Overcoming Complex Patient Recruitment Challenges with Data-driven Insights

Factors that make recruiting rare disease patients for clinical trials difficult include limited patient populations and stringent eligibility criteria.

Rare disease research represents an area of great interest and investment for pharma, but recruiting patients for rare disease clinical trials is notoriously difficult. Is the strategic use of data the key to moving forward?

Common roadblocks to rare disease recruitment

The rare disease market is projected to show a compound annual growth rate (CAGR) of 11.93% from 2025 to 2030, making it an area of interest both to sponsors and to the patients who await the development of lifesaving treatments. While the interest in developing rare disease therapies is high, core factors inherent in rare disease make recruitment and retention of patients in clinical trials difficult. These include:

1. Limited patient populations
   Although rare diseases are estimated to affect about 300 million people worldwide, roughly 10 percent of the global population, rare diseases affect fewer than 1 in 2,000 people in the EU and fewer than 200,000 people in the US (about 1 in 1,600 people). For the purposes of clinical trials, this translates into a small patient population, often scattered over a wide area. With such a small patient pool, the already difficult task of recruitment takes on additional layers of increased complexity. Finding the right patients for rare disease clinical trials requires searching for them throughout the world, making outreach time-consuming, tedious, and expensive. As such, investigators tend to rely on their own hospital databases or advertising in hopes of locating patients who meet their trial criteria. These tactics often require significant effort and typically yield only a small patient pool.
2. Lack of awareness and diagnosis
   Because individual rare diseases are so exceptional and since many rare diseases share features in common with a wide array of other diseases, health care providers often face challenges in accurately identifying symptoms in their patients. The result: misdiagnosis or underdiagnosis that can lead to years of uncertainty before a correct diagnosis is administered. Research shows that on average, patients visit five doctors and receive three misdiagnoses before eventually being correctly diagnosed with a rare disease. Norstella, Citeline’s parent company, documented an extreme, although not uncommon, patient journey, in which it was 26 years before the proper rare disease diagnosis was reached.  Patients lacking an accurate rare disease diagnosis from a medical professional cannot be referred to appropriate rare-disease clinical trials.
3. Stringent eligibility criteria
   The inclusion/exclusion criteria for rare disease clinical trial participation are often more restrictive than the participation criteria for other more common conditions. Rare disease trials tend to be focused on patients with highly specific profiles, such as those having rare gene mutations or those possessing specific biomarkers. This extremely restrictive inclusion/exclusion criteria can further shrink an already limited patient pool, making the task of patient recruitment even more challenging.
4. Geographic dispersion
   Locating enough patients to participate in rare disease clinical trials often requires casting a wide net that covers vast geographic areas, a necessity that further complicates patient engagement and recruitment. Conducting trials across disparate geographical regions requires sponsors to navigate a slew of new challenges in attracting potential rare disease trial participants, including logistical hurdles, cultural differences, and patient preferences. Each factor must be carefully considered and incorporated when designing and recruiting for these clinical studies.
5. High dropout rates
   As with all clinical trials, the ability to retain participants plays a key role in the success of rare disease research. Common barriers to participant retention include financial hardship, the burden of travel expenses, and the intensity and complexity of trial requirements.  The often lengthy and demanding protocols of rare disease trials can also deter potential participants. Each of these factors can lead to higher dropout rates, ultimately jeopardizing rare disease trial success.

Data-driven insights: A game-changer for rare disease recruitment

Even in the face of daunting participant recruitment and engagement challenges, moving forward in the rare disease clinical trial landscape is possible. Sponsors are discovering that adopting a tech-enabled, patient-centric approach — combined with the use of real-world evidence (RWE) and real-world data (RWD) — can be the key to overcoming the common barriers to rare disease clinical trial success.

By strategically combining powerful data from reference labs, medical claims information, electronic health records (EHR), and data about other clinical trials, rare disease clinical trial sponsors can formulate effective strategies that address these persistent pain points:

1. Pinpointing patient locations
   The arduous task of finding patients to participate in rare disease clinical trials can be simplified by leveraging the capabilities of data platforms to identify the locations of eligible patients. By analyzing and extracting critical datapoints from such diverse and massive datasets as claims data, EHR, social determinants of health (SDOH), and more, sponsors can proactively target their outreach efforts on areas where appropriate potential trial participants are located.
2. Improving diagnosis and awareness
   Sponsors can raise awareness about rare diseases and improve diagnosis rates by partnering with advocacy groups and leveraging powerful insights from real-world evidence (RWE). Data can also help identify diagnostic patterns, enabling healthcare providers to recognize potential patients earlier.
3. Optimizing eligibility criteria
   Data-driven solutions are critical for simplifying the complex process of expanding the participant pool for rare disease clinical trials. Using advanced analytics to synthesize complex data can help feasibility teams evaluate and refine eligibility criteria to expand the cohort of trial participants without compromising trial integrity. Teams can also use data to simulate the impact of clinical trial criteria changes and find the optimal balance between inclusivity and scientific rigor.
4. Selecting high-performing sites
   Choosing the right sites and investigators for rare disease clinical trials is both challenging and imperative for study success. Using data-driven site selection tools that combine historical performance metrics and vital patient location data empowers sponsors to streamline complex site and investigator selection processes. These tools enable sponsors to identify both historically high-performing sites while pinpointing investigators with access to higher volumes of the right rare disease patients for their trials.
5. Enhancing patient engagement
   Linking critical, patient-centric datasets to reveal important insights about the patient journey is crucial for successful patient outreach, recruitment, and retention. This essential data can include SDOH datasets that hold critical information about patient population behavior and preferences. Such insights are key for informing sponsors’ vital patient engagement strategies. These can include using effective communication channels to successfully connect to potential participants, designing clinical trials with an eye to lowering the barriers to participation, and maintaining effective engagement with rare disease patients throughout the study.

Moving forward in rare disease recruitment, powered by data

The challenges of rare disease clinical trial patient recruitment are vast, but so are the power and potential of leveraging critical RWE and RWD to overcome them. The strategic use of data from labs, claims, hospitals and hospital systems, EHR, and proprietary sources can be instrumental in improving and accelerating patient recruitment in rare disease clinical trials. Data-driven solutions can help locate sites and investigators and identify patient locations, eligibility, and preferences. By using them, rare disease clinical trial sponsors can streamline and refine the patient recruitment process, leading to more successful studies and, ultimately, the development of transformative therapies for rare disease patients.