INTRODUCTION
Madam Chairman and Members of the Committee. I appreciate the
opportunity to testify on the
important issue of promotion of unapproved uses of prescription
drugs and medical devices.
My name is William B. Schultz. I am the Deputy Commissioner for
Policy at the Food and Drug
Administration.
FDA SUPPORTS THE DISSEMINATION OF INFORMATION TO PHYSICIANS
Madam Chairman, I am here today to talk about uses that do not
appear in a product's FDA-approved labeling and are not approved
by the Agency. Such uses commonly are referred to as
"off label," "unapproved," "unlabeled," or "extra-label" uses.
The Food and Drug Administration
recognizes that, in certain circumstances, off label uses of
approved products are appropriate,
rational, and accepted medical practice. FDA knows that there
are important off label uses of
approved drugs. In this context, it is important that physicians
have access to accurate information
about drugs. But we also know that allowing the promotion of
these kinds of uses can have
negative public health consequences -- including exposing
patients to unnecessary risks and
destroying the incentive for companies to conduct the necessary
research to demonstrate that
products are safe and effective for these uses. Striking the
proper balance between the need to
regulate the promotion of unapproved uses for drugs and devices
and the need for reliable
scientific data and information on unapproved uses of approved
products is a difficult and
controversial challenge.
I would like to start today by explaining how, in passing and
amending the Federal Food, Drug,
and Cosmetic Act (FDC Act), Congress struck that balance and
what, as a result of Congressional
decisions, FDA can and cannot do with respect to off label uses.
The legislative history of the Federal Food, Drug, and Cosmetic
Act indicates that Congress did
not intend FDA to interfere with the practice of medicine. Thus,
once a drug is approved for
marketing, FDA does not generally regulate how, and for what
uses, physicians prescribe that
drug. A physician may prescribe a drug for uses or in treatment
regimens or patient populations
that are not listed in the FDA approved labeling.
Generally, FDA does not prohibit the dissemination of information
to health care professionals.
Physicians access information about off label uses through
compendia, journal articles, continuing
medical education programs, symposia, and professional meetings.
Physicians also have access to
a number of databases that provide information about off label
uses. For example, the National
Cancer Institute's Physician Data Query (PDQ) system is an
excellent source for oncologists to
obtain information about current oncologic therapies. The
National Library of Medicine (NLM)
offers a Medical Literature Analysis and Retrieval System
(MEDLARS), which is a computerized
system of databases and databanks pertinent to biomedical
research and patient care. NLM
currently offers free access to three databases relating to AIDS.
FDA does not regulate a
physician's access to any of these types of independent off label
use information -- no matter how
preliminary it may be. In addition, FDA does not prohibit a
manufacturer from providing a
physician information about off label uses if the physician
requests that information. Recently, the
Agency announced a proposed change to its policy with respect to
the dissemination of reference
texts (medical textbooks and compendia). Drug companies may
distribute independent reference
texts even if they contain certain information about off label
uses of approved drugs, as long as the
texts do not have a significant focus on an off label use of the
manufacturer supporting
dissemination of the text. FDA recognizes that all of these
sources of information can be very
important to good medical practice.
Although the FDC Act does not authorize FDA to regulate the
practice of medicine, it specifically
directs FDA to regulate the promotion of drugs and devices.
Promotional materials are unlawful if
they promote an unapproved use for the product; contain claims
relating to the dosing, safety or
effectiveness of the product that are inconsistent with the
approved labeling; or if they-lack a fair
and balanced presentation of information, i.e., of benefits and
risks. Although submission of an
article for publication in a journal is not promotional, the use
of such an article to sell a drug or
device is promotional.
Under current law, if a company wants to promote a use of a drug
or device it can do so by
submitting an efficacy supplement and getting that use onto the
label. As I will explain later in my
testimony, getting a use onto the label has benefits beyond being
allowed to promote. For
example, it ensures reimbursement from third party payors, it
helps to get that use included in
formularies, and it gives the medical community more complete
information about the product.
As I will further explain later in my testimony, the requirements
for efficacy supplements are often
significantly simpler than the requirements for applying for
permission to market a product in the
first place. Moreover, the Agency is considering a number of
measures that will make the
supplement process a more effective tool for getting additional
uses on the label of drug and
device products.
The Food and Drug Administration Performance and Accountability
Act of 1995, S. 1447,
bypasses the current approach. It would permit drug and device
companies to use journal articles,
textbook chapters, continuing medical education program
materials, and compendial information
relating to uses recognized for purposes of third party coverage
or reimbursement that discuss off
label uses to promote the sale of their products for those uses.
The bill also would permit drug
companies to use summaries of journal articles, textbook
chapters, CME program materials, or
information relating to uses recognized for purposes of third
party coverage or reimbursement to
promote the sale of their products for off label uses. Device
companies could distribute oral and
written information about off label uses that are part of an
"exchange" among health care
practitioners, health care reimbursement officials, and the
industry, that is exchanged for
"educational or scientific purposes," or that is presented at CME
programs, seminars, workshops,
or demonstrations for devices to promote the sale of their
products for those uses.
We recognize that the purpose of the bill is to enhance
dissemination of information and not to
facilitate or encourage promotion of off label uses. But we
strongly believe that if the bill is
enacted, that will I be its effect. Drug and device
manufacturers market their products principally
by sending sales representatives, referred to as detail men and
women, out to talk one on one with
physicians who might prescribe their products. A detailer's job
is to convince those physicians to
use and prescribe their products. They do this by providing
information that purports to describe
the usefulness of their products in the patient population.
Written materials such as journal articles
that discuss favorable studies of these products are powerful
tools in the hands of a detailer. If the
bill is enacted, drug and device companies will be free to use
these materials to promote off label
uses.
Pursuant to the bill, after a company receives FDA approval of a
drug or device for one use, it
would be permitted to promote that product, through these other
means, for other uses. The
material that companies could distribute often would be very
preliminary, based on poorly
designed or wholly uncontrolled studies. Companies could promote
the use of a product even
when the evidence merely suggests or can be interpreted as
suggesting that a product may work for
a specific use. Effectiveness would not have to be demonstrated.
Thus, if drug X is approved for
cancer patients, and there is some preliminary data that suggests
it is beneficial for patients with
crippling arthritis, the drug's manufacturer would be permitted
to promote the drug and encourage
its use for arthritis on the basis of this preliminary or
unsubstantiated data. This promotion would
be permitted even though the data have not been reviewed by
independent scientific FDA experts.
In addition, the clinical information that appears in materials
that the bill allows manufacturers to
distribute has not been validated in any way. For example,
neither peer reviewers nor textbook
editors review the data underlying a study described in a journal
article or textbook chapter. In
fact, peer reviewers and editors do not even see that data.
FDA has serious concerns regarding the promotion of indications
that have not been reviewed and
approved by the Agency. Because promotional activities of drug
companies and others are
substantially motivated by profit and market expansion, the
widespread promotion of prescription
drugs and devices for uses that have not been determined to be
safe and effective could be
detrimental to the health and safety of the public. Permitting
companies to promote drugs and
devices for off label uses could have a number of devastating
consequences for the quality of
medical care in this country.
PROBLEMS WITH PERMITTING PROMOTION OF OFF LABEL USES
The fundamental problem with permitting the promotion of off
label uses is that not all off label
uses are safe and effective. The only way to know which ones are
safe and effective is to collect
and analyze the data supporting a finding of safety and efficacy.
Because the data on off label uses
have not been collected and analyzed, their promotion raises a
number of serious concerns.
Undercutting the Efficacy Standard
Permitting the promotion of off label uses based on studies
reported in journal articles or other
texts that clearly are an inadequate basis for approval by FDA
would undercut the efficacy
standard.
A fundamental precept of drug and device regulation in this
country is that these products must be
proven safe and effective before they can be sold. The
requirement that these products must be
proven effective, on the basis of well-controlled clinical
studies, was first adopted by Congress in
1962. Congress specifically added the concept of effectiveness
to the definition of "new drug" in
order to ensure that the efficacy requirement would apply not
only to initial claims made for a
drug, but also to claims made after the initial new drug
application had been approved. 108 Cong.
Rec. S22044-46 (daily ed. October 3, 1962); S. Rep. No. 1744,
87th Cong., 2d Sess. Part 2 at
267, 271 (1962) ("on-what logical basis can one possibly argue
that the initial claim for a drug . . .
should be supported argue that the initial claim for a drug.....
should be supported by "substantial
evidence" but that successive claims... should not be so
supported?" 108 Cong. Rec. at S22045.)
The addition of the "efficacy standard" revolutionalized drug
development and approval, not only
in the United States, but worldwide, as well. Essentially, a
manufacturer cannot just sat that a
product works for a particular disease-or condition, it must
prove that the product works for that
disease or condition. The only way manufacturers can prove
efficacy is by submitting data from
well-controlled clinical trials for evaluation by independent
experts at FDA. Anecdotal reports
and poorly independent experts at FDA. Anecdotal reports and
poorly controlled observations do
not suffice because those kinds of reports may be wrong or may
not be an adequate basis for
conclusion. We know this because we have had experience with
this type of information. Many
drugs approved before 1962 turned out not to work when, after
1962, they had to be (and were)
studied. Even when such reports suggest efficacy, they fail to
provide important guidance in areas
critical to the effective use of a therapy such as dosage and
patient selection and management.
The solid foundation that is laid down by the efficacy standard
is one of the main reasons that
there is a strong sense of confidence in the drug products that
are on the U.S. market today.
Because the standard requires well-controlled clinical trials,
once FDA has made a determination
of effectiveness, there can be a high degree of confidence that
the drug will work. Thus, when a
manufacturer claims that a product is safe and effective for a
particular disease or condition,
doctors can be confident that the product is in fact safe and
effective for that disease or condition.
Patients, in turn, can have confidence in the quality of the
products they are receiving.
Eliminating the need for well-controlled studies would be a major
setback for the first-rate medical
care that the health care system in this country provides.
Consider some of the additional uses that
FDA has approved on the basis of such studies -- for example,
timolol, propranolol, metoprolol,
and atenolol to improve the survival of heart attack patients,
taxol for breast cancer, and interferon-alpha 2b for chronic
hepatitis B and C. Without the requirement to submit clinical
studies to prove
that drugs are effective for their intended uses, it is far less
likely that we would know that these
drugs will work to decrease mortality in heart attack patients,
to delay or prevent breast cancer
recurrence, or to treat chronic hepatitis B and C. In the
absence of the efficacy requirement, the
market will be filled with drugs that manufacturers claim work
and that physicians use because of
a belief that they work, but for which there is relatively little
evidence.
Disincentive to Conduct Studies
One of the most serious consequences of allowing companies to
freely promote off label uses is
that companies would have no incentive to conduct or fund the
necessary scientific research and to
present data to FDA to verify the safety and efficacy of those
off label uses. In fact, because the
Agency might. determine that the new use is not supported by the
evidence, there would be an
incentive to avoid FDA review. To use the example of the cancer
drug that may be useful for
crippling arthritis, why would the drug company undergo the
expense of actually studying whether
the drug works for arthritis if it could promote the drug for
arthritis based on preliminary evidence,
particularly since a thorough study might fail to establish
efficacy for arthritis?
In a world where off label uses can be widely promoted,
manufacturers would have an incentive to
do the minimal amount of studies necessary to obtain approval for
the first, narrowest/easiest
indication and then heavily promote the product for other broader
(and possibly more speculative)
uses. For example, interferon alpha 2b was approved for use in
hairy cell leukemia, of which there
are approximately 300-400 cases per year. It subsequently was
approved to treat chronic hepatitis
B and C, of which there are tens of thousands of cases per year.
If S. 1477 had been in effect, the
manufacturer of interferon alpha 2b could have sought approval
for hairy cell leukemia and then
just promoted for chronic hepatitis B and C -- the much broader
use -- based on preliminary data.
Interferon alpha 2b is just one of many examples of a second,
very different use being significantly
broader than the original use for which a drug was approved.
Under the approach taken in the bill, we might never learn
whether interferon alpha actually works
to treat hepatitis B yet the manufacturer could promote its use.
This is precisely the scenario that
Congress sought to prevent when it added the effectiveness
requirement to the definition of a new
drug. A group of Senators, lead by Senator Kefauver, argued that
unless the effectiveness
requirement was added to the definition of drugs, "the
expectation would be that the initial claim
would tend to be quite limited, which of course, would expedite
approval of the new drug
application. Thereafter, the sky would be the limit and extreme
claims of any kind could be
made," subject only to FDA's enforcement authority 108 Cong.
Rec. at S22046.
Because the incentive to conduct research on uses of drugs and
devices will decrease, the end
result will be that the dissemination of off label information
pursuant to this bill will actually
reduce the amount of information that health care providers
receive about drugs and devices.
Safety Issues
Widespread promotion of unapproved uses also raises significant
safety concerns. Even under the
current law, which prohibits the promotion of off label uses, we
know of a number of instances
where physicians have used drugs for off label uses that have
resulted in disastrous consequences.
For example, the drugs encainide and flecainide were approved for
life-threatening and
symptomatic, arrhythmias, which are abnormal rhythms of the
heart. In the late 1980's, physicians
began to prescribe these two drugs for heart attack victims who
were experiencing ventricular-premature complexes (VPCs), a type
of asymptomatic or minimally symptomatic arrhythmia.
(Asymptomatic arrhythmias are arrhythmias that can be detected by
tests, but which the patients
do not feel.) This off label use, which was supported by
published peer-reviewed journal articles,
was intended to prevent the well-documented increased mortality
of heart -attack victims who
have a high level, of VPCs by suppressing those VPCS. The use
was logical and became so
widespread that the National Institutes of Health decided to
study the effectiveness of encainide
and flecainide in these patients. To the surprise of almost
everybody, that study demonstrated not
only that the drugs were ineffective in reducing the risk of
death but that the drugs were actually
harmful in patients for whom it was being prescribed off label --
that is the death rate among those
receiving the drug was more than twice the rate of those
receiving a placebo. If these unapproved
uses had been heavily promoted by drug companies, it is estimated
that thousands more
unnecessary deaths would have occurred.
Another example relates to the widespread off label use of a
class of drugs called calcium channel
blockers (CCBs). These drugs are effective for patients
suffering from angina, which is chest pain
caused by insufficient oxygen to the heart muscle. CCBs have no
established role in patients who-have had a heart attack but have
no symptoms. These patients do, however, benefit from another
class of drugs, beta-blockers, which are known to reduce
mortality by 25-30% after heart attacks.
Nevertheless, CABS are widely used in this patient population and
there are publications that
could be interpreted as supporting this use. Because CABS and
beta-blockers generally should not
be used simultaneously, patients are receiving CABS in lieu of
clearly life-saving beta blockers.
Many, probably thousands, of lives are lost each year because a
drug of no known benefit is being
used for an unapproved use in place of a drug with known value.
Widespread promotion of this
use would make the problem even worse.
Yet another example of a case where the distribution of published
articles on off label use could
have resulted in very serious harm to the public involves the
fentanyl transdermal system
(Duragesic). Approved for use in chronic pain in patients
requiring opioids, the fentanyl patch
was not approved for acute post-operative pain because of concern
that it would cause respiratory
depression (a serious condition in which less air reaches the
lungs) in those patients not used to the
effect of opioids. A number of publications prior to the time of
approval, however, described the
drug as safe and effective for postoperative pain. After
approval, reports to FDA and the literature
documented life-threatening respiratory depression in
post-operative patients given the patches.
Extensive promotion of this off label use could have been
disastrous.
There are many other claims that could be promoted through
peer-reviewed journal articles-describing off-label uses that
could be detrimental to a large number of patients if they were
heavily promoted. FDA fears that problems illustrated by these
examples would be multiplied if
manufacturers were given free rein to promote unapproved uses.
Unbalanced View
Another significant problem with permitting companies to promote
unapproved uses by
distributing the type of information described in the bill is
that physicians may not receive a
balanced view of the available information. It is well
documented that there is publication bias.
Studies with favorable results have a greater likelihood of
getting published; studies with less
favorable results less often get published. More importantly,
even if-less favorable or
contradictory results have been published, companies have no
incentive to distribute articles,
textbook chapters, or other information recommending against a
particular use. Because the bill
permits companies to distribute certain chapters of textbooks or
mere summaries of journal
articles, chapters, and CME materials, with no obligation for
balance or comprehensiveness,
physicians may see only one side of an off label use story.
The current law governing promotion requires balance. Changing
the law to allow the distribution
of journal articles and other similar materials that discuss off
label uses will allow drug-detail men
and women to -provide materials that describe favorable study
results of their product for a
particular use, but without providing copies of materials that go
the other way.
I would like to illustrate with an example. Human growth hormone
currently is indicated for use
only in children who are short because they lack sufficient
growth hormone and children who are
short because of kidney problems. Its use in children who are
short, but have no growth hormone
deficiency or underlying kidney problem, is an off label use of
uncertain value and safety. We
identified four journal articles that discuss this off label use
-- two more or less supported the off
label use and two did not. If a physician receives information
about this off label use from a detail
person, it is possible that he or she will receive only the two
favorable articles. On the other hand,
if the physician were conducting his or her own research into the
subject, he or she would likely
locate both the pro and con articles. Given the approximately
$20,000 per year price tag of human
growth hormone, the pain a child must-endure because of multiple
drug injections each week, and
the potential adverse effects that growth hormone may cause (such
as diabetes and possibly tumor
growth), it is important that physicians see all pieces of the
scientific puzzle until the answer is
clear.
By using this example, I am not targeting a specific drug or drug
company. I am merely trying to
illustrate what-the bill would permit and why FDA has serious
concerns.
What makes this situation even more troubling is that when we
have evidence that a particular use
is unsafe or ineffective, federal confidentiality laws frequently
prohibit FDA from disseminating
that information. Thus, there are off label uses about which
positive studies appear in the literature
and negative data are contained in our files. However, depending
on its source, FDA may be
unable to use that information to ensure that the medical
community has all of the available facts
on which to base treatment decisions.
Even under current law, physicians have access to positive
articles about off label uses and FDA
may be unable to counter those positive articles with any
negative information that might be in our
files. However, under current law, company detail men and women
cannot use those articles to
promote potentially dangerous off label uses.
The Bill's Requirements Are Not Substitutes for
FDA-Review
The bill imposes very few requirements on the off label use
information that companies could
disseminate. Basically, the unapproved use must appear in a
peer-reviewed journal article, a
chapter from a recognized text, text from an approved CME
program, information relating to a use
recognized under Federal law for purposes of third party coverage
or reimbursement, or a
summary of one of the above. For devices, the information may.
also be from oral and written
information that is part of an "exchange" among health car e
practitioners, health care
reimbursement officials, and the industry, is exchanged for
educational or scientific purposes, or is
presented at CME programs, seminars, workshops, or
demonstrations. None of these sources has
procedures that confirm the validity of the data and information
contained therein.
The purpose of the "peer review" process, for example, is to
determine if an article is worthy of
publication. At its best, peer review can ensure that the reader
is provided with enough detail and
clarity to make a general judgment about the strengths and
weaknesses of the study. However,
there are no generally accepted standards for what constitutes
"peer review." Essentially,
anyone can establish a "peer review" journal; the rigor of the
review varies considerably.
Regardless of the rigor, there are severe limitations inherent in
the peer review process that make it
inappropriate to rely solely on a peer-reviewed journal article
for efficacy determinations. For
example, peer reviewers almost never receive the study protocol.
They cannot tell what the initial
hypothesis was or whether the final analysis represents the
planned analysis or an analysis crafted
with the results in hand. Peer reviewers do not have access to
the underlying data. The peer
reviewers must rely on the data and facts as they are presented
by the author. FDA, on the other
hand, does have access to the data and can verify the critical
statistical outcomes and the
conclusions of a study. Moreover, peer reviewers do not
necessarily have the, time or the
expertise in all aspects of the subject matter to adequately
review the information. In fact, a
survey reveals that a peer reviewer spends on average less than
three hours reviewing a
prospective article. The peer review process cannot guarantee
the correctness or authenticity of
the article, nor can it detect fraudulent or flawed research.
The data and information supporting off label uses that appear in
reference textbook chapters,
which could highlight off label uses of particular drugs or
devices, CME materials, and materials
related to third party coverage and reimbursement are even less
likely to be validated than that in
peer-reviewed journals. In f act, we have no reason to believe
that such data have been reviewed
or validated at all. Textbook editors do not review the data
underlying information about off label
uses that appear in those books. The recognition of suggested
uses in texts or treatment guidelines
for purposes of third-party reimbursement serve different
societal purposes. The decision to
include such uses is not based on the standards used by FDA to
substantiate safety and efficacy.
FDA has serious concerns about a provision that allows companies
to use these types of
unproven/unvalidated information for promotional purposes.
There are many instances when uncontrolled studies have supported
a use and subsequent well-controlled studies have failed to show
effectiveness. Moreover, the literature is laden with studies
that report preliminary findings -- e.g., studies that involve a
small number of patients and case
reports or are not properly controlled. Although the studies or
reports may be scientifically
accurate, they are not sufficient to show safety and efficacy.
Thus, companies should not be
allowed to use these less rigorous studies to promote off label
uses of approved products.
GETTING SUPPORTED OFF LABEL USES ON THE LABEL
As you know, a drug is approved for its initial indications via a
new drug application, which
includes data on the drug's safety and efficacy. A subsequent
indication is added via a
supplemental new drug application, which usually needs to present
only efficacy information to
support that new use. After review and approval by FDA, the new
use is added to the approved
labeling and can be promoted by the drug's manufacturer.
There are several good reasons for drug companies to submit these
"efficacy supplements":
-
Approval usually ensures that third-party payers will reimburse
for the use, as insurance.
companies virtually always pay for approved uses of drugs and
devices.
-
As health maintenance organizations continue to grow in size and
number, a sponsor's ability to
get their drug included in the HMO's drug formulary will be
significantly enhanced.
-
The physician, via the approved labeling, is given more complete
information about the drug's
uses, contraindications, adverse effects, and other important
information about the manufacturer's
product.
-
Drug companies can present the FDA findings to drug approval
bodies in other countries, thus
enhancing their ability to gain approval (and reimbursement) for
uses in other markets.
-
And, of course, the manufacturer can promote the use, whether
through the use of journal articles
or other means.
Unfortunately, in many instances these incentives have been
insufficient to persuade drug sponsors
to submit efficacy supplements. There appear to be two reasons
for their reluctance. First, they
fear they will be expected to spend millions of additional
dollars conducting new clinical studies to
convince FDA reviewers that the new use should be approved. And
second, they have often
complained-that efficacy supplements are given low priority by
FDA, resulting in delays of years
in getting new indications approved. These concerns -- or at
least the perception -- have been
valid in the past, and we at FDA must address them.
We have been working on ideas for encouraging and expediting
efficacy supplements for
unapproved uses and for otherwise addressing industry concerns.
We are doing a number of
things and have several ideas for additional progress in this
area. Let me summarize them for you:
Expediting Review of Efficacy Supplements
As you know from yesterday's testimony, the Prescription Drug
User Fee Act of 1992 (PDUFA) is
helping resolve the problem of timely reviews for drugs and
biologics. Under PDUFA, by 1997,
the Agency will make approval decisions on all new drug and
biologic applications (NDAS,
PLAS, and ELAS) within 12 months and within 6 months for priority
drugs and biologics. These
time frames apply to efficacy supplements as well. The approval
times for NDAS, PLAS, ELAS,
and efficacy supplements have decreased significantly, and the
backlog of pending applications
has also decreased markedly. In fact, for NDAS, PLAs, ELAs, and
efficacy supplements, the
Agency has exceeded the interim goals established by Congress.
For applications submitted in FY
1994, the Agency reviewed and acted upon 96% of the NDAS, PLAs
and ELAs and 73% of
efficacy supplements on time. [The interim goal for all of these
was 55%.) With adequate
resources, we are confident that we can make the same progress
for medical devices.
We should, however, be able to exceed the PDUFA targets. I
believe we should try to reduce the
6-12 month time frames. To do so, we will need to give
supplements a greater priority than they
have had in the past, and we are committed to that.
Fewer Data Are Needed Than Commonly-Believed
In addition to assuring companies that we can and will expedite
their supplemental applications,
we also need to address the industry perception that many
efficacy supplements do not warrant the
expense associated with getting them approved. Companies fear
that they must conduct multiple
and expensive new clinical trials and collect and analyze
thousands of pages of medical data, with
no assurances of approval. We need to more clearly explain that
in the vast majority of cases this
is just not so. Some off label uses could be approved by FDA if
the sponsor would simply
compile the existing literature and submit it to us. Others may
need only limited data or data
about the studies, such as protocols, data tapes, or verification
of endpoints, all of which is already
in existence but simply needs to be found and copied. In any
event, because FDA has already
learned much about the drug's actions and effects in humans from
the original application and has
considerable experience relevant to safety, the data required for
second and subsequent indications
is often far less than for the original indication. It is, in
sum, Madam Chair-man, a much simpler
process than generally believed and we must convince sponsors of
that. To that end, we intend to
draft a new policy statement articulating the data needs of the
Agency for efficacy supplements for
new indications.
Pediatric Labeling
We are already demonstrating how limited data can get more uses
on the label in the pediatric
area. We have recently promulgated new regulations that provide,
in certain cases, for pediatric
uses to be included on the approved labeling without new clinical
studies. Pursuant to these
regulations, when there is sufficient basis to conclude that the
course of the disease and the effects
of the drug are sufficiently similar in children and adults, drug
firms can rely on existing studies in
adults, extrapolate the data to children, and get those uses on
the label with relative ease. The only
new data that will ordinarily be needed are information about the
drug's course throughout the
body (e.g., blood and tissue levels) that will allow the proper
dosage to be established for the use
of that drug in children.
Seek Out the Most Appropriate Off Label Uses
As I said earlier, many off label uses are quite appropriate, and
some may even be the treatment of
choice. Although off label use is seen in all
medical-specialties, it seems to be most widespread in
certain areas, such as oncology and pediatrics. Beginning with
those specialties, we will work
with practitioners and their specialty associations to identify
the off label uses that are most
appropriate. We will then present those findings to the sponsors
of those drugs and urge them to
work with us to get the indications in the labeling. In many, if
not most, cases that will entail only
the compilation of existing information, not the design and
conduct of new clinical studies. We
have not done enough to reach out to the medical profession and
to drug sponsors on this issue, but
we believe we can get the majority of the most appropriate
current off label uses in the labeling
through this process.
The best way to get information to physicians about the best uses
of the drug and device
armamentarium, Madam Chairman, is to have it in the product's
labeling. Our collective goal
ought to be to get this done.
CONCLUSION
Public confidence in drug and device therapy has been built on
the recognized rigor of FDA's
approval process. It is important that we not change a system
that has the respect and confidence
of the health care community and the public. FDA recognizes that
there are important lifesaving
off label uses. FDA believes, however, that the best way to
address any concerns that the
information about those uses is not reaching medical
practitioners is to get those uses in the
labeling. We believe that the risks of allowing drug companies
to distribute journal articles and
other information about off label uses far outweigh any benefits.
I would be happy to answer any questions.