The spotlights bathe the pharmaceutical industry with a warm glow of global appreciation as the pandemic is being pushed back by science, manufacturing and supply chain brilliance.

The choruses of approval are richly deserved – from zero to effective vaccines within 12 months is a virtuoso performance – but look closer and the lighting is somewhat flattering.

It picks out the star performers but also illuminates the darker corners where inequalities and lack of diversity in clinical trials are a threat to the industry’s reputation and its ability to provide treatments for all.

When the curtain calls and applause for the industry’s transformative response fade, the danger is that core issues about levels of ethnic diversity in clinical trials may return to the footnotes.

Look behind the rave reviews and consider this fact: out of 1,518 COVID-19 studies registered on clinicaltrials.gov, only six are currently collecting data on ethnicity – less than 0.3%.

This is not just a COVID anomaly; disparity rages across clinical trials in major disease areas where there should be ample opportunity to recruit representative patient cohorts.
The reasons are complex and tangled with social inequalities and, although there are efforts to improve ethnic diversity in clinical trials by widening eligibility criteria and deploying technology, fundamental issues around connecting with minorities and creating an inclusive environment need greater attention.

The Patients as Partners Europe annual conferences are proving to be vital forums for encouraging debate about the need to involve patients in research and trials by bringing together voices from industry, patient groups and advocates, regulators, charities and health agencies.

It is a promising start but Ash Rishi, co-founder of patient engagement agency COUCH Health, witnesses a consistent lack of diversity across ethnicity, gender, age and socio-economic status in current clinical trials. “Around 80% of genome studies are done only on people from a European descendance which is, obviously, quite limited,” he said. “Females are under-represented in therapy areas such as cardiovascular disease and mental health. We have ageing populations, yet the over 65s are hardly represented in clinical trials. There is a lot to address.”

COUCH Health has just published the second issue of its Demand Diversity reports, which is a call to action to tackle the lack of diversity in clinical trials by building evidence and amplifying patient voices. The reports, which feature detailed interviews with patients from minorities, highlight gross under-representation in stark percentage terms and illuminate the cultural drivers, prejudices, mistrust, misunderstandings and myths that stack up as complex, multi-level barriers to equitable clinical trials.

COUCH Health has scored success in supporting trials sponsors by connecting with communities at a deep and personal level, going beyond patient advocacy groups. “Big, national charities do not necessarily have a diverse membership so we need to augment their great work by reaching further to get that patient voice from diverse backgrounds,” added Rishi, a former neuroscientist. “We need to go into communities and spend time understanding all the factors involved.

“For example, a few years back we created clinical trial advertising materials for a Triple Negative Breast Cancer study project and, as the condition adversely impacts the black population, we made it inclusive by featuring a black family, smartly dressed and smiling, on the front cover. We took it into a user-testing workshop and every person there said: ‘They don’t represent me, they are not me. I’ve never gone for a walk in the park dressed in Chinos.’ It was a lightbulb moment for me. We design and create in our offices and think we are doing great work but without testing it on a real audience, it is virtually worthless so we do not work in isolation any more. I think the lack of patient feedback may be an issue across industry.”

Regulators are striving to find ways to encourage more diversity but Rishi added: “There is positive work in the US with initiatives addressing the Hispanic and black communities but Europe is lagging behind,” he said. “When I speak to some clinical trials sponsors, they think it’s a racism issue. It’s not; it’s a health equality issue. There is need for more education and awareness.”

The Demand Diversity Report, which has focused on UK and US markets, calls for a suite of improvements, ranging from being more precise with language and cultural approaches, ensuring patient recruitment materials are relevant and real, and strengthening community outreach to underscore the value of clinical trials through to understanding practical elements such as family commitments and compensation.

Although drawing on a small sample size, the 2021 report conclusion is sobering: “Among the participants, many people expressed their mistrust in pharma, which generally stemmed from racial discrimination, suspicion over the financial motives of the pharmaceutical industry, and/or disparities in the quality of care they receive.”

By not involving more patients from relevant ethnic groups, industry restricts critical insights into diseases and developing therapies for them, limiting treatment and business potential.

Awareness of the significant issues and willingness to tackle them has grown in recent years and Annette Jack, founder of Egality Health, a start-up connecting culturally diverse community organisations and health research and clinical trials, believes industry has an opportunity to connect in ways it has previously underused.

“We are operating in an echo chamber and it feels like the entire system is talking to itself and repeating mistakes,” she said. “We almost have to get everyone in a room together in order to tackle some of the really tricky issues and find practical ways of working together. It is a challenge but I really believe this a great opportunity for industry to expand and improve how it works.

“There are genuine opportunities to build bold, new partnerships and communicate about research and clinical trials in a more effective and engaging way. The sector has to overcome some of the systemic mistrust of the pharmaceutical industry.”

The trials gap is reinforced by a body of evidence that includes a recent review of 12 UK diabetes trials which showed a 5.5% South Asian participation rate despite that group representing 11.2% of the UK type 2 diabetes population.

“There is a broad acceptance that this needs to improve,” added Jack, who was previously chair of the charity, Social Action for Health, and has worked as a policy and public affairs consultant for global pharmaceutical companies. “The regulators and public scrutiny are putting pressure on companies but how does a clinical trial manager, or the research coordinator or even a diversity inclusion lead engage with a broader section of society? The communication channels we are currently using are broken or simply don’t reach that broader spectrum of society.

“We work with a number of community leaders representing different minority ethnic groups across England at the moment. Their feedback is that their communities are willing to be involved in research and see the point of being involved in trials but feel they are not being spoken to about opportunities.”

A blood cancer charity recently reworked its approach to increasing respondents from culturally diverse groups after discovering its previous outreach only drew in white respondents of European descendance.

Jack is an advocate of seeking out the ‘unfiltered patient voice’ to inform communications. “Community organisations have trusted leaders with influence and they can be a conduit for disseminating messages way more effectively,” she said. “You can create new dialogues to engage with the parts of society that just haven’t engaged with health research before.”

Technology and its accelerated uptake during the pandemic are tools that will help recruitment and retention for trials but it cannot be seen as the sole answer to the lack of diversity, she said.

“There is a danger of being swept along by the potential to get more people involved in research by using this wave of technology,” added Jack.

“It helps, of course, but that face-to-face groundwork is still needed, such as getting out explainers and information at grassroots level, attending meetings and collaborating with existing community networks.

“We could get too swept up with the AI-genomics train and one day look back and wonder why 50% of the population are not on board.”

She is, however, hopeful that industry is keyed into the need to address health inequalities and drive new dialogues.

“There are community organisations that have expertise and existing networks that could widen trial engagement. You can build on what they know and their connections to create fair partnerships that have a benefit for all. It’s not reinventing the wheel; it’s about making sure you make strong connections within communities.

“This, after all, has a benefit for pharmaceutical companies beyond being the morally right thing to do as it increases access, adherence and can take cost and waste out of healthcare systems. There is a clear commercial benefit of getting this right.”

Su Smith, Director of Origins Health Insights, feels that pharmaceutical companies are willing to graduate from trademark approaches to clinical trials and embrace innovation across the spectrum of trials design, engagement and endpoints.

“In a sense, the easy route has been taken and not enough has been done to understand how the trial connects with patients,” she said. “Too many have been very academically driven, by doctors and pharma companies, with the aim of reaching the doctors’ objectives rather than the patients’.

“The trial design may make perfect sense to the clinical team but if it means nothing for the patients day-to-day then they will struggle to see the benefits. This means that people don’t engage in the first place or drop out, which is very expensive.

“A lot of patients fall away at informed consent stage because there is a lot of jargon that many don’t understand and don’t want to sign their name to. But, if the patient-related benefits are clearly communicated, then drop-outs should be reduced and that will save a massive amount of the cost of clinical trials, which adds to the drug’s final cost.”

Regulatory pressure, particularly from the FDA and more recently by the MHRA and EMA, is encouraging inclusivity and diversity, she added.

“We heard recently that the FDA responded to one company’s early clinical trial design by saying, basically: ‘You are going to study this product in chubby white guys with no hair so what about we give you a licence for them only?’ They were saying clearly that the trial was not diverse enough and wasn’t acceptable. This is a strong position to adopt and it’s good to see NICE and the EMA now want patient experience data.”

Origins, which helps clients connect with patients on the real-world experiences of living with conditions and responding to treatment, runs studies that provide representative data on gender, race and sexuality.

The pandemic has caused a recalibration with trials being decentralised – enabled by advancing technology – and a greater societal understanding of their place in healthcare.
“Clinical trials have come into focus in the public conscience and many people would now consider a clinical trial because they can see the benefits for themselves and for society,” said Smith. “There is momentum and we will see changes, but it needs to be kept at the front of our minds and we need to challenge all new trials to make sure they are representative of the patient population.
“The focus needs to be on both how we produce drugs that improve people’s health clinically but also have a positive impact on their lives. The time is right that equality and diversity are enshrined in everything we do but particularly in clinical trials.
“It will mean more people are amenable to going on a trial and less will drop out because they are relevant. It will make trials more cost-effective and, ultimately, result in treatments getting to as many people as possible.”
She added: “Trials should be inclusive of the patient experience. That is a starting point and when we think of the patient, it needs to be all patients, not just one.”

Danny Buckland is a journalist specialising in the healthcare industry