MHRA consultation on the UK clinical trials legislation and its outcome

Last updated: 16 August 2023

See updates at the end of the post.

The MHRA has launched a consultation on the UK clinical trials legislation.

It is consulting on a set of far-reaching proposals to improve and strengthen the UK clinical trials legislation (the Medicines for Human Use (Clinical Trials Regulations 2004 as amended) to help make the UK the best place to research and develop safe and innovative medicines.

The Medicines and Medical Devices Act 2021 provides the powers to update the legislation for clinical trials. This consultation outlines a set of proposals to reframe the UK legislation for clinical trials, responding to the needs of the sector to deliver a more streamlined and flexible regulatory regime, whilst protecting the interests of patients and trial participants.

Who are the intended participants of this consultation?

The MHRA is seeking the views of clinical trial participants, researchers, developers, manufacturers, sponsors, investigators, healthcare professionals, and the wider public to help shape improvements to the legislation for clinical trials.

What does the MHRA aim to achieve with the legislative proposals detailed in the consultation?

Through the legislative proposals outlined in the consultation the MHRA aims to update and strengthen the current clinical trial legislation to:

• Promote public health and ensure protection of participants remains at the heart of legislation
• Remove obstacles to innovation, whilst maintaining robust oversight of the safety of trials
• Streamline the regulation of clinical trials and reduce unnecessary burden to those running trials by embedding risk proportionality into the framework
• Facilitate the evaluation and development of new or better medicines to reduce the burden of disease on patients and society
• Ensure the legislation builds international interoperability so that the UK remains a preferred site to conduct multi-national trials.

Proposals for future of UK clinical trial legislation

The proposals for change are laid out under the following headings and a summary is provided below:

• Patient and public involvement
  • include a requirement for the involvement of people with relevant lived experience in the design, management, conduct and dissemination of a trial
• Research transparency
  • the legislation should include a requirement to publish a summary of results within 12 months of the end of the trial unless a deferral has been agreed
  •  the legislation should include a requirement to share trial findings with participants
• Clinical trial approval processes
  • Combined regulatory and research ethics approval -Amend the legislation to enable sponsors to make a combined MHRA / research ethics application submitted through a single UK ’front door’.
  • In order to support a combined ethics and regulatory submission, introduce a streamlined appeal process to enable a single process for a sponsor to appeal the joint decision
  • legislation to set out new maximum standard timeframes for the joint review and decision on a clinical trial application as follows:
    • an initial decision given on the application (i.e. approval or a request for further information) within a maximum timeline of 30 days from validation
    • a sponsor-driven timeline to respond to any requests for further information (nominally 60 days but with flexible extension
    • a combined MHRA and ethics final decision on a trial of a maximum of 10 days, following receipt of any Requests for Further Information (RFI) responses
    • the ability for the regulators to extend the timeframe for medicinal products or trials where the risks involved may be greater so that independent expert advice can be sought
  • allow withdrawal of the combined MHRA/REC application by the sponsor up until the final assessment decision is issued, with a proportionate fee paid
  • introduce a sunset provision on approvals, such that the approval will lapse if no participant is included within a specified period of time (for example within 2 years of the trial approval)
  • Requests for information (RFIs) and amendments -to allow a trial sponsor having sight of Requests for Further Information (RFI) when they are ready, rather than issued when the final part of the assessment is complete
  • allow the possibility of a RFI step for substantial amendments, as this will reduce chances of these being rejected (i.e. to receive an RFI during the review of a substantial amendment. Currently, amendments can only be approved or rejected.
  • clarify when a substantial amendment is required if a trial is being temporarily halted by the sponsor
  • Notification scheme for low-intervention trials – to introduce the concept of a notification scheme for low-intervention trials into legislation (through which a sponsor can notify the MHRA about a clinical trial where the risk is similar to that of standard medical care, and the clinical trial can be approved without the need for a regulatory review)
• Research Ethics Review
  • streamline requirements for the make-up of an ethics committee and delete the current granular requirements
• Informed consent in cluster trials
  • enable flexibility on consent provisions where the trial is considered to have lower risk i.e. low-intervention trials
• Safety reporting
  • remove the requirement for individual SUSARs to be reported to all investigators (will still be reported via Investigator’s Brochure updates)
  • remove the requirement to report SUSARs and annual safety reports to RECs
  • where justified and approved by the regulatory authority, SUSARs can be reported in an aggregate manner
  • remove the requirement to include listings of serious adverse events and serious adverse reactions in annual safety reports and instead include an appropriate discussion of signals/risks associated with the use of the medicinal product as well as proposed mitigation actions
  • extend the written notification for Urgent Safety Measures from no later than 3 days from when the measure was taken, to no later than 7 days
• Good Clinical Practice
  • clarify in legislation that regulators should take a proportionate approach throughout the clinical trial life cycle
  • future proof the applicability of GCP for electronic systems by introducing into legislation clarity over the design and control of electronic systems that impact on safety and results. This would include a responsibility for service providers, as well as Sponsors, to follow the principles of GCP
  • amend the legislation, so that there is a requirement for a proportionate Trial Master File, that must be directly accessible to MHRA inspectors, that it is retained for a minimum of 25 years, but that more detailed aspects, such as proportionality in the retention period, are covered in guidance
  • make it clear that participants that in addition to not paying for an investigational medicine, participants should also not be liable for treatment costs such as scans and consultations where a trial is being run by a private clinic, to make it clear that the participant should not bear a financial cost to take part in a clinical tri
• Sanctions and corrective measures
  • introduce the ability for regulators to refuse to approve a new study based on ongoing serious non-compliance with the legislation, where there could be significant harm to participants
  • improve the clarity on the suspension or termination of a clinical trial (to make clear that regulatory action might apply only to a specific part of the trial e.g. recruitment, dosing, a specific arm of the trial or related to a particular trial site)
• Manufacturing and assembly
  • introduce the term ‘non-investigational medicinal product’ into legislation to provide assurance on the quality and safety of these products
  • introduce risk-proportionate requirements in UK legislation for the labelling of investigational medicinal products such as those with a marketing authorisation and medicines manufactured at the point of care (and allow the sponsor to propose risk adapted labelling)
  • make an exemption from the need to hold a Manufacturers Authorisation for IMPs (MIA(IMP)) for the preparation of radiopharmaceuticals used as diagnostic IMPs where the process is carried out in hospitals, health centres and clinics (it would still need to be manufactured to an appropriate level of GMP, e.g. at a site holding a manufacturing specials licence.
• Definitions and other terminologies
  • update a number of definitions in the legislation to update UK terminology and promote international harmonisation of definitions

Under each heading, a proposal is provided, followed by a set of questions. You can view the proposals in full and questions here. Should you wish to view the questions only, they can be viewed here.

What were the start and end dates of the consultation?

Start date: 17 January 2014

End date: 14 March 2022

What was the outcome of the consultation?

On 21 March, the Government response to the consultation on legislative proposals for clinical trials was published. The UK MHRA will introduce a series of new measures with support from partners to make it faster and easier to gain approval and to run clinical trials in the UK.

Is there a timeline available of the proposed changes to the UK regulatory framework for clinical trials?

Yes there is and you can view it in this post.

Source: MHRA

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