From 28 April 2026, we will no longer use the term ‘amendment’ for changes to approved trials.
Instead, we will use ‘modification’ which is the terminology used by nations within the European Union to describe changes to clinical trials of an investigational medicinal product (CTIMP). This will make sure there is better alignment between the UK and the international research community.
This page describes how modifications will be categorised and gives examples of modifications for each category. If you’re looking for guidance on how to submit modifications for Research Ethics Committee (REC) or Medicines and Healthcare products Regulatory Agency (MHRA) review and the timelines for doing so, you can find this on the approvals process for modifications section of this guidance.
Substantial modifications
If the sponsor wants to make a substantial modification to an approved trial, they will need to submit a substantial modification request. This request must clearly identify the proposed substantial modification and state whether it relates to the REC and/or the MHRA so that it can be reviewed by the relevant regulatory authority. Substantial modifications may also need other approvals, for example Health Research Authority (HRA) and Health and Care Research Wales (HCRW) Approval, depending on the modification.
Substantial modifications are considered to be a modification to a clinical trial approval which is likely to have a substantial impact on the safety or rights of participants or on the reliability or robustness of the data generated by the trial.
Substantial modifications are further classified as Route A or Route B, and the MHRA will process a substantial modification differently depending on whether it is Route A or B. Full details on Route A and B modifications can be found on the MHRA website. This information is not provided here as these classifications are not relevant to the REC opinion.
For examples of what would be categorised as a substantial modification please see the examples of modifications section on this page.
Modification of an important detail
The 2025 regulations introduce the term ‘modification of an important detail’. This is a modification that does not significantly impact participant safety or rights, which the MHRA and REC only need to be made aware of for administrative or oversight purposes. These types of modification are not reviewed by the REC or MHRA and no outcome will be issued. They are for information only. These modifications may however need other approvals (for example HRA and HCRW approval).
For examples of what would be categorised as a modification of an important detail please see the examples of modifications section on this page.
Minor modifications
Minor modifications are changes that do not fall into the category of ‘substantial modification’ or ‘modification of an important detail’. This is not a term which is used in the 2025 regulations but is a term which we will use to describe these types of modification.
These can be implemented at any time without informing the MHRA and REC, although other approvals (for example HRA and HCRW Approval) may be required.
For examples of what would be categorised as a minor modification please see the examples of modifications section on this page.
Examples of modifications
Substantial modification
The changes below are examples of substantial modifications:
- temporary halt of the trial or temporary halt at a trial location within the UK
- re-start of the trial following a temporary halt
- significant changes to participant information sheets, consent forms, letters to GPs or other clinicians, letters to relatives/carers, and other similar documents (whether generic to the whole study or specific to a particular trial location)
- significant changes to recruitment and consent procedures, including the inclusion of adults lacking capacity in the trial
- significant increase or decrease to the radiation exposures to participants from the protocol
- change of insurance or indemnity arrangements for the trial
- change to the payments, benefits or incentives to be received by participants or researchers in connection with taking part in the study, or any other change giving rise to a possible conflict of interest on the part of any investigator or collaborator
- change of the chief investigator
- any other significant change to the conduct or management of the trial at particular trial locations
- any other significant change to the terms of the original REC application
- change of the main objective of the trial
- change of primary or secondary endpoints likely to have a significant impact on the safety or scientific value of the trial
- protocol modification due to new toxicological or pharmacological data or new interpretation of toxicological or pharmacological data which is likely to impact on the risk and benefit assessment
- addition of a trial arm or placebo group
- significant change of inclusion or exclusion criteria (for example age range) likely to have a significant impact on the safety or scientific value of the trial
- change of a diagnostic or medical monitoring procedure likely to have a significant impact on the safety or scientific value of the trial
- withdrawal of an independent data monitoring committee
- any other change of study design likely to have a significant impact on primary or major secondary statistical analysis or on the risk and benefit assessment
Modification of an important detail
The changes below are examples of modifications of an important detail:
- changes to the trial identification (for example the trial title)
- submitting the date that the first UK trial participant is recruited
- increase in duration of the trial, provided that the exposure to treatment is not extended, the definition of the end of trial is unchanged and there is no change to monitoring arrangements
- change to contact details for named contacts for the trial, for example the sponsor, sponsor representative or chief investigator
- change of investigator (other than the chief investigator) at a trial location in a multi-centre trial
- addition of new trial locations not listed with the original request for authorisation and REC application where there are no additional documents for submission
- change of the sponsor’s legal representative
- change of the sponsor
Minor modification
The changes below are examples of minor modifications:
- changes in the number of participants per trial site, if any change is insignificant in view of the absolute number of participants
- changes in the processes associated with recording keeping used by the research team for recording trial data
- internal changes to the sponsor’s organisation
- changes in the logistical arrangements for storing or transporting samples
- changes in technical equipment
- minor changes to the protocol or other study documentation, for example correcting errors, updating contact points, minor clarifications
Please note the following:
The change of investigator at a location, in a multi-centre trial, or the addition of a new location which requires investigator oversight will be a modification of an important detail under the 2025 regulations. The expectation is that sponsors will have arrangements in place to ensure selection of suitable locations and selection and training of investigators. These arrangements will need to be submitted to the REC for review with the initial application. Significant changes to these arrangements will be treated as a substantial modification. There will no longer be different expectations depending on whether the trial is taking place in the NHS or at a non-NHS location.
A change of sponsor will become a modification of an important detail under the 2025 regulations. This is because it will no longer be a legal requirement for the REC to consider the suitability of the sponsor. If the change in sponsor would require changes to insurance arrangements and/or study documents (beyond only changing the name of the sponsor within study documents) then this would be a substantial modification.
As with current practice, determining whether a proposed change is significant or insignificant will continue to be the responsibility of the sponsor.
Categorising and submitting modifications
From 28 April 2026, if you need to submit a modification, the process for doing so will follow the current process for submitting amendments. You will still need to complete the amendment tool (which will then be the ‘modification tool’), capturing the details of the trial and the proposed changes.
The tool will then categorise the modification based on the information you input, give you guidance on which regulatory bodies (for example the MHRA, REC, HRA) may need to review the modification and how you should submit it.
The modification tool is under development but will be available prior to the regulations coming into effect in April 2026.
Further guidance
Visit our amendments guidance page for more information on submitting modifications and how we process them under the new regulations. The MHRA’s guidance also explains the changes.