approach is more restrictive. The comparator must be the best proven intervention unless there is no proven intervention or there are a “compelling and sound methodological reasons”. |
| Urgent safety measures | In specified circumstances where there is an immediate risk, changes can be made before formal approval is issued. There is specific guidance on the process of initial notification then a written notification, before a substantial modification application is made. A flowchart of the process is also available. | Ethical approval must be obtained before any changes are made to comply with the declaration. |
| Post-trial access to treatments | There is no statutory obligation to provide access to an intervention identified as beneficial following the trial. | Access must be given to beneficial interventions after the trial concludes. |
Where any discrepancy cannot be worked around then detailed reasoning should be recorded as to the decision taken and compliance with UK regulations should be preferred.
New approvals processes and transparency requirements for Non-CTIMPS
Alongside the introduction of new legislation regulating CTIMPs (Clinical Trials of Investigational Medicinal Products), the HRA is amending its management of non-CTIMPs to promote consistency. It has helpfully set out flowcharts for the approvals process for non-CTIMPs themselves as well as for modifications to non-CTIMPs.
Transparency requirements are also being amended to correspond to those for CTIMPs. The deadline for registration of non-CTIMPs will no longer be six weeks after the first participant is recruited; instead, registration will be required by the earlier of the first participant recruitment or ninety days after approval. Further information on the registration process has been published by the HRA.
Changes to terminology
This section explains the terminology used by the MHRA and the HRA, including new terms and those with changes to the technical definitions.
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New terminology
“Non-investigational medicinal product” – a medicinal product to be used in the trial but not in as investigational medicinal product. For example, a challenge agent.
“Notifiable trial” – a trial where (a) there are no significant safety concerns, (b) the investigational medicinal product is authorised or approved for a recent similar trial in the United Kingdom, or has been authorised in the United States of America, European Union or a State of the European Economic Area, and (c) the trial does not involve anyone under 18 years of age, pregnant or breastfeeding or an advanced therapy medicinal product or one being used with humans for the first time. See the MHRA guidance on notifiable trials.
“Public registry” – a registry or data provider which provides publicly accessible information on the trial and is linked to the WHO International Clinical Trials Registry Platform
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Amended definitions
“Participant” – will replace the term “subject” to refer to any individual who is receiving the investigational medicinal product or is a control.“Trial location” – means any hospital, health centre, surgery, or other premises where the trial is conducted, including if applicable, a patient’s home or a mobile centre. This replaces the term “Trial site”.
“Health care professional” – this term will now be used instead of “authorised health care professional” as the criteria for who can be an investigator or a chief investigator. The following professions will be eligible:
- doctors,
- dentists,
- pharmacists,
- registered nurses,
- registered ophthalmic surgeons,
- registered osteopaths,
- registered chiropractors,
- registered midwives,
- or anyone registered under the Anaesthesia Associates and Physician Associates Order 2024 or as a member of a relevant profession within the meaning of article 2 of, and paragraph 1 of Schedule 3 to, the Health Professions Order 2001
“Chief investigator” – the health care professional (as defined above) responsible for the whole trial. Though the eligibility for this role has changed along with the definition of a health care professional, the duties of the Chief investigator are unchanged.
“Investigator” – the health care professional (as defined above) responsible for the trial at one trial location.
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Changes to approved Non-CTIMPs: “Amendments” to become “Modifications”
References to “amendments” to clinical trials will now be know as “modifications” in an effort to align terminology with the European Union. There will be three categories of modifications are discussed below:
“Substantial Modification” – includes any change likely to have a material impact on participants’ rights or safety or on the reliability of the data from the trial. Any changes to insurance, participant incentives, or anything likely to materially affect statistical analysis or risk assessment will qualify as a substantial modification.
“Modification of an Important Detail” – these changes will not impact safety or the robustness of data but may require HRA or HCRW approval. Examples include a new title for the trial, a change of sponsor or investigator, or an increase in the trial duration where treatment duration is not prolonged.
“Minor Modification” – this replaces “non-substantial amendment”. Any change which is not a “substantial modification” or “modification of an important detail” will be a minor modification. This might include changes to the logistics of storage or transport, the addition of a new site, or varying participant numbers.
These changes will not apply to research tissue banks or research databases. Further information and examples of each category of modification.
Insurance requirements
Recent warning from the MHRA on insurance checks
Recent inspections from the MHRA have identified Clinical Research Organisations and Phase 1 Trial Organisations have failed to check their insurance cover. They appear to have assumed that the REC check will identify if all insurance requirements have been met. However, that check only ensures that there is an insurance policy. It does not check that the cover is appropriate. That remains the responsibility of the sponsor and REC.
CROs and Phase 1 trial organisations must ensure that their insurance is appropriate for the trial they are conducting and covers all risks which may eventuate from it. It is key that proof of compliance is recorded in the Trial Master File. Where the insurance has exclusions, these must be matched with stringent precautions to ensure that the excluded individuals or circumstances do not end up part of the trial.
The key point is that whilst the REC may check insurance is in place and the nature of it, the onus remains on the sponsor and research site to ensure adequate cover. They should liaise to carefully check that scope of the policy is sufficiently wide. See the MHRA summary.
Legal risks for clinical trials
It is essential that a clinical trial has insurance for all its potential liabilities. That ranges from general accidents that could happen anywhere - such as slips and trips for visitors to a trial location (public liability) and accidents at work (employer’s liability) – through to those specific to the clinical setting, for example, defective clinical products (product liability) or improper administration of a clinical procedure (clinical negligence).
Contact the team
If you require assistance, Brodies’ Insurance team is experienced in defending high-value and complex claims, especially those arising in a healthcare setting. If you wish to discuss potential claims arising from a clinical trial, the necessary insurance for a clinical trial, or anything discussed in this blog, please contact Lynn Livesey who specialises in the investigation and defence of clinical negligence claims.
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