Examples of modifications
Substantial modification
The changes below are examples of substantial modifications:
- temporary halt of the trial or temporary halt at a trial site 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 site)
- significant changes to recruitment and consent procedures, including the inclusion of adults lacking capacity in the trial
- significant changes to the selection of suitable sites and selection and training of investigators
- 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 sites
- 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 (CTIMPs)
- 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 site in a multi-centre trial (CTIMPs)
- addition of new trial sites not listed with the original request for authorisation and REC application where there are no additional documents for submission (CTIMPs)
- change of the sponsor’s legal representative
- change of the sponsor
Minor modification
The changes below are examples of minor modifications:
- addition of a new site and/or investigator (non-CTIMPs)
- 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 record 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:
From 28 April 2026, the change of investigator at a site, in a multi-centre trial, or the addition of a new site which requires investigator oversight is a modification of an important detail.
Sponsors should have arrangements in place to ensure selection of suitable sites and selection and training of investigators. These arrangements should be submitted to the REC for review with the initial application. Significant changes to these arrangements are categorised as a substantial modification.
Expectations are now the same for all trials, whether they take place in the NHS or at a non‑NHS site.
A change of sponsor is a modification of an important detail from 28 April 2026. This is because it is no longer a legal requirement for the REC to consider the suitability of the sponsor. If the change in sponsor requires changes to insurance arrangements and/or study documents (beyond only changing the name of the sponsor within study documents), this is a substantial modification.
Sponsors are responsible for deciding if a proposed change is significant or insignificant.