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American Pediatric Society & Society for Pediatric Research Pediatric
Medical Devices |
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August
20, 2004 Division
of Dockets Management RE:
Docket Number: 2004N-0254 To
Whom It May Concern: On
behalf of the 60,000 pediatrician members of the American
Academy of Pediatrics (AAP), I am pleased to respond to the Food
and Drug Administration's request for comments on a therapeutic
issue of importance to neonates, infants, children and
adolescents - the availability of appropriately designed and
adequately studied medical devices.
These comments are also endorsed by the pediatric
academic research community that includes the Ambulatory
Pediatric Association, American Pediatric Society, Association
of Medical School Pediatric Department Chairs and the Society
for Pediatric Research. AAP
and the pediatric societies are grateful for the FDA's inquiry
into this issue. For
the last 40 years the AAP has been sounding the alarm that
children have been left behind on the therapeutic advances that
are available to the adult population.
Great strides have been made to improve the availability
of drugs and biologics for the pediatric population; however,
devices remain a therapeutic frontier yet to be adequately
opened for children. The
FDA must be commended for its efforts to explore the issues
surrounding pediatric medical devices.
At the behest of Congress, the agency has recently
undertaken a two-prong approach to understanding the pediatric
needs and possible solutions to improving the availability of
medical devices for children.
First, in response to provisions within the Medical
Device User Fee and Modernization Act of 2002 (MDUFMA - Pub. Law
107-250) the FDA requested that the Institute of Medicine (IOM)
prepare a report to Congress on postmarket surveillance of
pediatric medical devices, due in October 2006.
The AAP has been actively participating in IOM meetings
on this topic and will be providing testimony at an upcoming
meeting on August 31. This
report will have an important but limited focus on postmarketing
issues related to pediatric medical devices.
The
second prong is focused on pre-market issues related to
pediatric medical devices.
The questions posed in this federal docket (2004N-0254)
will help illuminate the need for and the challenges to
improving the availability of pediatric medical devices. Another
component of the pre-market assessment of medical devices is the
FDA's Guidance
for Industry and FDA Staff: Premarket Assessment of Pediatric
Medical Devices, on May 14, 2004.
It is notable that the only guidance issued by the FDA
focusing specifically on pediatric devices was issued just one
year ago. This document is an important step toward assisting
device manufacturers in identifying the types of information
needed to provide reasonable assurance of safety and
effectiveness of medical devices intended for use in the
pediatric population. We
are hopeful but not confident that this guidance will serve as a
catalyst to encourage development of more pediatric devices. More must be done to ensure that pediatric populations
benefit from existing therapies or are the recipients of newly
developed ones. Neonates,
infants, children, and adolescents suffer from many of the same
conditions as adults (e.g., bone fractures, hearing
loss/deafness, ventricular anomalies), yet optimal care of these
populations often require that adult devices to address those
conditions be modified for their use in children.
In addition, some conditions occur only in pediatric
populations and require devices specifically designed for
children's needs (e.g., many forms of congenital heart disease.) In all cases, pediatric populations deserve devices that are
safe and effective with respect to their age, size,
developmental status and other physiological characteristics.
In our view, it is not a question of whether pediatric
populations require devices appropriate to their needs, but
rather, how those needs can best be addressed.
Children's
medical device needs differ considerably from adults across a
broad range of illnesses, conditions, and subspecialties.
To ensure the optimal safety and efficacy of devices used
by children, it is critical that medical devices address the
particular needs of children, including:
In
responding to the FDA's request, our comments draw from both the
experiences of the pediatricians
and researchers and from the discussion and outcomes of a
stakeholders' meeting on pediatric device development co-hosted
by the American Academy of Pediatrics, the Elizabeth Glaser
Pediatric AIDS Foundation, the National Organization for Rare
Disorders, and the National Association of Children's Hospitals
on June 28, 2004. In
this meeting, participants including pediatricians, children's
advocates, biomedical engineers, medical device companies, the
FDA, the National Institutes of Health, and the Institute of
Medicine identified a range of unmet pediatric device needs, the
barriers to addressing those needs, and possible mechanisms for
increasing the availability of pediatric appropriate products. The
following is the AAP and pediatric academic societies response
to the three questions posed in the Federal Register Notice. For the sake of clarity, we have combined our comments on the
second and third questions, to more clearly link the barriers we
have identified with proposed solutions.
We
begin our comments with a general recommendation: The recent establishment of both an Office of Pediatric
Therapeutics (OPT) within the Office of the Commissioner of the
Food and Drug Administration and a Pediatric Advisory Committee
(PAC) are extraordinarily positive actions that will serve to
advance therapeutics for infants, children, and adolescents.
The AAP and pediatric academic societies strongly urge
the FDA to integrate pediatric devices in the agenda of both the OPT and the PAC. What
are the unmet medical device needs in the pediatric population
(neonates, infants, children and adolescents)?
Are they focused in certain medical specialties and/or
pediatric subpopulations? There
is clearly an unmet need for appropriate therapeutic devices for
pediatric populations. Examples
are numerous and varied, including the need to improve existing
devices or the creation of pediatric-specific devices.
The following examples illustrate needs:
The
vast majority of pediatricians and pediatric subspecialists we
surveyed reported that many of the devices they needed for their
pediatric patients simply were not designed and labeled for
pediatric use. The
lack of pediatric labeling meant that they were not always
confident of the optimal way to use a device nor did they feel
like they had sufficient knowledge of risk or potential adverse
events. Also, they
reported extensive off-label use of adult devices in children
that in some cases included the need to fashion make-shift
device solutions for pediatric use.
In other instances, available adult devices were entirely
inappropriate for use in children, often because of sizing.
In those situations, the providers were forced to use
older or less optimal interventions that they viewed as less
effective and/or higher risk.
It
is important to note that "off-label" use of a device
does not imply an improper or illegal use.
Indeed, this off-label use may represent the only, or
best, treatment available for a specific illness in a child at
the time the device is needed.
However, off-label use of a product should not be viewed
as the standard of care. In
addition, the lack of pediatric testing and labeling means that
the long-term impact of many devices now used by children is
unknown. For
example, we do not have a full understanding of the impact of
long-term device implantation in children (e.g., absorption rate
of polymer plating for cranio/facial devices; gastrostomy tubes)
or the impact of devices on organ growth for infants and
children (e.g., titanium devices used in oral/maxillofacial
surgery, "undersized" heart valves used in infants and
children). Also,
calcification on heart valves is an adverse event in children
that cannot be predicted from the adult experience. Another
important consideration is that the deficiency of pediatric
devices may translate to an issue of reduction of access to
appropriate care for infants, children and adolescents.
If proper therapeutic technology is not available for
children, then they may be denied appropriate care or the care
they receive may be sub-optimal compared to adults.
Two examples help illustrate this point:
According
to our pediatricians, having to use either inappropriately
designed devices or less advanced interventions may lead to a
range of problems with implications for children's health,
including:
What
are the possible barriers to the development of new pediatric
devices? Are there
regulatory hurdles? Clinical
hindrances? Economic issues?
Legal issues? What could FDA do to facilitate the
development of devices intended for the pediatric population?
Are there changes to the law, regulation, or premarket
process that would encourage clinical investigators, sponsors,
and manufacturers to pursue clinical trials and/or marketing of
pediatric devices? 1)
Barrier: Lack
of Market Awareness of Pediatric Need It
is important to state that the lack of availability of
appropriately designed and studied pediatric devices appears to
be based in part on a lack of understanding of need and
importance of devices for children; not an intentional effort to
bypass the therapeutic needs of infants, children and
adolescents. There
are important lessons learned from regulatory and legislative
efforts to advance the availability of drugs and biologic
products for pediatric populations that may be applicable to
devices. Part of
the solution to this barrier may be to actively encourage device
manufacturers to consider the pediatric population as they
proceed through the design and application process for new
devices or indications. Recommendations:
Congress should consider establishing the presumption
that devices manufactured for adults should also be required to
be designed for and tested for pediatric populations if the
indication occurs in those populations.
Similar to the Pediatric Research Equity Act, the
parameters of this requirement could be drawn to take into
account feasibility, medical and ethical concerns, and the
public health interest in not delaying the development of
devices for adults. 2)
Barrier: Lack
of Market Stimulus Analogous
to the situation with pharmaceutical products prior to the
passage of the Food and Drug Administration Modernization Act of
1997 and the Pediatric Research Equity Act of 2002, the most
significant barrier to the development of devices designed to
meet children's needs appears to be the small share of the
market represented by pediatric populations.
Without either a requirement to design and test products
for pediatric use or sufficient incentives to do so,
manufacturer interest in producing pediatric devices is limited,
particularly for conditions that occur in only small numbers of
children. Another
barrier that has been raised is that device manufacturers have
expressed ethical concerns related to conducting pediatric
trials. Over
the last number of years, there have been tremendous advances to
ensure that pediatric patients in clinical trials are
appropriately protected.
Ethical concerns can and have been addressed in clinical
trials related to pharmaceuticals.
There is no reason to expect that the device industry
need be any less successful in developing well-designed ethical
pediatric studies. Recommendations:
Congress should also consider the creation of financial
incentives, including grants or guaranteed loans for R&D to
small companies, modifying the existing Humanitarian Device
Exemption provision to allow for profit, and financial support
for prototype development and the conduct of clinical trials,
possibly through a network structure.
In
considering the creation of these incentives, Congress should
weigh carefully the magnitude of the benefit to manufacturers in
relation to the likelihood of the incentive to stimulate the
development of safe and effective products appropriate for
pediatric needs and important to children's health.
In addition, thorough consideration should be given to
minimizing the potential for misuse of any incentives and to
ensuring that federal support supplements, rather than supplants
existing manufacturer capacity.
In
addition, funding for the expansion of existing grant or loan
guarantee programs or the creation of new ones, should not be
limited to only federal contributions.
Congress should think creatively in identifying means to
partner with private entities to develop funding streams for
these programs that will be sustainable through tight federal
budgets. 3)
Barrier: Lack of
Mechanisms for Systematically Identifying Pediatric Device Needs While
individual pediatricians and pediatric subspecialists are well
aware of the needs faced by their individual patients, no
mechanism exists for systematically collecting this information
or for conveying it to device manufacturers or regulators.
Also, no process exists for prioritizing device needs
once identified, e.g., existing devices not sufficiently
studied, new devices, "low-hanging fruit".
In addition, FDA does not currently have a system for
identifying from device applications or approval which devices
have pediatric indications or have applicability to pediatric
populations Recommendations:
It appears unlikely that simply facilitating the
communication of needs by pediatricians to medical device
manufacturers will result in any significant increase in general
interest by device manufacturers in producing pediatric
products, for the reasons stated in the first barrier identified
above. However, the
development of a mechanism for sharing that information may be
useful in select circumstances in helping a manufacturer
identify a potential market for a new or modified product. In addition, such a mechanism could be useful for identifying
opportunities for collaboration between manufacturers with
pediatricians or institutions, (e.g., a manufacturer agrees to
try to modify a product for pediatric use with assistance from a
pediatric research specialist or children's hospital in
conducting a clinical trial.) We
would also recommend that FDA use the recent statutory
requirement to exempt pediatric devices from user fees as an
opportunity to create a system to identify and track pediatric
devices, both those specifically intended for use in children
and those devices labeled for adult or general use that are
intended for conditions that occur in pediatric populations.
Such a system could be used, for example, for FDA to
identify devices that require only slight modifications or
minimal additional testing to obtain a pediatric indication and
to communicate the necessary data requirement to the
manufacturer. This system could also be used to identify devices eligible
for incentives or should be subject to a requirement to test in
children. 4)
Barrier: Lack
of clarity about what types of data are acceptable to FDA as
valid scientific evidence to demonstrate safety and
effectiveness. Recommendations:
FDA should clarify for manufacturers acceptable data for
determining safety and efficacy of pediatric devices.
Specific issues that need clarification include the
acceptability of data gathered in the course of clinical care
without informed consent. For
example, it would be important for FDA to consider allowing
flexibility in developing standards for parameters of efficacy
in children that do not depend on measures of pulmonary
function, and accept those parameters as proof of efficacy. 5)
Barrier: Study
Designs Recommendation:
FDA should design studies of new medications that
utilize devices so that the drugs and devices will be studied in
ways that they will be used clinically.
For example, insist that all new hydro-fluoroalkane (HFA)
devices that will have pediatric labeling be studied with
spacers/holding chambers (e.g., devices that help the drug get
delivered to the lungs because the aerosol particles get held in
the spacer/holding chamber rather than requiring that small
children inhale exactly when the meter dose inhaler is
actuated.) In addition, in specific circumstances FDA should consider
allowing that certain studies be designed without placebo arms
for infants and young children, to improve the ability to
recruit patients into such studies. Thank
you for the opportunity to comment on such an important
pediatric issue. The
American Academy of Pediatrics and the pediatric academic
societies stand ready to work with the Food and Drug
Administration and Congress to discuss ways to improve the
availability of pediatric devices and to implement the proposed
recommendations. Sincerely, Carden
Johnston, MD, FAAP CJ:ehv Endorsed
by: |
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