Rare diseases were in the spotlight recently when an early-stage clinical trial involving gene-editing therapies from CRISPR Therapeutics announced encouraging results. Early clinical trial data indicated new safe and effective ways to edit genes inside the body to treat a rare disease.

The CRISPR therapy, often described as a genetic scissor, targets specific sections of DNA to repair, remove, or insert individual genes. Researchers are urgently developing new applications for these genome-editing therapies due to the tremendous promise for patients suffering from rare diseases.

In America, nearly 1 in 10 are affected by rare diseases, while rare and ultra-rare diseases impact 400 million people globally. Of the estimated 7,000 rare diseases, 95% currently have no treatment approved by the FDA.

Rare diseases are chronically debilitating and are often life-threatening. They disproportionately impact children, teens, and young adults, as many rare diseases are genetic in nature. Usually, the only hope for treatment comes in the form of clinical trials, yet the very essence of these diseases complicates these patients’ ability to participate in this course of treatment.

Factors such as geographic location, financial means, and medically fragile patients are significant challenges negatively impacting clinical trial enrollment, participation, and completion. Rare disease trials are limited in number, with a high percentage focusing on cancer-related diseases. Two-thirds of all clinical trials fail to enroll enough subjects, a long-standing issue in the healthcare system.

While CRISPR therapies offer tremendous hope for the future, it is critical for clinical trial sponsors and clinical research organizations (CROs) to address the unique challenges currently facing rare disease patients. Investing in a patient-first approach and removing barriers to clinical trial enrollment and retention will result in better outcomes for patients and trial sponsors alike.

Alleviating Financial Barriers to Trial Participation

The scarcity of treatment for rare and ultra-rare diseases results in inequalities for patients around the globe. Gaining access to appropriate healthcare creates heavy emotional and financial burdens for patients and their caregivers. The complexity of finding and managing clinical trial logistics increases these burdens for this group of patients and their caregivers. Many cannot realistically contemplate participating in a trial given the seriousness of their illness and lack of adequate financial resources.

Among the most significant issues for rare disease patients is the cost of clinical trial participation. While trial sponsors reimburse patients, a critical factor improving enrollment and retention rates, the out-of-pocket expenses required can be daunting. Nearly half of patients enrolled in early-phase clinical trials face monthly out-of-pocket costs of $1,000 or more.

Additional financial considerations, such as time off from work, childcare, travel to and from the trial site, lodging, and meals, are daily realities for patients and their caregivers.

For example, Clincierge was working with a trial sponsor on a rare disease trial in Turkey. During the trial, one of our patient coordinators noticed two trial patients were not submitting receipts for food costs incurred during site visits. When the coordinator inquired, the patients explained they did not have money to pay for meals upfront. The care coordinator arranged appropriate accommodations to ensure the two patients had ongoing access to healthy food choices. But stories like these highlight the tremendous obstacles some rare disease patients endure.

Mitigating Geographical Barriers to Trial Participation

Rare diseases are often complex to treat and require patients to be on-site at highly specialized research institutions, creating yet another challenge to enrollment and completion. Many rare disease patients live in remote locations requiring long-distance travel and extended accommodations in an area close to the trial site. Coordinating these logistics adds additional pressure to patients and their caregivers.

When international travel is required, considerations such as language variances, interpreters, culture, cross-border travel, visas, passports, and long-term accommodations must be considered for each patient. When issues arise for these relocated patients, geographic distance presents extreme challenges.

In a recent rare disease trial, a three-year-old Vietnamese patient and his mother relocated to Europe for treatment. The mother was diagnosed with and tragically succumbed to an aggressive form of cancer during the study, leaving the boy orphaned in a foreign country. Fortunately, the trial sponsor utilized patient care coordinators who urgently stepped in to help. The coordinators arranged the relocation of immediate family members to care for the boy while he completed treatment and assisted with adoption efforts.

While tragic, stories like these shed light on the unique and complex challenges of rare disease clinical trials, 85% of which do not retain enough patients through trial completion. Recognizing these complexities, the FDA has implemented measures to improve support in clinical trials and the development of safe and effective therapies for rare diseases.

Federal Efforts to Support Rare Disease Trials

In 1984, the Orphan Drug Act incentivized pharmaceutical companies to increase research and development for rare disease treatments. Three decades later, the legislation is creating marked results.

In 2021, the FDA approved 26 orphan drugs, half of which were treatments for rare cancers. While the total number of orphan drugs decreased 16% from 2020, orphan drugs accounted for more than half of all novel drugs approved in 2021.

Another legislative boost came in January 2022 with the enactment of the Clinical Treatment Act. This new law guarantees coverage of all “routine costs” associated with clinical trial participation for Medicaid beneficiaries. The Act aims to create access to clinical trials for often marginalized and historically underrepresented minority patient populations, a significant step forward in healthcare equality.

Other federal efforts to increase trial participation include designated research grants for rare disease trials, priority review of treatments for rare pediatric diseases, and outreach campaigns to professionals, advocacy groups, and patients.

Nonprofit groups work tirelessly to build awareness of rare diseases. Each year, Rare Disease Day occurs on the last day of February and is a coordinated global effort addressing these little-known diseases and their immense impact on the lives of patients and those who care for them.

Awareness efforts like these are crucial since patients with a rare or ultra-rare disease have fewer options compared to more prevalent diseases. In fact, most rare diseases (70%) are studied in fewer than 10 trials, and 28% have only been studied in a single trial.

So if a patient is lucky enough to find a trial for their rare disease, it is imperative for trial sponsors to do everything they can to reduce barriers to participation and help patients navigate all of the nuances of a trial. Because improved clinical trial performance ultimately leads to scientific success and life-saving therapies for patients.

  • Scott Gray

    Scott Gray is the Co-founder and CEO of Clincierge, the leader in patient support services for clinical trials. Since 2015, Clincierge patient coordinators have managed logistics and reimbursements in more than 300 clinical trials worldwide.


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