U.K. Has Strong Plan To Reform Clinical Trials

By Dan Schell, Chief Editor, Clinical Leader

The recent layoffs and regulatory changes at the FDA have created an atmosphere of uncertainty in the U.S., especially as it pertains to the clinical trials landscape. Meanwhile in the U.K., progress is afoot.

In April 2025, the U.K. enacted the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024, marking the most significant overhaul of its clinical trial regulations in two decades. Essentially, This reform aims to enhance patient safety, accelerate trial approvals, and position the UK as a leading destination for clinical research. According to Lawrence Tallon, MHRA (Medicines and Healthcare products Regulatory Agency) chief executive, “By streamlining how trials are approved and run, we are making the UK a more attractive place to deliver high-quality, innovative research.”

Key features of the new regulations include a streamlined, risk-proportionate framework that reduces administrative burdens, particularly for low-risk trials. A single application process now integrates regulatory and ethics reviews, expediting the initiation of studies. The reforms emphasize patient-centricity, mandating greater public involvement in trial design and conduct. Additionally, the updated framework seeks to address underrepresentation in clinical research by promoting inclusivity across diverse populations.

The legislation aligns the UK's regulatory environment more closely with the European Union's Clinical Trials Regulation, enhancing international collaboration and competitiveness. A 12-month implementation period began on April 11, 2025, with full enforcement set for April 10, 2026. Developed by the MHRA in partnership with the Health Research Authority (HRA), these changes reflect extensive consultation with stakeholders, including patients, researchers, and industry representatives.

These reforms come at a critical juncture, as evidenced by recently published data from the MHRA. An analysis of 4,616 clinical trial initial submissions received between February 2019 and October 2023 examines the U.K.’s clinical trial landscape based on the Integrated Research Approval System template. The findings not only establish an important baseline for stakeholders but also substantiate many of the concerns that have driven the reform agenda and illuminate the specific challenges that must be addressed.

Submission Trends: Evidence of Decline

The MHRA analysis reveals peak submission activity occurred in 2020, accounting for 22.8% of all submissions, while 2023 saw the lowest volume at just 17.2%. This decline is precisely what the government’s reform agenda aims to reverse.

Phase 3 trials dominated the landscape, representing 32.6% of all submissions, followed by Phase 2 trials. Phase 4 trials were notably underrepresented at just 5.2% of submissions. This distribution differs from global patterns reported by the WHO Global Observatory on Health Research and Development, which found Phase 2 studies to be more prevalent globally. The imbalance indicates potential structural issues in the U.K.’s research ecosystem that the reforms must address.

Too Much Reliance On Commercial Investment

The study highlights the dominance of commercial sponsors, which accounted for 85.1% of all submissions. That’s a lot higher than, say, the Australian New Zealand Clinical Trials Registry, where commercial sponsors represented just 36% of trials. This heavy reliance on industry investment makes the U.K. particularly vulnerable to shifts in global pharmaceutical research strategies, underscoring the urgency of Lord O’Shaughnessy’s review recommendations to enhance the U.K.’s attractiveness for international clinical trials.

Commercial sponsors showed a clear preference for Phase 3 trials (33.9% of commercial submissions), while noncommercial sponsors focused more heavily on Phase 2 studies (37.3% of noncommercial submissions). Perhaps most striking was the disparity in Phase 4 trials, where noncommercial sponsors were responsible for 18.7% of their submissions compared to just 2.9% for commercial sponsors — a sixfold difference that suggests academic and public institutions are more invested in post-marketing research than industry. This pattern aligns with the government’s goal of strengthening academic research capacity.

The Inclusivity Imperative

The MHRA analysis reveals that although 90% of trials intended to recruit both sexes, male-only trials (6.1%) outnumbered female-only trials (3.7%) by nearly 2:1. Elderly populations were included in 67.1% of trials, indicating relatively strong representation. However, the study found concerning gaps in certain vulnerable populations:

• Pregnant women were included in only 1.1% of trials
• Breastfeeding women appeared in just 0.6% of submissions
• Breastfeeding women were completely absent from Phase 1 trials

Among pediatric trials, adolescents were the most commonly studied age group (14.4% of all submissions), with progressively lower representation of younger children.

The new regulatory framework’s enhanced provisions for patient involvement in research address these representation gaps.

Therapeutic Imbalances Concerning

The MHRA data reveals concerning misalignments between research activity and disease burden. Cancer dominated the clinical trial landscape, representing 29.4% of all submissions, followed by metabolic/endocrine and neurological conditions. All other health categories each represented less than 10% of submissions.

Several critical gaps emerged when comparing research activity to public health needs:

• Pain and nephrology were the least represented therapeutic areas despite significant disease burden
• Cardiovascular disease trials accounted for just 5.2% of submissions despite being the leading cause of death
• Respiratory conditions (7.4%) and mental health (3.3%) were underrepresented relative to their prevalence and impact

As part of the government’s clinical trials reform, it would be beneficial to have targeted incentives that stimulate research in underrepresented therapeutic areas.  In essence, the reform agenda must do more than create a favorable regulatory environment; it must actively steer research activity toward areas of greatest public health need.

Innovation Indicators

The MHRA analysis provides insights into specialized trial types that serve as key indicators of innovation. First-in-human (FIH) studies represented 12.7% of submissions, with commercial sponsors accountable for 92.8% of these high-risk, early-phase investigations. Advanced therapy medicinal products (ATMPs), including cell and gene therapies, comprised just 3.4% of submissions, with 87.2% coming from commercial sponsors.

The modest percentage of ATMP trials reveals an opportunity for growth in a cutting-edge field that the government has explicitly targeted for development. The new notification scheme for lowest-risk clinical trials, which launched in September 2023, was not designed to address these complex, higher-risk studies. However, the broader regulatory reforms in the recent regulations include provisions for innovative trial designs that could potentially accelerate ATMP development while maintaining safety standards.

Connecting Data to Action

The MHRA’s analysis of clinical trial submissions establishes a critical baseline for evaluating the effectiveness of the U.K.’s ambitious reform agenda. However, the data also reveals nuanced challenges that may require additional attention. The heavy reliance on commercial sponsorship creates vulnerability to market fluctuations, suggesting a need for balanced investment in academic research capacity. The demographic and therapeutic gaps indicate that efficiency-focused reforms must be complemented by targeted incentives to address underrepresented populations and disease areas.

The government’s multifaceted approach to reform includes the Prime Minister’s “target to reduce the time from application to first participant from 250 to 150 days.” As implementation proceeds, regular assessment against this MHRA baseline data will be essential to measure progress and adjust strategies as needed. Lord O’Shaughnessy’s ongoing review process provides a mechanism for this continuous improvement, ensuring the reform agenda remains responsive to evolving needs and challenges.

The ultimate success of this reform initiative will depend on translating regulatory efficiency into tangible improvements in research activity, participant diversity, and therapeutic innovation. If successful, these reforms will not only reverse the decline in U.K. clinical trial activity but establish a new global standard for efficient, inclusive, and impactful clinical research.