Choosing Community-Based Centers To Boost Trial Diversity, Expand Patient Access
A conversation with Cullinan Oncology Chief Medical Officer Jeffrey Jones, MD, MPH, MBA
Enrolling a patient population in a clinical trial that’s representative of the patient population intended to be treated with the investigational drug is by all accounts every pharma’s best intention. At the same time, it’s no simple feat. Challenges persist, whether it’s a sponsor or CRO’s ability to choose appropriate sites, a site’s ability to fulfill its promised enrollment numbers, or patients’ ability to access, commit to, and complete a study.
For his part, Jeffrey Jones, MD, MPH, MBA, chief medical officer at Cullinan Oncology, is aiming to alleviate some of the burden by incorporating community-based centers into its oncology trials. In this Q&A, Jones discusses conducting trials in community-based centers to extend participation to underserved populations, partnering with centers that have experience in enrolling and supporting diverse patient populations, and adapting trial designs to match real-world patient care patterns.
Clinical Leader: Clinical trials have often been conducted in collaboration with academic institutions, but Cullinan has been working to expand its trials to more community-based centers. What qualities do these sites have that make this a priority for Cullinan?
Jeffrey Jones, MD, MPH, MBA: Even when academic centers are in large metropolitan areas, geographic proximity alone cannot ensure that a diverse patient population will access state-of-the-art care, including investigational therapies. If patients don’t receive care at academic centers where we have traditionally conducted trials, we must extend our clinical site footprint to be more inclusive. Patients residing in areas without ready access to subspecialty care often face both geographic and resource limitations that may leave them unwilling or even unable to travel to comprehensive cancer centers. To optimize care for these patients, we must bring clinical studies to the centers where patients receive care, which are primarily community-based sites.
Researchers have sometimes avoided community-based sites for trials because of perceived limitations of clinical research infrastructure, most notably trained personnel and, sometimes, specialized equipment needed to deliver investigational therapies or collect and process patient specimens. However, even early-phase clinical trials can be effectively conducted at a diverse range of sites when feasibility of implementation is considered at the design stage. By utilizing community-based sites, we can reach patients where they live, minimizing the logistical challenges patients may face when they need to travel to receive care, such as taking time off work or navigating childcare, paying for gas or travel expenses, and potentially having to pay for accommodation for an extended period near the center where they are receiving treatment. Designing trials that satisfy scientific objectives while affording ease of implementation is also important when enrolling patients at centers with resource constraints not typical for large academic centers. Site selection, then, is of utmost importance to ensure we are doing everything possible to extend the potential benefits of investigational therapies to the broadest group of patients and, ultimately, optimize care for all patients with cancer.
What underserved populations are you targeting that might not be served by academic institutions? In other words, who can you reach better through these community sites than the academic sites?
Ideally, the patient population we enroll in clinical trials should reflect the demographics of the patient population with the disease under study. We know that some patients from traditionally underserved populations may not seek care at comprehensive cancer centers, so we need to better understand where these patients typically receive care and extend our clinical site footprint to be more inclusive. For example, we are studying one of our investigational therapies in endometrial cancer. We know that the incidence of endometrial cancer, particularly the aggressive subtypes, is rising across all racial and ethnic groups, but there is a clear disparity, with increased incidence and poorer survival in certain populations.
The greatest annual percent change is in non-Hispanic Black and Asian women, about 2.5% for both. Non-Hispanic Black women have significantly higher incidence rates of aggressive endometrial cancers compared with non-Hispanic White women, and for almost every stage and subtype, the five-year survival rate for non-Hispanic Black women is significantly less than that of non-Hispanic White women. Endometrial cancer is a disease for which it is imperative we study the relevant population from the earliest stages of development to ensure our data are generalizable to the patient population most affected by the disease. Fortunately, we are partnering with both academic and community-based investigators for whom enrollment of a diverse patient population is a priority.
When identifying clinical trial sites to engage, what criteria or data do you use to determine a site’s ability to provide a diverse patient population?
We regularly engage with investigators who are committed to enrolling a diverse group of patients. Sometimes that is as simple as geographic diversity, ensuring that we are selecting sites in areas where we are more likely to access a diverse patient population. For example, one of our trials is enrolling patients with advanced endometrial and cervical cancers. We know that these diseases disproportionately affect patients from historically underserved patient populations, specifically non-Hispanic Black women. But ensuring these patients have access to clinical trials extends beyond demographic data and ZIP code analyses and means selecting collaborating sites and investigators who have forged long-term, trusted relationships with the diverse communities they serve. We try to be deliberate in seeking partners for whom clinical trial diversity is a priority and where their centers have dedicated resources (financial, organizational, staffing) to satisfy this objective. While most investigators and centers have the best of intentions, results speak volumes, so during the site qualification process we query to learn specific instances where they have been successful. This provides reassurance that the site can deliver against expectations, while helping us better understand the circumstances that predict success.
Even when selecting ideal site partners, barriers to patient enrollment can still exist. What are some of the ways Cullinan is solving patient challenges like reliable transportation and housing?
One of the best ways to tackle barriers to patient enrollment is by working with investigators and patient groups who are trusted partners in the communities we want to reach, and who can help us understand patients’ needs. For example, we work with some academic centers that extend access to clinical trials at their community-based satellite sites. In that case, we’re able to benefit from the resources of an academic institution while bringing trials to patients where they live. However, many community-based practice networks are similarly sophisticated as academic centers today, allowing us to leverage central administration of studies open at multiple community-based sites that don’t have ties to an academic institution. This helps limit the administrative burdens both for the sites and for Cullinan and brings trials to patients where they live.
We also partner with clinicians who have the necessary support services to facilitate trial participation -- transportation, housing, patient navigators for a complicated healthcare system, patient peer partners, and more. Sometimes this support is financial – reimbursing patients for the travel expenses they incur – other times it can be more specific travel assistance, such as helping patients identify lodging options near the treatment center that are suitable for their personal circumstances, as well as other necessary support services in areas unfamiliar to the patients. These clinicians know their communities and have an infrastructure in place to enable diverse patient populations to participate in trials.
Patient centricity has become a hallmark of conversations around trial design. In what ways does Cullinan design a protocol that adapts to patient lifestyles and accommodates their care expectations?
From the beginning, our team ensures we’re developing treatments that can be administered in a variety of practice settings. Some modalities, such as bi-specific and monoclonal antibodies, are inherently more community-friendly cellular therapies. Another strategy is to keep enrollment criteria broad for early-stage trials, narrowing the criteria as we learn more about how a treatment works. At Cullinan, we have a pipeline of modality-agnostic assets with potential for broad applicability across different patient populations and diverse clinical practice settings. When designing clinical trials, we also consider the frequency of visits for clinical evaluation, laboratory tests, and imaging studies. We always seek to strike a balance between collecting the data we need to make good development decisions, while also keeping the patient in mind and considering the feasibility of trial participation for a diverse range of sites and patients.
Time and time again, reports show that the diversity of patients enrolled in clinical trials does not match that of the patient population who will eventually need the therapeutic being studied. And it seems few sponsors are exempt from that challenge. In Cullinan’s studies, what patient enrollment gaps exist, and how are they being addressed?
There’s a scientific imperative to enroll a patient population for clinical trials that is most reflective of the population with the disease. For one of our programs, we identified an early efficacy signal in patients with higher-risk endometrial cancer. Our initial site footprint for this study did not include sites where we were mostly likely to enroll the diverse patient population representative of this disease, specifically, non-Hispanic Black women, and we quickly worked to remedy that situation. Similarly, our zipalertinib program targets exon20 insertion mutation non-small cell lung cancer, a disease that is more frequent in Asian and Asian American patients. In our trials for zipalertinib, we’ve identified trial sites on the West Coast and in metropolitan areas that are more likely to treat Asian American patients with lung cancer. We’ve also expanded sites in Southeast Asia to meet our target demographic for these trials.
About The Expert:
Jeffrey Jones, MD, MPH, MBA, is chief medical officer of Cullinan Oncology, a biopharmaceutical company focused on creating new standards of care for patients with cancer. With over 15 years of clinical development experience in academia and industry, Jones is an expert in clinical trial design and recruitment, drug development, medical education, and healthcare management. At Cullinan Oncology, Jones manages a diverse pipeline of clinical-stage programs that span therapeutic areas and modalities. His background as a clinician and extensive experience in medicine result in a dynamic approach to R&D in his current role, with research that starts by asking what physicians need to adequately care for patients. Jones holds an MBA from The Ohio State University Fisher College of Business, an MPH from the University of Texas School of Public Health, and an MD from the University of Michigan Medical School, completing his residency in internal medicine at McGill University.