Marie Thibault

FDA has tried to tackle the dilemma of off-label use of medical devices in children by giving industry guidance on extrapolating adult clinical data to pediatric use. In early May, FDA released draft guidance, titled “Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices.”

Today, there are few medical devices that are expressly labeled and indicated for pediatric use. FDA points out that part of the problem is the lack of enough pediatric patients to gather large trial sizes, hurdles around enrollment and consent, more deviation in traits like anatomy and physiology across pediatric groups than with adult populations, and the fact that in some cases, necessary blood reference samples are too large to take safely from a pediatric patient. As a result, many devices that are labeled for adult use are used off-label in children.

This new draft guidance points out how extrapolated data can be used, details full versus partial extrapolation, includes a extrapolation decision tree, explains limitations, and gives a number of hypothetical examples. Full extrapolation means the extrapolated data is meant to stand in for any prospective pediatric data, while partial extrapolation is used to supplement pediatric data. FDA states that, "given the range of potential differences between adult and pediatric patients, full extrapolation of existing clinical data to demonstrate safety is expected to be rare." 

In addition, deciding to extrapolate adult data for pediatric effectiveness is a separate decision than extrapolating for pediatric safety. According to the draft guidance, "because of the physiological differences between adult and pediatric patients that may affect device safety and the inherent difficulties in designing and powering clinical studies that provide comprehensive assessments of safety, extrapolation for safety is expected to be rarer than extrapolation for effectiveness."

The draft guidance pertains only to premarket approval and humanitarian device exemption submissions. FDA staff emphasized this during a May 19 webinar on the guidance, when a member of the webinar audience asked if this document could be used when considering 510(k) device submissions. 

Included in the document is an extrapolation decision tree that can be used to help decide whether adult data is a "candidate for full extrapolation," a "candidate for partial extrapolation," or "do not extrapolate." Some of the reasons that adult data should not be extrapolated include if there "is little knowledge of the disease or condition in pediatrics," "the device is not FDA approved or cleared for adults," or "statistical models cannot account for differences," among other factors. 

This month's draft guidance follows years of FDA consideration of pediatric medical devices and data extrapolation. Final guidance was published in 2004 on "Premarket Assessment of Pediatric Medical Devices" and was updated in 2014. Congress passed the Pediatric Medical Device Safety and Improvement Act in 2007 and FDA issued a final rule on Pediatric Uses of Devices in 2014, after scrapping an earlier 2010 version. Guidance around this rule was issued in 2014 as well. 

Marie Thibault is the associate editor at MD+DI. Reach her at [email protected] and on Twitter @medtechmarie. 

[Image courtesy of PRAISAENG/FREEDIGITALPHOTOS.NET]