On 21 March 2023, the UK Government published its response to the consultation on legislative reform proposals for clinical trials that took place from January to March 2022.
The current legislation governing clinical trials in the UK is the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended. This implements the EU Clinical Trials Directive 2001/20/EC and has not been amended to align with the subsequently introduced EU Clinical Trials Regulation 536/2014.
The proposed reforms centre on delivering “a more agile and flexible UK regulatory framework”, as part of the Government’s broader ambition to create a more appealing regulatory environment for life sciences innovation in the UK. The emphasis on promoting clinical research in the UK was highlighted by the recent Government announcement of an independent review into UK clinical trials, prompted by figures suggesting that the number of industry clinical trials initiated in the UK per year fell by 41% between 2017 and 2021. In addition, a decline in public engagement with clinical research (with a 44% drop in the number of participants recruited to commercial clinical trials in the last five years) highlights the need for reform in this area.
The Government’s proposed reforms involve streamlining the procedures supporting the approval and conduct of clinical trials, removing duplicative requirements, and enabling flexibility in a risk-based and proportionate manner.
The proposals also envisage a clinical trials regime that requires greater transparency and encourages, though notably will not require, a diverse range of patient and public involvement.
The main proposals with which the Government intends to move forward are discussed below.
Clinical Trials Approval Process
Notably, the Government intends to introduce a combined regulatory approval (i.e., approval granted by the Medicines & Healthcare products Regulatory Agency (“MHRA”)) and ethics approval process into legislation. This will significantly streamline the process of obtaining authorisation for clinical trials in the UK
In relation to the time for reviewing approval applications, the Government states that it “do[es] not intend to align with the timelines set out in the EU regulation as these are significantly longer and less flexible” than under the UK proposals. The latter will entail a timeline for completion of an application review within a maximum of 30 calendar days in general, with a maximum of 10 calendar days for a decision to be granted once the regulator has received responses to any requests for further information.
The Government plans to introduce a 60-day period for such responses to requests for further information, with additional flexible extensions available (details of which will be set out in guidance). Under the proposals, trial sponsors would also have sight of requests for further information as they are finalised per review discipline, rather than needing to wait for all reviewers to finish before the issue of requests.
Despite the proposed shortening of timeframes, the Government also seeks to align with the overall risk-based approach for clinical trials in providing the ability for regulators to extend the timeframe for review of a trial application where the risks to the participants may be greater. Guidance will be required to determine the types of trial or product which may trigger extensions.
In addition, the proposals introduce a notification scheme for low intervention trials (meaning those where the risk is similar to that of standard medical care), in which the sponsor would notify the MHRA about a clinical trial and the trial can be approved without the need for a full regulatory assessment. The Government intends to carry this proposal forward into legislation, but clear details as to the eligibility for such a scheme will be set out in guidance.
Further, the Government intends to enhance transparency surrounding clinical trials in order to encourage trust and participation in clinical research. Measures proposed to achieve such include the following:
- Formalising the registration of trials in a World Health Organization-compliant public register (unless a deferral is agreed by or on behalf of the research ethics committee) in legislation. This is already considered best practice and automated by the Health Research Authority within the approvals process.
- Introducing a legislative requirement to publish a summary of results from trials within 12 months of the end of such, reflecting EU requirements.
- Legislating to require the sharing of trial findings with participants in a “suitable format”, or an explanation of why this is not possible.
Respondents to the Government’s consultation resoundingly supported these proposals, which the Government confirmed it will legislate to implement.
The proposals also envisage revision of the pharmacovigilance aspects of clinical trials, intended to “reduce administrative burden” while maintaining high standards of participant safety. While responses on these proposals were mixed, the Government plans to proceed with certain measures. For instance:
- The Government will remove the legislative requirement for sponsors to directly report Suspected Unexpected Serious Adverse Reactions (“SUSARs”) to investigators and research ethics committees. This reform will not prevent sponsors from doing so if they choose to, but will remove a duplicative legislative requirement, because investigators will still receive safety information in other ways.
- The Government will legislate to enable SUSARs to be reported to the MHRA in an aggregate manner (emphasising that aggregate SUSAR reporting will not be mandatory and therefore will not be an additional burden). The legislative requirement to include individual listings of adverse events and reactions in annual safety reports will be removed.
- New legislation will extend the timeline for written notification to the MHRA of urgent safety measures taken to protect the safety of trial participants from three to seven calendar days.
Flexibility on Consent Provisions
Encouraging participation through simplification was a key theme of the Government’s proposals for clinical trials reform. As such, the Government plans to move forward with the proposals for enabling flexibility on participation consent provisions, so that a more proportionate approach is taken where the risks to participants are lower. For example, the Government will legislate to simplify the methods of obtaining informed consent for cluster trials (i.e., those conducted on existing approved medicines, where randomisation to a certain treatment is pre-determined by location).
The Government emphasises that despite lower-burden consent requirements, participants will still receive critical information in considering whether to participate. However, the reform aims to help avoid situations in which participants receive “long and detailed information that can be difficult to understand.”
Respondents to the consultation were largely in agreement with introducing a risk-based approach that supports participants giving their consent “in an easier way.”
Guidance developed in collaboration with patients and the public will flesh out the legislative provisions.
Good Clinical Practice
Finally, the Government seeks to enable “international interoperability” through the proposed reforms, encouraging trial sponsors to apply to the UK as part of multi-country trials and ensuring the acceptance of data generated from UK trials globally.
In this vein, the Government will legislate to specifically align UK requirements with the Good Clinical Practice principles of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“ICH GCP”).
Proposals Not Taken Forward
The Government’s response to the consultation also reveals the decision not to progress with certain initial legislative proposals, namely:
- the notion of enabling regulators to consider previous non-compliance when assessing new clinical trial applications, due to this potentially deterring sponsors from initiating trials in the UK;
- the collection of data on unlicensed medicines, on the basis that the Early Access to Medicines Scheme already delivers on the intent of this proposal;
- plans to legislate to ensure diverse representation among trial participants, on the basis that this is better approached through guidance, which would allow greater flexibility to update and adapt with new knowledge and experience; and
- legislation to ensure patient and public involvement, again leaving guidance to highlight best practice in this area.
The planned overhaul of clinical trial regulation in the UK will likely expedite the process of setting up and securing approval for trials and improve the UK’s alignment with clinical trials regimes abroad in certain respects.
Whether this stimulates the desired increase in the number of UK-based trials and enhanced public participation remains to be seen. Certain specific issues raised in the consultation still need to be addressed through guidance and divergence from EU rules in some areas, such as the content of applications, may lead to a greater administrative burden for clinical trials conducted across both the UK and the EU.
If you would like to discuss the proposed changes and what they may mean for your company’s operations, please contact Robin Blaney.