The UK government has published its long-awaited response to the clinical trials reform consultation, confirming a major overhaul will take place. The government response is available here. It will take forward many of the changes proposed in the consultation with new legislation, with a few exceptions.
The government intends that the new framework, which it describes as the biggest overhaul in UK clinical trials regulation in over 20 years, will “remove obstacles to innovation” and “streamline” the regulation of clinical trials, while maintaining patient safety.
The draft legislation is not yet available to assess fully the international comparative element, however the government recognises the importance of international interoperability. While not mirroring the EU regime, it is clear that one objective of the proposals is to ensure sufficient alignment in the substance of trial requirements, with many proposed changes focussed more on the process of trial approvals.
The proposals have been broadly welcomed, including by industry.
In further detail:
Context to the reforms
The UK government has announced that it will move forward with proposed significant reforms of the clinical trials regulatory framework following a public consultation (see our related post here).
The backdrop to these changes is concern and uncertainty about the current status and future of UK clinical trials, especially post-Brexit as the UK system has diverged from the EU (where the Clinical Trials Regulation came into force in January 2022, leaving the UK with the Clinical Trials Regulations from 2004 based on the old EU Clinical Trials Directive).
A 2022 report by the Association of the British Pharmaceutical Industry (ABPI) found that the UK’s clinical research industry was in a state of significant decline, constituting a “clear and serious” threat to the long-term future of the clinical research industry in the UK (see further our analysis here). Further, the UK has been performing poorly against international comparators according to KPIs published by the Medicines and Healthcare products Regulatory Agency and a recent report on key Life Sciences Competitiveness Indicators (see further our analysis here).
Recent government rhetoric has been focussed on securing the future of UK clinical trials and fostering innovation, as set out in a March 2021 policy paper, “The Future of UK Clinical Research Delivery”, and in the clinical trials consultation itself.
The government’s proposed approach in further detail
Broadly, the government plans to implement most of the proposals set out in the consultation via legislation, with a few notable exceptions.
The government considers that its reforms “will deliver on [its] vision for a more proportionate, streamlined, flexible and effective clinical research environment, putting patients at the heart and the UK at the forefront of innovative regulation for clinical trials.” Having analysed over 2000 responses, the government summarises that the reforms are designed to:
- Ensure patients and their safety are at the focus of all clinical trials and bring the benefits of clinical trials to everyone;
- Create a proportionate and flexible regulatory environment;
- Cement the UK as a destination for international trials; and
- Provide a framework that is streamlined, agile and responsive to innovation.
Key themes from the response include:
- Patient safety – patient safety will remain “at the heart” of the legislation and the foundation of clinical trials. It is apparent throughout that “appropriate” regulatory scrutiny will remain the key counterbalance to proposals around increased flexibility and streamlining;
- Transparency – consultation proposals relating to transparency will be taken forward in the new legislation, including a requirement to share trial findings with participants and to publish a summary of results within 12 months of the end of a trial;
- Flexibility, proportionality and risk-based decision making – the legislation will include an “overarching expectation” to consider proportionality, and the legislation will move away from a “one size fits all” approach to enable modern and innovative trials. Legislation will include the proposed notification scheme for “low risk” trials (dispensing with the need for regulatory review while maintaining research ethics committee approval requirements). Legislation will also proceed with the proposed simplified informed consent process for “lower risk” trials;
- Streamlining and approvals timelines– the government will proceed with the proposals to combine MHRA and ethics review. An initial review of the application will be required within 30 days of validation as standard, and a decision will be required within 10 calendar days of a response to any RFI. The legislation will seek to remove administrative barriers which are “duplicative” or which “do not provide additional value in identifying safety risks”;
- Public / patient involvement – proposals have been watered down here and the government will not be taking forward proposals to embed public and patient involvement in legislation. It will instead do this via “best practice guidance” in order to increase flexibility and avoid potential delays in trial set up and additional “administrative burden” which some respondents said may result from a legislative approach;
- Diversity – the government will also not be taking forward proposals to legislate to ensure diversity of clinical trial populations, which it suggests will enable a “flexible” and “adaptive” approach for the future.
International interoperability and alignment with EU rules:
A critical aspect of the reforms will be the interplay with international regimes, and the response indicates that many respondents urged consistency, alignment, and even harmonisation with EU and international rules.
It will not be possible to assess fully how the UK system will compare with EU rules until concrete drafting emerges. However, while full mirroring and alignment with EU rules is clearly not the intention, it is also apparent that the government is keen not to diverge too far from key international substantive requirements which could ultimately harm international interoperability.
The proposals recognise the importance of such interoperability and acknowledge the importance of ensuring that trial sponsors can apply to the UK as part of a multi-country trial, and that data generated from UK trials must be accepted globally. The response states that legislation will remain “fully aligned with international standards”, and the intention is that the UK will align with the Good Clinical Practice Principles of the ICH (International Council for Harmonisation of Technical Requirements).
Although the processes for approval of clinical trials in the UK are being streamlined, the government emphasises that the “core documentation and evidence to support a clinical trial application will remain aligned with international expectations”. In this regard, the government has decided to keep the list of core documents which must be submitted with a trial application as a legislative requirement rather than moving this to guidance, taking into account that that a “large deviation” from EU clinical trials requirements was not desirable. The government has also confirmed the intention to align certain key definitions in the legislation (such as “substantial modification”) with EU rules, and other key similarities are apparent, such as the planned notification scheme for “low risk” trials, which is akin to “low intervention clinical trials” in the EU regime.
On the other hand, the proposals signal a firm intention to move away from EU approvals timelines, which the government describes as “significantly longer and less flexible” than its own plans. Additionally, the proposed reliance on guidance rather than legislation for certain elements will inevitably enable more flexibility than the EU rules-based system can afford.
- Overall, there were no major surprises in the government response, broadly confirming the proposals previously put forward in the consultation.
- The UK’s ABPI has welcomed the announcement from the government, which it described as a “significant step forward for UK clinical trials…at a crucial time for industry clinical research in the UK”.
- The government has not yet provided any legislative drafting, so it remains to be seen how they will be implemented in detail, including important concepts such as how the UK will compare with its international peers.
- The decision to rely on guidance rather than legislation for certain key topics (e.g. diversity) is consistent with the approach taken in the medical devices reform consultation response (see further our analysis here, where a similar approach was suggested for example with respect to addressing health inequalities and biases). While enabling flexibility, this also introduces potential additional uncertainties.