Closing the Gap Between Interest and Enrollment

In recent years, general public awareness of clinical trials has grown significantly, driven in large part by the global spotlight on research during the COVID-19 pandemic. Widespread attention to vaccine development, emergency use authorizations, and real-time clinical trial updates brought the once behind-the-scenes world of research into everyday conversation. Digital advertising, social media campaigns, and online search tools have further extended this exposure, making clinical research more visible to the public than ever before. As a result, public perception of clinical trials now often sits at the intersection of cautious interest and uncertainty, marked by growing curiosity about participation but also lingering questions around safety, purpose, and personal impact. 

While this surge in visibility has been a welcome development for the advancement of medicine, particularly for sponsors and CROs seeking to create more predictable enrollment in both rare disease studies and more common indications, this increased recognition has not consistently translated into higher trial participation or universally positive sentiment. 

Despite the growing number of trials being initiated to address unmet medical needs and bring innovative treatments to market, 80% of trials still fail to enroll on time,¹ and 11% of investigative sites fail to enroll a single patient.² This disconnect highlights a larger issue: while the patient population may exist, many qualifying individuals remain unreached and disconnected from research sites or trial opportunities.

80% of trials fail to enroll on time,¹ and 11% of sites fail to enroll a single patient²

Reaching them requires more proactive strategies to effectively meet patients where they are through new research sites, robust chart reviews, and community outreach. It also requires a shift in how clinical research is introduced and framed, as too often, research is not presented or perceived as a valid therapeutic option, leaving many patients unaware of its relevance to their health journey. 

The gap between awareness and enrollment remains one of the most critical barriers to trial success today, driven by a range of patient-level challenges that current recruitment systems often fail to address. From slow or inconsistent follow-up after initial patient interest to complex eligibility criteria, patients face numerous obstacles that can quickly derail their journey. Emotional hesitation around participation, sometimes rooted in long-standing distrust of the research system, remains a significant barrier for many. To better turn interest into action, and ultimately enrollment, clinical trial recruitment must be grounded in a clear understanding of the patient journey and a commitment to meeting patients where they are.

Beyond the Referral: Understanding the Real Patient Journey

A patient’s first exposure to clinical research often happens unexpectedly, whether through a trusted physician, a social media ad, or a late-night internet search. According to the CISCRP 2023 Perceptions & Insights Study, about 37% of participants said they first heard about clinical trials through a doctor or research staff, while 22% discovered them online,³ a notable shift that underscores how much of the discovery process now happens outside of direct clinical interactions.

37% of participants said they first heard about clinical trials through a doctor or research staff, while 22% discovered them online.³

While digital outreach cannot replace the personal connection between a patient and their physician, when used thoughtfully, it can significantly extend reach, engage new patient populations, and open the door for meaningful, trust-based conversations, especially with individuals outside traditional healthcare environments. However, this moment of discovery is rarely straightforward. Many patients have little context for what trial participation actually involves, including how it works, what is expected of them, or whether it is relevant to their condition. In a recent U.S. survey of over 3,700 individuals, 41.3% reported not knowing about clinical trials,⁴ highlighting a persistent gap in understanding.

In a recent U.S. survey of over 3,700 individuals, 41.3% reported not knowing about clinical trials.⁴

This unfamiliarity can quickly become a barrier, especially if the next steps are unclear or if recruitment efforts feel impersonal. What may seem like a simple referral from a sponsor’s perspective is, for the patient, a pivotal and often emotional decision shaped by questions, doubts, and the need for trust. In reality, recruitment is not just a numbers game; it’s a human journey full of decision points. Each step introduces a new layer of emotional, logistical, or informational friction that can cause patient drop-off at any point. 

Early interest presents a vital opportunity for sites to build on the trust already established between the patient and their physician. It opens the door to conversations about research as a therapeutic option and helps explore the patient’s motivations for participating, whether seeking new treatment options after exhausting standard care, contributing to science, accessing care, or responding to financial incentives. 

Understanding these drivers allows sites to tailor communication, offer reassurance, and guide patients forward. For example, those motivated by altruism may respond best to messaging that emphasizes helping others or advancing future treatments. Paired with regular check-ins, this approach reinforces purpose and supports retention. Still, even with the right strategies in place, challenges often emerge between initial interest and enrollment.

Challenges Along the Way: Site-Level Realities and Participation Barriers

After a patient expresses initial interest and has been connected with the opportunity to participate, the prescreening phase quickly reveals the true complexity of recruitment. This is where emotional and logistical barriers most often surface. Patients may begin with genuine curiosity or motivation, but their momentum can fade as real-life concerns, such as missing work, arranging childcare, affording transportation, or managing health issues.

Others face deeper emotional barriers, including fear of the unknown, mistrust of research, or concerns about being seen as a “test subject.” One study found that 36% of patients expressed concern about being treated like a “guinea pig,”⁵ alongside fears around the safety of not-yet FDA-approved treatment options.

One study found that 36% of patients expressed concern about being treated like a “guinea pig.”⁵

This mistrust is particularly pronounced among ethnically diverse communities, where historical instances of unethical research practices have left a deep and lasting scar on many communities. For example, the story of Henrietta Lacks, a black mother whose cells were taken without consent in 1951 and became a cornerstone of medical research and scientific breakthroughs in polio, cancer, and gene mapping, remains a symbol of how research has at times been extractive rather than collaborative.

When these concerns go unaddressed, patients often quietly disengage. Without a physician-led invitation to consider research as a care option, interest fades. This raises an important question: “If a patient is brave enough to raise their hand, how quickly and empathetically do we respond?” 

At this stage, what is needed is a personal, humanized connection. A thoughtful conversation with a trusted physician or a timely call from a site team member can help validate a patient’s concerns, answer questions openly, and clarify what trial participation involves. Meeting patients where they are, emotionally, logistically, and informationally, can transform doubt into understanding and help patients feel supported in their decision-making process.

Many may not trust a sponsor or CRO, but they trust their doctor. “Some patients have been seeing me for years, and that relationship has developed, knowing I have their best interest at heart,” shares Dr. Pezhman Shoureshi, a principal investigator specializing in dermatology. “As such, when introducing the uncertainty of a new and promising therapy, recruitment comes with less skepticism.” When a principal investigator is respected in the community by name, reputation, or past care, it creates a foundation of credibility. Reaching hesitant or historically underrepresented communities requires approaching patients with empathy and relevance to their situation, fostering a connection of trust and helping convert initial curiosity to meaningful participation.

“Some patients have been seeing me for years, and that relationship has developed, knowing I have their best interest at heart. As such, when introducing the uncertainty of a new and promising therapy, recruitment comes with less skepticism.”

— Dr. Pezhman Shoureshi, Principal Investigator at Harpeth Valley Dermatology in Smyrna, TN

Furthermore, the prescreening process is a pivotal touchpoint for site staff. It is often the first moment of engagement with patients, via phone, text, or form, where staff confirm interest, educate, reassure, and answer questions before the individual ever steps foot on site. Most patients have never participated in a trial before and do not fully understand the purpose of screening visits, lab work, or randomization. The onsite team plays a key role in explaining the informed consent process, translating study procedures in plain language, managing expectations, and outlining the time and support involved. Educating patients and addressing common questions, such as “What is the purpose of the trial?” “What kinds of tests or treatments are involved?” “What are the possible side effects and benefits?”⁶ helps patients make informed and confident decisions about their trial participation. “Patients don’t need to be sold on research; they need it explained in a way that makes sense for their life,” says Dr. Sean Kerby, a principal investigator specializing in emergency and family medicine. “When we take the time to walk through what’s involved and why it matters, they’re far more open to moving forward.”

“Patients don’t need to be sold on research; they need it explained in a way that makes sense for their life. When we take the time to walk through what’s involved and why it matters, they’re far more open to moving forward.”

— Dr. Sean Kerby, Principal Investigator at Gulfport Memorial in Gulfport, MS

From the sponsor or CRO perspective, the recruitment funnel is often structured around key conversion metrics: referral in, prescreen complete, screen fail or enrolled. These benchmarks are essential for tracking progress and ensuring timelines are met. What can be harder to observe are the nuanced, relationship-driven interactions that occur between each of those steps. Recognizing this, many sponsors and CROs have taken meaningful steps to support site success, investing in local advertising funds, recruitment platforms, and patient education materials that help sites engage more effectively at the community level.

This recent progress has affirmed that true impact comes from partnership. Personalized patient engagement requires open communication between sites and sponsors, alignment on expectations, and a shared understanding that enrollment quality is just as critical as enrollment speed. When both parties commit to these shared goals, recruitment becomes a meaningful, community-informed process that leads to stronger enrollment outcomes and greater trust in research.

Patient Recruitment Through the Patient Lens

Improving enrollment outcomes starts with considering and rethinking recruitment strategies from the patient’s perspective. This means adjusting workflows to prioritize follow-up within the same hour or day, using real conversations rather than automated replies, and building upon the already established trust within patient-physician relationships. In a recruitment landscape driven by timelines and metrics, we must ask: “Are we connecting with patients at the peak of their interest, or after it’s passed?”

When sites are empowered to engage with patients authentically, they can provide the clarity, reassurance, and personal connection that many participants need to move forward. Patient-first strategies are key to patient recruitment and enrolling more participants in trials. Sponsors and CROs are increasingly recognizing that traditional, transactional models fall short and are moving away from controlling recruitment at a distance. Instead, they are supporting sites with tools, resources, and flexibility that reflect the realities of patient engagement.

They look to experienced teams for what works, whether strategically selecting sites based on new patient access, customizing messaging to reflect patient motivations, structuring realistic timelines, or allowing flexibility in how and when follow-up occurs. Recruitment is not a one-size-fits-all approach; it requires long-term relationship building, relevant communication, and an understanding of the non-clinical factors that influence participation. When sponsors, CROs, and sites align around a unified patient engagement strategy, grounded in shared goals, open communication, and mutual trust, the result is a more streamlined enrollment process, stronger retention, and higher-quality trial execution.

Ultimately, the stakes are high. When recruitment fails, trials are delayed, revenue is lost, and patients lose faith – sometimes in research altogether. Even a single day of trial delay can cost more than $500,000 in lost revenue.⁷ This is precisely why experienced sites matter – they know how to move quickly, connect meaningfully, and keep patients engaged from the first moment of interest. 

Even a single day of trial delay can cost more than $500,000 in lost revenue.⁷

Experienced sites understand how to engage diverse populations, as they have seen which strategies sustain participation and know how to remove friction at every step of the journey. These sites recognize that recruitment is not just about meeting a target, but it is also about building a bridge between scientific advancement and the people it is meant to serve. Rethinking recruitment as a shared, human-centered mission is how we move medicine forward, together.

References

1. Desai M. Recruitment and retention of participants in clinical studies: Critical issues and challenges. Perspectives in Clinical Research. 2020;11(2):51. doi:https://doi.org/10.4103/picr.picr_6_20
2. Getz KA. Enrollment Performance: Weighing the “Facts.” Applied Clinical Trials. 2012;21(5). https://www.appliedclinicaltrialsonline.com/view/enrollment-performance-weighing-facts
3. Center For Info & Study on Clinical Research Participation. 2023 Perceptions & Insights Study. CISCRP. Published 2023. https://www.ciscrp.org/wp-content/uploads/2023/11/2023PI_Participation-Experiences.pdf
4. Yadav S, Todd A, Patel K, et al. Public knowledge and information sources for clinical trials among adults in the USA: evidence from a Health Information National Trends Survey in 2020. Clinical Medicine. 2022;22(5):416-422. doi:https://doi.org/10.7861/clinmed.2022-0107
5. Catania C, Pas TD, Goldhirsch A, et al. Participation in Clinical Trials as Viewed by the Patient: Understanding Cultural and Emotional Aspects Which Influence Choice. Oncology. 2008;74(3-4):177-187. doi:https://doi.org/10.1159/000151365
6. Why Participate in a Clinical Trial? Cancer.gov. Published November 18, 2024. https://www.cancer.gov/research/participate/clinical-trials/why-participate
7. Getz K. How Much Does a Day of Delay in a Clinical Trial Really Cost? Applied Clinical Trials. 2024;33. https://www.appliedclinicaltrialsonline.com/view/how-much-does-a-day-of-delay-in-a-clinical-trial-really-cost-