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.
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. We also publish a summary of research reviewed by RECs in the UK.
We recognise that commercial sensitivity may be a concern in some sectors, including in Phase 1 trials. It is possible to defer registration on a publicly accessible database and/or publication of the research summary.
For further information on deferral of registration, please refer to the registration deferral policy and procedure.
Phase 1 review timelines and seven-day submission
We are working to ensure that the UK delivers timelines for giving the ethical opinions for Phase 1 trials that are short and predictable while maintaining robust ethical review.
We aim to give final ethical opinion to be given within 40 calendar days (well within the statutory 60 days set out in legislation), allowing for the clock to stop once where a provisional opinion is given.
We monitor adherence to our timelines (the statutory 60 days and our 40 day stretch targets), and identifying ways in which the review process can be made even more efficient.
The latest Phase 1 management information data shows the timelines for the review of Phase 1 applications from 1 Jan 2017 to 31 December 2017.
We have listened to feedback from stakeholders undertaking Phase 1 clinical trials that being able to book a Research Ethics Committee (REC) meeting slot in advance and submit an application closer to the REC meeting would be beneficial.
The majority of RECs in the United Kingdom which are recognised to review Phase 1 clinical trials in healthy volunteers now accept Phase 1 applications being submitted up to seven calendar days prior to the meeting date.
This policy was introduced in June 2013 and has allowed us to reduce the time between submitting the application and the application being ethically reviewed at a meeting than for other types of application.
To request that an application is booked in for seven-day submission please contact your preferred REC which is flagged to review Phase 1 studies.
The Over-Volunteering Prevention System (TOPS)
The Over-Volunteering Prevention System (TOPS) is a database that aims to prevent participants from taking part too frequently in trials of new medicines.
The system is free for organisations undertaking Phase 1 trials to use. These organisations must (this is a condition of REC approval in the UK) register participants on TOPS before they are recruited into a clinical trial.
Phase 1 Advisory Group
The Phase 1 Advisory Group was established by the HRA as a forum to discuss issues relating to the ethical review of Phase 1 trials in the UK and meets twice a year.
The membership of the advisory group comprises representatives of the following:
- HRA operations and approval staff
- 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 discusses topics including operational issues for the review of Phase 1 trials, training for REC members in ethical review of Phase 1 trials, and initiatives to improve the efficiency and effectiveness of ethical review.
Next meeting date: 30 October 2018
- Minutes: 27 July 2016
- Minutes: 09 February 2016
- Minutes: 30 June 2015
- Minutes: 10 February 2015
- Minutes: 25 July 2014
- Minutes: 6 February 2014
- Minutes: 25 July 2013
- Minutes: 8 February 2013 Generic Document Review Committee
Clinical trials units often undertake general, non-trial specific advertising and screening procedures to recruit potential trial subjects, prior to inviting them to participate in a specific trial.
Such activities preparatory to research are not part of the conduct of a trial as defined in the Medicines for Human Use (Clinical Trials) Regulations 2004 and, therefore, it is not a legal requirement for such activities to be reviewed by a REC.
However, it is our expectation that ethical advice regarding any proposed generic advertising is sought from the HRA, prior to its being used, as a matter of best practice.
To ensure consistency such advertisements are reviewed centrally by the Generic Document Review Committee.
This committee is comprised of three experienced members of Research Ethics Committees (RECs) recognised to review Phase 1 studies.
Examples of the types of advertising materials which have been reviewed by this group include posters, website adverts, and scripts for radio broadcasts and television adverts.
To obtain a review of your generic advertising materials, send a copy of the materials to: email@example.com.
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 which is undertaking the ethical review as usual, in line with the Medicines for Human Use (Clinical Trials) Regulations 2004.
Generic Screening Documentation
We have developed a template information sheet and consent form for organisations undertaking non-trial specific screening procedures (“generic screening”) to recruit potential trial participants, prior to inviting them to take part in a specific clinical trial in the UK.
The template and linked guidance has been developed in consultation with our Generic Document Review Committee and representatives from the Phase 1 Advisory Group.
Our 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 regarding 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.
Please refer to the guidance for using the HRA Generic Screening Information Sheet and Consent Form template for information regarding how to use the template Generic Screening Information Sheet and Consent Form.
Phase 1 Trials: applying for approvals. Further information regarding the MHRA accreditation scheme can be found on the MHRA website.
The MHRA also publishes guidance for applying for a clinical trial authorisation.
Phase 1 trials: guidelines
- the MHRA GCP guide includes a specific chapter on Phase I trials
- the GCP forum which has been created as a tool to help those involved in clinical trials of Investigational Medicinal Products to comply with the clinical trials legislation and GCP requirements
- ABPI guidelines for Phase 1 Clinical Trials
- strategies to identify and mitigate risks in first in human clinical trials – guidelines from the Committee for Medicinal Products for Human Use, European Medicines Agency.
Phase 1 trials: ethical issues
- Expert Advisory Group and Commission on Human Medicine process: letter to RECs chairs trials subject to assessment by Expert Advisory Group and Commission on Human Medicine – Guidance for Ethics Committees 14 August 2007
- 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 – the National Research Ethics Advisors’ Panel endorsed this following guidance regarding payments and incentives in Phase I studies produced by the Phase I Advisory Group.