At the beginning of July, the MHRA published its 2023 – 2026 Corporate Plan, which highlights, amongst many other topics, the importance of introducing new legislation and guidance on clinical trials in the UK to help provide the “stable and predictable regulatory environment that companies require”. The intention is that by 31 March 2026, the MHRA will implement a revised regulatory framework for clinical trials.
Work on a new clinical trial framework is already underway. On 21 March 2023, the MHRA published its response to the UK consultation (which ran from 17 January to 14 March 2022) on legislative proposals for changes to the law governing clinical trials, namely the Medicines for Human Use (Clinical Trials) Regulations 2004.
Responses demonstrated strong support to update and improve the legislation governing clinical trials, with most respondents agreeing that patient safety should remain the focus of the legislation, but with a more flexible and risk proportionate approach to decision-making. In line with responses to other recent consultations, the MHRA is looking to align with international standards rather than be limited by alignment with the EU. It is hoped that the implementation of the proposals will make it easier and more efficient to run trials in the UK, enabling greater patient access to new, safe and life-changing treatments, while retaining the UK as an attractive place for trials.
In terms of next steps, the drafting of the statutory instrument to update the clinical trials legislation is expected to be laid before parliament in the Autumn of 2023. Comprehensive guidance will also accompany the legislation.
Overview of responses to consultation questions
There were a total of 2,138 respondents to the consultation (the vast majority from individuals), with responses received from across the UK and internationally. The UK Government carried out an evaluation of each of the questions consulted upon and in its response set out its intended approach. An overview of some of the key areas of interest are set out below:
- Definitions and other terminologies will be updated to modernise UK terminology and promote international harmonisation. For example:
- Updated definitions of ‘clinical trial’, ‘clinical study’, ‘low intervention trial’ ‘non-interventional trial’ and ‘substantial modification’ will be introduced
- The term ‘subject’ will be replaced with the term ‘participant’
- The role of sponsors and the ability to co-sponsor trials will be clarified
- Guidance will be published on what constitutes a substantial or non-substantial modification
- Requirement for an EudraCT number will be removed and the IRAS number will be used as a UK reference
- Expansion of professional groups that can act as an Investigator
- The term ‘non-investigational medicinal product’, which is already referred to in guidance, will be introduced in legislation
- Legislative requirements to support diversity in trial populations will not be introduced; however, guidance will be published to ensure population trials are as representative as possible, and to help ensure that researchers understand how to achieve diversity in trials in a proportionate way
- Clinical Trials Approval Process: The UK Government aims to streamline this process by taking forward the following initiatives:
- Combined regulatory (MHRA) and research ethics committee (REC) approval and combined MHRA and REC final decision. Applications are to be reviewed within a maximum of 30 calendar days and a decision following receipt of responses to requests for information (RFI) will be available within a maximum of calendar 10 days. This approach has already been successfully piloted since 2018.
- Sponsor driven timeline to respond to RFIs, allowing a generous time to respond to RFIs from MHRA and/or REC (60 days with flexible extension) with the aim to avoid multiple rounds of RFIs.
- Extension of regulators’ assessment timelines to obtain independent expert advice where a trial may present greater risks to participants.
- Introduction of a sunset provision, meaning that approval for trials in which no participants have been recruited will lapse after a specific period of time (a proposed 2 year period); there will be exceptions for certain trials (for example, rare disease).
- Notification Scheme for Low Intervention Trials: This scheme, already set out in MHRA guidance, may be used where the risk to the participant in the trial is similar to standard medical care. This will enable approval without a full regulatory assessment, though a REC opinion will still be required. This scheme is likely to be restricted to trials involving licensed products used either within the licensed indications or where there is established clinical practice.
- Safety Reporting: Pharmacovigilance aspects of trials will be updated to reduce administrative burden and remove duplicative requirements whilst maintaining safety.
- SUSARs to be reported in an aggregate manner where justified and approved, to facilitate the assessment of links between adverse events and a medicine, which cannot properly be evaluated on an individual basis. This will not be mandatory and will only be acceptable if pre-specified criteria are met.
- The requirement to include listings of serious adverse events and serious adverse reactions in annual safety reports will be removed and instead an appropriate discussion of signals/risks associated with use of product, plus proposed mitigation, should take place.
- Good Clinical Practice (GCP): Legislation will incorporate more elements on risk proportionality with the aim of facilitating a culture of trial conduct that is proportionate and ‘fit for purpose’ for both researchers and regulators.
- Service providers of electronic systems that may impact participant safety or reliability of results will be required to follow principles of GCP, including systems that generate, collect and manage trial data, and those that provide trial management or randomisation capabilities.
- UK legislation will include specific reference to the ICH GCP principles, requiring compliance with all principles but not mandating compliance with the entire ICH guidance where this is not necessary. Linked to this, on 26 May 2023, the MHRA launched a public consultation on the implementation of recent change to the ICH guideline.
- Patient and Public Involvement: The consultation sought views on introducing legislative requirements for patient and public involvement in the set-up of new clinical trials. This will be addressed in guidance, rather than legislation, with the aim of involving those with relevant experience as a patient, family member, or carer in the design, management, conduct and dissemination of trials in a more meaningful way. Guidance will contain clear definitions, make expectations clear, while allowing for a flexible approach to be taken and prevent additional legal burdens.
- Research Transparency: In line with developments in the EU, provisions on increased transparency will be introduced. This will include:
- Registration of a trial prior to its start
- The publication of a summary of results within 12 months from the end of trial in a World Health Organisation compliant public register, unless a deferral is agreed
- The sharing of trial findings with participants in order to build trust and incentivise patients and the public to participate in research
- For all of the above, possible exemptions may be agreed with the competent authority where justified, on a case by case basis
- Sanctions and Corrective Measures: The consultation put forward proposals for additional proportionate sanctions and corrective measures to support regulatory oversight of clinical trials. The proposal that regulators should be permitted to take into account information on serious and ongoing non-compliance that would impact participant safety when considering an application for a new study will not be taken forward, due to important unintended consequences, such as a reduction to trials being run in the UK and increased reluctance to adopt proportionate approaches. However, the proposal that regulatory action may be taken against a specific part of a trial rather than the trial as a whole will be implemented into legislation.