On May 6th, 2015 the FDA released a draft guidance on Leveraging Existing Clinical Data for Extrapolation of Pediatric Uses of Medical Devices. This guidance expands on the information provided in the final Premarket Assessment of Pediatric Medical Devices guidance originally published in 2004 and updated in 2014. The FDA believes that leveraging relevant clinical data may lead to more devices being approved for pediatrics. The guidance defines pediatric patients as 21 years or younger at the time of diagnosis or treatment.
As noted in the press release from May 6th, the objectives of the new draft guidance are as follows:
- To increase availability of pediatric devices by leveraging existing clinical data for use in pre-market approval applications (PMAs) and humanitarian device exemptions (HDEs).
- To explain when this is appropriate and to describe the approach to determine whether extrapolation is appropriate.
- To describe statistical methodology that can be used to leverage the data.
Extrapolation of adult data is limited to situations in which the course of the disease or condition and the effects of the device are sufficiently similar in adults and pediatrics. One example given in the guidance where extrapolation may be appropriate is in studies of devices that create intracranial arteriotomies in adults. This information can offer insight into the effectiveness of the device in pediatrics in the 13-21 year age range. This data may be used because it is widely accepted that cerebral vasculature of this pediatric age group is similar to that of adults.
The quantitative information gained from existing adult data can be incorporated either by full or partial extrapolation. Full extrapolation involves data from adult studies standing in for any potential pediatric data and is expected to be rare because of the potential differences in populations. This would also include consideration of other data sources including virtual simulations, bench data, mechanical models and case reports. Partial extrapolation from adult data combines existing data with pediatric data sources and would occur more frequently than full extrapolation.
A number of conditions are examined when considering the appropriateness of extrapolation including:
- The similarity between adult and pediatric populations
- Quality of adult data
- Decisions as to whether there is reasonable assurance of the safety and effectiveness
- Expected differences in the characteristics of the device, disease and outcomes for adult and pediatric populations
Some special considerations that affect only the pediatric patients include:
- Growth of the child during the device performance period
- Specimen sample quantity may be too large for neonates
- Reference values may be different for pediatric population
- Metabolic differences for therapeutic drug monitoring devices
- Increased impact of time exposure to younger subjects
The FDA states in the guidance that extrapolation will only be permitted when done in a manner that supports reasonable, scientifically sound conclusions about medical device effectiveness and safety based on valid scientific evidence. Extrapolation could be one solution to the potential challenges of pediatric clinical trials, which include small and scattered pediatric populations leading to small trial sizes; challenges in informed consent; and limited reference sample volumes from neonates or small children.
Do you feel that extrapolation from adult clinical data may provide a safe and effective way to gather information for pediatric trials?