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ACORI RESEARCH REVIEW: MARCH 2025

Digital Twins in Clinical Research: Accelerating Drug Development With Virtual Patients

Artificial intelligence (AI) continues to transform every aspect of clinical research, so much so that even study participants can now take digital form. Imagine a scenario in which researchers can test a new therapeutic agent in a virtual patient to ascertain its safety and efficacy, protecting a human patient from potential toxicities. This is the essence of a “digital twin”—a concept gaining traction in health care but originally introduced in the 1960s by NASA to simulate spacecraft performance.

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In health care, a digital twin is an exact replica of a real patient, modeled down to the molecular level. As Thomas Klabunde, global head of translational disease modeling at Sanofi, explains, “When generating the virtual patients, we take all of the available data on disease biology, pathophysiology, and known pharmacology, and integrate it into a single computational framework.” This digital twin can then be used to forecast how its counterpart—an actual patient—might respond to a given treatment.

The digital twin’s outcomes help inform clinical decisions for its real-world counterpart, such as the need for additional monitoring to mitigate adverse events. Additionally, real patient data continuously refines the digital twin, optimizing its predictive capabilities. As Mollica et al explain, “The continuous update with real-life data is used to dynamically optimize the predictive performance of the [digital twin].” This bidirectional connection between the digital twin and human patient is a fundamental concept.

For clinical trials, digital twins can accelerate drug development by shortening study timelines and reducing costs. Patient recruitment is often the primary bottleneck in clinical research, particularly for rare diseases. With the use of digital twins, sponsors can reduce enrollment needs and bypass barriers to recruitment. For instance, in Alzheimer research, studies found that the use of digital twins could reduce control arm sizes by 33% and boost statistical power by up to 10%, potentially saving many months of recruitment time and cutting costs considerably. According to Unlearn, a start-up focused on digital twin development, removing 25% of the control group for a clinical trial with 1000 patients “could translate into four to five months of shorter time to complete enrollment in [the] study; and 50%...[could] save you close to a year in terms of your clinical trial timeline.”

Although human patients are still needed for late-phase studies, digital twins can play a pivotal role in early-phase trials by enabling researchers to determine optimal dosing virtually. These virtual counterparts improve research efficiency and promote patient safety by sparing study participants from early-phase treatment toxicities. Furthermore, digital twins could help mitigate data disparities in clinical research by enabling more broad representation of historically underrepresented populations. However, their reliability depends on the quality of the data used to create them, making it critical to avoid amplifying biases from existing datasets.

One of the main challenges in adopting digital twins for clinical research is the need for robust, standardized health care data. The lack of comprehensive data sources and standardization currently limits implementation. But even if high-quality data were widely available, ethical concerns surrounding patient privacy and security must be addressed.

As the use of digital twin technology grows, another significant challenge is the lack of regulatory oversight in the US. Currently, the FDA does not have the resources to adequately qualify the statistical methods used to create digital twins, meaning that much of the process right now is unregulated. If digital twins are to become more universal, then it will be necessary for regulatory bodies to establish protocols for standardization and guidance, not only for the development of the twins, but also for the use of patient data.

Despite the challenges surrounding digital twin technology, it has the potential to provide immense benefits to clinical research and personalized medicine. Human patients can never truly be replaced, but virtual replicas can pave the way for faster and more accessible treatments for real patients.

Understanding Perception: Black Patients’ Perspectives on Barriers to Clinical Trial Participation

Despite widespread efforts to enhance diversity in clinical research, the proportion of Black patients in clinical trials remains low, with only 5% to 7% of trial participants identifying as Black Americans, even though about 14% of the US population is Black. Many barriers to trial participation persist, from logistical and socioeconomic struggles to institutional and systemic hurdles. As we work to improve representation of Black patients in clinical studies, it is essential to understand the challenges from all angles, including where patients are coming from, and what their priorities are. A recent study from the University of Maryland assessed psychosocial factors influencing patients’ decisions to participate in a clinical trial; patients with curative gastrointestinal, thoracic, gynecological, or head and neck cancers across 2 study sites were surveyed about their beliefs.

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Among 138 eligible patients, 97 patients agreed to complete the questionnaire, and 42 patients were Black. Compared to non-Black patients, Black patients were less likely to be married, and more likely to live with family, have a lower median income, and a larger mean Charlson comorbidity index. No significant differences were observed in insurance status, education, employment status, cancer stage, or treatments between the 2 groups. Although both cohorts were equally asked to participate in a clinical study, Black patients were more likely to agree with statements such as “illness/death is determined by God’s will,” “God determines wellness, not research,” “research harms minorities,” “research will provide more information about their health that they would rather not know,” and “There [is] nothing for them or their community to gain by participating in research.”

These findings highlight the significance of religious faith in guiding the medical decision-making of Black patients as well as the general distrust and misunderstanding that Black patients have toward clinical research. According to lead author Charlyn Gomez, “[this] research has identified some really important themes that should be discussed with patients as part of the recruitment process, such as spirituality or faith, as well as recognizing the elephant in the room that is a justifiable mistrust stemming from structural racism and historical practices in clinical trial programs.” Simply discussing goals of the study is not enough; clinicians need to meet patients where they are, acknowledge their beliefs and misgivings, and educate them about the benefits of clinical research for the individual and the community.

Increasing representation of Black patients in clinical studies is the only way to ensure that treatments and interventions are as effective in Black individuals as they are in other populations. When certain groups of patients are underrepresented in a clinical trial, the results of the study will be limited in their applicability and generalizability. For instance, the widely used Oncotype DX test was found to be significantly less accurate for Black women compared with non-Hispanic White women. While the exact racial distribution of tumor samples used to develop Oncotype DX was not reported, the NSABP trial from which tumor samples were derived consisted of only 6% Black patients, and the study validating the prognostic accuracy comprised only 5% Black women. What this shows is that underrepresentation of Black patients—or other marginalized patients—in primary studies leads to suboptimal applicability of the intervention in the end population.

Understanding the perspectives of Black patients gives clinicians insight into what to focus on when developing research recruitment strategies. A previous study addressing similar themes of the role of faith in clinical research identified several key components of interventions seeking to enhance participation of Black individuals in research. Based on focus group discussions with members and leaders of Black churches, the study concluded that interventions should encompass a long-term, relationship-building process; create trust through church services, activities, meals, conversations, and cancer screenings; and include testimonials from patients who have participated in clinical trials. Moving forward, Gomez et al plan to conduct their own focus groups to further delineate the attitudes and beliefs of Black patients toward clinical research, with the goal of designing interventions to improve recruitment of Black patients.

In-Person Clinical Trial Education: A Key Step Toward Closing Trial Participation Gaps Among Native American Patients With Cancer

Cancer is the second leading cause of death in the US and among Native Americans. To ensure the safety and efficacy of new and emerging anticancer therapies and improve outcomes for Native American patients with cancer, it is necessary to diversify clinical trial accrual. However, Native Americans are underrepresented in clinical research, accounting for < 1% of clinical trial participants. A study presented at the 15th Annual Academy of Oncology Nurse and Patient Navigators conference evaluated the effectiveness of an in-person clinical trial education program in promoting understanding and perceptions of clinical trials among Native American patients with cancer.

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In the 2020 census, approximately 3% of the population in the US identified as American Indian or Alaska Native (either alone or in combination with another race group). Nationally, the incidence of certain types of cancer, including lung, colorectal, and kidney cancers, and malignancies associated with infectious agents, are higher among Native Americans than among White populations. The prevalence and mortality associated with cancer varies widely among Native Americans by geographical regions within the US. Overall, though, clinical trial participation among Native Americans with cancer has remained at a disproportionately low level, at around 1%. Lack of clinical trial representation can lead to overgeneralization of study findings and extrapolation of treatment safety/efficacy to underrepresented populations, potentially resulting in suboptimal therapeutic benefit and outcomes.

Developing a Customized and Meaningful Clinical Trial Education Program

To address disparities in trial participation, the American Indian Navigation Program members at the Stephenson Cancer Center in Oklahoma developed an augmented model of navigation that incorporated a clinical trial education (CTE) component. The CTE component, created with input from an indigenous community advisory board, was delivered in person to Native American patients with cancer at their initial navigation visits. Key aspects of clinical trials were covered in the CTE, including types of trials, ethical treatment, informed consent, risks and benefits of participating in trials, and the importance of trials to clinical research. The study evaluated the effectiveness of the CTE over a period of 11 months, from September 2023 to July 2024, using a 6-item pre- and post-CTE survey.

A Closer Look at the Study Participants and Data

The average age of the study participants was 58 years (± 13 years), and a majority were female (57%). Twenty-five different types of cancer were presented in the study population, with prostate cancer being the most common, reported in 11%. Pre- and post-CTE surveys did not indicate any differences in the 13% of patients who had prior clinical trial experience. Neither age nor gender were associated with significant changes in pre-/post-CTE understanding or perception of clinical trials.

Of the 96 participants in the study who completed the pre-/post-CTE surveys, the likelihood of the participants seeking out information on clinical studies and discussion of trials with their clinicians and family/friends increased significantly. CTE also improved participants’ understanding of the importance of trial participation among minority populations. However, certain other key measures were not significantly altered. There was no significant difference in the likelihood of participants searching actively for or joining clinical trials.

The study authors highlighted several areas for future focus, including education that may promote proactive searching and willingness to enroll in clinical trials and assessing whether improved awareness of clinical trials translates into increased participation. They also noted barriers to engagement and that any misgivings or misconceptions about joining clinical trials need to be identified and addressed to close trial participation gaps among Native American patients with cancer.

Barriers to Diversifying Enrollment in Clinical Trials

Clinical trial participation among historically underrepresented groups, including racial/ethnic minority populations, is a long-standing issue in the US. A range of underlying causes contribute to disparities in clinical trial participation, including lack of trust in medical institutions or providers, limited/lack of access to health care facilities/providers, and patient-provider communication challenges related to cultural or language-based factors.

The study highlights the importance of developing educational programs tailored to Native American patients with cancer, with input from community members. Delivering a customized CTE program as part of the initial navigation visit improved participants’ awareness and attitudes about cancer clinical trials. However, the study also highlighted the importance of continued efforts to educate and engage Native Americans with cancer regarding the importance and utility of clinical trials.

The Role of the Clinical Trial Nurse Navigator: Impact on Trial Screening and Enrollment

Effective patient recruitment and enrollment are critical to the success of clinical trials in oncology, yet these processes are often hindered by complex eligibility requirements, patient hesitancy, and logistical barriers. To address these challenges, cancer care teams can leverage the expertise of clinical trial nurse navigators (CTNNs), who streamline screening, improve patient engagement, and facilitate trial participation. Integrating CTNNs into routine oncology care is an underrecognized opportunity to optimize trial enrollment and retention.

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Proactive Eligibility Screening

Clinical trial nurse navigators can identify eligible patients early in their care journey. To optimize the screening and enrollment process, cancer care teams can implement a structured approach that begins with identifying potential participants by systematically reviewing oncology clinic schedules and upcoming appointments. Integrating CTNNs into multidisciplinary team meetings ensures that research opportunities are considered in routine clinical discussions, fostering collaboration between clinical and research teams. Additionally, leveraging electronic health records and clinical decision support tools allows for the proactive identification of potentially eligible patients based on disease characteristics and treatment history. Establishing a direct communication channel between CTNNs and research teams further expedites eligibility assessments and patient referrals, improving efficiency and patient access to clinical trials.

Patient Education and Engagement

Patients often hesitate to participate in clinical trials due to misconceptions or fear. To overcome this challenge, cancer care teams can develop standardized patient education materials that clearly explain trial objectives, risks, and benefits in accessible language. Incorporating CTNNs directly into patient consultations allows for real-time education, enabling them to answer concerns and normalize clinical trials as a viable treatment option. Utilizing patient testimonials and peer support networks can further build trust and confidence in trial participation, making the process more relatable and reassuring. Additionally, creating a structured follow-up system ensures that patients receive ongoing support, addressing their questions and reinforcing their confidence in trial participation throughout their care journey.

Addressing Barriers to Participation

Beyond education, cancer care teams must proactively identify and mitigate barriers that may prevent eligible patients from enrolling. CTNNs can contribute toward this goal by offering logistical support, such as transportation assistance, financial counseling, and flexible scheduling to accommodate patients’ needs. Another useful strategy is the implementation of real-time feedback loops where CTNNs track reasons for patients’ declines and adjust outreach strategies accordingly.

Case Study: University of Florida (UF) Health Cancer Center

UF Health Cancer Center has successfully integrated an oncology clinical trial nurse navigator, Jennifer West, BSN, RN, CCRC, ONN-CG, into its clinical research infrastructure. Over the last 2 years, she has successfully contributed to increasing trial enrollment and retention rates using the following key strategies:

Systematically screening new patient referrals to the oncology and surgery clinics
Proactively communicating potential eligibility to clinical research coordinators
Tracking patient inquiries through the institution’s clinical trial website, NaviGATOR
Identifying and addressing individual patients’ barriers to participation.

By embedding CTNNs within oncology care teams, institutions can significantly improve the efficiency, patient-centeredness, and success of clinical trial enrollment and retention. Cancer care teams are encouraged to adopt these evidence-based strategies to ensure equitable access to innovative treatments while advancing oncology research. For teams looking to implement or optimize a CTNN program, collaboration with institutional leadership and ongoing assessment of navigation strategies are key to sustaining impact and driving continuous improvement in trial participation rates.

Expanding Access to Clinical Trials Through APP Involvement in Rural and Underserved Communities

In recent years, there has been growing recognition of the valuable role advanced practice providers (APPs) play in clinical research, particularly in underserved and rural areas. One such initiative is the ongoing effort to leverage APPs as principal investigators (PIs) in National Cancer Institute (NCI) Community Oncology Research Program (NCORP) trials and involve APPs in protocol design, oversight, and enrollment efforts. To ensure the sustainability of clinical research, adequate provider staffing must also be in place to meet direct patient care needs. These considerations are particularly relevant in locations such as Hawaii and northern Wisconsin, where access to clinical trials is often constrained by geography.

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Paving the Way: Nationwide Survey and NCI Recognition

Beginning in 2020, Christa Braun-Inglis DNP, APRN-Rx, FNP-BC, AOCNP, led efforts to conduct a nationwide survey to better understand opportunities to integrate APPs into clinical trials. This survey of 271 practice groups revealed that while 97% of APPs provide direct clinical care to patients enrolled in clinical trials, only:

37% order investigational drugs;
24% gain consent from patients for clinical trials;
15% participate in institutional oversight/selection of trials;
5% serve as principal investigators; and
3% engage in protocol development.

These findings captured the attention of NCI, prompting policy changes to recognize APPs as PIs, thereby enabling them to lead both industry-sponsored and NCI-funded trials. Another major policy shift occurred in 2021 when the NCI Cancer Therapy Evaluation Program and NCORP issued a memorandum allowing qualified APPs to write patient orders for study agents without requiring a physician investigator’s co-signature. Since these updates, 10 APPs in Hawaii have now successfully enrolled patients in cancer clinical trials through NCORP, focusing on important areas of research such as financial navigation and survivorship.

Hawaii’s Leadership in APP-Driven Research

The University of Hawai‘i Cancer Center has emerged as a key advocate for APP leadership in oncology clinical research, particularly in community settings. Through NCORP funding, the majority of trials conducted in the state are community-based, ensuring increased access to research opportunities for underserved populations. Hawaii’s involvement with SWOG Cancer Research Network has further propelled this movement, leading to the development of the SWOG virtual Advanced Practice Provider (APP) Clinical Research Workshop, which offers 3 continuing medical education credits via the HOPE foundation. This educational program provides an overview of NCI-sponsored clinical research collaboratives, such as the National Clinical Trials Network (NCTN) and NCORP, while also reviewing the processes required for APPs to become nonphysician investigators and the foundations of protocol development.

Mentorship and Internship Programs: Empowering APPs in Research

Hawaii has also implemented a mentorship initiative through an NCORP parent grant, establishing an internship and mentorship program that is already shaping numerous careers. The Mentoring Intervention for Advanced Practice Providers Across the NCTN program is a year-long mentorship intervention designed to engage APPs with SWOG and the NCTN through direct guidance from an experienced peer mentor. This program has successfully engaged providers across the state, positioning them as top recruiters for supportive care trials in Hawaii. This initiative has solidified APPs as integral members of clinical trial enrollment teams, working closely with research coordinators and serving as key stakeholders in the research process.

Meeting Community Needs: The Role of APPs in Rural Health Care

To sustain clinical research efforts, it is necessary to ensure adequate clinical staffing to meet patient care needs, particularly in historically under resourced rural community settings such as rural Wisconsin. Brian Burnette, MD, at Green Bay Oncology has implemented a model where APPs and physicians share a 50/50 split in patient volume, which has significantly improved the clinic’s ability to meet the needs of its community. Expanding the APP workforce in this manner enables providers to see more patients without increasing the number of physicians—a potential way to alleviate the time burden required to implement clinical trials in under resourced rural locations. APPs and physicians collaborate to reach rural communities located 100 to 200 miles away from the hospital by allowing APPs to manage rotating clinic days at different physical locations. Without the help of nurse practitioners and physician assistants, Green Bay Oncology would not be able to adequately serve its patient population.

APPs at Green Bay Oncology are expected to be highly independent and well-trained, undergoing a structured onboarding process that spans 6 to 12 months. This process includes mentorship from an APP and a physician, as well as virtual lectures to ensure all sites have access to necessary training. Physician champions such as Dr Burnette play a crucial role in integrating APPs into the team and fostering their involvement in patient care and clinical trial enrollment. Additionally, Green Bay Oncology has leveraged an online clinical trial search tool that organizes trial opportunities by disease category and disease site, enabling patients and providers to explore trial options more efficiently. The platform also allows users to schedule appointments online to discuss clinical trial opportunities with a member of the multidisciplinary team.

Recognizing Success: High Accrual Rates and National Impact

At the 2024 annual NCORP meeting, 6 APPs were recognized for their high accrual rates in NCI trials, sparking further discussions on how to increase APP participation and success in clinical research. With 46 NCORP sites nationwide and approximately 1,200 registered APPs, opportunities for expanded APP involvement in clinical trials continue to grow. However, the key to success lies in educating administrators and stakeholders about the value APPs bring to sponsored research. By fostering a deeper understanding of their capabilities, access to clinical trials can be expanded, particularly in rural and island communities.

As the demand for additional education and resources for APPs increases, it is clear that expanding APP involvement in clinical research holds immense potential to facilitate clinical trials as part of the standard of care in oncology. These efforts will continue to shape the clinical research landscape, allowing clinical trials to become more accessible to rural and underserved communities.