The Precision Blog

Rare Disease Clinical Trials in Pediatric Populations: Lessons Learned

Written by Traci Fulton | Oct 28, 2021 1:28:00 PM

Sponsors are likely to encounter compounding complexities when running pediatric rare disease trials.

Individually, rare disease and pediatric clinical studies present noteworthy challenges, but together, they can tie logistical knots that impact families and cause costly delays. With more than 150 successful rare disease clinical trials supported, including several pediatric indications, this article outlines our top lessons learned and offers advice 15 years in the making.

Rare diseases affect nearly 300 million people globally and most of them are children1,2 

In pediatric hospitals, beds are regularly filled with children battling a rare disease—approximately one third of whom will not live to see their 5th birthday.3 With an average time to diagnosis of six to eight years,4 high mortality rates, and no clear progression nor established standard of care, the margin for uncertainty in research is zero. 

Participation in a clinical study can be a difficult ask, and these children are often severely ill. Managing the side effects of investigational products, transporting children to sites for visits, and running labs or assessments can create an overwhelming environment for everyone involved. For sponsors, these challenges are compounded by the increasing intensity of competition in study recruitment and gaining consent amidst heavily restricted travel. 

The influx of companies exploring the rare space, together with the growing demand for improved patient-centricity is rapidly changing traditional study logistics, opening the door for innovative and outside-the-box strategies to drive enrollment and reduce the burden of participation.

Competition and cost make patient-centricity an essential strategy in rare disease pediatric research.

One obvious yet inescapable hurdle of rare disease pediatric research is the small pool of patients from which to recruit. With more and more choices available, families sit firmly in the driver’s seat. Variables like geography, study design, and trial goals are important factors that contribute to the willingness to enroll one’s child in a clinical trial. While some of these variables may not be within a sponsor’s control, there are ways to make studies easier and more appealing to potential patients and caregivers.

Educational videos

These immensely powerful tools help to ease feelings of uncertainty, giving caregivers the information necessary to feel comfortable with the prospective therapy’s mechanism of action, the study’s requirements, and what potential outcomes are expected.

Study branding

Marketing is the most important way in which sponsors can raise awareness of an upcoming study. When well-executed, those information-seeking parents and caregivers will proactively inquire about enrollment criteria and share promising findings within trusted online circles.

Study portals

Among the many factors affecting a patient’s experience is the transfer of information. Portals streamline data sharing, helping to mitigate the disruption of household routines due to study participation.

Concierge services

When in-person appointments are required, travel can be a sore subject. The special needs of very ill children make access to travel agents and seamless reimbursement a real difference-maker in this population’s decision-making.

 

Participating sites may also be affected by a pediatric rare disease study

Adding a complex trial on top of the already-taxed resources of most study sites can be a battle. In addition to the personnel requirements, there are beds and access to equipment, like infusion pumps or respirators, required to meet the needs of these very (often terminally) ill children. Experience shows us that employing strategies to minimize the burden can help encourage sites to participate. Examples include: 

  • Providing inclusion and exclusion cards, in addition to standard recruitment and engagement materials, as well as a laminated schedule of events for easy use in clinical settings  
  • Pocket protocols, visit checklists, and a study reference manual, together with Frequently Asked Questions, for at-a-glance information and greater time efficiencies 
  • CRO-led trainings and streamlined communication pathways, like identifying centralized points of contact or outlining meeting cadence before study initiation, help to streamline study-related work 

As rare disease pediatric patients are frequently immune-suppressed, remote care, telemedicine and in-home nursing visits have shown to further reduce the efforts of on-site staff. The adoption of decentralized clinical trials surged during COVID-19, and the outcomes have been largely favorable, demonstrating positive potential for specific populations. 

The nature of these study populations may require patients to cross state or even country lines. Understanding and mapping the regulatory environment of each site as it relates to patient consent is critical both to study success and efficient patient enrollment.

Consent and assent in pediatric rare disease clinical trials.

It is essential that patients and caregivers have the time to review study consent forms in their own time at their home. This allows them to review the information, understand the risks and benefits, ask questions, and evaluate the impact participation will have on the family. Many sites and CROs are moving toward e-consent platforms which are even more accommodating to patients and their families.

 

Managing emotions plays a tremendous role in a rare disease pediatric study’s success.

Kids will be kids and parents…parents. Remember, enrolling a child into a clinical trial can offer hope – if not for a cure today, for one that helps future patients – but until then, it is a burden. Children experience a rollercoaster of emotions ranging from fear and isolation in unfamiliar surroundings to the inconvenience in accommodating study schedules and site visits. Caregivers too can be anxious or even wary.  

Through our experience working with child participants in rare disease studies, we’ve identified several study adaptations that can make study participation easier for everyone. 

Families should only be contacted by trusted people

Familiar physicians or an advocacy group are ideal for reaching out and the communication should always be tailored to the audience.

Do not expect caregivers to “get it” right away

While caregivers are very much subject matter experts in their child’s disease, with innovative therapies being developed with complex mechanisms of action, avoiding medical jargon, asking questions to confirm their understanding, and providing ample time for discussions about the study and the child’s health helps build trust.

Streamline study visits when possible

Short visit times help parents who are taking time off work, managing transportation issues, and securing the extra help that may go in to transporting a child.

Put yourself in the caregiver’s shoes

Focusing on the holistic elements surrounding enrollment helps to build trust, show empathy, and reduce the emotional toll of study participation. This, in turn, creates a differentiated environment which is more attractive to families and increases the chances of enrollment and a timely study start.

Key takeaway

Rare disease clinical trials in pediatric populations require special consideration and adaptation to meet the unique needs of these vulnerable patients and their families. By focusing on patient-centricity through educational tools, branding, portals, and concierge services, sponsors can ease the burden of participation. Supporting study sites through training, checklists, and remote care options further facilitates enrollment and retention. Most importantly, approaching caregivers with empathy, familiar contacts, clear communication, and streamlined visits cultivates trust in the research and emotional resilience for everyone involved.

While rare disease pediatric trials will always be complex, these strategies help advance new therapies to improve health outcomes and quality of life for children battling devastating illnesses.

Explore Precision’s novel approach to Rare Disease research >

References:

1. American Journal of Managed Care. Triplet Therapy for PAH May Reduce Disease Progression vs Doublet Therapy. https://www.ajmc.com/view/triplet-therapy-for-pah-may-reduce-disease-progression-vs-doublet-therapy. Accessed October 26, 2021.

2. Global Genes. Rare Disease Facts and Figures: 1 in 10 Americans is Living With a Rare Disease. https://globalgenes.org/2009/02/27/rare-disease-facts-and-figures/. Accessed October 26, 2021.

3. Rare Geonomics Institute. Get the Facts on Rare Diseases. https://www.raregenomics.org/rare-disease-facts. Accessed October 26, 2021.

4. World Economic Forum. It takes far too long for a rare disease to be diagnosed. Here’s how that can change. https://www.weforum.org/agenda/2020/02/it-takes-far-too-long-for-a-rare-disease-to-be-diagnosed-heres-how-that-can-change/. Accessed October 26, 2021.