Phase 1 clinical trials

Phase 1 review timelines and seven-day 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.

Our fast-track research ethics review is also available for global clinical and phase 1 trials for any disease area.

Phase 1 application process

This flowchart shows how combined review works for Phase 1 studies and the steps applicants go through to submit an application.

Trial registration and publication of research summaries 

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. It is possible for applicants and sponsors to request a deferral of registration on a publicly accessible database.

For more information on clinical trial registration and deferrals, visit our Research Registration page.

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, it is expected applicants share any proposed generic materials with the REC before they are used in recruitment as a matter of best practice.

To ensure consistency, all generic recruitment materials are reviewed centrally by the Generic Document Review Committee.

This committee comprises two experienced members and former members of Research Ethics Committees (RECs).

Examples of the types of generic materials reviewed by this group include:

• posters
• website adverts
• scripts for radio broadcasts and television adverts
• website scripts/privacy policies
• patient cards
• participant brochures
• Frequently Asked Questions leaflets
• advertising on social media, for example Facebook or Twitter
• screening information sheets and consent forms
• the HRA template for generic screening information sheets
• GP letters
• Clinical Trial Unit internal participant guidance/rules documentation
• posters and publicity campaigns

To obtain a review of generic materials, please send copies to: phase1.advertreview@hra.nhs.uk.

Materials submitted to the Generic Document Review Committee should not be related to a particular trial. If documents have been designed for use in a specific Phase 1 clinical trial, they must be submitted to the REC undertaking the ethics review, in line with the Medicines for Human Use (Clinical Trials) Regulations 2004.

Generic Screening Documentation

Our template information sheet and consent form is available for organisations undertaking non-trial specific screening procedures (generic screening) to recruit potential trial participants, before inviting them to take part in a specific clinical trial in the UK.

The generic screening information sheet and consent form template is to be used for the generic screening of healthy volunteers only. It should not be used for enrolling potential participants into a particular trial. There is supporting guidance to provide information on how the generic templates can be used for Phase 1 research.

All trial specific documentation (including Participant Information Sheets and Consent Forms) must be submitted to the Research Ethics Committee and must be ethically approved.

Phase 1 Advisory Group

The Phase 1 Advisory Group was established by the HRA as a forum to discuss issues relating to the ethics review of Phase 1 trials in the UK.

The advisory group brings together:

• HRA operations staff
• Chairs of NHS/Health and Social Care (HSC) RECs with Type 1 recognition to review phase 1 trials
• Phase 1 trials units
• Association of the British Pharmaceutical Industry (ABPI)
• Bio-Industry Association (BIA)
• Contract Clinical Research Association (CCRA)
• Association of Human Pharmacology in the Pharmaceutical Industry (AHPPI)
• Medicines and Healthcare Products Regulatory Agency (MHRA)
• Association of Clinical Research Organizations (ACRO).

The Phase 1 Advisory Group meets twice a year. Topics discussed include operational issues, training for REC members and initiatives to enhance the efficiency and effectiveness of ethics review. If you would like to read minutes of previous meetings, please contact us at foi@hra.nhs.uk

Additional Guidance

MHRA Phase 1 accreditation scheme

The MHRA also publishes guidance for applying for a clinical trial authorisation.

Phase 1 trials: guidelines

• MHRA GCP guide – includes a specific chapter on Phase 1 trials
• GCP forum - a tool to help those involved in Clinical Trials of Investigational Medicinal Products (CTIMPs) comply with the clinical trials legislation and GCP requirements
• ABPI guidelines for Phase 1 Clinical Trials – reflects current EU legislation for the performance of Phase 1 clinical trials
• Strategies to identify and mitigate risks in first in human clinical trials – European Medicines Agency (EMA) guidelines from the Committee for Medicinal Products for Human Use.

Phase 1 trials: ethical issues

• Insurance in Phase 1 Trials guidance developed by the Association for the British Pharmaceutical Industry, the Bio Industry Association and the Clinical Contract Research Association in consultation with the Department of Health and the National Research Ethics Service
• Incentives in Phase 1 Trials – National Research Ethics Advisors’ Panel endorsed guidance regarding payments and incentives in Phase 1 studies, produced by the Phase 1 Advisory Group.