Lionel Kankeu Fonkoua, MD, discusses the need for diverse representation across cancer clinical trials and research, emphasizes some of the disparities in enrollment criteria for these research efforts, and details some of the planned and ongoing initiatives at the Mayo Clinic that seek to facilitate change in the field.
To effectively advance equity in cancer care, collaborative efforts must focus on improving representation and retention on clinical trials as well as access to care, according to Lionel Aurelien (Lionel) A. Kankeu Fonkoua, MD.
“When it comes to advancing equity in cancer clinical trials and translational research in general, if the goal is to develop products that are going to be benefit all patients, we need to take this seriously and do our part. This is a multifaceted problem [that does] not have a one-size-fits-all [solution],” Fonkoua said in an interview with OncLive® following a Global Liver Institute Webinar. “The solutions are going to come from the vast majority. Different stakeholders need to be actively involved on the federal level, the regulatory level, and the industry level. To my colleagues and providers, what you can do to do your part is ensure that you offer every patient the opportunity to enroll in a clinical trial. That’s probably the most impactful thing that you could do.”
In the interview, Fonkoua, who is a medical oncologist at the Mayo Clinic, in Rochester, Minnesota, discussed the need for diverse representation across cancer clinical trials and research, emphasized some of the disparities in enrollment criteria for these research efforts, and detailed some of the planned and ongoing initiatives at the Mayo Clinic that seek to facilitate change in the field.
Fonkoua: Clinical trials and clinical research is the way that we bring about novel treatments and therapies for all patients. It is critical that what we develop is applicable and usable by all patients, so that they can all benefit. However, one striking statistic is that underrepresented racial and ethnic minorities continue to disproportionately shoulder the burden of cancer and are not represented in clinical trials. For example, African Americans represent about 15% of the cancer population, yet only about 2.9% enroll in clinical trials.
Diving further into that, when looking at prostate cancer, for example, you realize that when compared with their White counterparts, the incidence of prostate cancer in African American men is about 70% higher. However, looking at prostate cancer trials, only about 10% of African American [patients] are represented. This is a disease where the incidence is the highest in the [underrepresented] population, but less than 10% of that population is represented. That’s the gist of problem.
The intent with clinical trials is to develop new treatments. Obviously, you don’t want to harm patients along the way. Therefore, there are very strict and stringent eligibility criteria to minimize that risk for patient participants. Unfortunately, those criteria may create biased results by representing only the healthiest patients, or those from certain racial ethnic backgrounds.
For example, Black patients tend to be disproportionately excluded from trials based on some standard exclusions. Looking to creatinine serum or creatine clearance, which is a known indicator of poor kidney function, Black patients tend to have a lower creatinine clearance than White patients. We need to adjust for that when we establish criteria. A value of 30 mL/min or higher is probably better than just a strict cutoff of 40 mL/min because then you can include some Black patients.
Other factors, such low albumin, a marker of malnutrition, and infectious disease status, are significantly more likely to be found in racial and ethnic minorities; [these patients] are more likely to be malnourished and have comorbid infectious diseases. Those are parameters that are going to inequitably exclude them from clinical trials.
Looking into liver disease or liver cancer, one eligibility criteria is a Child-Pugh score, which has traditionally been used to assess liver function. Most clinical trials exclude patients who have Child-Pugh B or C scores, only including the healthiest patients. However, when you look at real-world [data] and real practice, the majority of our patients do not have a score of Child-Pugh A. Therefore, based on the data that we generate from the drugs that we test, we don’t necessarily know the safety and the efficacy [of these agents] in those who have Child-Pugh B or C scores, which is the majority of the patients that are seen in the real world. We rely on real-world evidence, but not objective, high-level clinical trial data. In a nutshell, those are some of the eligibility criteria that can limit the participation of these underrepresented minorities, as well as the extrapolation of data from clinical trials to the real world.
The disparities are multifaceted, and involve many different parameters, many of them being social determinants of health. These range from health literacy to health behaviors, as well as social support, social needs, and access to health care. When you ask about barriers to access, that’s very important, and part of the problem. Most patients that we see in academic centers [have access because that is] where many of these trials are housed; these minority patients don’t have access. They live in communities where they don’t have the clinical trial infrastructure.
To answer your question, these patients do not have access to basic routine care. They may not have timely and appropriate cancer screening, or [they have] delayed diagnosis, and can potentially miss an opportunity for their best treatment, including a clinical trial. We really need to bridge the divide between their routine, primary care, and clinical research. If we don’t diagnose them, we can’t link them to appropriate care, including the best treatment, which includes clinical trials.
Thankfully, there have been ongoing efforts. More recently, the COVID-19 pandemic brought some of these existing disparities to the forefront [of everyone’s minds]. Therefore, there’s been a lot of ongoing initiatives, even [on the] federal [level]. At the regulatory level, the FDA issued guidance in April 2022 that called for improvement in clinical trial enrollment, [with a focus on including] historically excluded racial and ethnic populations. This FDA draft guidance is out there and is intended mostly for industry sponsors, but also investigators, so that they know what the FDA is expecting in terms of addressing a diversity and inclusion plan when designing clinical trials.
Institutionally, here, at the Mayo Clinic, there have been several internal initiatives. A lot of disease groups have formed community outreach engagement and diversity councils. [We] really aim to have a culturally tailored community outreach, education, and engagement plan to mitigate some of the patient and community level barriers to participation in clinical trials.
There are also training programs for providers to mitigate unconscious provider bias. This is because one barrier to accrual is not offering a patient a clinical trial. There’s a bias from providers, thinking that patients from certain socioeconomic backgrounds may not be able to participate, but there are studies that have shown that when offered, more than half of these patients would take that opportunity. There are training programs, at Mayo Clinic and across institutions. At the 2023 ASCO Annual Meeting, a ‘Just Ask’ training program for providers [was offered] to mitigate that implicit unconscious bias.
Another aspect that’s key is access, ensuring that patients from these communities have access to academic centers where a lot of the clinical trials and the best practices are; that’s an ongoing [challenge]. Many institutions, including the Mayo Clinic, are trying to find ways to facilitate access for routine care to bridge that divide between routine primary care and research. Workforce diversity is also an important aspect of this, to make sure that we have a healthcare workforce that is representative of the patients who we are hoping to attract. That facilitates not just the enrollment, but also the retention of patients in clinical trials.
One key profession that’s emerging is patient navigators. One role that we have here, at the Mayo Clinic, are patient navigators that serve as a bridge between the investigators and the patients. They help patients navigate and understand their unique needs in the context of their psychosocial environment, ensuring sure that we do everything we can to enroll and retain them on the trial.
In terms of workforce diversity, there are several programs out there. One unique program is the Robert A. Winn Diversity in Clinical Trials Award Program, which I was fortunate to be a recipient of. This is a 2-year program that aims to train, develop, and mentor diverse community-oriented researchers and physicians from various backgrounds to help increase the diversity of patients enrolled in clinical trials. This is hoped to enhance the development of therapeutics for all populations.
Moreover, 80% of clinical trials are housed at academic centers, but most patients who actually need them are in the community. There has been an effort to try to decentralize clinical trials to make it easier for patients to access them in the community rather than having to travel and go to unfamiliar territory [for treatment], as this also comes with the burden transportation. These are patients who have cancer; if on top of that they need to deal with transportation barriers and travel, that’s not ideal. Therefore, easing the burden on the patient by decentralizing clinical trials, and bringing the clinical trials to them is something that the Mayo Clinic, as well as a lot of other institutions are doing.
Lastly, in the digital era, we’re trying to use our digital tools to try to automate patient screening and trial matching, to easily screen patients for the trial. [We can then] match them with the right trials at the right institutions. Those are some of the efforts that are ongoing, not just at the Mayo Clinic, but at different institutions across the country.
We notice data suggesting that, when offered, more than half of patients are going to enroll [to clinical trials]. This idea was [enforced] by the ‘Just Ask’ training program offered by ASCO to help mitigate the unconscious bias that may be happening. I encourage all of you to take that and ensure we do our part of at least offering screening and providing patients with the opportunity to enroll in a clinical trial.