Overcoming challenges in rare disease research with patients

It’s an exciting time in rare disease research, with many pharmaceutical and biotech companies including never-before-studied rare diseases as part of their pipelines, bringing hope to thousands of patients around the globe.

With increasing recognition from regulatory bodies of the importance of incorporating the patient voice throughout the drug development process, qualitative research with patients with rare and ultra-rare conditions is extremely valuable. However, conducting qualitative research in rare disease is not easy and researchers face many obstacles to success.

Our team at Sprout Health Solutions has participated in over 27 rare and ultra-rare disease studies, giving us significant firsthand experience in identifying strategies for overcoming some of these challenges.

By definition, a rare disease is a condition with fewer than five cases per a population of 10,000 and, in ultra-rare conditions, the numbers are even smaller. Therefore, finding patients to participate and engage in studies can be a huge barrier to success. We’ve identified five strategies to help mitigate some of the challenges associated with small sample sizes.

When developing a recruitment strategy, think about multiple methods of recruitment:

• Engage with both a patient advocacy group and a specialised recruitment partner
• Incorporate an international recruitment strategy, as there will likely be advocacy groups with patients and families around the globe who are eager to participate 
• Attend patient events or conferences. For an interview study involving one of the rarest subtypes of an ultra-rare paediatric condition, I set up a table at a family conference where I shared study fliers and invited families to participate. I was able to make connections with two families that ultimately participated in the study. Attending the conference also allowed me to strengthen connections with a key patient advocacy organisation.

Community buy-in and endorsement can be critical in the success of rare disease research. Therefore, engaging with patient advocates and making them partners in the research process can be key. For example, in an online survey study we managed, a patient advocacy group and patient advocates were included as research partners from study design through publication.

Collaborating with clinical experts is important for any condition, but particularly useful when access to patients is limited. Interviewing experts on their experiences treating patients with a rare condition can not only provide valuable insights into describing the condition, but clinicians often have insights on what patients and families share with them about the impacts of a disease.

Individuals with rare and ultra-rare diseases can be overwhelmed with requests for research participation. One way of reducing the burden of another request is to use alternate data sources, such as online patient forums, the FDA’s Voice of the Patient reports and social media to supplement more traditional qualitative data collection methods.

Many rare conditions can be quite debilitating and patients may find it challenging to participate in traditional qualitative research methods, such as in-person interviews or focus groups. Therefore, offering alternative, more patient-focused methods of data collection, such as telephone or web-based interviews, can be important.

• Consider the length of interviews and offer participants an option to break interviews into smaller chunks across multiple days or offer several smaller breaks
• For some, an interview may not even be feasible, so data collection using online surveys with free-text responses that could be completed at a patient’s own pace could be a useful alternative
• In one Sprout study in a rare disease where fatigue was a primary and debilitating symptom, interviewers received special training to identify signs of participant fatigue. Participants were also given the option to break up the interview over two days.

Navigating the complexities of patient research and engagement in rare and ultra-rare disease demands a multifaceted and patientcentric approach. By addressing recruitment challenges, fostering ongoing engagement and recognising the unique aspects of each rare disease, qualitative researchers can contribute to advancements in treatment and care for these underserved patient populations. This, in turn, contributes to more effective drug development efforts for rare and ultra-rare diseases.