Clinical trials of investigational medicinal products in human participants
After ethical review – guidance for sponsors and investigators
This document sets out important guidance for sponsors and investigators on the conduct and management of clinical trials of investigational medicinal products (CTIMPs) following ethical review. The guidance is supplementary to the ethical opinion provided in the letter from the Research Ethics Committee. However, some reporting procedures described below are statutory requirements under the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 ('the regulations'); this is indicated in the text. Failure to comply with these requirements could lead to the Research Ethics Committee recommending to the Medicines and Healthcare products Regulatory Agency (MHRA) that the clinical trial approval should be suspended or terminated.
This document should be read in conjunction with the UK Policy Framework for Health and Social Care Research which sets out principles of good practice in the management and conduct of health and social care research in the UK including responsibilities for research transparency.
1. Further communications with the Research Ethics Committee
1.1 Further communications during the trial with the Research Ethics Committee that gave the favourable ethical opinion (hereafter referred to in this document as 'the REC') are generally the responsibility of the lead sponsor. However, the sponsor may delegate responsibility to the chief investigator or another representative.
1.2 Where there is more than one sponsor for the trial, it is recommended that the lead sponsor or its representative takes responsibility for all communications with the REC. However, one of the co-sponsors or joint sponsors may take responsibility for each of the following group of functions:
- substantial modifications, a modification of an important detail, minor modifications and the conclusion of the trial
- urgent safety measures
2. Registration
It is a legal requirement that the sponsor must register a clinical trial in a public registry by the earlier of the following:
(a) the date on which the first individual is recruited to be a participant in that trial
(b) 90 days after the date of approval of the clinical trial
For the purposes of this condition a public registry means a primary or partner registry of, or a data provider to, the WHO International Clinical Trials Registry Platform provided that the registry, or the data provider, facilitates public access to information about the UK trial.
For clinical trials involving both UK and EU sites a record in EU Clinical Trials Information System (CTIS) will not satisfy this condition as the UK component of the trial will not be visible.
Failure to register is an offence under the regulations.
Phase 1 studies in healthy volunteers only will automatically be given a deferral from full registration until 30 months after the global end of study provided that the sponsor registers the required minimum information in a public registry before the date on which the first individual is recruited or 90 days after the date of approval of the clinical trial, whichever is the earlier.
CTIMPs will have study information sent to the ISRCTN registry to facilitate registration unless a deferral or waiver applies or it has been indicated in the application that the trial is registered, or will be registered, on ClinicalTrials.gov.
3. Commencement of the trial
3.1 If the trial does not recruit within 24 months of the date of the favourable ethical opinion the approvals are deemed to have lapsed but can be extended upon request.
3.2 Under the regulations the sponsor must obtain Clinical Trial Approval (CTA) from the MHRA before commencement of the trial.
3.3 The trial should not commence at any location until management permission has been obtained from the organisation responsible for the care of the participants at the location.
4. The Over-Volunteering Prevention System (TOPS)
For Phase 1 studies involving healthy volunteers, the sponsor is expected to ensure that all participants enrolled into the study are registered with The Over-Volunteering Prevention System (TOPS).
5. Duration of ethical opinion
5.1 The favourable ethical opinion of the REC for a specific research study applies for the duration of the study, except where action is taken to suspend or terminate the opinion, subject to approved substantial modifications. Where the duration of the study is to be extended beyond the period specified in the application form, a modification should be submitted to the REC.
5.2 The favourable ethical opinion provides legal authority to hold 'relevant material' for research on premises which are not licensed by the Human Tissue Authority (in England, Northern Ireland and Wales only – this requirement does not apply in Scotland). Where a favourable ethical opinion provides this legal authority, 'relevant material' can be held under the terms of the ethical opinion until the end of the period declared in the application; and approved by the REC.
5.3 Samples may be held after the end of study date has been reached, for verification or quality checking of the research data. This should be detailed in the protocol which is approved by the REC and should be for a defined period of time (and no longer than 12 months). After this period legal authority to hold any 'relevant material' for this project on premises which are not licensed by the Human Tissue Authority will expire (in England, Northern Ireland and Wales only - this requirement does not apply in Scotland). To ensure that any continued storage of 'relevant material' for this project is lawful (in England, Northern Ireland or Wales), either the tissue must be held on premises with a storage licence from the Human Tissue Authority, or an application made for ethical review of another project before the favourable ethical opinion (including the additional time after the declaration of the end of study, if applicable) of the existing project expires. Otherwise the tissue would need to be destroyed in accordance with the Human Tissue Authority Codes of Practice and Standards on Research (code E).
6. Modifications
6.1 If the sponsor proposes to make a modification to the CTA, the regulations require that a modification request must be submitted to the REC and/or the MHRA (as appropriate).
6.2 A substantial modification on which an ethical opinion has been requested must not be implemented until a favourable ethical opinion has been given by the REC, unless the changes to the trial are urgent safety measures (see section 7).
7. Urgent safety measures
7.1 The sponsor or the chief investigator, or the local principal investigator at a trial location, may take appropriate urgent safety measures in order to protect the trial participants against any immediate hazard to their health or safety.
7.2 The regulations require that the REC and the MHRA must be notified within 7 days that such measures have been taken, the reasons why and the plan for further action.
8. Phase 1 studies in healthy volunteers and patients
8.1 For Phase 1 studies in healthy volunteers or patients, it is expected that the accuracy of any data used to make major safety decisions, including dose escalation decisions will be ensured via quality control (QC) processes (either by the unit or by sponsor monitoring) including pharmacokinetic (PK) or pharmacodynamic (PD) data especially those that that are linked to protocol stopping criteria. There should be a dose escalation process where the principal investigator(s) and the sponsor review all the data required as specified in the protocol and make a documented decision.
9. Conclusion or early termination of the trial
9.1 Under the regulations, the sponsor must notify the REC and the MHRA in writing that the trial has ended within 90 days of the conclusion of the research. Unless otherwise specified in the protocol, the conclusion of the trial is normally defined as the last visit of the last participant or the completion of any follow-up monitoring and data collection described in the protocol. Any change to the definition of the conclusion of the trial should be notified to the REC and the MHRA as a substantial modification.
9.2 If the trial is terminated early, the sponsor must notify the REC within 15 days of the date of termination. An explanation of the reasons for early termination should be given.
10. Final report
10.1 A final report on the research should be provided within 12 months of the conclusion of the global study.
11. Reporting results
11.1 A summary of the results of the clinical trial must be published within 12 months of the end of trial in the same public registry or registries (if more than one) as the trial was registered in unless a deferral or waiver applies.
11.2 Where the main findings are also to be submitted for publication in a journal, this should be done within 12 months of global study completion, to be published through an open-access mechanism in a peer-reviewed journal.
11.3 A summary of the results written in a manner that is understandable to laypersons must be offered to all relevant persons unless a deferral or waiver applies.
12. Review of ethical opinion
12.1 The REC may review its opinion at any time in the light of any relevant information it receives. It has no power to legally withdraw the opinion it has given but may draw the attention of the MHRA to any serious concerns and may recommend that consideration is given to suspending or terminating the CTA.
12.2 The sponsor or chief investigator may at any time request that the REC reviews its opinion, or seek advice from the REC on any ethical issue relating to the trial.
13. Serious breaches of good clinical practice or the protocol
13.1 Under the regulations the sponsor must notify the MHRA of any serious breach of the conditions or principles of good clinical practice (GCP) or of the protocol, within 7 days of the matter coming to its attention. A breach should be regarded as serious if it is likely to affect to a significant degree the safety or physical or mental integrity of the subjects of the trial, or the scientific value of the trial. It is requested that the sponsor should also notify the REC of such breaches within the same timescale. There is no requirement to notify minor breaches of GCP or the protocol.
13.2 A minor deviation from the protocol to deal with unforeseen circumstances should be exceptional and is not considered to be a serious breach of the protocol provided that it is approved by the chief investigator, either in advance or after the event. However, if the deviation would meet the criteria for a substantial modification it must be notified to the REC under the regulations.
13.3 There is no statutory provision for the REC to approve proposed deviations from the protocol for individual participants. It is the responsibility of the sponsor to consider whether protocol modifications should be made in such cases. Where the modification is substantial, it must be notified to the REC under the regulations.