Clinical trials for medicines: notifiable trials
Guidance on categorising certain clinical trials as ‘notifiable’.
This guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025.
These amendments come into force on 28 April 2026.
Until this date, this guidance is in draft and should only be used to support sponsors in preparing for the implementation of the new regulations. Please see Clinical trials for medicines: apply for authorisation in the UK and Clinical trials for medicines: manage your authorisation, report safety issues for the guidance that should be followed prior to 28 April 2026.
We welcome your feedback on the new draft guidelines.
Legal status of this guidance
The following guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025. These amendments come into force on 28 April 2026. For assistance in determining whether a clinical trial is within the scope of these Regulations, see the Is it a clinical trial of a medicinal product? algorithm (please note that this document will be updated in due course).
Part 2 of Schedule 1 to the Clinical Trials Regulations requires that the investigator and sponsor have regard to all relevant guidance with respect to commencing and conducting a clinical trial. Investigators and sponsors (and any individual or organisation that the sponsor delegates trial-related activities to) must, therefore, ensure that they are fully aware of the information within this guidance and act accordingly to achieve and maintain regulatory compliance.
Automatic authorisation by the licensing authority
To enable a streamlined, risk-proportionate approach to its review of applications, the licensing authority is categorising certain clinical trials as ‘notifiable’. Applications to approve these trials will receive automatic authorisation from the licensing authority.
Under regulation 16(2)(b) of the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025, which come into force on 28 April 2026, notifiable trials must be identified as such in the application for a clinical trial approval.
Please note that if the licensing authority provides automatic authorisation, the trial still cannot proceed unless a combined decision that the trial is approved (or approved with conditions) is received. As the ethics committee reviews notifiable trials through the same process as non-notifiable trials, the initial combined decision on clinical trial approval will be issued within 30 calendar days of validation.
Eligibility for notification and automatic authorisation
The two tables below clarify the definition of a notifiable trial, per regulation 11A of the Clinical Trials Regulations, and describe the criteria that should be met for a trial to be considered eligible for notification and automatic authorisation. Where the trial meets at least one of the inclusion criteria and does not meet any of the exclusion criteria, the trial would be eligible for automatic authorisation.
Sponsors are responsible for using the criteria to assess whether a clinical trial is notifiable and should clearly document their justification for this decision. If an application is eligible for automatic authorisation but is incorrectly submitted for full review, the application may be invalidated and will need to be resubmitted correctly. The licensing authority will also monitor and may audit applications for automatic authorisation.
In addition, the table below includes a number of additional criteria that the licensing authority believes has the potential to increase the risk associated with a notifiable clinical trial.
Where a trial is notifiable per the above criteria, but also meets one of the additional criteria in the table below, applicants should make this clear in the cover letter. The licensing authority will use this information to determine whether to exercise its right to undertake a full review of a notifiable trial before issuing a decision.
Applying for approval of a notifiable trial
Submitting an application for approval of a notifiable trial
Applications for approval of a notifiable trial must be submitted through the same combined review process with the same accompanying documents as applications for non-notifiable clinical trials. The cover letter must include a statement that the application is for approval of a notifiable clinical trial.
The same documents must be submitted because:
- this documentation is required for the ethics committee review, which follows the same process for both notifiable trials and non-notifiable trials
- if the licensing authority does not accept the notification and instead conducts a full review of the application, all necessary documentation will have already been provided
- the documentation may be needed to facilitate any audit or inspection of applications for approval of notifiable trials that the licensing authority wishes to undertake
Depending on the specific inclusion criteria the trial meets, additional information should be provided as part of the full application per the table below.
| Inclusion criteria | Additional information |
|---|---|
| The clinical trial meets Condition A (see Table 1: Inclusion and exclusion criteria) | Provide an appropriate Summary of Product Characteristics (SmPC), the name of the marketing authorisation (MA) holder and MA number for each IMP, and indicate protocol sections that support dosing in line with the licensed usage or provide justification to support use of the IMP as established practice, including the literature information and/or any recognised guidelines |
| The clinical trial meets Condition B (see Table 1: Inclusion and exclusion criteria) | Provide the CTA or IRAS number for the previous UK approval and indicate protocol sections (plus IB and IMP dossier sections, if relevant) that support dosing in line with the previously approved trial |
| The clinical trial meets Condition C (see Table 1: Inclusion and exclusion criteria) | In the submission, confirm the regulatory authority that has approved the trial and provide evidence of this approval (or, for the Food and Drug Administration, confirmation that after 30 calendar days there has been no notification of a clinical hold), the date of approval, any conditions issued and, if applicable, the link to the trial on a published database |
Review of applications for approval of a notifiable trial by the licensing authority
The application will undergo the same validation checks as those for a non-notifiable clinical trial.
Once an application is validated, the applicant will receive confirmation via email that the licensing authority has received the notification. The licensing authority will then check the application against the eligibility criteria for notifiable trials to determine whether it is appropriate to provide automatic authorisation.
If the application meets the eligibility criteria:
- confirmation of automatic approval from the licensing authority will be issued via email within 14 calendar days of validation
- the trial cannot proceed unless a combined decision that the trial is approved (or approved with conditions) is received. As the ethics committee reviews notifiable trials through the same process as non-notifiable trials, the initial combined decision on clinical trial approval will be issued within 30 calendar days of validation
If the licensing authority finds that the application does not meet the eligibility criteria, or if the licensing authority considers that there are other reasons for conducting a full review of the application (for example, there is increased risk associated with the trial per the criteria in ):
- the applicant will be issued with a letter stating this, and the reason for objection, via email within 14 calendar days of validation
- the application will then automatically undergo review as a non-notifiable clinical trial, with an initial combined decision issued within 30 calendar days of validation. The applicant does not need to resubmit their application or documentation
- the applicant may withdraw the application before full assessment occurs and the application fee will be refunded
The full process is summarised in the figure below. Please note that this diagram shows the maximum possible timelines, so the time to a decision may be shorter than this.
Please note that the licensing authority reserves the right to undertake a full review before issuing a decision, even where the trial is eligible to be notified per the criteria in this guidance. This may be, for example, where the licensing authority is aware of additional concerns related to the IMPs, their supporting data or any other aspect of the proposed clinical trial design or management. In such cases, the licensing authority will contact the sponsor to inform them of this.
Please note that the licensing authority reserves the right to undertake a full review before issuing a decision, even where the trial is eligible to be notified per the criteria in this guidance. This may be, for example, where the licensing authority is aware of additional concerns related to the IMPs, their supporting data or any other aspect of the proposed clinical trial design or management. In such cases, the licensing authority will contact the sponsor to inform them of this.