Call goes out for simpler clinical trial regulation in UK

Clinical trials are strictly regulated to ensure patient safety, but the current framework in the UK is stifling early-phase clinical research, making it harder to advance novel therapies through development, and may be too inflexible to protect patients.

That's the view of two experts in clinical research – Prof Charles Vincent of Imperial College London and Dr Ulrike Lorch of contract research organisation (CRO) Richmond Pharmacology – who have called for a simplification of regulations in an editorial published in the British Journal of Clinical Pharmacology.

There's no better argument for tight controls on in-human studies than the infamous TGN1412 trial in the UK in 2006, which left six men fighting for their lives after a single infusion of a test antibody, attracted media attention from around the world, and changed how trials are conducted forever.

However, Vincent and Lorch argue that a gap is emerging between the governance of clinical trials and the reality of running them, especially for early-stage studies that are becoming increasingly diverse.

That is in part due to the rising complexity of the medicinal products being tested, which makes it hard to define standard procedures.

"Early phase trials are becoming increasingly heterogeneous, and this requires a different approach to standards and guidelines akin to the 'mass customisation' seen in industry," they write in the paper.

"Mass customisation allows products to be made to individual customer requirements but is only achievable because each of the many components is built in a standard fashion with rigorous quality control."

While there's no doubt that standards and guidelines are necessary, they are not sufficient to maintain trial safety even in the most professional hands, according to the paper, which describes a COVID-19 study that involved controlled infection on subjects with the SARS-CoV-2 virus.

While the study adhered closely to standards and guidance and was run in a highly professional manner, a number of risks have since been identified to both patients and staff, including situations in which "voluminous guidance" was simply impossible to follow.

In future, a better solution would be a "toolbox" of standards, guidelines and local work instructions which can be adapted by investigators to bridge the gap between regulation and reality.

An approach based on modules of regulation and regulatory guidance could be updated more frequently to counteract the current lag in clinical trial practice and provide "lean processes" that can be easily understood and followed.

"Each trial will still have clear and defined standards and safety procedures, but the precise nature of these standards and procedures may vary between trials," write Vincent and Lorch. "Regulators need to recognise that any guidance will need to be adapted by clinical trial professionals into practical local procedures that meet quality standards."

The paper has been published against a backdrop of declining levels of activity in the UK clinical research sector, with a pharma industry-sponsored study finding a 41% drop in industry trial starts between 2017 and 2021.

A review of the sector led by former health minister Lord James O'Shaughnessy and published last year recommended sweeping changes to the way clinical trials are run and regulated in the UK and a target of doubling the number of people taking part in commercial studies in the next two years.

The Medicines and Healthcare products Regulatory Agency (MHRA) announced changes to regulations governing clinical trials in 2023 that included measures to make it faster and easier to gain approval for studies.