When clinical research professionals think about clinical trials, two types often come to mind: those for critically ill patients, where experimental treatments offer a final chance at survival, and those involving healthy volunteers who participate out of altruism, curiosity, or financial incentives. However, a significant and equally important segment of clinical trials lies in the middle: studies targeting individuals managing chronic conditions or living with the risk of future disease. These trials aim to improve quality of life, refine prevention strategies, and build knowledge for future care. For these patient populations, participating involves profoundly personal and practical psychosocial considerations. Unlike last-resort trials, these studies do carry hope for immediate, lifesaving outcomes. Instead, they require participants to weigh long-term, sometimes intangible benefits against immediate disruptions to their lives. The question participants face isn't just, "Will this help me?" but also, "Is this worth the trouble?"
A systematic review by Sheridan et al. highlighted several key motivations for clinical trial participation, including perceived personal benefits, altruism, and trust in healthcare providers. For one, participants were more likely to enroll when they had a strong, positive relationship with their doctor. ¹ In addition, adverse health could also favor research participation. One review of trials in acute conditions found that patients in pain said they were willing to agree to anything to address their pain. ² Still, barriers to participation persist and are numerous and varied. When discussing trial recruitment, the review noted that some patients felt too ill to participate and others who were happy with their current health were less likely to enroll for fear of disrupting it. Fear was a significant obstacle, particularly concerns about side effects, risks of the intervention, or general uncertainty surrounding the trial. This fear was especially pronounced in trials targeting diseases like HIV or Alzheimer's, where stigma, safety concerns, or even the possibility of discovering one's diagnosis could deter participation. ³
Deciding whether to join a clinical trial often involves navigating uncertainties about health, identity, and potential disruption. Patients with well-managed conditions, such as allergies, asthma, or diabetes, may fear destabilizing their health or routines. Participants might wonder, "Why upset what's already working?" Patients with asymptomatic or dormant conditions — such as autoimmune disorders, neurological risks, or controlled respiratory or cardiovascular conditions — face subtler challenges. For patients who feel they've achieved a balance in managing their health, trial participation can feel like an unnecessary disruption that invites unwelcome scrutiny. Participating in a trial can transform a dormant risk into an active identity, forcing individuals to confront a diagnosis that might otherwise remain in the background. A participant might ask, "Does this trial make me a patient when I don't even feel sick?"
For individuals with diseases identified by biomarkers long before symptoms appear — such as Alzheimer's, Parkinson's, or chronic kidney disease — a trial may heighten the visibility of their condition. This shift in identity can deter participation, as trial involvement forces them to explain their risks to others, perhaps for the first time. One participant might reflect, "Why define myself by a condition I don't even have symptoms of yet?" For those carrying hereditary risks, such as genetic mutations causing hereditary breast and ovarian cancer syndromes (HBOC), Lynch syndrome, or family histories of diseases like familial hypercholesterolemia, sickle cell disease, or Huntington's disease, trial participation can serve as a constant reminder of relatives' struggles or a potential future they cannot entirely ignore. Many participants experience survivor guilt, reflecting on opportunities they now have that were unavailable to loved ones with more advanced diseases or those who have passed away. These emotions are often compounded by the demands and exhaustion of caregiving for affected relatives. Participation can feel less like an empowering step and more like an emotional burden, especially when unresolved grief or trauma tied to a family history of the condition is involved.
In pediatric trials, parents must carefully weigh the potential benefits of trial participation against its impact on their child's well-being and identity. Even when a trial offers potential benefits, parents often hesitate, fearing it could make their child feel "not normal." The visibility of trial participation — frequent appointments, medical procedures, or changes to routines — can amplify feelings of difference or isolation for children. One parent might ask, "Will this trial make my child feel like there's something wrong with them when they've always seemed fine?" Logistic and financial challenges compound these concerns for families. Parents must balance trial participation with school schedules, extracurricular activities, work commitments, and the needs of siblings. A caregiver might reflect, "We're already juggling so much — how can we take on even more?" Families managing chronic conditions often find these added responsibilities overwhelming, especially when the child's condition is stable and the perceived need for participation feels less urgent.
Debra M., whose 7-year-old son is in a clinical food trial, shares, “For our family, joining a clinical food trial isn’t just about the research — it’s about the hope. Knowing that our son could have a safer future, if he accidentally consumes peanuts, gives us a sense of optimism we didn’t have before. The process certainly involves a lot. Between the skin pricks, blood tests, and food challenges, there are plenty of adjustments and a lot of comforting and consoling our 7-year-old who asks, ‘Why do I have to do this?’ It’s not always easy, but we see it as an investment in his future as well as a chance to help other families like ours.”
Healthcare providers play a pivotal role in whether patients consider clinical trials. However, many providers hesitate to recommend trials to those with stable conditions or dormant risks. This hesitation may stem from concerns about burdening patients, limited knowledge of trials, or time constraints in discussing trials that aren't lifesaving. Providers may inadvertently assume disinterest in high-risk populations, unintentionally closing the door on prevention-focused research. In pediatric trials, providers face additional complexity in addressing the child's and the caregiver's concerns.
Social determinants of health (SDOH) further compound these challenges. Factors like socioeconomic status, access to reliable transportation, education, and systemic inequities in healthcare significantly affect the ability to participate. Even if they are interested, individuals from underserved populations may lack the resources or time flexibility to commit to trials. A lack of culturally sensitive outreach may also deter participation, particularly among minority communities where distrust of medical research is prevalent due to historical and systemic injustices. Tailored recruitment efforts that address these barriers are critical to improving equity and diversity in clinical research.
Addressing these psychosocial and practical barriers requires innovative and patient-centered approaches. Behavioral health professionals can play a critical role by providing emotional support, identifying and addressing unique challenges, and offering practical solutions and interventions. Emotional support can normalize fears, anxieties, and guilt, offering a safe space to process these emotions. Counseling can reframe trial participation as a proactive, empowering choice rather than a disruptive burden. Providing culturally sensitive, personalized information can alleviate uncertainty and build trust. Flexible trial designs and financial support can reduce logistical strain, particularly for caregivers balancing family responsibilities. Engaging peer mentors, community leaders, or support groups can help normalize participation and reduce isolation.
As Sarah McKeown-Cannon, SVP Head of Clinical Research at Heartbeat, explains, “Ultimately it comes down to truly listening and understanding the needs at an individual level. The decision to participate for many patients often ends up being a practical one and not medically driven. We can no longer just be patient-centered, but instead provide patients with flexibility in how we address their individual concerns, from ‘out of hours’ appointments or access to travel support. A one-size-fits-all approach can no longer be the solution.”
By implementing these patient-driven strategies, researchers and healthcare providers can ensure that trials are not only accessible but also respectful of participants' unique circumstances and challenges.
Clinical trials focused on chronic conditions, latent risks, and hereditary syndromes are critical to advancing medical research and improving lives, yet they present unique and complex challenges. By addressing the logistic, emotional, and societal barriers participants face — such as the fear of disrupting stability, stigma tied to health risks, or the burden of caregiving — researchers can create trials that align with the realities of participants' lives.
Gil Bashe brings a multifaceted perspective to clinical research as the parent of a child with a rare disorder called hEDS, a Marfan Foundation and American Diabetes Association board member, and Chair of Global Health and Purpose at FINN Partners. “As a parent and patient advocate,” he reflects, “I have seen how the decision to participate in a clinical trial transcends personal benefit; it becomes a statement of hope and solidarity. For families managing rare disorders, participation offers a higher calling: the chance to transform personal experience into a pathway for future solutions. While the journey demands resilience and disrupts routine, the power of belonging to a community united in curating knowledge cannot be overstated. Clinical trials allow patients and caregivers to turn uncertainty into action, ensuring that their life story contributes to advancing care for others.”
To succeed, these trials must transcend scientific rigor, fostering environments rooted in trust, empathy, and patient-centered engagement. When trials are designed with these considerations at their core, they advance scientific discovery and ensure that research serves the people it seeks to benefit in tangible, respectful, and empowering ways.
By Emily Epstein, LMSW, clinical behavioral healthcare specialist, Weill Cornell Medicine
