ver the past two decades, the UK’s clinical trials regulatory landscape has undergone a profound transformation, driven by both necessity and opportunity. From leaving the European Union and the COVID-19 pandemic to implementing new legislation, the evolution of digital infrastructure has been central to maintaining the UK’s position as a global leader in clinical research.

This article outlines the journey of how the Medicines and Healthcare products Regulatory Agency (MHRA) and Health Research Authority (HRA) leveraged information technology to streamline regulatory processes (for example, the new 14-day notification scheme introduced in October 2023), maintain consistency and predictability, and prepare for the future’s increasingly complex and innovative clinical trials.

The Journey Begins

The Medicines and Healthcare products Regulatory Agency (MHRA) was established as the UK’s regulator for medicines, medical devices, and blood components in 2003. Research Ethics Committees (RECs) were formally established in the NHS in 1991 and are responsible for safeguarding the rights, safety, dignity, and well-being of research participants. RECs are overseen by the Health Research Authority (HRA) in England and equivalent organizations in the other UK nations of Scotland, Wales, and Northern Ireland. Both the MHRA and RECs are mandated to review Clinical Trial Authorisation (CTA) applications within statutory timeframes, such as the 30-day timeline from receipt of initial CTA submissions to an assessment decision and a 35-day decision timeline for CTA amendments. The Clinical Trial throughput is high; for example, more than 5,000 applications were assessed in the last financial year (2024-’25).

Going Paperless

By the time the EU-wide Medicines for Human Use (Clinical Trials) Regulations 2004 came into force, the MHRA had already developed a digital platform to support and manage the vast volume of application documentation. These early systems improved data accuracy, security, and auditability, and laid the groundwork for more integrated solutions.

The Integrated Research Application System (IRAS) was launched in 2008 by the National Research Ethics Service, now part of the HRA, allowing electronic submission of documents for ethical approval. In 2009, the MHRA became an IRAS partner; however, the electronic submission portals remained separate, and the sequential nature of reviews still posed challenges.

Integration of Digital Systems

To address this, in 2018 the MHRA and HRA, in collaboration with the other UK Nations, launched the Combined Ways of Working (CWoW) pilot, now known as the Combined Review. This initiative connected the separate national digital case management systems, enabling seamless interoperability and parallel digital reviews by the MHRA and RECs, almost halving timelines from an average of 91 days without a combined decision to 54 days with a combined decision in its pilot of 100 CTA applications. Most recently (in June 2025), the time to combined decision was 41 days.

Adapting through Uncertainty

The MHRA had played a key role in the development of the EU Clinical Trials Regulation (CTR) published in 2014, with the date of launch depending on the implementation of a fully functional IT system.

However, in June 2016, the UK voted to leave the European Union before implementation. This presented both industry and regulators with an opportunity to develop a new national framework for clinical trials in the UK, even though its mandate to comply digitally with the forthcoming EU CTR remained. To overcome these uncertainties and to manage emerging transitional arrangements effectively, strategies for BOTH outcomes (of independence from, and compliance with) the EU were integrated into the CWoW project, in particular the entry and exit points of clinical trial applications. The HRA developed a new part of IRAS which combined the entry point for both MHRA clinical trial application and submission to the REC for the Combined Review process, while the MHRA developed a platform and workflow compatible with the EU CTR to reach a single outcome.

On the one hand, this approach allowed UK processes to comply with the EU Clinical Trials Regulation, should the UK be an EU member state when the Regulation applied. On the other hand, if the UK had left the EU, the UK would have a fully functional standalone IT system which provided a front-end application submission and management system for trial sponsors and researchers.

The EU Clinical Trials Regulation came into effect on 31 January 2022, by which time the UK had fully adopted its robust standalone system for Combined Review.

The COVID-19 pandemic tested the resilience of these systems by necessitating remote working. The MHRA had already completed a new integrated digital platform that fully supported securely and effectively working from home prior to the first pandemic lock-down. Rapid updates to digital systems allowed RECs to adapt overnight to reviewing applications online, piloting virtual meetings, and transitioning to fully online application management.

All these factors proved the value of the Combined Review process by enabling continuity in clinical trial approvals during a period of unprecedented disruption.

Real-Time Analytics and Performance Monitoring

In 2023, the MHRA faced a significant backlog in CTA assessments due to the cumulative impact of the EU Exit and associated responses, the COVID-19 pandemic, and transformational changes in MHRA operations.

In initially addressing this backlog, intensive manual data manipulation was necessary to provide a clear overview of CTA assessment priorities through twice-a-day reporting. However, it became clear very quickly that this approach was not sustainable to support timely decision making. To improve performance, the MHRA introduced a real-time reporting tool: an automated dashboard with a built-in early warning system to ensure that all statutory timeframes would continue to be met. Implementation in August 2023 resulted in significant time reductions, from a few hours to a few minutes per report.

These analytics helped stratify risk and complexity levels in trials, which later informed and supported the introduction of a risk-proportionate approach, such as the New Notification Scheme for low-risk trials in October 2023, which approved eligible trials in phase 3 and 4 within 14 days of application receipt, halving the time to trial approvals and accelerating, for example, development timelines for a study on a recombinant FVIII therapy for the treatment of hemophilia A. By 2024, the dashboard had become a management tool for clinical trial assessment teams to enhance workflow oversight and accountability and support improved customer communications.

Real-time performance data is currently supporting the oversight of the UK Prime Minister’s target, a key objective of the Government’s 10-Year Health Plan announced in April 2025 to reduce the time from CTA application submission to first participant to under 150 calendar days.

Legislative Reform and Future Readiness

Major legislative changes in 2025 have further shaped the regulatory landscape. Enabled by the Medicines and Medical Devices Act 2021, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 are set to take effect in April 2026. Further upgrades to IRAS will provide a solid foundation on which to build to deliver the new regulations, with the Combined Review service being a key element of the amended regulations.

These reforms demand significant enhancements to IT systems, for which the MHRA has developed artificial intelligence (AI) and large language model (LLM) systems to modernize working and maintain consistency and reliability of a new and improved service. The intent is not to replace the expertise of assessors but rather to give them more time to focus on higher risk analyses and judgments. These tools support the delivery of assessments, staff training, and capacity for activities such as official and external stakeholder advice, engagement, and correspondence.

Healthcare and research partners UK-wide are now further developing IRAS for the future. New improvements to our technology will deliver digital services that span the end-to-end journey to plan, approve, set up, manage, and complete research. Using modern agile, user-centered methodologies, the new services will be rolled out in phases to deliver early value to users through carefully managed transitions. The earliest phases of the transition will focus on research outside clinical trials, which currently operates on older technology. Throughout 2026, the HRA will build on this foundation to offer new digital services for clinical trials via the research systems program.

Transparency and Public Engagement

The 2025 UK Clinical Trials Regulations amendments also mark a milestone in research transparency. When the new regulations come into force on 28 April 2026, it will be a legal requirement to register clinical trials of investigational medicinal products (CTIMPs) on a WHO-recognized registry, publish summary results, and offer lay summaries to participants. The HRA has partnered with ISRCTN, the UK’s clinical trial registry, to automate registration via IRAS, simplifying compliance and reinforcing the UK’s commitment to openness in research.

The MHRA has taken this data-driven approach further in its analysis of 4,616 UK initial clinical trial submissions, publishing valuable insights about the whole UK trial landscape. Further analyses from the digital platform will continue to support horizon scanning for unmet needs in clinical research.

Conclusion

The UK’s journey from fragmented paper-based processes to a fully integrated, data-driven regulatory ecosystem reflects two decades of strategic investment and cross-agency collaboration. At the heart of this was a strong vision based on embracing risk proportionality and activating real-time data within the MHRA’s processes, to increase the pace of decisions and to drive positive outcomes for patients. Key lessons learned included the need to consider contingencies in plans to facilitate flexibility in managing change, incorporate ideas where there is clear synergy, and tackle challenges in a modular fashion. As clinical trials grow more complex and innovative, the MHRA and HRA are well-positioned to meet future challenges, ensuring that the UK remains a world-class destination for clinical research.