Diversity by design: the importance of DE&I in oncology trials

“First, do no harm”; is an ethical axiom at the heart of medical research; physicians worldwide pledge to uphold the oath to serve patients. Clinical trials offer a practical example of how this value can be realised in drug development, reinforcing the importance of understanding and evaluating the safety and efficacy of new therapies in a controlled environment (clinical trials) before they reach patients at large.

However, within this clinical trial landscape there remains a significant ethical and scientific gap. For many years, clinical trials in oncology have almost exclusively catered to specific demographics when selecting trial subjects – namely White participants – a stark contrast to the reality of the diverse racial and ethnic populations that make up society – and, often, actual epidemiology and disease burden.

Under-representation of diverse populations in cancer clinical trials is a well-documented and unnecessary barrier to understanding the true safety and efficacy of novel treatments across population subgroups. Amid a growing body of evidence to support the need for Diversity, Equity, and Inclusion (DE&I) in oncology, there is a groundswell of final acknowledgement, awareness and, action that diversity is not an optional luxury in clinical research. It is an imperative.

“By not allowing everybody to have equal access, independent of who you are, where you live, what you look like, or what your ethnic background is, we’re exacerbating the still significant lack of health equity in our medical systems,” explains Nick Kenny, chief scientific officer at Syneos Health.

Understanding barriers to diversity in oncology trials

Despite ongoing calls (for decades) to address disparities in health and healthcare in the US, health inequity remains a prominent and unnecessary barrier to treatment for patients in marginalised communities. These discrepancies are mirrored in the clinical trial landscape, where traditional study designs – through lack of intentional design and awareness – cater disproportionately to the medical needs of White participants when evaluating the safety and efficacy of a potential new treatments.

The result of this conventional approach is an oncology trial landscape that, while not actively excluding participants along racial, gender, sexual, or age lines, unintentionally creates barriers to access for diverse populations – and a significant scientific and medical gap in our knowledge of how these new medicines will truly behave in the real world.

“Just asking people to join clinical trials is such a significant issue in particular communities,” explains Dr Stephen Keith, senior medical director at Syneos Health. “If you ask African-American or Hispanic patients if they want to participate in clinical trials, more than half will say: ‘Yes, we would like to do that’, but if you’re not asked, you can never get the opportunity.

“This is not just a moral issue,” he continues. “This is scientifically and clinically significant because if a drug is labelled for an indication across all population groups, but yet you’ve not demonstrated the safety and effectiveness in at least most population groups, we’re really doing a disservice to our patient population.”

According to Dr Keith, patients in underserved communities face significant hurdles along the path to inclusion in oncology trials. For example, even if an individual is invited to participate in oncology research, that study may not be easy to reach in their community, or they may not be granted leave from work for the necessary time required for the trial and its assessments. When considered in isolation, such socio-economic barriers may seem relatively minor, but these factors result in well documented lower enrolment in studies and tragically low representation.

“If you look at the demographics of patients who were enrolled in all of the immuno-oncology drugs that have swept the market in the past few years, in some instances, less than 1% of those patients were minorities in the US,” says Kenny. “Here is a complete class of drugs with novel mechanisms that are now in use across a broad range of cancers, and we actually don’t really know how they’re going to behave in specific patient sub-groups…leading to a blind spot of concern. We just don’t know what we don’t know.”

Active listening: earning the trust of patients

Addressing the current imbalance in the US healthcare ecosystem cannot be achieved by the biopharmaceutical industry or healthcare providers alone. For both Drs Keith and Kenny, it is essential to include underserved communities in the conversation and actively listen to their lived experience and insight into systemic issues that prevent underrepresented communities from not only enrolling in clinical trials but in accessing healthcare in general.

“As an industry, we need to listen to patients,” says Kenny. “We need patients to educate us about what they see when they look at what we do, what they don’t understand, and what the barriers are.

“Soliciting these opinions and actually feeding the information into trial designs is critical,” he continues. “You have to have this unique mindset that intentionally drives you to challenge all your prior assumptions and say, ‘Can this protocol actually get to the right people? When I get it there, will they actually get in?’”

Here, a process of what Kenny calls ‘reverse-education’ can benefit both patients and industry experts. By actively listening to the community early in the trial development stage, companies can leverage a broader understanding of participant needs when selecting research sites and developing trial protocols.

“In drug development, the pressure is on to get patients into a trial, find out if the drug works, and either kill it or put it onto the market. Where and how you found those patients really was not given a whole lot of attention. It was all: ‘we need to get this trial done and evaluate things quickly’,” says Dr Keith.

“We need to locate sites within underserved communities or at least adjacent to those communities and facilitate physical access, just like all other patients involved in the trial. We need to make sure that physicians in those communities know about studies and know how to say: ‘Hey, this minority patient with breast cancer may be eligible for this study’.”

However, as Drs Keith and Kenny stress, there is no one single “one-step” solution to solving health inequity in cancer trials. Establishing sustainable and meaningful change requires dedicated time and effort to earn the trust of underserved communities and develop meaningful symbiotic relationships, an element that has been missing in previous efforts to improve diversity in clinical research.

“Recently, we’ve seen a convergence of social awareness, social injustice, evidence generation, and rapidly evolving high priority medicines that finally have gotten to this point,” explains Kenny. “It is a matter of trust and long-term investment. This has to be a grassroots effort by all of us, with all the people in our organisation, the customers we work with, and the sites we work with pulling together to achieve this goal.”

Creating a multi-dimensional ecosystem

Of course, to effect change among patient communities, companies must also elevate DE&I within the healthcare and biopharma workforce. Facilitating a diverse group of stakeholders creates a complete jigsaw puzzle comprised of different experiences and backgrounds, which come together to reveal a broader understanding of the clinical trial experience.

“When we talk about community too, that includes the staff at the hospital,” explains Dr Keith. “When we think about trust, people trust people who look and behave and act like them, who have a sense of community with them. That’s equally true, whether it’s your study nurse or your physician.

“We see institutions and foundations investing heavily in training minority investigators and nurses, as well as top-down management from institutions to promote diversity within their own staff, features that have proven extremely successful where they are implemented.”

The necessity of DE&I in the trial space has not escaped the eye of regulators in the US. As Drs Keith and Kenny note, seeing key diversity and inclusion priorities for Syneos Health reflected in recent clinical trial guidance from the US Food and Drug Administration (FDA) is an encouraging sign that the industry is on the right track to ensuring that all those who want to participate in oncology trials are given the opportunity to do so.

“It was a bit eye-popping when we compare it to other guidance that we’ve seen because it really is the first time that the FDA has been prescriptive about what to do. The regulator has never done that before,” explains Dr Keith.

“To be able to incorporate DE&I factors into our trial design and intentional efforts, and then to see different components of our strategy mirrored in the FDA draft guidance, it was a validation of we’re on to something, we’re on the right track,” agrees Kenny.

Driving actionable change for future cancer patients

Enhancing diversity in clinical trial populations will not happen overnight. There is no switch to flip that will immediately improve inclusivity; instead, the path to diversity in the trial space is made up of dedicated and deliberate efforts to reach out to and engage underserved communities.

Recent developments, including the publication of updated FDA guidelines, are a positive sign that DE&I is moving from the fringe of healthcare to stand as a vital pillar of the drug and treatment development landscape. But to be truly realised, stakeholders across oncology must commit to challenging the accepted norms of traditional practices, using the insights provided by underserved communities to shape a system that benefits the many, not just the few.

“We need to do a better job,” concludes Dr Keith. “I just hope we can sustain this enthusiasm and translate it into a permanent commitment instead of just a fashionable thing to do.”

“It is a matter of trust and long-term investment, and not just around the particular individual study. You have to invest in those institutions and organisations within the community that people trust. That’s our challenge.”

Nick Kenny, chief scientific officer, Syneos Health, has over 21 years of experience in clinical development and consulting. Passionate about rapidly moving compelling new science for unmet medical needs through the development process to arrive at early and innovative decisions.

Nick has been with the company since 2006. He grew and led the Oncology team until moving to the CSO role in 2018 where he now oversees the Medical Team for Syneos Health, the Consortia Models for e.g. Rare Diseases, Cell and Gene Therapy, Patient Voice. Leads our Patient Diversity in Clinical Trials initiatives and is an executive leader on the DE&I Council. Senior representative to the Forum for Collaborative Research. Early career in biomedical research in the UK, US and Canada. Faculty appointment at the University of Vermont Medical School for several years. Past experience in biopharma consulting. Nick is a Cancer survivor (Hodgkin’s Lymphoma). He is also president, board of directors, Hospice of Wake County.

Stephen Keith, MD, MSPH, senior medical director, Syneos Health has over 25 years of experience in biopharma industry in vaccines development (e.g. influenza Type B, meningococcal, pneumococcal, and Group B Strep. as well as diphtheria, tetanus, pertussis, and inactivated polio vaccines). Joined Syneos Health in 2018 as medical leader and also serves leadership role with Patient Diversity initiatives.

Previously, held C-level positions at 3 biotech companies, and was a general partner in a life sciences venture capital organisation.

Prior to entering the pharmaceutical industry, served as health policy advisor to the U.S. Senate Committee on Labor and Human Resources, under Senator Edward M. Kennedy. MD Pediatrician by training /practice, and RW Johnson Clinical Scholar at UCLA with qualifications in Public Health. Faculty member at the Charles Drew Medical School & UCLA School of Medicine (Pediatrics). Fellow of the Academy of Pediatrics, and Diplomate of the American Board of Pediatrics.Board of Directors of National Medical Fellowships, and Community Health Charities.

Syneos Health® (Nasdaq:SYNH) is the only fully integrated biopharmaceutical solutions organization purpose-built to accelerate customer success. We lead with a product development mindset, strategically blending clinical development, medical affairs and commercial capabilities to address modern market realities.

To learn more about how we are Shortening the distance from lab to life®, visit syneoshealth.com or subscribe to our podcast. If you would like to get in contact with someone from Syneos Health® click here.

Don’t miss your complimentary subscription to Deep Dive and our newsletter