Super Times for Clinical Trials in the UK
The very established practices of ethical human experimentation are changing, partly, due to related new methods forged in the fire of a terrible pandemic, and partly to long-held ambitions made reality by technological advances.
What is clear is that clinical trials in the near future will look very different to what they looked like a decade ago.
UK Policy Developments - Pulling It All Together
The UK wants to be a science and technology superpower. This is a great ambition, and it necessarily has clinical research at its core. In the earlier days of the superpower agenda, the House of Lords was not particularly impressed with progress. However, it is clear that the government is pursuing it with vigour.
The government has commissioned an independent review focused on unlocking growth and investment opportunities relating to commercial clinical trials. In the background, although the superpower agenda involves the UK nations punching above their weight at the international level, the number of clinical trials in the UK has decreased. The independent review is expected to yield recommendations in spring 2023 which the government hopes will reverse that trend.
The main UK policy on clinical research is in "Saving and Improving Lives: The Future of UK Clinical Research Delivery". The review will consider how the 10-year vision in that policy paper can be built on, which will include looking at the work of the Recovery Resilience and Growth (UK RRG) programme. Following the main policy paper, the government published implementation plans for the periods 2021-2022 and then 2022-2025. The current plan, which recognises that this is a pivotal moment in which to make changes, seeks to harness the explosion in innovative technologies and make the UK one of the best places in the world for clinical research. The plan suggests that this will require digital enabling and a pro-people, pro-innovation environment.
Turning to outward looking policy, the Department of International Trade's Board of Trade published a paper on inward investment and export opportunities in the sector. The recommendations are designed only for government to consider, but they present an influential and optimistic view of UK life sciences.
Also at the international level, the UK and Argentina led on a World Health Assembly resolution concerning improvements to clinical trials. The improvements covered funding, collaboration, and the expansion of principles to a broader range of health technologies. This is a good indication of the UK ambition to lead global efforts and key international discussions in the sector.
Finally, returning home to think about money, in the most recent budget, the Chancellor confirmed several important aspects of UK policy that are relevant to clinical trials, including:
- The adoption of Sir Patrick Vallance's interim recommendations on regulation, which have inspired an increase in MHRA funding (further recommendations are expected). Also, in general, the Chancellor has identified life sciences, digital and advanced manufacturing as sectors of the future requiring smarter regulation.
- The establishment of the Department for Science, Innovation and Technology and the announcement of 'Investment Zones' in 12 growth clusters across the UK.
- The acknowledgement that the UK's digital and life sciences sectors are amongst the largest in the world and that the UK needs more lab space.
- The budget supports the development of East West Rail between Oxford and Cambridge - key regions in the sector.
- The budget contains encouragement for the MHRA to maximise its use of Brexit freedoms and accelerate patient access to treatments. Accordingly, the budget confirms that the MHRA is exploring international partnerships and developing a recognition framework.
- The budget refers to "a fully operational swift approval process", which is expected to be ready from 2024 and intended for impactful new medicines and technologies (the Chancellor specifically identifies cancer vaccines and AI therapeutics for mental health as the sort of products that would benefit).
We look forward to more detail, particularly on the last two points, which will support the superpower agenda and have knock-on implications for the design and planning of medicine development programmes.
Related Health Data Policy
It is not possible to consider properly the most relevant clinical research developments without considering broader developments relating to health data and the infrastructure of the NHS.
In the UK Government's main policy document on health data (Data saves lives), the Government refers to funding provided to UK Biobank, NHS DigiTrials, the Health Data Research UK Hubs, the Innovate UK digital pathology, imaging and artificial intelligence (AI) centres of excellence, and the Global Alliance for Genomics and Health (GA4GH). This is a good indication of the importance of health data to the broader life sciences sector. Looking more closely at NHS DigiTrials, the policy mentions a recruitment pilot for the NHS Galleri trial, which involved using digital techniques and a digital platform for identifying and issuing invites to prospective subjects.
The Government wants the UK to be the most advanced and data-enabled clinical research environment in the world. It sees the immense importance of NHS datasets and is seeking to build on digital platforms like NHS DigiTrials, which, among other things, attempts to improve subject recruitment.
Ultimately, the idea is to identify feasibility issues, allow speedy set up and better recruitment processes, reduce cost and resolve time commitment issues, and implement innovation in research design. The government has specifically identified genomics, cell-based therapies and digital therapeutics as important innovative fields. NHS DigiTrials has been used for impressive, large-scale studies, including Galleri and RECOVERY. With the examples it proudly includes in the policy, the government is promoting the concept of using digital platforms to exploit routine NHS data to great effect.
Also, the Government’s 10-year strategy for genomic healthcare (Genome UK) describes the ambition of the UK to integrate genomics into the NHS and use genomic data in research and clinical care. This may affect the nature and extent of clinical trials in the UK. At a basic level, clinical trials are likely to involve as a matter of good practice key elements of patient genotyping and stratification backed up by sophisticated diagnostics.
UK Clinical Trial Regulation - Changes on the Horizon
The UK government, through the MHRA, (frustratingly) took until 21 March 2023 to analyse feedback from the consultation on legislative changes which closed 14 March 2022. It has now published its detailed response. The consultation proposed significant changes to the UK legislative framework for clinical trials and the response, in general, records the support for those changes. In legal terms, the response will spark off the process for a new statutory instrument (SI) amending the Medicines for Human Use (Clinical Trials) Regulations 2004. The legislation will need to be drafted and the legislative process will then follow, so there is still much to do but the publication of the response is an important milestone. Let's be fair, there are significant developments happening in the EU (such as the overhaul of EU pharmaceutical legislation) as well as other parallel UK projects (such as writing the new regulatory framework for point of care (POC) manufacturing), all of which may affect the UK clinical trials regulations. So, these are not changes to rush through. And over 2000 responses to the consultation were analysed. However, there is increasing urgency if the UK is to achieve its superpower ambitions.
The commitment in the 2021 Life Sciences Vision was to radically improve existing legislation and, among other ambitions, cut bureaucracy and red tape. In the consultation document, the MHRA described the need to deliver a more streamlined and flexible regulatory regime that secures access to medicines. It also referred to the necessary balance against the interests of patients and trial participants, but the hope is that the changes will enable a thriving clinical research environment that works for innovative trial design and delivery. With that background in mind, the government's response indicates what changes it will propose. However, the devil will be in the detail of the new SI and the new guidance referred to in the response. The sector is likely to welcome the suggested streamlined approval and consenting process for low-risk studies. International businesses will also be comforted by statements about the UK's intention to align to ICH GCP standards.
If you feel like you need some further fuel for optimism, consider the following indicators of progress:
- A great example of the policy supporting regulatory innovation is the award to the MHRA of funds under the Regulators' Pioneer Fund for a project investigating the improvement of clinical trials using AI.
- A clear streamlining success is the launch of combined reviews under the UK's ethical review and regulatory authorisation frameworks. This is expected to be given a legislative footing.
- The MHRA recognises that certain clinical trials are now carried out in non-traditional ways. It has published guidance on complex trials, which encourages applicants to engage early with the MHRA and come prepared to justify necessary major adaptations that are anticipated and provide reassurance about data integrity.
Are We Super?
I would say yes. And I think there is a fantastic opportunity to use our powers to do significant good. The UK is in the process of looking carefully inward at what it wants to be, and outward at its potential impact at the global level. Like the situation or not, there are post-Brexit flexibilities that allow the UK to take a bigger role in international leadership, but the opportunity to do so will not last forever. We should all stand behind the superpower agenda
The UK policy environment points towards key sectoral focus points in overlapping areas. Imagine the Venn diagram showing life sciences, digital and advanced manufacturing sectors overlapping against a background of health data infrastructure. Thinking about it in that way, it is easy to imagine a very bright future.
A stunning example is used in the UK 'data saves lives' policy. It refers to the RECOVERY trial, conducted through the NHS DigiTrials platform, identifying dexamethasone as a life-saving COVID-19 therapy, which went on to save 22,000 lives in the UK and more than 1,000,000 beyond our borders. And that happened in 100 days. Sounds super to me.
This article was first published by MedCity.