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How the right technology and tools can accelerate progress in rare disease clinical trials


Although diseases such as Ehlers-Danlos syndrome, Sanfilippo syndrome and Hemophilia are considered rare, their impact looms large.

Rare diseases, defined as occurring in fewer than one in 2,000 individuals, affect more than 300 million people across the globe, and most have considerable unmet medical needs.

The need for more research into rare diseases is clear, but researchers face significant challenges, ranging from recruiting participants who have been diagnosed with one of the 7,000 different rare diseases to selecting meaningful endpoints to drawing conclusions. Technology has emerged as a potential solution.

The need for more clinical trials in the rare disease space

Rare diseases are often overlooked and underfunded. In the absence of clinical trials to research innovations that could alleviate symptoms or alter disease progression, those diagnosed with rare diseases are left without effective treatments.

“This research is critical to families whose lives are touched by life-threatening rare diseases,” says Lynsey Psimas, Ph.D., director of sales and pharma services at Pearson Assessments US. “Clinical trials lead to scientific breakthroughs and offer hope for life-changing treatments.”

Some efforts have been made to promote research into treatments for rare diseases: Congress passed the Orphan Drug Act of 1983 to provide financial incentives to pharmaceutical companies and device manufacturers to foster innovation, and the U.S. Food and Drug Administration (FDA) provided $23 million in funding to support research into 21 different rare diseases in 2016. However, the need for ongoing clinical trials remains.

Key challenges of rare disease clinical trials

Researchers who undertake clinical trials for rare diseases face numerous challenges, from recruitment to study design.

Barriers to recruitment

The inclusion criteria for rare diseases are narrow, the population sizes are small and the geographic area of potential trial participants is dispersed, making it difficult to find, recruit and retain clinical trial participants. One study found that 30% of clinical trials for rare diseases were discontinued; lack of patient recruitment was a primary reason that trials were canceled.

Recruiting diverse patient populations is also challenging. The FDA suggested trial sponsors should establish protocols that make it easier for patients to participate, including contracting with local imaging and testing facilities and facilitating remote or digital visits, to encourage a broader trial participant pool.

Researchers face additional barriers after patients are recruited: Clinical outcome assessments (COAs) are not necessarily developed or psychometrically validated in the languages and countries where rare genetic diseases occur, Psimas notes.

To overcome that challenge, Pearson Clinical Assessments offers highly sensitive, valid and reliable COAs that can be translated and culturally adapted to the target population for a global trial.

Selecting meaningful endpoints

The small number of patients living with rare diseases, the complexity of the conditions and a lack of detailed knowledge of the disease can make it difficult to select meaningful endpoints and metrics.

Pearson Clinical Assessments offers COAs with the psychometric precision necessary in clinical trials and research. Metrics such as Growth Scale Values (GSVs) were developed to detect change over time and offer a psychometrically superior way to measure change compared to raw scores, age equivalents and other commonly used endpoints, Psimas adds.

In selecting endpoints, trial design should also include a review of the clinical development programs for the same and other rare diseases, engaging with physicians who specialize in the rare disease and patient advocacy groups, and seeking input from the FDA and other regulatory agencies.

Study design

Double-blind, placebo-controlled studies might be considered the gold standard in clinical trials, but it can be difficult or unethical to recruit patients with rare diseases for a placebo-controlled study. Employing different study designs, including crossover trials, adaptive trials, case-control designs and observational studies, can help overcome this challenge.

“At Pearson, we can help identify which COA best fits the trial design,” Psimas says. “Our COA portfolio includes reliable and valid PRO, ClinRO, ObsRO, and performance measures used by pharmaceutical, biotech and medical device companies conducting clinical research.”

Recruitment for rare disease trials is challenging and time-consuming (and the small patient population makes it difficult or even impossible to re-run a trial), so choosing the right trial design is essential to ensure analysis methods provide the best chance for evaluating new drugs, devices or therapies.

Ethical considerations

Children under the age of 18 make up half of the rare disease population. Researchers must take into account the ethical considerations associated with recruiting children for clinical trials.

In 2022, the FDA released draft guidance to help protect children who participate in clinical trials and encourages sponsors to view informed consent as an ongoing process that includes regular conversations with children, parents and clinicians during trials.

Drawing conclusions

Given the small sample sizes, researchers must consider whether data generated during studies should be considered representative of the entire patient population. Some researchers suggest that rare disease researchers need to rethink statistical significance due to the vulnerability of P-values to deviations.

“At Pearson, our team of clinical experts offer scientific consultation to help maximize data analysis and support robust and reliable data collected in clinical studies,” says Psimas.

How technology can pioneer clinical trials for rare diseases

The centralized sites that work well for traditional clinical trials can be significantly less effective for conducting clinical trials for rare diseases due to the small patient populations who are spread out across the country (or around the globe). Decentralized clinical trials (DCT) have emerged as a solution.

In DCTs, organizers use digital health technologies (DHTs) to communicate with patients; supplies are delivered to their homes, and specimens are shipped back to the lab. In rare disease trials, remote data collection enables larger and more diverse trial enrollment. Since some rare diseases cause conditions that make it difficult for affected people to attend traditional in-person trials, this method makes it easier for diverse populations to participate.

While the setup has proven beneficial, the need for infrastructure and advanced data analytics can prove challenging for smaller pharma companies and contract research organizations (CROs) focused on rare diseases.

“Many COAs were developed and psychometrically validated for use on paper,” says Psimas. “In the last few years, particularly during COVID, there has been an industry-wide shift to collecting data using electronic data capture technologies or eCOAs.”

Pearson works with trial sponsors to adapt tests for virtual administration and review content for eCOA migration to ensure validity is maintained during electronic test administration.

Technology has created opportunities to innovate in clinical trials for rare diseases. Having the right partner can help ensure that trials include tools that are aligned with industry guidance, fit the trial design, reflect the languages and cultures of trial participants and yield reliable data. This, in turn, can help overcome the barriers associated with conducting clinical trials and lead to more research into rare diseases.

For more information about how Pearson COAs can support rare disease research, contact Pearson Assessments for a consultation.