ACORI Research Review: December 2024

Artificial Intelligence (AI) Integration Into Clinical Trials
Recent advances in AI technology present an opportunity to transform clinical trial accessibility and equity. The summit facilitated discussions on how AI-powered tools can streamline clinical trial processes. AI applications, such as virtual waiting rooms and protocol assessments, could reduce the administrative burden on coordinators and IT teams, and potentially be integrated into existing electronic health record systems. To drive innovation in clinical trial design and delivery, it is essential to support initiatives that standardize data capture and sharing.

Aligning Inclusion and Exclusion Criteria to the Real World
There is an ongoing need for more flexible inclusion criteria and a reevaluation of patient eligibility guidelines. By considering the experiences of patients and providers more regularly, trial sponsors can design trials that are simultaneously inclusive and scientifically rigorous. Sponsors should also consider scientific and medical necessity when designing a schedule of assessments to ensure potential patients will not be excluded based on ability to access care. Elevating community sites and ensuring the representation of diverse populations in trials are critical steps forward.

Decentralized Clinical Trials: Overcoming Operational Challenges
Decentralized Clinical Trials (DCTs) provide a significant opportunity to expand trial participation, but redesigning trial oversight and introducing flexibility in protocol design remain challenging. Reworking guidelines for principal investigator (PI) oversight and ensuring appropriate funding and budgeting models will be essential to DCT success. Developing a playbook that includes guidance documents, operational advice, and case studies will help streamline the process and build capacity for decentralized models. Additionally, incorporating electronic consents, reducing repetitive assessments, and leveraging real-world data for inclusion/exclusion criteria will enhance trial accessibility while maintaining scientific rigor.

Utilizing Advanced Practice Providers in Clinical Research
The role of advanced practice providers (APPs) in clinical research is evolving rapidly, and it’s crucial to recognize the potential APPs have to enhance the landscape of clinical trials. Whether they are nurse practitioners, physician assistants, or clinical nurse specialists, APPs are increasingly becoming integral to the health care team, but their participation in clinical trials as Principal Investigators (PIs) is still facing barriers that need urgent attention. One of the key advantages of involving APPs is their ability to form deeper connections with patients, which is essential for optimizing trial designs for diverse populations. Summit participants agreed that industry partners need to be engaged to explore these barriers and advocate for APPs to be included as PIs, making it clear that APPs bring a unique set of skills that can meaningfully contribute to clinical trial success. Highlighting successful real-life examples of APP researchers and developing evidence-based guidelines will help to raise awareness of the beneficial role APPs can play in this space.

Conclusion
The ACORI Summit outlined a comprehensive strategy to improve inclusion in oncology clinical trial design. AI innovations can enhance decision-making and foster collaboration across cancer centers to increase trial opportunities and participation. Additionally, integrating APPs as PIs in clinical trials can expand diversity and build capacity in community practices. By refining trial oversight, decentralizing trials, and revisiting restrictive inclusion/exclusion criteria, we can make clinical trials more inclusive, efficient, and patient-centered.

The Scope of the Problem: Limited Access to Trials in Majority of US Counties
According to the study, as of 2022, more than 70% of US counties had no active cancer treatment trials, a gap that disproportionately affects rural and socioeconomically vulnerable communities. While urban centers, particularly those with large medical institutions and cancer centers, offer multiple trial options, vast expanses of nonmetropolitan regions are severely underserved with fewer opportunities for patients to participate in potentially life-saving cancer trials. Even more troubling is the fact that these areas tend to overlap with regions with the highest cancer mortality rates.

The study revealed a troubling statistic: 86% of nonmetropolitan counties lacked any cancer trials, in stark contrast to 44% of metropolitan counties. This geographic divide reflects a broader pattern of inequity in health care access, with vulnerable populations in these rural regions facing significant barriers to participating in cancer clinical trials.

Impact of Geographic Disparities on Patient Access
The lack of access to clinical trials is more than a theoretical issue; there are real consequences for patients with cancer. Cancer trials often provide access to innovative therapeutic approaches that can be crucial for patients who have exhausted conventional treatment options. However, for individuals living far from academic research centers, participating in these trials may be an insurmountable obstacle due to logistical challenges such as long travel distances and limited funds for travel (including overnight stays during treatment).

The study found that 26% of adults aged 55 and older lived more than an hour away from a site with a broad portfolio of active cancer trials. For this patient demographic, which is already most likely to receive a cancer diagnosis, this geographic barrier adds another layer of difficulty on top of significant physical and emotional burdens associated with cancer diagnosis and treatment. In addition to geography, the study found a strong correlation between social vulnerability—a composite measure including factors like income, education, and access to health care—and the availability of clinical trials. Counties with higher levels of social vulnerability were significantly less likely to have cancer trial opportunities available. These regions also tend to have fewer oncologists and less robust health care infrastructure, further exacerbating the challenges faced by patients and caregivers in these areas.

The Road Ahead: Expanding Access to Clinical Trials
The ASCO study emphasizes that simply opening more clinical trials in major cities will not address the issue of geographic inequity. To improve trial infrastructure in underserved, nonmetropolitan areas, the following strategies are suggested:

• Increase the number of community-based research sites: Cancer care sites in underserved counties can become hubs for clinical trials if given the resources, training, and support to host them. Initiatives like the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) have shown success in expanding research into community settings.
• Leverage technology: The rise of telemedicine and remote patient monitoring offer new ways to involve patients in clinical trials without requiring them to travel long distances to do so.
• Use decentralized trial models: In recent years, the oncology research community has increasingly explored decentralized trials that allow patients to participate in studies from their local clinics with their primary oncologist or even from their homes. This flexible, patient-centered option could involve patients otherwise excluded due to distance or logistical challenges.
• Reduce barriers for community-based practices: Many smaller oncology practices face significant financial and logistical barriers to running clinical trials on-site. Efforts to reduce regulatory burden, streamline trial processes, and provide additional funding could make it more feasible for community practices to engage in clinical research.
• Broaden eligibility criteria: Ideally, inclusion/exclusion criteria cited in trial protocols will reflect the real-world diversity of patients with cancer. Expanding eligibility criteria would help to ensure trials are accessible to a broader, more realistic cross-section of patients. This would include patients from rural areas, minority groups, and those with comorbid conditions who are often excluded from traditional trial designs.

Conclusion
The findings of this study underscore the need to improve geographic access to cancer clinical trials across the United States. With over 70% of US counties lacking active clinical trials, there is a clear imperative to act. By focusing on expanding community-based research sites, leveraging modern health care technologies, and implementing thoughtful clinical trial protocols, it is possible to improve geographical access. The research community, policymakers, health care providers, and other multidisciplinary care team members have an ethical obligation to ensure that cancer research is inclusive of all patients.

At first, Avera Cancer Institute tried to adopt another tool, but ultimately found the deployment too cumbersome for their health system. The tool had many superfluous functions that Avera Health did not need. However, experimenting with this platform inspired the institution to develop its own application that would be simpler to use and easier to deploy. Officially launched in early 2024, Avera Cancer Institute’s CancerTrialMatch application is their solution to the dilemma of inefficient trial navigation.

The application, developed in house by data engineers and bioinformaticians, is clean, easy-to-read, and self-explanatory. At the top of the webpage, a global search bar allows providers to enter in a disease state, genetic mutation, or other characteristic, from which the system will generate a list of pertinent trials. There are also advanced filter options where a provider can input other details such as disease stage, trial phase, line of therapy, and more. Every trial listed includes a direct link to the protocol, which was added based on provider feedback. In addition to generating a list of available trials, the application can provide a grid view that displays trials based on different stages of disease and phases of study.

Avera Cancer Institute has about 120 trials of various phases available at a time, all of which are integrated into their CancerTrialMatch application. The institution has also added in trials from just-in-time programs to which it has access. When a trial is added, the study information is extracted directly from clinicaltrials.gov. To determine which new trials to add, the institution holds a weekly research and development meeting where opportunities are presented, and any trials set to open will be incorporated into the database. One helpful piece of feedback that the CancerTrialMatch team received was to list trials in their onboarding phase so that providers could be informed about upcoming trials and have a better idea of which trials to offer in a certain time frame.

The CancerTrialMatch database is regularly updated by members of the clinical regulatory team and cancer research team. As soon as a study or arm of the study is closed or filled, a team member will update the application. Although the updates do require manual entry, the interface is easy enough to use so that keeping the trial status up to date has not been a burden. Overall, the provider feedback for the app has been largely positive and supportive. When the app was initially launched, a few providers were involved in testing the program for a few weeks and since then, the transition from the institution’s old SharePoint system to the application has been smooth and straightforward.

At this point, the institution plans to continue using the application as it is and making minor adjustments when needed. In terms of next steps, a substantial goal would be to automatically match patients to trials based on specific biomarkers or other inclusion criteria. The vision is that providers could either select a patient and obtain a list of applicable trials or select a trial and acquire a list of potentially eligible patients. However, in order to implement this functionality, the institution would need to link the application to the electronic health record or create a separate patient database that would be embedded into the CancerTrialMatch app. Either strategy would be a significant undertaking, and it remains to be seen if the application will be further advanced in this way.

The CancerTrialMatch application has streamlined the clinical trials process at Avera Cancer Institute by drastically reducing the amount of time involved in searching for trials, and thereby enabling providers to enroll patients into trials faster. Most importantly, the application was able to make a significant impact to the institution’s processes without requiring a lot of effort or manpower to establish. As a community cancer center, Avera Cancer Institute encourages other community sites to consider adapting similar low-barrier-to-entry programs to address operational needs, with the ultimate goal of enhancing efficiency in clinical trials and expanding access to clinical research.

Part of the reason for the poor outcomes is that pancreatic cancer is notoriously difficult to treat, and although advancements have been made, the overall treatment landscape has not changed much in the last few decades. Thus, research is vital to the fight against this cancer, especially early on in the course of disease to circumvent the limited treatment options and rapid progression. Patients with pancreatic cancer on clinical trials have also been reported to have better outcomes than those not on trials. However, according to historical data, only 4.5% of patients with pancreatic cancer enroll in clinical trials. So, the question remains—How do we engage more patients in pancreatic cancer research?

The Pancreatic Cancer Action Network (PanCAN), founded in 1999, is the largest nonprofit organization dedicated to pancreatic cancer and seeks to address this issue with its Clinical Trial Finder and Comprehensive Database. In this platform, patients or caregivers can request to be contacted by a PanCAN Patient Services Case Manager to discuss clinical trials or they can enter their information to search the database independently.

The PanCAN Clinical Trial Finder is one of the most comprehensive and up-to-date databases for pancreatic cancer clinical trials in the US. To maintain its repository of trials, PanCAN not only uses clinicaltrials.gov to find new trials, but also receives information directly from trial sponsors about new studies that are being opened. There is also a section on the website where investigators can submit information about their clinical trials. Currently, the PanCAN trials database has about 150 to 180 active phase 1 through phase 3 therapeutic trials.

When a patient is using the PanCAN Clinical Trial Finder to search for a trial, they need to answer a few questions about their disease status. If the patient cannot answer a question at any point, they can request to be contacted by a patient services case manager. Alternatively, patients may request to be contacted directly by a case manager if they do not wish to use the search engine. The case managers come from a variety of science or health care backgrounds and undergo extensive training in pancreatic cancer, clinical research, and the PanCAN Clinical Trial Finder database. There are Spanish-speaking case managers for patients in need of Spanish-speaking services.

Once a case manager is requested, they will reach out to the patient within 1 business day. Based on the patient’s responses, the case manager will review available clinical trials within the database and identify appropriate trials for the patient. Patients are then encouraged to review the list of clinical trials with their oncologists.

If a patient is experiencing logistical challenges during enrollment, the case manager will do their best to help the patient navigate these barriers. For instance, if a patient is not hearing back from a trial site, the case manager will reach out to the sponsor or clinical trial site directly. Case managers can also advise patients about resources for financial assistance when needed. Most recently, PanCAN has developed a navigation program that will provide even more in-depth guidance to patients and caregivers and help them overcome as many barriers to clinical trial participation as possible.

Patients who work directly with a case manager will receive a follow-up within a few weeks to confirm enrollment into a clinical trial or to ascertain the barriers preventing enrollment. Once patients are set up with a trial or their next line of treatment, the case managers serve as an ongoing resource for patients and caregivers should they need to seek out PanCAN resources again.

Throughout the life of the program, the PanCAN Clinical Trial Finder has provided over 100,000 clinical trial search results to patients, caregivers, and health care professionals. Of the individuals who contributed to follow-up surveys regarding their clinical trial status, over 12% of respondents reported enrolling in a clinical trial after using PanCAN’s services. Not only does PanCAN help to expand access to pancreatic cancer trials, but it also provides extensive resources to patients and caregivers about clinical research. Patients and caregivers can reference informative pages featuring commonly asked questions, pancreatic cancer research updates, blog posts, and a variety of educational webinars. Many of these resources are also available in Spanish.

It goes without saying that there is an overwhelming amount of information available about clinical trials, yet—at the same time—not enough easily digestible information. As an organization, PanCAN recognizes and understands the complexities in clinical research and aims to inform patients, caregivers, and providers that they are not alone in navigating this space.

For patients and caregivers, PanCAN Clinical Trial Finder and Comprehensive Database, the PanCAN Patient Services Case Manager, and navigation programs help to empower more patients with pancreatic cancer to enroll into clinical trials. For providers who treat patients with pancreatic cancer, PanCAN can serve as a useful resource to reduce the amount of time spent finding the right trial for the patient and can help investigators scope out the clinical trial landscape. Lastly, but importantly, PanCAN continues to fight against the stigma that clinical trials are a last-line treatment option; for patients with pancreatic cancer, a frontline clinical trial may be the answer to reaching meaningful clinical milestones.

Understanding the barriers to trial participation among Hispanic patients is the first step toward overcoming them. Through various community and patient focus groups, the ALA has identified several important themes within the Hispanic community regarding clinical research. The most obvious is the need for more education about clinical trials. Many Hispanic patients simply do not know what clinical research entails, how they may benefit from trials, and what their options are. A fear of uncertainty about experimental treatments and an inadequate understanding of the purpose of a trial may deter patients from wanting to participate. Thus, it is important to educate patients and caregivers about the risks, benefits, and goals of research. But education alone is not enough; information campaigns must be effective by using Spanish-translated materials and simple language to raise awareness and dispel misconceptions.

From a socioeconomic perspective, logistical barriers such as transportation issues, childcare concerns, lack of access to specialized cancer centers, and lack of insurance can play a significant role in precluding Hispanic patients from participating in trials. Importantly, immigration status can also be a big concern for these patients; one participant in an ALA focus group noted that, “If [Hispanic patients] have to reveal whether they are here legally or not, or they don’t feel safe regarding their immigration status, then they won’t participate in a clinical trial.” Barriers also exist at the physician and institutional levels in the form of unconscious bias, lack of trial awareness, lack of cultural competency, and lack of research staff to sufficiently support Spanish-speaking patients.

An interesting clinical hurdle to trial participation is the recent movement toward precision oncology, especially in lung cancer. While advancements in precision medicine are critical to the oncology treatment landscape, the emphasis on precision medicine can also unintentionally gatekeep against patients who have reduced access to molecular tumor testing. Patients with lung cancer who have undergone next-generation sequencing are twice as likely to participate in a trial compared with those who have not. It has been reported that Hispanic patients receive biomarker and molecular tumor testing at rates around 22% compared to more than 30% for Non-Hispanic Whites, thus contributing to their underrepresentation in precision oncology trials. Molecularly-driven clinical trials should continue to be a focus in oncology, but efforts must be made to expand access to biomarker and tumor testing in underrepresented patients to promote equitable inclusion in precision oncology trials.

Mitigating barriers to trial participation requires a multipronged approach. From an institutional standpoint, physicians and research staff need to be educated, not only about available trials, but about cultural competency as well. In general, patients report more trust toward their physicians and are more willing to seek and share information when their physicians demonstrate motivation to learn about other cultures. It is also imperative to develop Spanish-language educational materials that are written at appropriate health literacy levels. One study notes that merely translating a consent form from English to Spanish is not enough; the consent should be worded in a way that clearly conveys the general concepts. Moreover, Spanish-speaking research staff should be available to answer questions and explain concepts when needed.

Massey Cancer Center at Virginia Commonwealth University has shared strategies that they have used to enhance trial accrual of Hispanic patients, such as employing dedicated resource specialists and social workers to assist with logistical hurdles of transportation issues, childcare needs, and legal assistance. They have also prioritized communication training for all providers to ensure that a provider’s phrasing does not isolate or inadvertently discourage patients from participating in a trial. To accelerate the process of matching patients with appropriate trials, the institution piloted an automated screening tool that greatly reduced the amount of time necessary to evaluate patients and enabled all patients in the system to have an opportunity for evaluation.

Beyond the institutional level, community outreach is an integral part of raising awareness about clinical research in the Hispanic community. At the Mays Cancer Center in San Antonio, community outreach efforts have utilized Spanish-language television, Spanish-language daily newspapers, and Spanish radio stations to provide information about clinical research. Aligning with community organizations (eg, local church groups), is another useful strategy to raise awareness in specific patient populations.

As lung cancer research continues to evolve, it is paramount that all groups of patients have equal access to novel therapies and treatment approaches. Hispanic patients have long been underrepresented in lung cancer trials, resulting in suboptimal outcomes compared to Non-Hispanic White patients. It is time to turn the tide for these patients and actively work toward dismantling the barriers that preclude them from participating in clinical trials.

Mission and Purpose
Despite therapeutic advancements in cancer care, significant racial disparities persist in clinical trial access, referral, enrollment, and patient outcomes. The ACT WONDER²S study is designed to address these disparities by leveraging a community-centered approach that prioritizes patient and provider education as well as digital tools to facilitate the clinical trial referral process. At its core, the study is testing the effectiveness of an intervention delivered via community health educator (CHE)-led outreach and digital technology for the patient, community physician, and cancer center physician/research staff.

Study Design, Methodology, and Outcome Measures
The ACT WONDER²S study employs a cluster-stratified randomized design, informed by the Socio-ecological Model (SEM). This multilevel approach considers individual, community, and systemic factors influencing real-world clinical trial participation. The Precision Engagement Tool (PET) is a geospatial mapping resource that has enabled the research team to identify 14 priority zones, which were randomized into intervention and control groups. The first 7 priority zones will receive the full suite of interventions, while the remaining 7 will act as controls (receiving no interventions). The priority zones include underserved communities within Moffitt’s catchment area with a high demographic representation of Black and Hispanic individuals. Local physicians (including community oncologists and primary care physicians), and community organizations (eg, churches, nonprofits, etc) are also identified within each region. All study interventions were developed utilizing the following guiding principles:

• Learner Verification: ensures materials are accessible and resonate with the target audience
• User-Centered Design (UCD): focuses on usability of digital tools from the end-user perspective.

Study outcomes will include the percentage of Black and Hispanic patients referred to and enrolled in NCI-sponsored therapeutic clinical trials at Moffitt Cancer Center. Sources of data include Oncore (measures trial enrollment), Moffitt Cancer Registry (records patient demographics and cancer types), and the Soarian Scheduling System (quantifies referrals to Moffitt). Outcomes linked to interventions are evaluated using the RE-AIM QuEST framework, which assesses reach, effectiveness, adoption, implementation, and maintenance for systematic translation at each level.

Example Interventions
All 16 study interventions are classified as either community and education components or digital tools. Examples of digital tools include:

• Trial Connect Portal: establishes a direct line of communication between community physicians and Moffitt clinical trials staff, streamlining the referral process.
• Choices DA: a patient-centered decision-aid platform designed to inform patients about clinical trials, dispel myths, and help patients clarify their values and preferences when considering trial participation.

Examples of provider and patient-focused educational initiatives include:

• Community Clinical Trials Education: designed for a lay audience, these educational sessions contain facts and myths about clinical trials, review risks and benefits of participation, highlight the importance of diversity in clinical research, and provide useful clinical trial resources.
• Implicit Bias Training: 750 Moffitt physicians and clinical research staff members were offered the Just Ask! Increasing Diversity in Cancer Clinical Research training developed by ACCC. Additionally, continuing medical education (CME) course opportunities were provided to community physicians focusing on implicit bias in the context of clinical trials. Information about the Trial Connect Portal was included within the CME course itself.

A Model for Nationwide Change
The ACT WONDER²S study serves as a powerful model for nationwide change in addressing racial disparities in clinical trial participation. The cluster randomized study design will provide strategic evidence-based insights into which interventions should be utilized as meaningful drivers of change. Using the multilevel combination of community-driven engagement, educational initiatives, and cutting-edge digital tools, this innovative approach demonstrates the potential for health systems to dismantle barriers to equity in oncology research. As the study progresses, findings at the 6-month and 2-year time points have the potential to inform national efforts, setting a new standard for inclusive clinical trial practices. Eager to share her insight, ACT WONDER²S research scientist Lindsay Fuzzell, PhD, is happy to elaborate on details of the program with organizations that could be impacted by the study’s findings. She can be reached at: lindsay.fuzzell@moffitt.org.