Download Theattached information wasreceived by FDA fiomthe OficeofManagement and Budget. This

EWEi3/98
08:52
NO.573
Theattached information wasreceived by FDA fiomthe OficeofManagement and Budget. This
informationwas received by OMB at a meeting with the attendees on the list enclosed This
meetingwas held on July28, 1998, OMB staff have statedthatthe meeting was held in
accordance with the guidelines specified in Executive order 12866.
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202 395 6974
OMB DEP DIR MGMT
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P. 03/06
395 6974
Changes Necessary
toconforrn
Proposed
Regulations
onDissefination
ofInformation
onOff-Label
Congressional
Intent
us~ to
1. Definition
~eterminatiofi.
1nvestiiPation” and “Scientifically
of ’’Chical
The law authorizes
distribution
of scientific articles, peer reviewed
, . . which would be considered
by experts, “about a clinical investigation
insuring quality and accuracy, the proposed re~ati~ns
restrict scientific articles and reference publications
two ways.
to be
sound by such experts”. Instead of relying on peer review as the basis
scientifically
for
Sound”
wo~d
S@TIfiCEHItlY
eligible for dissemination
in
First, the proposal crafts a narrow definition of “clinical investigation”,
which restricts “clinical investigations”
Second, the proposed
clinical investigations
to those that are prospectively
regulation would authorize FDA to determine
described in articles are “scientifically
intended that a scientific journal’s peer reviewers,
planned.
whether the
sound.
Congress
and not FDA, be the judge of
scientific soundness.
The definition of “clinical investigation”
proposal
In addition,
investigation
the entire concept of FDA review of whether
is scientifically
2. “Economimllv
manufacturer
6hould be deleted horn the
sound must be deleted.
Prohibitive”
who seeks to disseminate
ExceM,ion.
itiormation
The law requires that a
about a new use either certifj
that It has filed (or within 6 months will file) a supplemental
NDA5LA
use, or will subxuit a proposed protocol and schedule for conducting
\\wc
. 59239al
- 08s1sss.0!
a clinical
for the new
studies
98/03/98
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DMB
necessary todoso.
DEP
395 6974
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The law authorizes
Secretary determines
thatitwouldbe
necessary for the mbmission
P. 134/06
.202 395 6974
an exception to these requirements
economically
ofa supplemental
prohibitive
application.
ifthe
to incur the costs
The law requires
FDA
to consider (in addition to other considerations it may find appropriate) the lack of
availability
of exclusive marketing
population
rights for the drug and the size of the patient
expected to benefit fkom the approval of the supplement.
The proposed regulation
factors specfied
exception
available
only in the case in which the estimated
new use exceeds the estimated
Enormously
cost of studies of the
about pricing and market share would be required
The final regulations
requiring that estimates
prohibitive”
total revenue from the drug (less expenses).
detailed information
to be submitted.
ignores the mandate to consider the two
in the statute and instead makes the “economically
should dispense with the entire concept of
of economic benefit to the manufacturer
from all sales of
the drug be less than the costs of studies of the new use. In its place, l?DA should
establish
a simple, bright line teet, based on the two statutory criteria, speci&ing
that (1) no market exclusivi~
Waxrnan-Hatch
resulting from patents, orphan drug exclusivity
statutory exclusivity
provisions
or
are available for the medical
product that is the subject of the scientific publication
or
(2) the patient population
likely to be served by the new indication will not exceed an established
number,
such as 100,000,
3.
fkom
~~wc
“Ethical” Exce~ tion. The law likewise authorizes
the supplement/protocol
. 59$8%31
- 00915
s2,01
requirements
2
P005/007
an exemption
on the basis that it would be unethical
B8/03/98
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OMB DEP
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the FDA, in determining
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DIR
to conduct the studiesnecessary
202
MG1’lT
for the supplemental
applicaticm.
395
6974
whether such studies would be unethical,
report spells out circumstances
determination
to consider
suggests consideration
application
the standard of care: examples
or practice guidelines.
of the exemption
But the proposed
regulations
to situations in which withholding
course of a clinical trial would present an unreasonable
Again, in the interests
Congressional
The Iaw also
of whether the new use involves a combination
involving more than one sponsor.
m the
that may be used by FDA in making its
as to whether the new use represents
include inclusion in specified compendia
P. 05zD6
The law requires
whether the new use involved is the standard of care. Detailed language
conference
of products
would limit
the drug in the
risk of harm to patients.
of creating only a very narrow exemption,
FDA has ignored
intent.
The final regulations
FDA in determining
should establish a bright line to be applied by
whether to grant an exemption
on ethical grounds,
The bright
line test should be (1) that the new use represents the standard of care, as
represented
by inclusion in specfied
new use involves a combination
grant exceptions
4.
or practice guidelines;
of products of more than one sponsor.
60 Dav Review Period.
proposed regulations
determine
compendia
on other grounds on a case-by-case
FDA make a determination
or (2) the
FDA should
basis.
Despite the fact that the law requires that
on an application
contemplate
P006/’007
to disseminate
within 60 days, the
that during the 60 day period FDA could
that FDA requires more information.
In .sLuchcase, the proposed
EHz03/98
DB:53
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(IMB DEP DIR MGMT
12:15
regdationsimpose
on FDAno
apprcwing/disapproving
day requirement
20.2 395 6974
time fkames for obtaining additional
the application.
The final regulations
by requiring that any judgment
decision to allow or disalIow disseminatio~,
i.nformation
P007/@
P .a6A36
and
should honor the 60
as to completeness,
as well as the
be made within the 60 day statutory
period.
5. ~
w Use”. The law applies to dissemination
of
scientflc information on a “new use” of an approved drug, defined as “a use not
included in the labeling” of the product.
regulations
and its preamble
approved indications
The definition of “new use” in the proposed
should be narrowed
to delete comparative
claims for
and claims for subpopu.lations.
TOTQL P .06