Clinical trials for medicines: expert advice
Source: gov.uk (2025-10-01)

Clinical trial applications that need expert advice from a specialist group or committee.

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 (https://www.legislation.gov.uk/uksi/2004/1031/contents).

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 (https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-authorisation-in-the-uk) and Clinical trials for medicines: manage your authorisation, report safety issues (https://www.gov.uk/guidance/clinical-trials-for-medicines-manage-your-authorisation-report-safety-issues) for the guidance that should be followed prior to 28 April 2026.

Legal status of this guidance

The following guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (https://www.legislation.gov.uk/uksi/2004/1031/contents) (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (https://www.legislation.gov.uk/uksi/2025/538). 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? (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/949145/Algorithm_Clean__1_.pdf) algorithm.

Part 2 of Schedule 1 to the Clinical Trials Regulations requires that the investigator and sponsor (https://www.hra.nhs.uk/planning-and-improving-research/research-planning/roles-and-responsibilities/) 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.

Trials requiring expert advice

The licensing authority and ethics committee (“the authorities”) may consult with a relevant committee or specialist group on an application for clinical trial approval before issuing a decision.

While expert advice can be sought about any clinical trial, the authorities will consider factors such as the investigational medicinal product (IMP)’s mode of action, the nature of the target, and the relevance of animal species and models when determining whether to consult a committee or specialist group.

A non-exhaustive list of circumstances in which expert advice may be needed is as follows:
- the licensing authority has significant safety concerns about a novel compound being used in a UK trial for the first time
- similar products have raised significant safety concerns in other clinical trials
- the clinical trial (especially if first-in-human) uses a novel compound that acts (directly or indirectly) via a cascade system with potential amplification effects that might not be sufficiently controlled by a physiological feedback mechanism
- the clinical trial (especially if first-in-human) uses a novel compound that acts (directly or indirectly) via the immune system with a novel or not well-characterised target or mechanism of action
- the clinical trial (especially if first-in-human) uses a compound where structure of the active substance is novel, e.g. a new type of engineered structural format such as those with enhanced receptor interaction as compared with the parent compound
- the novel compound used in the clinical trial (especially if first-in-human) targets a receptor that may have differing levels of expression and biological function in healthy individuals compared to individuals with the relevant disease
- there is insufficient available knowledge of the structure, tissue distribution, cell specificity, disease specificity, regulation, level of expression and biological function of the human target of the novel compound used in the clinical trial (especially if first-in-human), including down-stream effects
- the novel compound used in the clinical trial (especially if first-in-human) may act via a species-specific mechanism and animal models are unlikely to predict activity in humans
Where the applicant identifies the need for expert advice

Prior to submitting an application for clinical trial approval, the applicant should use the criteria above to assess whether their trial may need to be reviewed by a specialist group or relevant committee. If unsure, contact the licensing authority for advice by emailing xxx@xxx.xx with a summary of the nature of the compound, its target and mechanism of action, and the relevance of the animal models. While the licensing authority will provide an opinion based on the information provided, it is possible that this may change following review of the full application and expert advice may then be sought.

If the applicant believes that expert review is required, they should:
- email the licensing authority (xxx@xxx.xx) at least 14 calendar days before submitting the application, stating their intention to submit an application for clinical trial approval that may require review by the Clinical Trials Biologicals and Vaccines Expert Advisory Group (CTBVEAG) and specifying their preferred CTBVEAG meeting date (https://www.gov.uk/government/organisations/commission-on-human-medicines/about/membership#clinical-trials-biologicals-and-vaccines-eag). The licensing authority will confirm by email that the review has been scheduled. Please note that where expert advice from any specialist group or relevant committee other than CTBVEAG is required, the licensing authority will discuss this with the applicant
- submit the full application through IRAS (https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk#applying-for-approval-for-a-clinical-trial) (using the same process as for trials not identified as requiring expert advice) at least 4 weeks in advance of the CTBVEAG meeting at which the trial will be discussed
- the function of the target in humans
- participants’ ability to maintain a normal physiological response to challenge in the presence of the IMP
- rationale for transition from pre-clinical to human testing, particularly with regard to highly species-specific molecules
- handling of potential for on-target and off-target effects in the clinical environment
- the doses used in the relevant animal species (particularly with regard to the use in the animal model of the starting dose to be administered to humans)
- a rationale for the starting dose in humans (including, for example, receptor occupancy)
- a rationale for the trial population (particularly for the use of healthy volunteers)
- a rationale for the administration schedule of the initial and subsequent cohorts, including the time interval between doses administered to individual participants
- a rationale for the dose escalation particularly regarding potential adverse reactions
- a rationale for the proposed trial location, including the facilities available
Where a specialist group or committee is consulted, the maximum timeline for the authorities to issue a decision on clinical trial approval is extended by 90 calendar days (to 120 calendar days from the date of validation). The combined decision will be issued through IRAS (https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk#initial-review-of-applications-by-the-authorities) through the same process as for trials not identified as requiring expert advice.

If the application identified as needing expert advice is an application for clinical trial approval that has been amended following a request for further information (https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk#requests-for-further-information), the 10-calendar day timeline for the authorities to issue a decision is extended by 30 calendar days (to a maximum of 40 calendar days from receipt of the further information or amended application), unless the IMP to be used in the clinical trial is an advanced therapy medicinal product, in which case the timeline is extended by 60 calendar days (to a maximum of 70 calendar days from receipt of the further information or amended application).

The timelines associated with obtaining expert advice on an application for clinical trial approval are summarised in the figure below. This diagram shows the maximum possible timelines (except the time between submitting the application and the expert advice meeting). The time to a decision will be shorter than this for almost all applications. Please note that:
- if expert advice is sought on an application for clinical trial approval, it will not necessarily also be required in the event that the applicant receives a request for further information for that application and submits an amended application
- it is possible to obtain expert advice on an amended application following a request for further information, even if it was not sought on the original application
Flowchart summarising the process of applying for clinical trial approval for applications requiring expert advice. (https://assets.publishing.service.gov.uk/media/68da869849e17d00a56ffb75/Fig1._Expert_advice.pdf) (PDF, 169 KB, 1 page)

Where the authorities identify the need for expert advice

If the applicant does not identify that expert advice may be needed, but the licensing authority or ethics committee determines during their review that it is, the applicant will be informed within 30 calendar days of validation and asked to provide information (as above) to facilitate the experts’ discussion.

Extensions to timelines are the same regardless of whether the need for expert advice was identified by the applicant or the authorities.