Diversity has been a huge buzzword in the clinical trial space in the past few years. There has been a huge push to ensure that patients feel represented in clinical studies and to improve the gender and ethnicity of trial participants.
The World Health Organization (WHO) has gone beyond race and gender however in its guidance to sponsors and contract research organisations about best practices for clinical trials. The guidance reads: “…clinical trial cohorts have often lacked diversity, with under-representation of certain populations, resulting in them being underserved by clinical trials”.
Released in September 2024, the guidance addresses more factors where diversity is lacking in clinical trials. This includes patients of ethnic minorities and stigmatised populations such as those from the LGBTQI+ populations and age extremes. The guidance goes on to recognise the need to include pregnant and lactating women, patients from lower socioeconomic backgrounds and patients who face language barriers.
WHO’s chief scientist Dr. Jeremy Farrar said: “This new guidance aims to improve the diversity of trial participants to ensure research benefits the broadest range of people possible, decisively moving away from a one-size-fits-all approach.”
According to 2022 data, less than 5% of clinical trials included pregnant women and only 13% included children. WHO says this has reduced the quality of evidence, affecting care and access to interventions. The absence of adequate trialling in underrepresented populations can lead to a cautious approach to treating them, which negatively impacts their health.
VeriSIM Life founder and CEO Dr. Jo Varshney said: "The WHO’s new guidance on clinical trials reinforces vital practices to improve diversity, equity, and inclusion, especially for under-represented populations.
"Historically, drug developers face limited incentives to address the needs of patients with lower economic potential, as including them in trials often incurs costs that don’t align with anticipated returns. But if we can reduce or eliminate these costs, we could shift this paradigm.”
Important to include patients from low-income countries
Gilead made history as the first sponsor to include pregnant and lactating women in a Phase III human immunodeficiency virus (HIV) study, PURPOSE 1 (NCT04994509) which showed perfect efficacy (100%).
In November, Moupali Das, executive director of HIV clinical research at Gilead, said that it is vital to include patients who are most impacted by the disease in studies.
“I’m filled with such hope as I think about what the PURPOSE programme could mean for people who are members of groups that are disproportionally affected by HIV,” Das said.
“Potential new PrEP choices could be a key resource in helping to end the epidemic.”
"The WHO's new guidance sets the stage for building robust clinical trial infrastructure, especially in low- and middle-income countries. By developing a blueprint for conducting efficient trials domestically, biotechs all over the globe can accelerate the time-to-market for their essential medical interventions,” says Michael Young, co-founder of Lindus Health.
Of course, some studies have been run on patients from lower-middle-income countries that do not have the necessary infrastructure to perform studies.
On this, the guidance states: “Regulatory bodies, including ethics committees, can only respond quickly in emergencies if they have adequate resources and capacity. Therefore, it is essential that resources are provided for training personnel in proportionate regulatory processes and research ethics in normal times. This area is sometimes neglected in considerations of research capacity strengthening but it is vitally important.”
One way that WHO believes this population could be targeted is by using cluster randomised trials.
“Cluster randomised clinical trials can be used in numerous settings in both high-income countries and low-middle income countries but are in particular increasing in popularity in low-middle income countries or resource-limited settings, as many of their design features lend themselves well to priority areas of research in these environments,” the guidance states.
Regulatory guidance will help in implementing WHO guidance
The WHO guidance is unusual in prioritising the inclusion of groups such as lower socioeconomic backgrounds and pregnant women while the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidance’s have typically focused on ethnic diversity, added Young.
“Sponsors are increasingly recognising the importance of diversity in clinical trials, driven by regulatory requirements and the ethical imperative to ensure that medical research benefits all populations. However, unless this WHO guidance is adopted by the big regulators, I don't think this is likely to have much impact on trial design,” Young explains.
Dr. Oren Cohen, chief medical officer and president, clinical pharmacology at clinical research organisation (CRO) Fortrea says that it is all good and well asking sponsors to improve the diversity of patients, but sponsors need to act on that advice to ensure that underrepresented patient populations feel represented in clinical trials.
“Ultimately, I believe that there's another step in making sure we train and produce adequate numbers of investigators from minority groups that are underrepresented,” Cohen explains.
“We can’t expect patients to travel long distances to very unfamiliar environments where people don't look like them or talk like them - it's very disconcerting. This is something we need to solve at a root cause level, but I didn't really see a lot of that addressed in the WHO guidance. There are certainly many aspects of this where one could go very much deeper.”
Cognivia CEO Dr. Dominique Demolle said that she agrees the WHO guidance aligns with that of the FDA and EMA on different topics.
Demolle says: “The recent draft guidance from the FDA about the Diversity Action Plan is a clear mirror of what is in the WHO recommendations. There is also clear alignment with the new ICH E8 guidance which highlights including pregnant women, lactating women, and more children. Clearly, now we are moving a step further with providing an opportunity for underrepresented populations from low-to-middle socioeconomic countries who do not normally have the chance to participate in a clinical trial."
There could still be barriers to diversity
Despite the support the WHO guidance would likely receive, largely down to its close alignment to major regulatory guidance, Demolle believes that with global studies, there could still be some issues with countries that may not have the infrastructure to run large global studies. There are also questions as to whether the FDA will accept data from patients in certain countries due to Section 569B of the Federal Food, Drug, and Cosmetic Act.
“I think the real challenges will come with the implementation - accessing the patient and keeping the patient in the trials - this will be a challenge. This could also be where there is a lack of clarity from the FDA, are they going to accept minority populations from other countries? Of course, many studies are global so it is not just about recruiting these underrepresented populations in the US but globally,” Demolle added.
eClinical Solutions senior director Jason Housley said that sponsors are almost fearful of how data may be interpreted by the FDA if it is potentially perceived as ‘inadequate’ which is halting innovation when it comes to patient populations in studies.
“There are a multitude of examples of this 'transformation-killer',” Housley explains. He adds that this concern by regulators can be around patient population selection, the collection of "interesting or niche" data; and data validation.
“Still the industry takes a belt-n'-braces approach due to the perceived risks around inadequate quality. All this despite multiple regulatory papers encouraging risk-based approaches,” Housley concludes.
