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Summary in Thirty Seconds
Over the past five years in the UK, the number of patients participating in clinical trials and the number of clinical trials being conducted has dropped markedly.
Additionally, only half of ongoing UK clinical trials are running on schedule.
Reasons for these problems include the COVID-19 pandemic, Brexit, the complicated UK clinical trial approval process, and massive staff shortages in the National Healthcare System.
In the past year, numerous proposals have been made to address these problems and an independent review is ongoing to recommend improvements to the system that will make carrying out clinical trials easier.
Conducting clinical trials in the UK will take adaptability to regulatory revisions as well as creativity to overcome trial enrollment issues.
Large Declines in Participants and Trials
Over the past five years, the National Health Service (NHS) in the UK had seen a 44% drop in the number of participants recruited (22,000 fewer people enrolled) for commercial clinical trials.[1]The number of Phase III clinical trials being conducted in the UK fell by 48% from 2017 to 2021.[2] The UK’s ranking for the number of phase III trials being conducted has fallen from fourth to tenth in the past five years in global rankings:
Global rankings and number of industry clinical trials initiated in 2021, by country and phase[3]
Reduced access to clinical trials is particularly concerning for patients with limited treatment options, including more than 3 million people in the UK living with rare diseases, dementia, and advanced cancer.[4] A UK life science advisor stated that the bureaucracy which was simplified during the pandemic to fast-track trials had “crept back into the system and ossified” and the overstretched NHS workforce is losing its research capacity.[5] As an indicator of the problems with UK trials, official figures show just 52% of trials in the NHS are running as scheduled, which, while a significant improvement in the past year, is still far behind the target of 80% of trials being delivered to time and target by June 2023.[6] At the NHS status update in January 2023, 56% of studies were still in set-up beyond their planned opening date compared with 70% in set-up beyond schedule at baseline in May 2022. The NHS intends to shut down any trials missing their target to start recruiting by more than 90 days, with one in 10 trials being monitored under its Reset Research program set to close prematurely. Reset is the approach being implemented to recover the UK’s capacity to deliver clinical research.[7] Since May 2022, five hundred trials have been closed under the initiative.
Reasons for Problems
Many factors have played into issues with clinical trials in the UK, including two historical factors: the COVID-19 pandemic and Brexit. Brexit has removed the UK from direct participation in the Clinical Trials Information System; thus, clinical trials held in the UK must use the British Medicines and Healthcare products Regulatory Agency gateway.[8] An additional factor is the UK’s lengthy approvals process, which can leave clinicians and their patients out of international multicenter trials.[9] The UK process can take twelve months or more to get started, so by the time a trial is approved, other, non-UK sites may be ending recruitment. In 2020, the UK's median time between a clinical trial applying for regulatory approval and that trial delivering its first dose to a participant was 247 days.[10] For comparison, one study at a US comprehensive cancer care center found a median clinical trial activation time of 185 days; after implementing a streamlining process, the median activation time dropped to 132 days[11]—roughly half the time of UK trial activations. Related to these problems is a workforce crisis with the NHS, with over 100,000 staff vacancies, including 12,000 empty physician positions.[12]
Proposed Solutions
At the start of 2022, the NHS proposed several changes to their clinical trial regulations, which can be found at Proposals for legislative changes for clinical trials - GOV.UK (www.gov.uk). Such proposals include combining the regulatory and research ethics approval process; simplifying safety reporting; and loosening informed consent for cluster trials. The Association of the British Pharmaceutical Industry (ABPI) has proposed three short-term recommendations to improve the poor status of clinical research in the UK: prioritize interventional industry clinical trials; improve set-up processes for industry clinical trials; leverage industry trials to boost NHS research capacity and culture.[13] In February 2023, the UK Office for Life Sciences commissioned an independent review of the UK clinical trials landscape to offer recommendations for improvement.[14]
The Bottom Line
Conducting clinical trials in the UK presents unique challenges, particularly now that the CTIS is fully implemented in the EU and independent of the UK post-Brexit. Currently, regulations for conducting clinical trials in the UK are being reviewed and will likely be revised based on the recommendations, so it is important for those considering a clinical trial in the UK to stay up to date with these changes. Clinical trial set-up and follow-through aided by those familiar with the evolving UK regulatory system will be vital to smooth and successful ventures. Creative solutions to enhance enrollment can be implemented as well, such as the use of social media, assistance from patient advocacy groups in the UK and elsewhere, and raising healthcare provider awareness of rare diseases and biomarkers through educational outreach efforts.
[1] NHS patients losing access to innovative treatments as UK industry clinical trials face collapse (abpi.org.uk) [2] BMJ 2022;379:o2540 [3] Rescuing patient access to industry clinical trials in the UK (abpi.org.uk) [4] Patients losing out amid slump in NHS clinical trials, warn top clinicians | Medical research | The Guardian [5] Patients losing out amid slump in NHS clinical trials, warn top clinicians | Medical research | The Guardian [6] Research Reset Status Report (Public) 17 January 2023 (reissued 23_01_2023).pdf - Google Drive [7] Research Reset Status Report (Public) 17 January 2023 (reissued 23_01_2023).pdf - Google Drive [8] Consequences of Brexit for Clinical Trials in Europe (appliedclinicaltrialsonline.com) [9] Patients losing out amid slump in NHS clinical trials, warn top clinicians | Medical research | The Guardian [10] Steep drop for UK industry clinical trials between 2017 and 2021 (europeanpharmaceuticalreview.com) [11] JCO Oncology Pract. 2020; 16(4):e324-e332 [12] Staffing crisis deepens in NHS England with 110,000 posts unfilled | NHS | The Guardian [13] rescuing-patient-access-to-industry-clinical-trials-in-the-uk.pdf (abpi.org.uk) [14] Lord O’Shaughnessy to lead independent review into UK clinical trials - GOV.UK (www.gov.uk)