.tmb-propic-md.jpg?Culture=en&sfvrsn=c25d2b2f_9 "Professor Louis Chesler (Profile pic)")
A new UK-based study is shedding light on a quiet but consequential problem in cancer research: whether some people have less opportunity than others to participate in clinical trials. The findings show that some trials may unintentionally be inaccessible to groups of patients who could benefit from cutting-edge treatments.
Clinical trials are essential to advancing cancer care, offering patients early access to promising therapies while helping scientists determine what works best. Yet participation remains strikingly low. Earlier research has shown that only one in 10 adults with cancer in the UK take part in trials, with restrictive eligibility criteria often cited as a major barrier.
The new review, carried out by researchers in the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU), London, takes a closer look at this barrier by examining the inclusion and exclusion criteria used in trials focusing on bladder and head and neck cancers. The findings – published in the journal Trials – suggest that, while patient safety remains paramount, some commonly used criteria may disproportionately exclude already underserved populations.
Explicit and implicit barriers
The team analysed records from 38 bladder cancer trials and 30 head and neck cancer trials, which included an average of 483 and 357 patients, respectively. All the included studies were designed to assess the efficacy or safety of treatments for one of these cancers. The team also only considered phase II or III, multi-centre randomised controlled trials that had at least one site in the UK and recruited patients between 2013 and 2023.
One of the most striking findings of the study is the extent to which certain groups are explicitly prevented from taking part in trials. For instance, the review found that 41 per cent of studies included a history of HIV as an exclusion criterion. In many cases, this applied even to individuals whose condition was well controlled with modern treatments.
This has important implications for equality in research. According to the guidance provided in the National Institute for Health and Care Research’s INCLUDE Project (Innovations in Clinical Trial Design and Delivery for the Under-served), NIHR-INCLUDE, people living with HIV are considered a potentially underserved group in clinical trials. Moreover, HIV diagnoses are more common among certain communities, including gay and bisexual men and transgender individuals. Excluding patients with well-controlled HIV may therefore reinforce existing inequalities in terms of who benefits from medical advances.
The study also uncovered less obvious barriers, revealing that although some eligibility criteria may appear neutral at first glance, they can still disproportionately affect certain groups. As an example, a requirement for fluency in the dominant language or restrictions based on geographical location, while relatively rare, were still present in a small number of trials. These could limit participation for people requiring language support or those living farther from major research centres.
Beyond specific criteria, the researchers argue that the cumulative effect of multiple exclusions can significantly narrow the pool of eligible participants. This effect risks producing trial populations that do not reflect the diversity of patients seen in real-world clinical practice, potentially limiting how widely the results can be applied.
Rethinking trial design for the future
Rather than criticising individual studies, the authors frame their work as a call to rethink how trials are designed. They describe the research as a “methodological advance” aimed at helping trial designers better understand the broader impact of their decisions.
The study goes beyond simply listing common exclusion criteria. Through detailed analysis, it attempts to interpret how these criteria align with guidance such as NIHR-INCLUDE, which encourages researchers to consider the needs of disadvantaged populations from the outset of trial design.
Importantly, the aim is not to remove safeguards but to apply them more thoughtfully.
The authors suggest practical solutions, such as creating additional study cohorts for patients who might otherwise be excluded – for example, those with certain types of metastases. Such approaches could allow more people to participate without compromising safety or scientific integrity.
There are also broader systemic changes on the horizon. UK regulators, including the Health Research Authority and the Medicines and Healthcare products Regulatory Agency, are currently piloting new guidance that encourages researchers to justify eligibility criteria that may exclude underserved groups. Although this justification is not yet mandatory, the proposal represents a significant move towards more inclusive research practices.
A global challenge with local impact
Although the study focuses on two specific cancer types within the UK, its implications are far-reaching. Similar patterns have been observed internationally, where participation in cancer trials is also low – close to 7 per cent in the United States, for example.
At a global level, inequalities are even more pronounced. Oncology research is heavily concentrated in high-income countries, while some regions, including parts of Africa and South Asia, have little or no representation in trials for certain deadly cancers.
Against this backdrop, improving inclusivity within UK trials could form part of a broader effort to make cancer research more equitable worldwide. The authors emphasise that building a stronger evidence base will be key. They hope to see similar analyses conducted across other cancer types, enabling comparisons and identifying where the biggest gaps lie.
For patients, the potential benefits are clear. Expanding access to clinical trials could mean earlier access to new treatments that are tested in populations more representative of those who will ultimately use them.
However, the study’s impact will depend on whether the wider research community takes up its findings.
By publishing the research as part of a collection focused on equality, diversity and inclusion, the authors hope to spark conversations and encourage others to examine their own practices.
In doing so, they aim to ensure that the next generation of clinical trials not only advances science but does so in a way that is fair, inclusive and reflective of the diverse populations they are meant to serve.
Improving patient access
First author Dr Georgiana Synesi, who recently completed her PhD at the ICR, said: “The primary role of eligibility criteria is to keep participants safe and ensure that trial results are meaningful. But our work shows that certain criteria may unintentionally prevent some groups from accessing research opportunities.
“Although some of the stricter criteria only appear in a small number of studies, it is still surprising to see such exclusions in the modern day.”
Rebecca Lewis, Research Inclusion Lead and Clinical Trials Programme Manager at the ICR-CTSU and second author on the paper, said: “This project is innovative because we conducted a thorough statistical analysis and extensive literature research to interpret the findings in terms of monitoring inclusivity, rather than simply identifying common exclusion criteria.
“By trying to understand the purpose and impact of eligibility criteria, we hope that more patients can be safely included in future research.”
Senior author Professor Emma Hall, Director of the ICR-CTSU, said: “The ultimate goal for those of us designing and running clinical trials is to make them more equitable, diverse and inclusive. We are optimistic that, with buy-in from a wide range of triallists across the UK, our work will lead to patient benefit in the future."
Image credit: Gerd Altmann from Pixabay (modified)
