The start of the overhaul - low-risk UK clinical trial approvals made quicker

The scheme is intended to apply to initial applications for Clinical Trial Authorisation (CTA) for clinical trials assessed as having the lowest risk, but the MHRA expects this to cover about 20% of applications. Applications using the notification scheme will be processed in less than 14 days, says the MHRA. The statutory review period is currently 30 days (see regulation 18 of the Medicines for Human Use (Clinical Trials) Regulations 2004 - although note the 'may', and not 'must', in relation to the 30 day period).

Applications that will not benefit:

• Phase 1 CTA
• Phase 2 CTA - the MHRA clarifies that it usually considers phase 2 to include proof of concept, dose-finding, dose-response or proof of efficacy trials.
• First in Human CTA
• Amendments

Applications (both commercial and non-commercial) that may benefit:

• Phase 4 CTA
• Phase 3 CTA - subject to exclusions

The guidance contains some commentary intended to help identify trial phases. Phase 4 trials are post-marketing or surveillance trials relating to licensed medicines, and phase 3 trials include those involving more than 300 participants (with some exceptions) that are multicentre, include pivotal pre-marketing trials and evaluate the efficacy and safety of the drug, usually with a comparison to placebo or standard of care treatment.

Phase 4

For this type of trial, the sponsor must demonstrate that:

• The investigational medicinal products (IMPs) have UK, EU or US marketing authorisations and that the IMPs (except for placebo) will be used in accordance with them.
• There are no ongoing safety concerns with the IMP(s). The MHRA considers that temporary halts/clinical holds, unresolved urgent safety measures or post-marketing regulatory restrictions (in other trials) are "safety concerns". The relevant safety concerns are those that the sponsor is aware of.

Phase 3

For this type of trial, the sponsor must demonstrate that it meets one or more of the following criteria:

• The IMPs have UK, EU or US marketing authorisations and that the IMPs (except for placebo) will be used in accordance with them.
• The trial is already approved in the USA or EU based, broadly speaking, on the same submission documents. The guidance elaborates on this.
• Within the previous 2 years, the MHRA approved a phase 3 clinical trial that, broadly speaking, was the same. The guidance also elaborates on this. For example, that previous study must have investigated the "same indication", which the MHRA interprets strictly as meaning the same target disease (not a subset or subtype), of the same severity, in the same age group and (if relevant) in the same drug combination or line of treatment.

Also, the trial will not be eligible if any of the following exclusion criteria apply:

• The IMP is not 'first in class', as it does not use a new and unique mechanism of action. It is also neither an Advanced Therapy Medicinal Product (ATMP) or a combination ATMP.
• The trial does not have a complex, innovative trial design that allows for major adaptations (the MHRA refers to two documents that provide guidance on these concepts).
• The participants in the trial are not under the age of 18, pregnant or breastfeeding.

Process

The application is made through the combined review process in IRAS and no document exemptions apply. Applicants need to register their interest, which is done by filling a form linked in the guidance.

Once an application is received, the MHRA will confirm within 14 days if the application is accepted or if any criteria are not met. If the latter, then an objection decision is communicated and the normal 30 day period will apply. If the criteria are met, then the MHRA will grant authorisation. Those with sharp eyes will have noticed that the MHRA does not exactly promise to authorise in 14 days.

The overhaul

The MHRA describes this as the start of the overhaul of clinical trial regulation (the biggest overhaul in 20 years). Looking back, a 'notification scheme for low-intervention trials' was one of the proposals in the outcome of the consultation on legislative changes for changes to the clinical trial approval process. The consultation was published in January 2022.

Combined review, according to the HRA, has already halved the review time compared to five years ago. There is still the need for a positive Research Ethics Committee (REC) opinion, but the HRA has suggested that it will explore opportunities to use the fast-track Research Ethics Service to continue the streamlining.

The MHRA is clearly proud of its new risk-proportionate approach. And it should be. It will no-doubt help get things moving in UK clinical research. The guidance and press release make it clear that the criteria remain under review and may change; they may even include riskier clinical trials if the initial work goes well.

Although it is great to see the start of the 'overhaul', one is left wondering whether the initial, major effort should be on smoothing the journey for innovative trials of innovative medicines. Would that not be the way to make the UK a natural home for cutting edge medicine?

Are you watching the overhaul of UK clinical trial regulation? If you want to discuss legislative and regulatory developments, contact Harry Hamilton Jennings, in our Pharmaceuticals and Life Sciences team on 07789 533 122, or complete the form below.