Pediatric Rare Disease Clinical Trials

There are many challenges to overcome when running a clinical trial, and if pediatric rare disease treatments 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 those in children – 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 and you can find yourself facing major challenges. Why is this, and how can clinical trial sponsors overcome the challenges?

Geographic dispersal requires collaboration

People living with the same 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. Rare disease trials 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, such as a CRO, with regulatory expertise in the countries in which the trial will be run.

Trial design requires innovative thinking

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 trials.

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. There are usually too few participants to make grouping and control comparison a powerful approach. What’s more, the people can be very different, 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 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.

Patient involvement can boost recruitment

If you find collaborators and design the perfect 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.

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 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 these and ensure a pediatric rare disease clinical trial is approved, started and managed well. 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.

Read about our experience in pediatric and rare disease clinical trials, and contact us to talk about yours.