Pediatric Rare Disease Clinical Trials

There are many challenges to overcome when running a clinical trial, and if treatments for pediatric rare diseases are being tested, those challenges can be significantly greater. Siron Clinical has expertise in these crossover therapeutic areas – here’s how we overcome the obstacles.

Today, over 300 million people are living with a rare disease globally. More than 6,000 rare diseases have been identified, and they affect between 3.5% and 5.9% of the population. Most rare diseases (72%) are genetic, and 70% of these start in childhood.

Rare diseases – particularly pediatric rare diseases – have been difficult to develop, test and approve treatments for. As a result, more than 90% of rare diseases have no approved treatment.

Clinical trials involving orphan drug development can be difficult to set up and run, and pediatric trials have specific obstacles, too. Combine them in a pediatric rare disease trial and you can find yourself facing major challenges. Why is this? And how can clinical trial sponsors overcome the challenges in pediatric clinical trials?

Geographic Dispersal of Pediatric Rare Conditions Requires Collaboration

Children living with the same pediatric rare disease are often in different countries. This means that in order to develop a treatment, researchers and clinicians in those countries need to work together.

According to FDA representatives: “Designing efficient rare disease clinical trials with clinically meaningful endpoints… requires close collaboration…”

Such collaborations frequently happen across national boundaries. Clinical trials for pediatric rare diseases are therefore often conducted internationally, involving multiple sites in several countries. These trials are subject to different regulations and can be affected by various local cultures and languages.

Since the first step to success for a pediatric rare disease clinical trial is getting it off the ground, this means complex regulatory approval will be required. Sponsors can ensure the best start by finding a partner with regulatory expertise in the countries in which the trial will be run. For example, a rare diseases CRO with pediatrics trials expertise could be a highly beneficial partner.

Pediatrics CRO services and rare disease CRO services are also increasingly available on a more flexible basis under a functional service provider (FSP) model, helping sponsors overcome challenges in pediatric clinical trials while enabling them to retain overall control.

Trial Design Requires Innovative Thinking and Pediatrics Trials Expertise

The gold standard for clinical trial design is the randomized controlled trial (RCT). But what do you do when it’s not possible to run an RCT? That is one of the challenges of pediatric rare disease clinical trials, largely due to the nature of pediatric rare conditions.

An RCT tends to require large sample sizes, and the participants are grouped and may be given the treatment on trial or a placebo for comparison. This raises two issues for pediatric rare disease trials.

Firstly, clinical trials for rare disease therapies involve small numbers of participants simply because there are fewer people available for the trials because the diseases involved are rare. Because of this, there are usually too few participants to make grouping and control comparison a powerful approach. What’s more, the potential participants can be very different from one another, resulting in a heterogeneous sample, which may rule out an RCT.

Secondly, there are ethical concerns about giving participants placebos. Many rare diseases in children can shorten their lifespan. If a child participates in a clinical trial and is randomly assigned a placebo, they do not have the chance to (potentially) benefit from the intervention on trial. Parents may therefore be reluctant to enroll their children in a pediatric rare disease clinical trial at all.

One solution is innovation in trial design. Alternative trial designs can be used to get the results needed with a smaller number of participants, ensuring that everyone has access to the treatment. These may include, for example:

• Adaptive – with a more flexible methodology, this approach allows for smaller sample sizes
• Delayed start – after a first placebo-control phase, all participants receive treatment in the second phase
• Cross-over – all participants receive treatment and placebo, essentially functioning as their own controls

Patient Involvement Can Boost Pediatric Rare Disease Recruitment

If you find collaborators and design the perfect pediatric rare disease clinical trial, you still face the challenge of recruiting participants. There are, by definition, relatively few people with any given rare disease, so you may need to recruit a substantial proportion of them for the trial.

When considering recruitment, it is helpful to look at the barriers to enrolment. Why would a parent decide not to enroll their child in the trial? For example:

• Travel burden – reaching the trial location takes too long or the journey is difficult because of the disease
• Burden of participation – patients or parents feel the burden of participation is out of proportion
• Logistics – it isn’t possible to coordinate schedules of the clinical trial team, child and parents
• Trial design – the parents have objections to the approach, for example, the use of a placebo

Talking to patients and their families before the whole process starts can help. In one study, Patient Think Tank (PTT) members recommended involving patients in the design of the trial. And it’s important to plan for continuous, transparent communication throughout the trial process to ensure participants remain involved in the trial.

The increased decentralization of trials offers a solution to many logistical barriers. Telemedicine and other remote technologies can improve access and reduce the need to travel, helping more people participate in clinical trials for rare diseases. Working with a rare disease CRO that has experience with remote monitoring, for example, can be greatly beneficial. Pediatric rare disease clinical trials present a number of specific but significant challenges. But there are ways to overcome challenges in pediatric clinical trials and ensure such a trial is approved, started and managed well. One helpful option is to partner with a pediatric CRO or rare disease CRO with pediatrics trials expertise. And there are many good reasons to make the effort, not least helping the millions of children whose lives may be cut short by their rare diseases.

Pediatric rare diseases can pose many challenges for sponsors, from trial design to recruitment. Working with a CRO that provides pediatrics CRO services and rare disease CRO services can help boost the trial’s success. Siron Clinical has 25 years of experience in these fields, and our experts know how to overcome the challenges you might face. Read about our experience in pediatric and rare disease clinical trials, and contact us to talk about yours.