How are devices approved for paediatric patients?

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ver the last decade or so, medical device innovation has gathered pace. In 2018, the US Food and Drug Administration (FDA) approved 35 high risk and 44 low-risk novel medical devices, compared to 22 and three respectively in 2010. New technologies, such as artificial intelligence and 3D printing, have opened new possibilities, and the industry has been highly responsive.

Unfortunately, not all patients have benefited equally from this wave of innovation. Paediatric device approvals continue to lag behind adult ones, with many devices never approved for use in infants and children.

Between 2009 and 2019, only 24% of all FDA-approved devices had labelling inclusive of paediatric populations. Even within that bracket, there is a skew towards older age groups. Over 90% of that paediatric labelling is for 18-21-year-olds, who are considered part of paediatrics when it comes to medical devices.

Often, paediatricians will use a device ‘off-label’, which has never been formally tested in children. Although they may have evaluated the devices themselves, using small studies, they lack the assurance of large clinical trials. The parents are placed in the awkward position of choosing between a device only approved for adults, or no treatment at all.

“When a device is used on a paediatric population ‘off-label’, it hasn’t been designed, evaluated and approved for that population,” explains Dr Vasum Peiris, chief medical officer for paediatrics and special populations at the FDA’s Center for Devices and Radiological Health (CDRH).

“It exposes the patient to a different benefit-risk profile, which may not have been fully evaluated prior to the device coming on the market. When that occurs, it can in some instances lead to potential for adverse events that may not have been thought about.”

Dr Daniel Burnett, an advisor on the Pediatric Device Consortium at UCSF and CEO of JustAir, has several projects in the paediatric space. These include a device to treat pectus excavatum, a feeding tube to optimise neonatal feeding and a device to monitor breathing in babies in developing countries. He points out that children have distinct biological needs, and should not simply be regarded as small adults.

“There has been a big push lately to look at sex as a biological variable in studies, as simply studying the device in males does not allow you to always directly translate to females,” he says.

“The same is true, and even more so, in the paediatric population. Not only is the physiology different in paediatric versus geriatrics, the actual device sizing is also an issue. For this reason, I am a proponent of also looking at age as a biologic variable.”

In 2018, Dr Peiris spoke out about this problem at the first Stanford Pediatric Innovation Showcase, and then again at the FDA Public Meeting on Pediatric Medical Device Development. He made the point that the gap between paediatric and adult medical device approvals was widening, meaning younger patients were becoming more vulnerable.

“The data that we shared during the FDA public meeting really captured the fundamental issue, which is the fact that so few of the novel technologies that are being developed into medical devices are being developed for paediatric patients,” he says.

“Over more than a decade of our PMA and HDE [humanitarian device exemption] devices, less than 10% of those approved through the CDRH are labelled for the 18-year-old-and-under population, and only about 3% to 4% are labelled for the neonate population.”

There are a few reasons why this might be. The paediatric population is a fraction of the adult population, not to mention a population that gets sick less. This means the overall market is much smaller. The devices can also be harder to design and there are complexities around enrolling children in clinical trials.

“Children are a vulnerable population, so consent for studies must be obtained from their parents,” points out Dr. Burnett. “Having a sick child is very emotional and most parents aren't in the mind space to enrol their children in studies. In addition, the FDA and clinicians are also more protective of this vulnerable group and studies may require more burdensome regulatory pathways.”

Dr Peiris adds that these populations are small, heterogeneous and geographically dispersed, meaning evidence generation becomes challenging.

“It can be difficult to engage these dispersed patients in a clinical trial and clarify the information necessary to ensure that a new device is safe and effective,” he says.

“Let’s say that for a paediatric device that’s being developed, we ask for 50 patients in the clinical trial, and let’s say that the sponsor is able to contract with one institution that deals with about ten of these cases each year. It would take about five years to collect all 50 patients.”

In the three years since the FDA meeting, the situation has improved somewhat. The 2019 US federal budget included an additional $1m for the FDA ‘to improve infrastructure for conducting paediatric device trials’. The FDA has also issued guidance documents on real-world evidence, and how it can be applied to paediatric devices.

Most notably, Dr Peiris’ team has developed a strategic framework called SHIP-MD (‘the system of hospitals for innovation in paediatrics – medical devices’). This is a broad collaborative effort, with input from the public and private sectors, which strives to create a network of hospitals and academic medical centres that care for children.

“It is intended to create an economy of scale around paediatric medical device development, so that it makes sense for innovators and sponsors and companies to enter this market,” he explains. “Fundamentally, we want to de-risk this process, both from a financial and a product development standpoint.”

With the new system in place, the clinical trial sponsor would be able to contract with multiple institutions simultaneously. To revert to the earlier example, if five hospitals were contracted rather than just one, you’d be able to generate the evidence in one year rather than five. This would speed up the process and cut costs for the sponsoring company.

“That type of system can certainly begin to alter the traditional business thinking around entering the paediatric medical device market, says Dr Peiris. “We really want to create a system that helps to incentivise companies to enter, sustain themselves and innovate in this market.”

He hopes that once the economies of scale become apparent, we may reach a point where devices are being developed for children on a regular basis. We may even see devices being developed specifically for children, before being brought on-label for adults via a kind of ‘reverse extrapolation’ process.

Overall, he thinks industry has an opportunity here to shake up its business models around paediatric device development.

“If I was to provide one simple piece of advice, especially for the companies that have a broad portfolio of medical technologies and medical devices, it would be to begin to consider how you'd be able to bring those devices on-label for paediatrics,” he says. “Think about perhaps setting up a centre of excellence for paediatrics within your organisations and institutions.”

While the challenges aren’t likely to go away any time soon, the situation is at least being given the attention it deserves. Some recent high-profile device approvals may also give grounds for optimism – including Medtronic’s paediatric dialysis machine and the first game-based digital therapeutic for children with ADHD.

“It is a tricky problem, since this is a vulnerable population and needs extra protections,” says Dr Burnett. “I am hoping that the key resistance points in developing devices will relax so that more innovators will be interested in this market despite its smaller size.”