Food and Drug
Administration
Center for Drug Evaluation and Research
Pediatric Oncology
Subcommittee of the Oncologic Drugs Advisory Committee
Jody
Pelusi, R.N., Ph.D. Gregory
Reaman, M.D.
Victor
Santana, M.D. Alice
Ettinger, R.N. Jerry
Finklestein, M.D.
Patrick C Reynolds, M.D. James
Boyett, M.D. Nancy Keene
(patient rep.)
Henry
Friedman, M.D., Ph.D. Susan
Cohn, M.D.
Malcolm Smith, M.D. Francesco Pignatti, M.D. Katherine Cheng, M.D.
Anne Mathieu-Boue, M.D. Gilles Vassal, M.D. Harald Schweim, M.D.
Mark Bernstein, M.D.
Anne
Hagey, M.D., Abbott Alan
Melemed, M.D., Lilly
FDA Participants
Richard Pazdur, M.D. Joseph Gootenberg,
M.D. Steven
Hirschfeld, M.D.
These summary minutes for the
I
certify that I attended the
_______________________________ _______________________________
Thomas H. Perez, M.P.H., R.Ph. Victor
Santana, M.D., Chair
Executive Secretary Chair
The Pediatric Oncology
Subcommittee of the Oncologic Drugs Advisory Committee,
of the Food and Drug Administration, Center for Drug Evaluation and Research
met
The
Committee discussed pediatric labeling of oncology products.
The Committee received a briefing document from the
FDA in preparation for this meeting.
There were approximately 40 persons in the
audience. The meeting was called to
order at
The
scheduled presentations began at
History of Pediatric Labeling Steven Hirschfeld,
M.D., Ph.D.
Case Studies of Case 1 By - Anne Zajicek, Pharm.D., M.D.
Pediatric Submissions Case 2 By - Ramzi Dagher, M.D.
for Oncology Products Case
3 By - Steven Hirschfeld, M.D., Ph.D.
Case 4 By - Susan
Honig, M.D.
Case 5 By - Alla Shapiro, M.D.
The presentations were
followed at
The
Open Public Hearing was held at
At
At
12:15 p.m. the Subcommittee paused for Lunch, and reconvened at 12:50.
The Subcommittee adjourned at 2:10 p.m.
Questions to the
Committee
Federal
government initiatives are aimed at developing therapeutics for pediatric
patients and including product information in the approved package insert or
product label. Although the majority of
children with cancer in the United States are treated on protocols from
National Cancer Institute supported study groups, the majority of products used
in children with cancer are used without dosing and safety information in the
package insert. Given that the U.S. Congress has indicated in the Best
Pharmaceuticals for Children Act of 2002 that pediatric use information should
be included in product labels as one of the mechanisms to publicly disseminate
that information, consider each of the following situations.
If
adequate and well controlled trials in children that independently establish
safety and efficacy are submitted to the FDA as a New Drug Application (NDA) or
Biological Licensing Application (BLA) or as a supplement to an NDA or BLA,
then product labeling would follow standard procedures. The situations that
follow describe circumstances when information other than adequate and adequate
and well controlled trials sufficient to independently establish safety and
efficacy are submitted.
The first questions pertain
to the situation where a product is approved (safety and efficacy established)
for an adult indication and the same disease or condition exists in a pediatric
population.
Previously the Pediatric
Subcommittee of the Oncologic Drugs Advisory Committee, at a meeting in
November 2001, recommended that to extend efficacy from an adult indication to
a pediatric population (use extrapolation), pediatric dosing studies and a
demonstration of clinical proof of concept should be performed.
1. If a product is approved for an adult disease or condition that also exists in children and extrapolation is used, consider what information you would consider necessary and appropriate to be in the product label.
Factors may include:
·
Dosing
·
Safety information
·
Proof of concept data regarding clinical effect in children
·
Separation of pediatric and adult safety data if differences exist
The Committee members
indicated that all information available should be included. Beyond the factors listed in the question the
committee mentioned the following other important information that it would
like to see included; pharmacokinetics, pharmacodynamic endpoints, dosing
schedules (as much precise information to guide dosing in children),
unacceptable toxic dose, dose limiting toxicity, and bioequivalence.
2. If pediatric dosing and
safety information are available but clinical proof of concept has not been
established, consider whether dosing and safety information be included in the
product label. This circumstance could
arise if studies were done in children with diseases other than the one that is
being considered for an indication yet extrapolation is being considered on the
basis of other evidence.
A statement of dosing and
safety may be included with comment on the limitations of the data.
The next question pertains
to the situation where there is not a linkage between an adult indication and
data from pediatric studies.
3. If pediatric dosing
information and proof of concept data exist for a pediatric disease or
condition that does not exist in adults, what information, if any, should be
included in the product label.
An
example may be that a product is approved for second line colorectal cancer in
adults and pediatric data are available for dosing and pharmacokinetics plus a
single arm phase II study showing a modest response rate in 20 pediatric
patients with refractory or relapsed neuroblastoma (There is no existing
product with this profile).
Factors may include:
·
dosing
·
safety information
·
clinical response data
The Committee agreed that
primarily dosing and safety information should be included. The information should be qualified with a
statement that efficacy has not been established in the approved indication.
The
following question pertains to the situation where there is no evidence of
clinical benefit in a pediatric oncology population and there are data of a
lack of activity
4. If dosing, safety, and lack
of activity information are available from studies that enrolled children with
cancer, consider what information, if any, be included in the product label.
Factors may include:
·
a statement restricted to stating that no meaningful clinical activity
has been observed
·
the number and diagnoses of the patients in the studies
·
dosing information
The Committee agreed that
primarily dosing and safety information should be included, and a statement
that no clinical activity was observed relative to a specific study or inquiry
with confidence intervals or other qualifying information as appropriate.
The following question pertains to the situation where no efficacy or
safety data are available in pediatric patients.
5. When no efficacy or safety data are available in pediatric patients
consider if a statement that safety and efficacy have not been tested in
children be included in the product label
A statement may be
appropriate if the date is referred to and qualifying information is
included. Refer to the meeting
transcript for the committee’s discussion of this question.