Reducing Barriers to Participation in Clinical Trials for Rare Diseases

Clinical Researcher—August 2021 (Volume 35, Issue 6)


Scott Gray


In the United States, a rare disease is defined as an illness affecting fewer than 200,000 people. Similar definitions apply across the globe, with some variations in the incidence rate. Ultra-rare diseases are even less common, and impact just one in every 50,000 individuals.

There are approximately 7,000 known rare and ultra-rare diseases, and 6% of the world’s total population suffers from one. However, less than 10% of rare diseases currently have an available treatment approved by the U.S. Food and Drug Administration (FDA). Thus, it is imperative to move new drugs and therapies through the lengthy channels of development with maximum efficiency. Yet the very nature of rare diseases complicates clinical trial participation.

The process of bringing novel drugs and therapies to market for rare and ultra-rare diseases is extremely challenging for a variety of reasons. Patients with such diseases frequently have cognitive or physical impairments that place limitations on their mobility, which in turn can restrict their clinical trial participation.

The smaller patient population also translates into greater challenges for pharmaceutical companies to identify and recruit potential trial participants. Often, patients with a rare indication live in rural areas without access to healthcare and must travel long distances to clinical research sites in order to participate. The complexities of managing travel logistics create emotional and financial burdens for the patients, who are already under physical and emotional stress. Many cannot contemplate participating in a trial because of these additional challenges.

The FDA is actively investing resources to “catalyze product development for rare diseases,” and the majority of its programs are centered around patient advocacy and education to encourage clinical trial participation. Similarly, patient logistics companies can help drive trial participant recruitment and retention. Patients and caregivers say they feel comforted and empowered when they are connected to a logistics coordinator who has demonstrated they have their best interests at heart.

Logistical Considerations in International Clinical Trials

Ethnic populations suffering from rare and ultra-rare diseases are often concentrated in remote areas of the world. Rare and ultra-rare disease trials frequently require international travel for patients due to the smaller concentrations of them being dispersed across the globe.

Clinical study managers often do not have the knowledge or expertise to anticipate the additional assistance involved in arranging the complex international and cross-border logistics required of many rare disease trials. How will the study team manage communications between their home government and the patient’s government? Does travel require a visa, passport, or international travel insurance? What travel and lodging accommodations unique to a patient must be considered?

It is absolutely crucial to tailor specific solutions which anticipate the needs of a patient while meeting the requirements of the clinical trial. Considerations include:

Communication—Patients often require a translator or interpreter when participating in an international clinical trial. Providing these services ensures full understanding of the overall proceedings of the study, for both the patient and/or caregiver and any other travel companions who will be involved. Conversations with the physicians and site staff should be in the native language of the patient, beginning at recruitment and continuing through consent, and throughout the duration of the clinical trial. Patients who feel at ease with a translator or interpreter who understands their language and cultural expectations are much more likely to enroll in a clinical trial and stay enrolled until the end.

Transportation—Rare and ultra-rare diseases often present a host of accessibility and mobility challenges for patients. Patients are often very ill or have diseases that are debilitating and impact cognition and/or mobility. For patients with those challenges, a customized travel plan must be created. Visas, passports, and other documents also need to be managed on an individual basis. Country regulations must be researched, and compliance is mandatory for the validity of the trial and the protection of the patient.

Accommodation—In some instances, accommodations may only mean an overnight hotel stay. In others, it is a long-term relocation for the duration of the study. Often in the case of rare diseases, the entire family travels with the patient, relocating for extended periods of time. Thorough knowledge of the protocol requirements, combined with a deep understanding of the patient’s unique needs and family structure, allows for proactive planning, ongoing support, and repatriation.

International travel is not always straightforward, and challenges often vary between different regions and countries. Patient logistics coordinators should be familiar in the specific requirements of the geographic locations of the patients assigned to them and have a true understanding of the unique nuances of the cultures they support. Working with an expert saves clinical trial participants crucial time and money by making it easier to manage the ins and outs of visas, passports, and medical requirements like vaccinations.

International Patient Management During the Pandemic

During the COVID-19 pandemic, trial participants still needed to receive potentially life-saving therapies, but strict sanitation measures and limitations on in-person visits created roadblocks in the established norms for their study participation. Many were forced to adjust or, in some cases, totally replace their travel itineraries.

Patient logistics management companies had to constantly monitor and react nimbly to the rapidly changing travel restrictions during the pandemic. Having local patient coordinators close to the patients themselves enabled rapid response despite frequent regional regulation changes. Patient coordinators worked around-the-clock in many instances to ensure alternative transportation methods were available, as many flights were cancelled. They ensured accommodations matching accessibility needs for the participant would be sanitary and available for quarantine and beyond, and dietary needs could be met daily, in spite of restaurant closures and reduced capacity at food markets.

With the impact of COVID-19 and its variants continuing well into 2021, unexpected hurdles for participants in rare and ultra-rare disease trials will continue to arise and require creativity in planning international logistics. For clinical study teams lacking the resources and experience necessary to enable compliant and secure travel for patients in particular countries, partnering with an experienced patient support services team is often the only way to ensure participant retention and a trial completion that is both on time and on budget.

Why a Logistics Management Vendor Makes a Difference

To date, the FDA has approved drugs and biologics for more than 800 rare disease indications. In 2019, the agency approved 22 novel drugs and biologics with orphan drug designation. Even in the wake of pandemic, we have continued to see significant progress in treating rare diseases and ongoing interest in developing rare disease treatments, despite their unique challenges. This is partially due to initiatives like the Orphan Drug Act and the FDA’s Orphan Products Clinical Trials Grants Program, which create incentives to offset the costs of developing drugs in this space and increase their potential return on investments.

Going forward, the Orphan Drug Technology Modernization effort is expected to streamline the orphan drug designation request process by moving from a paper-based process to a cloud-based submission portal. Given the complex nature of these studies, as more clinical trials for rare and ultra-rare diseases are planned, support services for facilitating patient logistics will become more sought after. Partnering with a company that specializes in patient logistics can help streamline a clinical trial from its earliest stages.


Research teams who appreciate the unique needs of rare disease patients and invest in a white-glove approach on behalf of trial participants can reduce barriers to participation. For clinical study teams and site staff, this means easier patient recruitment at the beginning of a study and fewer dropouts through the duration of the trial—with the added bonus of having more time to dedicate to the trial itself. For pharmaceutical sponsors, efficient recruitment and higher retention improves trial performance, which ultimately culminates in getting treatments to market sooner.

Scott Gray is co-founder and CEO of Clincierge, a provider of logistics management services for clinical trials.