Blog: clinical trials regulations – changes to definitions and terminology

Dr Catherine Blewett, Senior Development Manager

On 28 April 2026, new regulations for clinical trials go live in the UK. They represent the most significant overhaul to the regulations in 20 years.

The regulations introduce some changes to the definitions and terminology used in relation to clinical trials of investigational medicinal products (CTIMPs).

This blog aims to highlight these changes and provide some further information about why these changes are being introduced and what they will mean for sponsors and investigators.

‘Participant’ replaces ‘subject’

The amended regulations refer to ‘participant’ instead of ‘subject’ when talking about individuals who participate in trials.

We see this change as an important step forward to recognising that individuals voluntarily participate in trials, rather than being the subject of a trial.

The definition remains the same, an individual, whether a patient or not, who participates in a clinical trial as a recipient of an investigational medicinal product or of some other treatment or product, or without receiving any treatment as a control.

‘Trial location’ replaces ‘trial site’

The amended regulations also change the term ‘trial site’ to ‘trial location’, meaning a hospital, health centre, surgery or other establishment or facility at or from which a clinical trial, or any part of a trial, is conducted.

This change recognises that more trials now include decentralised methods, such as trial activity taking place at participants’ homes and mobile research units.

It will still be necessary to acknowledge the legal and other responsibilities of organisations and investigators. However, the intention is that referring to ‘locations’ instead of ‘sites’ better recognises the flexible nature of clinical trials in modern times.

‘Modifications’ replaces ‘amendments’

Another key change is the move from ‘amendments’ to ‘modifications’.

A public consultation in 2022 asked whether the UK should adopt the terminology ‘modification’ to align with the terminology used in the European Union (EU). Responses to the public consultation highlighted the benefits of international alignment and indicated support for this change of terminology.

The definition of ‘modification’ remains the same in principle, a modification to the terms of the request for approval of the trial or the particulars or documents accompanying the request for approval.

Modifications are categorised into ‘substantial modification’ and ‘modification of an important detail’.

A substantial modification is further sub-categorised into Route A and Route B, with different requirements for the Medicines and Healthcare products Regulatory Agency (MHRA) assessment depending on the categorisation. However, for the Research Ethics Committee (REC) review, there is no sub-categorisation as all substantial modifications continue to require review by a REC.

For the purposes of REC review, the definition of substantial modification remains the same as ‘substantial amendment’ in principle – a modification to a clinical trial approval which is likely to have a substantial impact on the safety or rights of the participants or on the reliability or robustness of the data generated in the trial.

Modification of an important detail is something new which is introduced in the amended regulations. These are modifications which the REC and MHRA need to know about for administrative or monitoring purposes but do not require any assessment or approval.

This change means that a more proportionate approach can be applied to certain changes, such as the change of sponsor or principal investigator at a site, which will only require notification for information rather than review by the ethics committee.

For modifications which are neither ‘substantial’ nor ‘modification of an important detail’, the regulations do not provide a definition. However, these types of modification will be referred to as ‘minor modifications’ by the REC and MHRA.

Our Amendment Tool on IRAS will be updated to reflect the changes. A version of the updated ‘Modification Tool’ will be made available for information only purposes soon, so that sponsors and investigators can familiarise themselves with the tool before they need to use it in practice.

Change to definition of a chief investigator

There will also be a change to the definition of ‘chief investigator’, which will mean that more clinical roles will potentially be suitable to be a chief investigator on a trial.

The amended regulations change the definition of chief investigator from ‘authorised healthcare professional’, limited to doctor, dentist, nurse or pharmacist, to ‘healthcare professional’.

A full list of healthcare professionals who can take on the role of chief investigator can be found on our updates to existing definitions guidance. It’s important to note that regardless of the healthcare professional role, chief investigators must be registered with a relevant professional body. This is important because this means they will be accountable through their professional body. It will still be necessary for chief investigators to be qualified by education, training and experience to hold this role, which is something the REC will consider as part of the review process.

However, what this change means is greater flexibility with who can take on the role of chief investigator, where appropriate, based on the nature of the trial and activities undertaken by the healthcare professional in their day to day role.

Introducing new terms

The amended regulations also introduce some new terms.

Notifiable trials

‘Notifiable trials’ are trials which have no significant safety concerns with any of the investigational medicinal products, as far as the sponsor is aware having made reasonable enquiries, and which meet certain defined conditions. These conditions include the investigational product being authorised for use, and used in accordance with its authorisation, in the UK, and a trial involving a higher dose, frequency or duration having previously been approved in the UK.

The amended regulations brings the ‘notification scheme’, which has been a voluntary scheme for such trials, into legislation and will mean that all trials meeting the defined conditions will by default go through the notification route.

These types of trial do not require assessment by the MHRA, as relevant safety features have previously been reviewed and approved, however they still require full review by the REC. While assurance for safety issues relating to the investigational medicinal product can be taken by the MHRA due to previous approvals, this isn’t the same for ethical issues as they do not provide assurance about things such as recruitment and the potential for trials to be overly burdensome for participants.

Non-investigational medicinal product

A definition for ‘non-investigational medicinal product’ is provided as a medicinal product used or to be used in a clinical trial, as described in the protocol, but not as an investigational medicinal product. This will cover medicines which are used in a clinical trial but are not the medicinal product which is being investigated.

Providing this definition in legislation will mean that these non-interventional medicines can be regulated in a similar way to investigational products.

Public registry

The amended regulations introduce certain legal requirements to register clinical trials and to publish a summary of results. The expectation is that registration and publication is in a ‘public registry’.

The regulations provide a definition of ‘public registry’ as a primary or partner registry of, or a data provider to, the World Health Organisation International Clinical Trials Registry Platform, provided that the registry facilitates public access to information about the trial in the UK. This means that it must be possible for members of the public to identify and access information about trials in England, Scotland, Wales and Northern Ireland.

Get ready for the regulations

These changes to the clinical trials regulations aim to provide greater proportionality to running clinical trials and to make the UK the best place in the world to run clinical trials.

The HRA and MHRA have published a suite of guidance to support sponsors and those involved in setting up and delivering clinical trials to meet the requirements of the updated regulations.

The amended regulations come into force on 28 April 2026 so we strongly encourage organisations to read our guidance and to review and update their internal policies and procedures in preparation for this critical date.