The FDA has been addressing the broad issue of diversity in clinical trials since the 1980s, when it issued guidance on the importance of studying the effects of drugs in elderly populations. Since then, it’s published guidelines around gender and sex differences in the clinical evaluation of drugs, and developed measures to address the under-representation of racial and ethnic minorities.

In recent years, the focus on race and ethnicity has intensified, resulting in a global effort to promote the benefits of clinical trial participation and increase inclusion from diverse populations.

The rationale is well understood. Clinical trial populations must reflect the real-world population most likely to use an approved drug, and since few diseases are specific to a single demographic, trial populations must also be broad and representative. Unfortunately, however, the diversity gap that’s long bedevilled trial participation remains wide, and certain groups are still greatly under-represented. It’s a huge issue. The struggle for inclusion plays into – and indeed exacerbates – wider narratives around health disparities and inequalities, and the social determinants of health.

In November 2020, the FDA issued new guidance to help industry enhance the diversity of clinical trial populations through broadening eligibility criteria and adapting trial designs. The report is an attempt to shift the conversation from ‘why’ to ‘how’ – offering a series of recommendations to help companies develop more inclusive trial practices and drive more proportional representation from marginalised populations. However, making the leap from good intentions to authentic achievement requires significant change. So how is industry faring? And what do companies need to do to improve performance?

At the headline level, the signs are encouraging. “Pharma is increasingly committed to ensuring trial populations are more diverse than they perhaps were in the past,” said Nuala Murphy, President, ICON Clinical Research Services. “A good example is Pfizer’s COVID-19 vaccine trial, which was conducted at around 150 trial sites across the US, Argentina, Brazil, South Africa, Germany and Turkey. The trial not only targeted geographies with high infection rates, but it was also designed to ensure the vaccine was developed in countries where the patient population was adequately represented. Over 42% of overall trial participants came from diverse ethnic backgrounds.”

Certainly, the rapid development of COVID vaccines was a phenomenal achievement made possible through unprecedented global collaboration. Similarly, the diversity seen in trial populations was no doubt driven by a worldwide determination to find a way out of the pandemic. These were exceptional circumstances. The challenge, moving forward, is to build on the learnings to ensure the successful approaches companies adopted aren’t the exception, they’re the rule.

Mark Evans, Managing Director, Havas Lynx Faze, thinks a wholesale change in approach is required. “With 70% of trials failing to recruit, the focus right now is often on finding the easiest patients to recruit – without realising that using the same old approaches risks missing out on a huge group of underserved people. ‘Site burden’ continues to be an unacceptable reason for failing to recruit patients when the burden patients face is far greater and happens every day.

“We need to shift from the old model of catering to the needs of sites and focusing only on site burden, to the unique needs of the patients we are trying to serve. If we do this effectively and authentically, trials will need to start considering the real people they are intended for rather than the ‘echo chamber’ at which they are often designed without a representative group of patients involved.”

The answer, as always, is to focus studies around the needs of patients. But companies must make sure their attempts to be patient-centred are reflected in behaviours not buzzwords. “Patient-centricity was a conversation about good intentions rather than business critical,” said Mark Evans. “As such, many companies haven’t moved it high enough up on their agendas, often restricting it to a few specific roles and a PR story or two. It’s important that the current focus on diversity in trials doesn’t go down the same route. We need to understand it’s not just the right thing to include all people, but that the long-term success of trials and products depends on understanding and serving the real people we’re trying to help and make real change to address the fundamental challenges faced.”

Jo Fearnhead-Wymbs, Vice President, Patient Engagement, Ashfield MedComms, said early patient engagement is critical when it comes to developing new medicines. “We cannot make assumptions, we need to talk to the patients who’ve got experience of the condition we’re targeting to identify what’s important to them in the real world. Diversity and inclusion in that engagement process is essential. If we want to design studies around endpoints that are relevant to patients – rather than just focusing on clinical markers identified by expert medics – we need the broadest possible exposure to the target population. Ultimately, we have to ensure that clinical trials sample the people who are going to get the most value from a medicine – because if we’re not sampling typical patients, we’re not being realistic.”

There are some key challenges surrounding diversity in clinical trials, particularly around achieving broader representation from minority ethnic populations. “When you look at the reasons why people don’t want to participate in clinical trials, a long-standing legacy of mistrust in industry is obviously a huge and well-known issue – but it’s not the only one,” said Jo. “Real-life challenges present major obstacles too. Factors like childcare, sick pay coverage, site location and transportation are all barriers to participation – and, sadly, some of these challenges appear to disproportionately affect minority ethnic communities. Once again, this highlights the importance of early patient engagement to understand those barriers and design studies that help overcome them. Companies need to think proactively about the burden that taking part in a study heaps on the shoulders of those participating – and adapt protocols so they encourage enrolment and representation from diverse groups.”

So how do you increase diversity? “There’s increased sensitivity to ensuring eligibility criteria really drives diversity into clinical trials,” said Nuala Murphy. “Location plays a key role here. It’s important to select investigators that are in areas that really do provide access to diverse patient populations. We do a lot of work upfront to assess the diversity of the communities in the sites we choose to work with.

“There’s also a piece around trial design. Are you making it easy for people to be in clinical trials? For example, if you’re working in rare diseases, or with severely disabled populations, is it better to bring the trial to the patient, rather than asking the patient to come to the trial? There’s an increased focus on ‘decentralised’ trials – shifting trials more towards the home setting. If you remove the burden on patients having to be on site every second week – spending hours with clinicians in busy clinics, when in fact they could be monitored remotely and visited by a nurse when necessary – it lends itself to greater participation and greater diversity.”

Mark Evans agreed: “It’s not just about widening the criteria; it’s about understanding the inherent bias inbuilt into that criteria, and understanding that the trial design needs to be built around the needs of real patients. Are we making site visits a burden to those with jobs – those without sufficient income to pay their own travel expenses? Fundamentally this rules out those of a lower socioeconomic group, which in turn creates bias against a specific group of people.”

So how do you get it right? “Companies need to redouble their efforts in understanding the real-world challenges facing particular populations when it comes to taking part in clinical trials,” said Jo Fearnhead-Wymbs. “One way of doing this is through the use of Clinical Trial Simulations (CTS), which allow sponsor companies to test different trial designs with target cohorts before exposing patients to any treatments. The process generates qualitative data on the engagement and experiences of patients and can be used to inform protocol design.”

A great example of this is a CTS from AstraZeneca which looked at patient engagement factors for diverse populations in lupus. “The study simulated clinic visits with patients in two distinct groups – African American females in Atlanta, GA, and white females in Altoona, PA,” said Jo. “It showed that Atlanta study patients had very different requirements – including a need for strong community support, emphasis on transportation and childcare, and placed greater importance on time commitment and understanding the personal benefits of participation. These insights were used to improve patient recruitment, retention, compliance and advocacy.

“Use of CTS is growing across the industry – although often in very specific target patient groups. Their application in diverse populations, particularly among minority ethnicity groups, can only help improve representation in clinical trials.”