Natural History – Case Study: Ultra Rare Disease in Subjects Aged 3 Years and Younger

Allucent is a clinical research organization (CRO) with global reach and deep expertise in rare disease research. Our company was hired to support a multicenter, pre-Phase I non-interventional study of an Ultra-Rare Disease (1 in 50,000 newborns) that centered on young male children, aged 3 years and younger, who are afflicted with the disease. Allucent is proud to have supported this important rare disease natural history research, the patients, and the sponsor involved. Children and parents dealing with this rare disease face a very difficult road. We are hopeful a therapy and/or cure can be found for children suffering from this disease, and are proud of the research conducted in support of this goal.

As part of this observational study, Allucent maintained eight sites spread across five countries. Four of the sites were located in the United States and one in Canada while the rest were in Europe – France, Germany, United Kingdom.

Studying an Ultra-Rare Disease in Newborns & Toddlers

This Ultra-Rare disease affects 1 in 50,000 newborns. Of those impacted with this disease, 50 percent will pass away before 18 months. This combination of factors makes recruitment more difficult than would be experienced in studying other conditions. However, this is to be expected anytime a rare disease with a low mortality rate is involved. Recruiting for this observational study was actually streamlined because of several unique factors. For one, the Sponsor identified key opinion leaders involved with this ultra-rare disease and those individuals helped with recruitment. Further, the Sponsor worked with a robust patient advocacy group that focuses on this condition. They helped the funding organization identify sites and patients who would be willing and able to participate.

The challenges we faced with the study were very different from an issue of recruitment. Allucent was able to successfully navigate these issues because of our involvement with the sites, our excellent sponsor and the close relationships built to support the study. However, CROs and sponsor organizations should understand and anticipate these challenges when studying a rare disease with a high mortality rate and low life expectancy. Outreach and collaboration with the supporting community around a rare disease is so important to the research especially when doing new and exploratory work in a rare disease.

Language Barriers & Traveling Patients

The rarity of this ultra-rare disease meant that patient and caregiver travel was likely a necessity. In addition, patients were likely to cross borders to participate and patients and their caregivers may not speak the local language of the research site to which they were assigned. To deal with this the sites either needed to have team members that could speak the patient and family’s native language or the sponsor had to hire local translator support.

Language is a major issue and can prohibit patient participation in rare disease when patient travel is required. The patient, or in this case the patients’ family, needs to be able to understand what is happening in the study and interact meaningfully with researchers. In rare disease every patient matters and this is especially true in an ultra-rare indication thereby increasing the importance of every single patient’s participation and retention.

Preparing for SAEs

In a very ill population, SAEs may be common. This was the case for this ultra-rare disease due to the complexity of it and patient state (ventilators involved). This fact complicates matters when patients need to travel as part of study participation, and are potentially away from their home for days. Patients may experience an SAE while staying near the research site. As such, local facilities needed to be able to accommodate their language needs in the event of an emergency. It’s important for the sponsor, CRO and site to aid the patient and their caregivers with local language support where possible. This helps with patient retention and is just the right thing to do. The Sponsor for this study really supported the patients and their caregivers as much as possible.

Supporting Patients

The severity of this disease means that patients require a higher availability of care. Many participants were on ventilators and required nurses accompany them on travel to and from the research sites. Additionally, the Sponsor was willing to provide overnight nursing during their long stays in hotels especially when only one caregiver/parent could accompany the patient. We also had to make travel arrangements to ensure patient support and safety on these trips. While setting up airfare and hotel stays are not uncommon in research, the nature of this disease meant that we may need to make those accommodations for care workers and mode of transportation as well.

Consent and Data Privacy Laws

This study presented several complexities surrounding consent. Physical therapy tests were used to evaluate the progression of the disease in patients. All physical therapy tests have to be videotaped to verify that tests are being done in the same manner across sites and ensure that no therapists needed retraining to ensure consistency amongst those evaluations. This was a required part of the study. Data privacy laws are very different between countries. Being aware of those standards and having experience in navigating them helped our team adapt the consent process.

Allucent was able to deliver a successful pre-Phase I, non-interventional study because of our deep expertise in rare disease, our experience working in different countries, our flexibility to respond to sponsor, site and patient needs. Going forward, we are continuing our work with the Sponsor in the research of this ultra-rare indication and expanding those efforts into a rapid Phase I/II/III breakthrough study. We are grateful for the opportunity to continue this important research.

Co-authored by Barbara Bennett, Senior Clinical Trial Leader

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