We are in an era of evaluation and, while it may not be as significant to human development as the Stone, Bronze and Iron Ages, it could be the time when clinical trials become truly diverse and provide medicine with major advances.
The clinical trials system has often been labelled prehistoric due to an inherent lack of inclusion and an inability to represent wider populations, but it stands on the brink of transformation.
A groundswell of intent from pharmaceutical companies and regulators is fusing with learnings gained from the pandemic to create an inflexion point where healthcare disparities and inequalities start to reduce. It also signals fresh potential for existing drugs and new generations of cell and gene therapies to reach more patients.
The stats are still stacked against diversity: the FDA reported that, although 40% of the US population is from minority racial and ethnic groups, an overwhelming 75% of 32,000 participants in the trials of 53 approved novel drugs were white. Teva, in its quest to promote greater diversity, underscored the issue by reporting on its website: ‘Only 30% of the participants were over 65 years of age and more than half of the patients were located in the US.’
But pharma is moving, and at pace. Europe’s recent Clinical Trials Regulations enshrine the need for diversity in clinical trials while GSK and Bristol-Myers Squibb are among companies laying down templates that improve connections with communities that can feel alienated from healthcare systems.
“If people don’t feel included, represented and even welcome, they’re less likely to play a part in healthcare and are less likely to have a voice,” said Ash Rishi, founder of COUCH Health, a creative health patient engagement agency with global reach.
“This leads to them feeling disconnected, so they are even less likely to put pressure on the system to improve their representation.
“There are a lot of factors to consider, but that shouldn’t be a barrier, and nor should cost. If you use cost as a reason not to explore diversity and equity in clinical trials then you will face a cost impact further down the line.”
Building trust
The National Academies of Sciences, Engineering and Medicine reported to the US Congress that failure to have diverse clinical trials could cost industry a huge loss of revenue and shackle the advance of innovative therapies, as well as contributing to poor health and premature deaths.
The hurdles of mistrust, poor logistics and inflexible criteria are not insurmountable according to Rishi, who said: “Change is happening and we are getting a lot of requests from companies looking for a greater understanding of what they need to do and how they need to reach different communities.
“We are also working on projects in communities that build trust and have embarked on benchmark research in this area and it will be illuminating to see the results over the next five to ten years as diversity, equity and inclusion becomes even more an integral part of clinical trials.
“Diversity and inclusion are now mentioned all over the healthcare landscape but it cannot be restricted to slogans and statements; there has to be an active mission to achieve deeper understanding. Blacking out social media for Black Lives Matter is a great social statement but it needs to go beyond that.
“Trust is still a big concern among some communities, so authenticity is important if we want to achieve something meaningful. We need to get our insights directly from these communities, the patients, and not from our assumptions of what they might think and want. Companies that do more outreach will generate more trust.”
Greater voice for minority groups
COUCH, whose mantra is ‘to make health more human for everyone’, specialises in amplifying the voices of patients and communities and has just commissioned global studies to generate more practical evidence on how clinical trials can be recalibrated.
“It is exciting and our clients do have a long- term strategy, which we will see becoming an essential part of clinical trials in the coming years,” says Rishi. “A lot of information and education still needs to be shared but I feel positive about the direction industry is taking.
“For example, one pharma company has changed its lexicon to make it more inclusive. It dropped the word ‘burden’ from its language because it was not how people see their conditions. Those small actions all add up to a more inclusive environment.”
He also believes that greater research and attention needs to be employed in creating clinical trials for people with multiple comorbidities rather than a single condition.
“The world is changing and different minorities and ethnic groups are getting a greater voice,” Rishi added. “It is our job to understand their concerns and change systems so that everyone has fair access to health.”
Sarah Alwardt, who leads healthcare consultants Avalere Health’s Evidence and Strategy practice, observed that industry is recognising the scale of the diversity problem. “Industry understands that it will not solve this by saying nice words because that doesn’t translate to anything,” she said.
“But it is a big challenge. In oncology, for instance, you have only 4% of the patient population participating in clinical trials, yet the moment a drug is approved it can apply to 100% of the patient population, even those that were never contemplated, tested or represented in the regulatory decision.
“We cannot afford not to change because industry will end up paying for the deficiencies at some point. Take a trial for triple negative breast cancer, for example, that was done predominantly on white women when it disproportionately affects black women. The diversity wasn’t there in the trial so the drug only gets used by white women, not black women. The manufacturer would lose out on sales as well as the opportunity to help a community in need.
“Health equity is a business problem.”
Practical steps in the real world
Real-world evidence, powered by digital and technology advances, is already a powerful tool for marginalised and deprived communities and it has a pivotal role to play in clinical trials.
“I’m a real-world evidence evangelist,” added Alwardt. “Using evidence about how a drug, a condition and comorbidities affect people in real life will help us reach and understand broader populations than the narrow clinical trial selection, and that is an exciting prospect.”
The FDA’s insistence of more real-world evidence being included in clinical trials is a major advance and Alwardt advocates a series of practical steps to make it easier for patients to participate in trials.
“Concerns such as transportation and location are important,” she said. “If you are a single mother with two children and the treatment centre is 100 miles away from where you live, then it might as well be on Mars. There is a lot to be said for looking into trial design and having decentralised trials.
“We can consider having one of the two arms of a clinical trial as real-world evidence or a historical data arm. The FDA has already approved drugs that way and has shown a certain willingness to continue looking at that option. But industry should address how it will use real-world data from the very beginning of the development cycle because patient-reported outcomes, patient value and shared decision-making tend not to be considered as evidence until much later on.”
Alwardt believes in using every scrap of intelligence, information and data available to improve representation. “We should bring in social scientists, look at everything that epidemiologists have done, bring in community leaders and address their issues from a position of knowledge rather than producing a leaflet that says how good our trial is,” she added. “I believe there is a huge opportunity to move population health forward.
“Clinical trials will still be the gold standard but we can be more inclusive, add diversity and use existing data to conquer some of the issues that hold us back. I’m excited that things are coming together now.”
