Putting a prototype car through its paces involves exposing it to all weathers, terrains, shocks and every factor that might have an influence on its ability to reach optimum performance, maximum efficiency and high levels of safety.

Exposing it to a spectrum of stresses and strains to see how it handles for drivers of all shapes and sizes gives it a credibility that purchasers can evaluate and appreciate.

New drugs are fully tested and approved, of course, but the current clinical trials system is nowhere near as comprehensive as its car manufacturing counterpart. Where driver’s seats can be adjusted for a full range of personal requirements, clinical trials remain stubbornly one-paced and in need of remodelling.

Clinical trials are the highway to new treatment, but their diversity is stuck in the slow lane. The telemetry makes for dismal reading: A study by the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research in 2020 highlighted that, of the 32,000 participants enrolled in the trials that approved 53 new drugs, 75% were white, 8% were black and only 6% were Asian.

The disproportionate number of drug trials dominated by male participants was emphasised in Caroline Criado Perez’s landmark book, Invisible Women, where she identified a litany of inequalities that disadvantaged women in health, such as only 25% of participants in 31 landmark trials for congestive heart failure conducted between 1987 and 2012 being female. She also discovered that a study into metabolic diseases in 2017 featured no women at all.

“Increasing diversity in clinical trials has been on the radar for a while but progress has been more in terms of evolution rather than revolution,” said Chloe Patel, senior scientist at Sprout Health Solutions, which focuses on helping pharmaceutical companies ensure the patient voice is central in drug development through clinical outcome assessments and behaviour change initiatives.

“We have known about the need to increase equity in research for a long time, but it is only over the last five to six years that it has been getting serious attention. It is a topic that comes up every day, from patient groups and from the pharmaceutical industry, because everyone knows we must strive for more diversity in clinical trials. I think we now understand more about what diversity is and what we must do to improve it. We can help co-create a better future with patients.

“There is a long way to go but, overall, the clinical trials environment is improving.”

The need to remove outdated barriers has been highlighted in order for health equity to become a reality rather than a distant hope.

The FDA’s draft guidance, Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Subgroups in Clinical Trials, recommends that sponsors of medical products develop and submit a Race and Ethnicity Diversity Plan to the agency early in clinical development.

‘A study by the US FDA’s Centre for Drug Evaluation and Research in 2020 highlighted that, of the 32,000 participants enrolled in the trials that approved 53 new drugs, 75% were white, 8% were black and only 6% were Asian’

It is a gear change, but the scale of the diversity hill climb is framed by research from patient-centric data analytics company Phesi, which analysed the more than half a million patients that participated in US cancer clinical trials over the past 15 years and discovered that 42% of US cancer trial cohorts did not include African-American patients and 48% had no Hispanic-American patients.

Patel sees the removal of outdated and needless barriers as a prime task to redress the balance. “It’s so important that we overcome barriers, such as trial location, by making it easier for patients to participate without having to travel to specialist hospitals, which may be some distance away,” she said.

“We’ve partnered with clients on decentralised trials in the UK where staff can go to a patient’s house to collect blood and do tests if needed or find alternative sites that are close to the patient’s home.

“We also work with our clients to remove unnecessary criteria from patient eligibility so we can facilitate the inclusion of under-represented patients and ethnicities, which are needed to ensure results become more representative.”

Sprout, which has expertise across behaviour science, clinical outcomes assessments and insights research, conducts projects for pharma and biotech clients worldwide. Patel added that her team insists on working with diverse groups of patients when it is mining for insights and experiences that enrich research and clinical trials.

“The trial should represent the patient population that the treatment aims to benefit,” she observed.

Enrolment for cancer clinical trials has stayed stubbornly just below 5% with ethnic, racial, rural groups and women significantly misrepresented. Logistics and cultural concerns play a huge role in that, but the language and terminology used at recruitment also has an influence on patients’ willingness to volunteer.

“From a communication point of view, I think we, as scientists, could be better at communicating clearly with patients,” Patel observed.

“Information about trials can appear to be written in a completely different language. You may refer to trial phases 2 and 3 that means nothing to a patient. But if you explain that in phase 2, we test the drug on a smaller number of patients and during phase 3, we test the drug on a larger group of patients, the information about trials becomes more accessible as the language used is easier to understand.

“I believe there are many different barriers that we can dismantle to improve diversity. It will take time, but I’m encouraged by the commitment for change that we see across healthcare.”

Sue Neilen, senior director at Evoke Galliard, believes a climate to accelerate change has developed.

“After years of discussion, the shift is taking hold,” she said. “Clients are scrutinising their own performance, building information and putting it in the public domain to promote discussion. Others are setting goals and holding teams accountable, investing in internal training to ensure their people are following strategies that address key obstacles.

“It is right up there on the health agenda – a prerequisite to health equity. Race, ethnicity, age and gender can all impact how different people respond to the same medicine or treatment. It’s imperative that we recruit participants representative of the population, or in the case of rare diseases, those most impacted by the condition.

“There’s certainly an obligation to ensure that patients who sign up to clinical trials are as diverse and reflective of the real-world community as possible. The COVID-19 studies demonstrated that clinical trial diversity is possible, even in challenging circumstances.  These are lessons, which are being taken forward. There’s no going back.”

Evoke Galliard, a healthcare communications agency with special expertise in clinical trials communications, brings behavioural science, patient engagement, data and analytics and omnichannel marketing to bear on creating effective clinical trial projects.

“Understanding a community group and their behaviours is central to ensuring that our communications have the right impact,” added Neilen. “So is beginning an open-ended conversation with community or patient advocacy groups. Then it’s a case of knowing where to find them – the channel or space that hard-to-reach participants that are often excluded from clinical trials go to for information. Drawing on that expertise can give trials a head start.”

She underscored that industry has to face challenges of unconscious bias, historical mistrust of research and lack of awareness, as well as the often-significant time commitment asked of patients.

Neilen added: “Increasing diversity is borne of building relationships with underserved groups, which doesn’t occur overnight. Forging community ties comes from listening and responding in a way that recognises and affirms people of all cultures, ethnicity and other diversity factors. There’s still a lot of groundwork to be put in with patient advocacy groups to achieve meaningful and sustainable change.”

“We dismantle the barriers by putting in the work internally – whether that’s learning or unlearning things, changing processes and challenging biases, or challenging external practices – that’s the way we engage with those communities and their trusted leaders.  Diversity shouldn’t be an afterthought. It’s an investment in the credibility of scientific endeavour.”

Neilen advocates the involvement of patients at an early stage so their insights can democratise study design and accelerate recruitment, and she welcomes guidance from patient groups and drug regulators in the EU, UK and US that are reframing clinical trials.

“But the onus remains with the sponsor to work in partnership with communities to address health inequalities and to improve enrolment and retention of participants from minority groups,” she added. “We’ve already seen the US FDA demand post-marketing studies of six approved new molecular entities after raising questions about the inclusivity of clinical trial populations. Going forward, what’s obvious is that demonstrating a diverse participant base will be key for regulatory approval.

“Ultimately, diversity in clinical trials is part of a bigger conversation about health equity for all and its impact on specific ethnic groups who, despite having a disproportionate risk for certain diseases, are significantly under-represented in clinical trials. People everywhere now recognise that irrespective of age, gender or ethnicity, everyone should have the opportunity to participate in and benefit from medical research.”