Healthcare worker pushing little girl in wheelchair in a hospital; rare disease clinical trials challenges concept

Rare Disease Clinical Trials: Challenges and Opportunities Researchers Face

Patients with rare disorders and their families suffer immensely. Beyond the challenges that a medical condition itself creates, access to treatment is difficult, most diseases don’t even have FDA-approved therapeutics, and there are rare disease clinical trials challenges themselves, including participation.

Below, we will explore what some of those hurdles are — including trial design, patient outreach, and data collection and analysis — and what researchers are doing to push the boundaries of rare disease research.

Designing Rare Disease Clinical Trials

One of the biggest challenges in studying rare diseases is the fact that so many patients are children.

As corresponding authors Albert Fung and Xiaomeng Yue from the University of Cincinnati Academic Health Center write, child patients present a number of follow-up challenges: the ethics of enrolling children in clinical trials, whether those families live close enough to a doctor who can diagnose a rare condition, whether those families have access to rare-disease support networks, and whether we as a scientific community know enough about the condition to conduct clinical research.

“Furthermore, because the number of patients for each rare disease is small, the study design is often restricted in clinical development programs,” Fung, Yue, and their co-authors write. “Clinical endpoints, such as potential biomarkers, are often not well-defined and may not have regulatory precedence.”

What’s more, the design of any such clinical trial will always be complicated because rare diseases don’t tend to cluster geographically. Patient populations are global and sparse.

“By necessity, many rare disease clinical trials are multicentre, often multinational, for sufficient patient recruitment, even in phase I and II trials,” consultant dermatologist Jemima E. Mellerio writes in the British Journal of Dermatology. “This can challenge protocol harmonization, ethical review, indemnity, organization of clinical services, standards of care and cultural diversity.”

Mellerio also notes considerations like language barriers and time-zone differences are other rare disease clinical trials challenges, which can make conducting such a trial too burdensome or too expensive for some sponsors.

Person speaking to group of people, sitting in a circle, at a meeting; rare disease clinical trials challenges concept

Identifying Rare Disease Patients and Conducting Outreach

In a piece for Clinical Leader, Kinnari Patel, president and COO at Rocket Pharma, lays out some practical steps that research organizations and sponsors can take to make rare disease trials more patient-centric.

“In practice, companies and researchers should meet with patients and their caregivers before designing a human study to hear about the challenges they face,” Patel writes. “Insights around the journey to diagnosis, finding appropriate medical care, and the burden of living with a life-threatening disease are all relevant to the drug development process.”

But this begs the question of how researchers even find those patients, especially when the potential trial participant pool might number a few dozen people worldwide. Rare disease networks are helpful in making these connections. Organizations such as the National Organization for Rare Disorders, the Rare Diseases Clinical Research Network, and the European Joint Programme Rare Diseases all help connect patients with care providers, researchers, patients advocates, and other support resources.

We’ve noted before how important it is to include the voice of the patient in any rare disease clinical research, and these networks are an excellent place to begin outreach, communication, and building a patient-focused understanding of any such condition.

And as the team at ClaritasRx points out, researchers can build strong relationships with these organizations by “improving the generation and sharing of scientific evidence related to rare diseases.

“As with any area of research, orphan drug development may be hindered by limited data or lack of access to available data. Because data on rare diseases tends to be scarcer by definition, these limits can hinder efforts to create effective rare disease treatments.”

Healthcare professional using tablet for for data analysis or lab study; rare disease clinical trials challenges concept

Managing Data From Disparate and Siloed Sources

That last point hints at one other major challenge: How do rare disease researchers get access to meaningfully robust datasets?

Natalie Douglas, founder of healthcare business accelerator Lucidity, outlines the many ways this is challenging — because it’s hard to find enough patients, because it’s hard to generate sufficient information even when you do find those patients, because rare disease data is often siloed and inoperable, because there are consent agreements and data ownership questions that limit access to valuable datasets.

“The ability to firstly capture patient and caregiver data in order to advance research and drug development is, of course, essential but to be able to use it as well is a significant current problem that is challenging the industry and regulators alike,” Douglas writes.

“Changing the drug development process to become more patient centric will not only help patients with rare diseases but those with more common ones as well, leading to significant benefits to payers and health systems as well.”

In Nature Medicine, Mike May writes that real-world data is proving to be a boon to rare disease research. Even wearables, smartphones, and smartwatches — sources the FDA is trying to ensure won’t create fragmented or inferior datasets — could open up treasure troves of useful data, May reports.

At the same time, harmonized, clinical-grade data remains siloed away in research publications. This makes collaboration difficult for researchers who, by necessity, must conduct their work on a global level and thus must rely on the support and the insights of fellow researchers across borders and time zones.

“Lack of access to patient data lessens the value of any specific program because individual companies and institutions are unable to accumulate a critical mass of knowledge that can substantially de-risk drug development,” write Nathan Denton et al., in the Orphanet Journal of Rare Diseases.

Learn More

At Anju, we are working to ensure clinical researchers everywhere get access to the data they need and have access to support networks that allow them to optimize their clinical trials.

For rare disease clinical trials, the hurdles are tall. That’s why our eClinical services were designed to augment the capabilities of any research team. We can help integrate or migrate data, and we can help ensure your electronic data capture processes provide rigorous data validation, flexible reporting, and quality data extractions.

And our TA Scan solution gives you a way to create a single source of truth in your research by mining data from across hundreds of thousands of clinical trials taking place around the world.

To learn more about how Anju can support the rare disease clinical trials challenges you face in your research, schedule a demo today.

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