In a previous blog post, we discussed the UK government’s proposed changes to the regulatory framework governing clinical trials. Marking the start of this legislative change is a new notification scheme for the lowest-risk clinical trials (the scheme), published on 12 October 2023. The scheme is based on the proposal set out in the Medicines and Healthcare Regulatory Agency’s (MHRA) consultation earlier this year, which was supported by 74% of respondents.
The scheme allows for the processing of eligible clinical trials by the MHRA in less than 14 days, instead of the statutory 30 days. The scheme currently only applies to clinical trial authorisation (CTA) applications for Phase 4 and certain Phase 3 clinical trials deemed as low risk, and provided they meet the MHRA’s eligibility criteria, set out below. Initial “first in human” Phase 1 or Phase 2 trials and clinical trial amendment applications will not be eligible.
The scheme aims to reduce the time taken to get lowest-risk clinical trials up and running, to give UK patients quicker access to potentially life-saving medicines, without undermining patient safety. The MHRA encourages clinical trial sponsors to use the scheme for all eligible trials and estimates that this will include 20% of UK initial clinical trial applications.
Where an application is made under the scheme, MHRA guidance states that an authorisation will be granted within 14 days unless any of the eligibility criteria are not met. If the MHRA considers that the application does not meet the scheme criteria, an objection decision will be communicated to the applicant within 14 days, and the application will continue under the usual 30-day timeframe.
Applicants should aim to address common issues identified during applications to avoid delays. An opinion from a research ethics committee remains a requirement for eligible trials, but is not currently part of the scheme. The Health Research Authority has stated that it is keen to explore how the fast-track Research Ethics Service can complement the scheme to further accelerate high quality research.
The eligibility criteria for clinical trials to be approved under the scheme will be kept under continual review and may be subject to change, including the potential to expand the scheme to some medium-risk clinical trials. In its current form, the following criteria must be met for Phase 4 and Phase 3 trials:
- Phase 4 trials (i.e. post-marketing or surveillance trials of licensed medicines) must meet both of the following criteria:
- All investigational medicinal products (IMPs) are licensed and used according to the relevant UK, USA, or EU marketing authorisation (except for placebo); and
- There are no ongoing safety concerns with the IMP(s), for example other trials on hold, with unresolved urgent safety measures or post-marketing regulatory restrictions.
- Phase 3 trials (i.e. pivotal pre-marketing trials and evaluate the efficacy and safety of the drug) must meet at least one of the following criteria:
- The trial has already been approved in the USA or in the EU based on the same protocol and investigator’s brochure as submitted to the MHRA, and for EU approvals, the same version of the IMP dossier. For clinical trials approved in the USA only, the IMP dossier submitted to the MHRA must document the same IMP manufacturing process.
- The MHRA has approved in the last 2 years a previous phase 3 clinical trial of the IMP(s): at the same dose (or a higher dose), dosing frequency (or a higher frequency), route of administration, and for the same indication (even if the trial was with a different clinical trial sponsor) and utilising the same manufacturing process.
- IMPs are licensed and used according to the relevant UK, USA, or EU marketing authorisation (except for placebo).
- In addition, a Phase 3 trial must not include any of the following:
- Complex, innovative trial design (e.g. basket, umbrella and platform) that allows for prospective major adaptations such as the addition of indications or IMPs via future amendments
- Paediatric participants
- Pregnant or breastfeeding participants
- IMP is first in class
- IMP is an advanced therapy medicinal product
Applicants should complete a form to register their interest and applications for the scheme should be submitted via the combined review process using the UK Integrated Research Application System. After registration, the applicant will be issued with a cover letter template and notification scheme criteria form to be completed and included as part of the submission.