A new draft guidance document quietly issued last week by the US Food and Drug Administration (FDA) is intended to explain how medical device manufacturers can show their devices are safe for use in pediatric populations.
There is often a "paucity of scientific evidence available to substantiate submissions for devices that are indicated for use in the diagnosis or treatment of pediatric patients," FDA explains in the forward of its new draft guidance, Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices.
That's not concept unique to medical devices. Pharmaceutical products share the same "paucity" of data, mostly owing to ethical concerns or difficulty recruiting pediatric patients for clinical trials. As regulators often say, children are not simply "small adults." They metabolize and process medication differently than do adults, which can make it difficult for companies to extrapolate data obtained in adults to pediatric patients (e.g. the proper dosing or the safety profile of a drug).
But unlike pharmaceuticals, medical devices can benefit from data extrapolation. That's because their primary mode of action is typically mechanical in nature—not chemical or biological. While that can still pose some serious design challenges and physical limitations, it means that a device which is safe and effective in adults will in many cases be safe and effective in children as well.
That's good news for regulators—and the companies they regulate, too.
"FDA believes that leveraging relevant available clinical data, when appropriate, may lead to more devices being approved for pediatric indications, which will increase the availability of medical devices with appropriate labeling to support safe and effective device use in pediatric patients," FDA's Center for Devices and Radiological Health (CDRH) in its new guidance. "This approach will potentially streamline the requirements for establishing a pediatric intended use claim, and enhance and encourage pediatric device development programs."
For companies, that means they could obtain a larger market for their products with relatively little effort.
Thinking About Extrapolation
What will it take for companies to extrapolate clinical data to pediatric uses? As FDA explained in the guidance, companies will need to follow "scientific principles."
"If it is determined that clinical data are needed, it may be that the course of the disease and the device’s effects are similar in adult and pediatric patients," FDA noted. "In such a situation, the pediatric indication may be supported by the adult data with limited additional safety data in the pediatric population.”
In other words, data extrapolation does not exist in a vacuum. Rather, it relies upon basic confirmatory evidence which is generally narrower in scale than the initial testing in adult populations.
"The agency recognizes that the amount and type of evidence required will depend on a number of factors, including the nature of the device, what is already known about the product in the adult population (if relevant), what is known or can be extrapolated about the device to the pediatric population, and the underlying disease or condition being treated," FDA added.
FDA may determine that because the course of the disease or condition is "sufficiently similar in adults and pediatric patients," adult data may be used to support pediatric applications. "Full extrapolation of safety data is expected to occur rarely," FDA wrote.
The guidance goes on to explain the details of the extrapolation process. For example, sponsors may leverage existing clinical data either in full or in part, depending on the applicable variables.
One of the major challenges, FDA said, is likely to be related to the safety of medical devices. "Extrapolation for safety is expected to be rarer than extrapolation for effectiveness," FDA adds. Other challenges that might limit extrapolation include a lack of knowledge about the disease in the pediatric population, inability to borrow endpoints, if the device is not approved or cleared for adults, and whether human factors or growth affect the safety of the device in pediatric patients.
Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices