Phase 1 Clinical Trials: Regulatory Requirements and Procedures

All investigational medicinal products (IMPs) go through a series of trials before they can be licensed for use. There are usually four phases of trials in humans (clinical trials). A Phase 1 trial is usually the first time that an IMP is tested in humans and so it will usually investigate the safe dose range and potential side effects, how it is metabolised and whether it might work in patients.

Phase 1 Review Timelines and Combined Submission

We are working to ensure that the UK routinely delivers ethics opinions for Phase 1 clinical trials within a short timeframe, while maintaining robust ethics review. All Clinical Trials of Investigational Medicinal Products (CTIMP) applications, including Phase 1 studies, must use our combined review service. This means applicants submit one combined application to the REC and MHRA via the new part of IRAS, and benefit from a more streamlined regulatory and ethics review. We aim to give a final ethics opinion within 40 calendar days (well within the statutory 60 days set out in legislation).

Following feedback from our research community, applicants undertaking Phase 1 clinical trials may reserve a Research Ethics Committee (REC) meeting slot in advance of making their submission and submit an application closer to the REC meeting. The majority of RECs in the UK that are recognised to review Phase 1 clinical trials in healthy volunteers accept Phase 1 applications submitted up to seven days before the meeting date. To make a request for seven-day submission for an application, applicants should contact their preferred REC which is flagged to review Phase 1 clinical trials. Additionally, our fast-track research ethics review is also available for global clinical and phase 1 trials for any disease area.

Key Regulatory Data Summary

• Target Ethics Opinion Timeline: Within 40 calendar days.
• Statutory Ethics Deadline: 60 days.
• Late Submission Window: Up to seven days before the REC meeting date.
• Trial Registration: Automatic registration on ISRCTN Registry from 1 January 2022.

Trial Registration and Public Transparency

Registration of clinical trials in a publicly accessible database is a condition of the favourable opinion from a Research Ethics Committee (REC). We also publish a summary of research reviewed by RECs in the UK. From 1 January 2022, trials submitted through combined review will be automatically registered on ISRCTN Registry when given full approval. We recognise that commercial sensitivity may be a concern in some sectors, including in Phase 1 trials. Consequently, it is possible for applicants and sponsors to request a deferral of registration on a publicly accessible database.

The Over-Volunteering Prevention System (TOPS)

The Over-Volunteering Prevention System (TOPS) is a database, free to all UK organisations undertaking Phase 1 trials, that aims to prevent participants from taking part too frequently in trials of new medicines. Organisations must register participants on TOPS before they are recruited into a clinical trial. This is a condition of the REC favourable opinion in the UK.

Generic Document Review Committee

Clinical trials units often undertake general, non-trial specific advertising and screening procedures to recruit potential trial participants, before inviting them to participate in a specific trial. These particular activities are not part of the conduct of a trial as defined in the Medicines for Human Use (Clinical Trials) Regulations 2004, meaning there is no legal requirement for the associated documents to be reviewed by a REC. However, to ensure consistency, all generic recruitment materials are reviewed centrally by the Generic Document Review Committee.