Having a sick child can be one of the hardest jobs of parenting. Having a sick child that requires treatment and care beyond a quick visit to the local doctor or nurse, or light fluids and lots of rest can cause the worry to rise exponentially. And what if treatment involves a procedure involving an experimental medical device? A recent guidance published by the FDA on March 24, 2014 attempts to clarify the department’s thinking on how to effectively protect the pediatric population. This guidance comes after the FDA issued a finale rule on January 10, 2014 amending PMA regulations to require inclusion of information relating to pediatric subpopulations that suffer from the disease or condition that a device is intended to treat, diagnose, or cure, and the number of affected pediatric patients. This guidance caps off a series of rules and guidance’s issued over the last 13 years when, in 2001, the FDA issued an interim rule to comply with the Children’s Health Act of 2000. This interim rule mandated that all pediatric research in the US offer additional protections to ensure pediatric patient safety.
Between 2001 and today, there were three additional laws enacted to ensure protection
of our most precious population.
- 2002 – Medical Device User Fee and Modernization Act (MDUFMA). This act entails that medical device advisory panels “includes, or consults with, one or more pediatric experts” and requested a study as to whether postmarket surveillance provide “adequate safeguards regarding the use of devices in pediatric populations.”
- 2007 – Food and Drug Administration Amendments Act (FDAAA). This act required any sponsor of a premarket application, humanitarian device exemption or product development protocol to submit information to FDA regarding how many pediatric patients are affected by the disease or condition their product is intended to treat.
- 2013 – Title V of the Food and Drug Administration Safety and Innovation Act (FDASIA) established new requirements to ensure that pediatric studies are completed.
The 2014 rule and guidance stems from the MDUFMA of 2002. The recently issued guidance had three primary objectives.
- To help define the pediatric population and pediatric use for medical devices.
- To help identify the types of information needed to provide reasonable assurance of the safety and effectiveness of medical devices intended for use in the pediatric population.
- To help define the guiding principles and protections sponsors should consider for pediatric subjects in device clinical trials.
Pediatric subgroups have been broken into four groups: Newborn (Birth - 1 month), Infant (1 month - 2 years), Child (2 years – 12 years), and Adolescent (12 years – 21 years). Additionally, the agency recognizes that factors other than chronological age may be more appropriate indicators including “subject’s weight, body size, physiological development, neurological development, and neuromuscular coordination”. It is interesting that the upper age limit has been raised to 21 years and the FDA concedes that this definition is controversial and potentially “arbitrary”. The age also runs counter to federal and state laws regarding the age appropriate for informed consent.
For conducting a clinical study, the FDA recommends that a number of factors be kept into consideration. These recommendations center around the fact that what is appropriate in adults may not be appropriate in children. This includes anatomical and physiological differences, activity and maturity level, immune status, hormonal influences, disease or condition, growth and development, height, and weight. Additionally, there is not a one size fits all mentality for how device trial data for adults may be applicable to children. Furthermore, what may be appropriate for comparing adult trial data with the adolescent subgroup may not work with the infant subgroup. It is recommended that labeling of devices should include whether the intended use is for all pediatric subgroups or specific pediatric subgroups. The FDA is committed to “following the least burdensome principles” and recommends that when developing medical devices for pediatric use that the manufacturer take into consideration both pediatric subgroups and risk assessment and mitigation. For risk assessment and mitigation, the following factors should be considered.
- Age and degree of physiological maturity of the child
- Nature and natural history of the clinical condition to be treated
- Presence of complication clinical conditions
- Safety and effectiveness of the device that may have been demonstrated in older patients, or that is expected on the basis of other clinical or preclinical investigations
- Likely duration of device use and its impact on the growth and development of the child
Ultimately, the device itself will determine which pediatric subgroup is appropriate and what risks need to be assessed and mitigated. Hopefully with this FDA guidance, manufacturers will have the proper tools at their disposable in developing pediatric devices that are both safe and effective. To put this in perspective there are currently 12,803 registered studies involving a medical device, of which 520, or 4.1%, involve pediatric devices. With these additional steps over the last 14 years put into place, parents can be more assured that the next time their child gets sick that the proper safeguards have been put into place to protect them and effectively treat to make them better.
Do you have experience working in pediatric clinical trials? Do you feel these laws and guidances are enough?
Photo Credit: Stanford Medical History Center