The Need for Diversity in Clinical Studies

In an ideal world, clinical trials would test the efficacy and safety of investigational products in population subsets that closely resemble the full diversity of their intended market across all aspects. These would include gender, sex, race, age, socioeconomic status, disease state, their place of residence and a host of other factors. But clinical trials are already an expensive endeavor – widening participation often comes not only with an increase in cost, but also with a need for eligibility criteria that increase the risk of the trial failing. This article will focus on the benefits of diversity and the reasons why it may be lacking.

Past Failings from Lack of Diversity

Increasingly, clinical trials are performed in the same large hospitals or research centers – which often translates to patient pools consisting of the same urban, often disproportionately white, populations that can afford to attend such sites. Such biases can have grave consequences for treatments – and even basic medical advice: for example, the association of UV exposure with higher skin cancer incidence is a widely held belief, but one of the longest studies to date has not found this association to be true in black and hispanic populations. 

Another excellent demonstration of the disparity between clinical trial populations and the market they seek to serve lies in the field of multiple myeloma. In America, 20% of multiple myeloma patients are African American, yet they only account for 6% of myeloma trial participants. In light of this fact, the lower survival rates for African Americans with myeloma, compared with their white peers, may seem unsurprising. The benefit of using a more diverse trial pool would not only provide immediate translation in improved outcomes, but it would also make products more accurate: myeloma disproportionately affects Black Americans, but findings for investigational products have to be extrapolated from wealthy, white trial participants. 

Raising Awareness, Expanding Pools

The drive to push for diversity frequently requires trial coordinators to reach out to new demographics – which may often be an expensive endeavour. But this can have bigger long-term benefits. Expanding beyond traditional trial demographics will also grow the overall participant pool, which will translate to larger enrolment rates overall. COVID-19 has shown that there is a lot to be done to increase public awareness regarding clinical development – and the pandemic has certainly led to higher health literacy across the population. The benefits of forging partnerships with new care providers that can grow a trial’s patient pool are not to be discounted. 

PhRMA, the association for Pharmaceutical Research and Manufacturers of America, has also drafted its own principles for increasing clinical trial diversity. Of note is their drive to broaden eligibility criteria for trials. This is particularly important for exploring the relationships between comorbidities and the effects an investigational product may have on them. Areas of medicine which deal with age-related disease are disproportionately affected by comorbidities – such as cardiovascular disease and cancer; patients are unlikely to merely have a single disease. Studies which remain too conservative in enrolling patients with other conditions may thus present findings that are suitable for a younger, healthier population that does not really exist. More stringent standards of investigation that enable the most relaxed eligibility criteria that are safely possible would lead to more generalizable data, and increase the pool of available participants.

Cost: The Most Significant Barrier

Unsurprisingly, one of the most central patient barriers to any clinical study is cost. Recruiting from wider pools of patients beyond the often urban surroundings of traditional care centers faces many challenges which can be boiled down to cost:

1. – The travel expenses associated with visits to on-site facilities
2. – Physicians with the network, awareness and capacity to refer to clinical trials are often those in more prestigious, and expensive, healthcare facilities
3. – Clinical trials for many conditions, such as those in oncology, may be considered when other, already established, lines of treatment have failed: having these treatments in the first place carries another cost
4. – The time spent at the trial also carries a cost: patients may not be able to afford time off, or may require carers to look after any dependents they have while they are gone

While reducing cost-related barriers may seem insurmountable, solutions do exist. These can involve increased adoption of Decentralized Clinical Trial (DCT) technology to facilitate more remote elements in a study, where possible. DCT technology has experienced a rapid growth throughout the COVID-19 pandemic, and it is expected to become a mainstay of clinical development. Patient costs can also be reduced by increasing partnerships with a wider array of healthcare centers and practitioners that can tap into more diverse pools, and provide a greater geographical diversity of sites used by the trial.

Indeed, regulators recognize the need for improved diversity in clinical studies, as seen by the FDA publishing guidance on the subject in 2020. But diversity is not merely needed on a local, national scale – the threats we face have become increasingly global, but the majority of our trials still take place within Western Europe and North America. The FDA found that even though the USA constitutes 4% of the world population, over 31% trial participants were US citizens. Increasing foreign presence not only grants better diversity for extrapolating findings to a global population, but also comes with cost savings. Clinical studies can be notably cheaper in emerging countries, while also maintaining the same standards of compliance.

This article merely sets out to explore the benefits of diversity in a variety of aspects of clinical study – and the gains made from increased diversity are plentiful. The ways for such diversity to come about are also abundant, but they require healthcare and regulatory professionals to step outside of their traditional comfort zones, develop new partnerships and embrace technological innovations. These must be steps we are willing to take to achieve product development cycles that better reflect the world we live in.

Nick Zoukas, Former Editor, PharmaFEATURES

Join us as we discuss the need for increased diversity in clinical trials in Proventa International’s Clinical Operations Strategy Meeting in San Francisco on 11 May 2022, featuring industry-leading experts sharing their insights.