Pediatric
Advisory Subcommittee Meeting
Open Meeting
February 3
& 4, 2004
Overview
CDER’s Division of Medical Imaging and Radiopharmaceutical Drug Products
reviews and regulates imaging drugs that are administered in vivo and are used
for diagnosis or monitoring of disease with a variety of different modalities,
such as radiography, computed tomography (CT), ultrasonography, magnetic
resonance imaging (MRI) and radionuclide imaging. We are meeting to seek your advice on the
role that imaging drugs play in the diagnosis and management of cardiac disease
in the pediatric population.
Specifically we are seeking advice on the types of imaging drugs being
used routinely in the pediatric population and the purpose of that use. We are also interested in discussing the
safety profile of these drugs and the potential clinical benefits of their
use. This information will help the
Division understand where there is a critical need for further cardiac imaging
drug development for the pediatric population.
This information will help us prepare and issue relevant written
requests for pediatric studies.
To
prepare you for these deliberations, you will hear a series of expert
presentations on the use of cardiac imaging drugs in the pediatric
population. These presentations will be
focused on the four main imaging modalities: MRI, CT, ultrasound and nuclear
imaging. The drug classes to be
discussed include gadolinium, iodinated contrast, microspheres
and radiopharmaceuticals.
This
briefing book provides additional background material including several recent
review articles and the Draft Guidance for Industry; Developing Medical Imaging
Drug and Biologic Products (Parts1-3).
The draft guidance reflects the Agency’s current thinking on the
development of imaging drugs and biological products. The draft guidance discusses such issues as
safety, clinical indications and trial design.
Also
included in this briefing book are labels for each of the drugs to be discussed
by Dr. Solomon Iyasu, Medical Team Leader with the
Division of Pediatric Drug Development, on the morning of February 3. Per
section 17 of the Best Pharmaceuticals for Children Act, Dr. Iyasu will report on adverse events for the following drugs
that were granted market exclusivity under 505A of the Federal Food, Drug, and
Cosmetic Act: Paxil (paroxetine), Celexa (citalopram), Pravachol (pravastatin) and Navelbine (vinorelbine). We have included the labels for each of these
drugs in your background package so you can review them prior to the meeting.
Introduction
To
date the Division has not issued a written request for pediatric studies for
any imaging drugs with cardiac applications that are approved for use in
adults. Of those approved, the iodinated
contrast agents are the only drug class that has labeling for use in the
pediatric population for cardiac imaging.
Many of these drugs are approved for conventional angiography and are
labeled for use starting at the age of 1 year.
Other cardiac imaging drugs that are routinely used in adults and
sometimes in children do not have pediatric labeling.
Traditionally
adult cardiac imaging drug approvals have been based on data from studies
performed in a population suffering from coronary atherosclerotic disease. This disease process is not noted to be
prominent in the pediatric population and therefore, extrapolation of the adult
efficacy data to the pediatric population has not been considered a viable
option. To date, we have received waiver
requests for pediatric studies which cited lack of use in a substantial number
of pediatric patients and the lack of the occurrence of atherosclerotic
coronary artery disease in this population.
Many
of the products that are approved in adults detect or measure such parameters
as myocardial ischemia, left ventricular opacification,
and endocardial border delineation which intuitively
should have potential use in the pediatric population. Therefore finding the appropriate pediatric
populations in which this type of data would have clinical benefit is one of
the goals of this discussion.
Since
many of these products are not labeled for pediatric use, we have limited
safety information for this population.
Any information that we have stems from voluntary reports of adverse
events to FDA’s Adverse Event Reporting System (AERS). A search of this database was performed for
each drug class. One or two of the more
widely used marketed products per drug class were used for purposes of the
search. There were no reports noted for
specific drugs in the radiopharmaceutical and microsphere
drug classes. There were, however,
several reports noted by drug for the gadolinium and iodinated drug
classes. Most of these were reports of
nausea and vomiting and of allergic type reactions for the gadolinium drug
class and allergic type reactions (one of which resulted in death) for the
iodinated drug class. This database does
not allow for sorting based on the purpose of the study, therefore trends in
use could not be identified as part of this search. It is important to note that several
gadolinium products and iodinated products are approved for use in the
pediatric population for CNS imaging.
The
agenda for the Pediatric Advisory Subcommittee meeting begins the morning of
February 3 and will include presentations on each imaging modality on that
afternoon. The meeting will conclude with deliberation on a series of questions
to be held on
Draft
Questions for February 3 & 4, 2004
1. Given the differences in
cardiac disease processes that occur in adults and children, in what cases (if
any) can adult data from approved imaging drugs be extrapolated to pediatric
patients in whom cardiac imaging is needed?
If so, in what cardiac disease states?
2. Assuming further studies in
pediatric patients are needed, we would like you to further define the gaps in
our knowledge regarding imaging agents to be evaluated for cardiac imaging
applications.
Please discuss each of the following questions for
each imaging modality (cardiac CT, cardiac MRI, cardiac US, and cardiac nuclear
imaging)
a) What imaging agents need
further study?
b) What populations should be
studied?
c) What disease states should
be studied?
d) What endpoints should be
used?
e) How should a trial be
designed?
f) How should the standard for
comparison be defined? Is there a
gold-standard?
3. Are there new developments
in the field of adult cardiac imaging that may have potential application to
the pediatric population? Can we
anticipate the need for future drug development for pediatric cardiac
imaging?