International Journal of Impotence Research (2008) 20, 135–144
& 2008 Nature Publishing Group All rights reserved 0955-9930/08 $30.00
www.nature.com/ijir
REVIEW
‘Off-label’ drug use: an FDA regulatory term, not a negative
implication of its medical use
WA Meadows and BD Hollowell
Reminger & Reminger Co., L.P.A., Cleveland, OH, USA
As physicians continue to prescribe more and more drugs, plaintiff’s attorneys in the wake of tort
reform are attempting to carve out or create informed consent cases based on the Food and Drug
Administration’s (FDA) labeling requirements and the doctors’ communications with their patients
as it relates to those requirements. The theory of tort litigation revolves around whether the doctor
disclosed to his patient the fact that he prescribed a drug in an ‘off-label’ manner, or for a purpose
not approved by the FDA’s testing process. This article argues that the doctor’s decision to inform
the patient of the ‘off-label’ status of the prescription is not relevant to the physician’s standard of
care for an informed consent case. First, the FDA has specifically stated that its procedures and
requirements have no effect on the practice of medicine and that the FDA does not prohibit doctors
from prescribing drugs in an ‘off-label’ manner. Second, the FDA’s approval of a drug is immaterial
to the effectiveness in the drug’s ‘off-label’ use. In fact, prescribing medication in an ‘off-label’
manner can constitute the standard of care in many cases. Third, a doctor’s duty is to practice
medicine and treat his patient, not inform the patient of the FDA’s non-medically related labeling.
Therefore, doctors should not be branded with the additional duty of disclosing non-pertinent
information, such as the FDA’s medically irrelevant distinction, to their patients.
International Journal of Impotence Research (2008) 20, 135–144; doi:10.1038/sj.ijir.3901619;
published online 15 November 2007
Keywords: Learned Intermediary Doctrine; doctor; physician; off-label; standard of care; duty;
FDA; informed consent
The FDA’s present approval process for
prescription of drugs
The Food and Drug Administration (FDA) now
‘plays a role in almost every aspect of the approval,
marketing, labeling, advertising, and promotion of
both over-the-counter and prescription drugs.’1
A company may spend six to eight years and up to
$1.7 billion dollars getting a drug approved by the
FDA.2 The FDA will ultimately approve only 40–
60% of all drugs submitted for its review.3 The FDA
will approve a drug after the drug has successfully
navigated a preclinical study and three FDA phases
of clinical testing.4 Thus, the process to obtain FDA
approval is laborious and expensive.
Correspondence: BD Hollowell, Reminger & Reminger Co.,
L.P.A., 1400 Midland Building, 101 Prospect Avenue,
West, Cleveland, OH, USA.
E-mail: [email protected]
Received 21 June 2007; revised 12 September 2007;
accepted 18 September 2007; published online 15
November 2007
If the drug is found to be safe and effective through
all three phases, the company may then submit a
new drug application with the FDA.5 The new drug
application will include the results of the preclinical
animal trials and of the human clinical studies, the
drug’s ingredients and components, detailed chemical and biological information, a summary of the
risks and benefits, the manufacturing, processing
and packaging methods, an environmental impact
statement and samples of the proposed labeling.6 All
this information is submitted so that the FDA has a
sufficient amount of information to determine: ‘(1) if
the drug is safe [and] effective in its proposed use(s)
and whether the benefits of the drug outweigh its
risks; (2) whether the proposed labeling is appropriate and what (if anything) should be changed; and
(3) whether the methods used in manufacturing the
drug and the controls used to maintain its quality are
adequate.’7
The drug’s labeling requirements are comprehensive.8 The FDA considers the label to be the ‘display
of written, printed, or graphic matter upon the
immediate container of any article [y].’9 ‘ ‘Labeling’
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WA Meadows and BD Hollowell
136
means all labels and other written, printed or
graphic matter (1) upon any article or any of its
containers or wrappers, or (2) accompanying such
article.’9 In other words, the drug’s label is ‘all labels
and other written, printed, or graphic matter’ on any
article, container or wrapper of the product and any
other item that may accompany those items.10
Specifically, labeling includes any ‘brochures, booklets, mailing pieces, detailing pieces, file cards,
bulletins, calendars, price lists, catalogs, house
organs, letters, motion picture films, film strips,
lantern slides, sound recordings, exhibits, literature
and reprints [y] and references published [y] for
use by medical practitioners, pharmacists, or nurses
[y].’11
Furthermore, the United States Supreme Court
found that the word ‘accompanying’ means any
‘matter that supplements or explains the product.’12
Thus, the matter does not have to be physically
attached to the product but rather only needs a
textual relationship to it.13 Thus, ‘[l]abeling is
generally understood to include any written material that supplements or explains the product, is
disseminated by the manufacturer, and reaches the
customer, doctor, or patient either before, with, or
after the product.’14
Moreover, the drug’s official ‘labeling cannot
contain instructions for off-label uses [y].’15 As
such, ‘[m]anufacturers can still be prosecuted for
illegally ‘misbranding’ a drug if the drug’s labeling
includes information about its unapproved uses.’16
The label of a drug or device is misbranded ‘if its
labeling [contains] false or misleading information.’17 In particular, a label may be misbranded in
one of the following two ways: (1) the information
found on the label and (2) the information omitted
from the label.18 Thus, the drug is considered
misbranded if every intended use is not listed or if
it fails to contain adequate instructions for each
use.19 In determining whether a label is misbranded,
the FDA will consider not only any ‘representations
made or suggested by statement, word, design [and/
or] device [y] but also the extent to which the
labeling or advertising fails to reveal [material]
facts.’20
Interestingly, upon a physician’s request, a manufacturer may, however, supply the physician with
any information the manufacturer wishes regarding
the drug’s off-label uses.21
If the FDA does approve the drug for public
marketing, ‘the drug can be marketed for the uses for
which it was investigated and labeled.’22 Even after
the FDA has cleared the drug to be marketed, the
FDA still monitors the drug and has the power to
order a change in its label or to order a complete
recall of the drug.22 The FDA also does extensive
investigations of the manufacturing facility’s production of the drug, including the purchase of raw
materials, its manufacturing process and its security.23
International Journal of Impotence Research
The FDA regulation of off-label uses of
prescription drugs
Once a drug is approved for a specific purpose, the
drug can then be used for any purpose, even if the
FDA did not approve of that purpose.24 Using the
drug for a purpose not indicated on its FDAapproved label is called an ‘off-label’ practice.25
Off-label practices can happen in the following three
ways: (1) use by patients, (2) prescribed by physicians or (3) marketed by manufacturers.25 Specifically, a physician may prescribe a drug off-label ‘to
treat unapproved conditions or in unindicated
combination, dosage amount, or frequency.’25
When Congress passed the 1997 Act, Congress
ensured that the FDA would not interfere with a
physician’s practice of medicine. Within the 1997
Act, Congress included the following limitation to
the FDA’s power: ‘Nothing in this Act shall be
construed to limit or interfere with the authority of a
health care practitioner to prescribe or administer
any legally marketed device to a patient for any
condition or disease within a legitimate health-carepractitioner-patient relationship.’26 As such, Congress’ caveat in the 1997 Act clearly restrains the
FDA from entering into the province of a physician’s
care of a patient.
The FDA has consistently shown refrain from
entering into that province. An FDA Drug Bulletin
states that ‘once a [drug] product has been approved
for marketing, a physician may prescribe it for uses
or in treatment regimens or patient populations that
are not included in the approved labeling.’27 In that
same Bulletin, the FDA also states that ‘ ‘unapproved’ or more precisely ‘unlabeled’ uses may be
appropriate and rational in certain circumstances,
and may, in fact reflect approaches to drug therapy
that have been extensively reported in medical
literature [y].’27 The agency further commented
that ‘[v]alid new uses for drugs already on the
market are often first discovered through serendipitous observations and therapeutic innovations
[y].’27 The agency has reaffirmed this position
numerous times.28
Historically, neither Congress nor the FDA has
tried ‘to regulate the off-label use of drugs by doctors
by limiting prescribing choices.’29 The FDA has no
power to limit a physician from prescribing a drug
for off-label purposes,30 as the FDA does not
regulate the practice of medicine.31 The FDA does
not interfere with a doctor’s ability to prescribe
drugs off-label due to the physician’s need to treat
each patient individually.32 Accordingly, the FDA
does not have the power to interfere. Furthermore,
the FDA has no power to regulate how an individual
patient will use a medication prescribed by his or
her physician.
The FDA is, however, able to regulate one of the
three off-label practices: the manufacturer’s marketing and selling of the drug.33 (A drug manufacturer
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WA Meadows and BD Hollowell
markets a drug off-label when it promotes a product
for non-FDA-approved purposes, users, dosages or
combinations.)33 Despite the FDA’s lack of power to
intervene in a doctor’s ability to prescribe drugs offlabel, Congress passed legislation to allow the FDA
to regulate how a drug manufacturer disseminates
off-label information.30 Prior to 1997, a manufacturer could only promote an FDA-approved drug for
its FDA-approved purposes.34
In 1997, however, Congress passed ‘the first major
drug reform legislation in thirty five years.’35 The
1997 Act was enacted in an effort ‘to protect the
public’s health and safety by ensuring distribution
of only truthful, nonmisleading information regarding uses of prescription drugs.’36 More specifically,
the Act was initiated to allow the FDA to control the
manner in which a drug manufacturer distributed
information of a drug’s off-label uses to physicians
in enduring materials.37 This Act, however, as the
FDA admits, is ‘one of the most demanding
challenges faced by the agency in its 92 year
history.’38
Importantly, Congress again expressly admitted
that its legislation does not interfere with a physician’s practice of medicine. Congress stated that the
legislation is not ‘to limit or interfere with the
authority of health care practitioner to prescribe or
administer any legally marketed device[/drug] to a
patient for any condition or disease within a
legitimate health care practitioner-patient relationship.’39
Nonetheless, concerning this legislation and the
FDA, with its interest in promoting public health,
the information provided by a manufacturer to a
doctor may be incomplete, thus leaving doctors less
than fully informed about the drug.40 As one court
stated, even truthful information may be misleading,
as a company may provide to the physician ‘one
article that supports use of their drug, even if there
exists considerable evidence to the contrary.’41 The
FDA was also concerned that a manufacturer may try
to bypass the FDA’s extensive and expensive
regulations by simply disseminating information
about their drug’s off-label uses.42
Since the FDA restricts how a manufacturer may
directly disseminate information, manufacturers
have promoted its products’ off-label value through
indirect means. The indirect methods are usually
more educationally focused.43 The most common
indirect methods of promotion are the following: (1)
pharmaceutical company sponsored research published in editorials in scientific journals and (2)
medical education programs for doctors.44 In fact,
the 1997 Act specifically allows a manufacturer to
distribute peer-reviewed articles and medical texts
to physicians.45
The 1997 Act allows pharmaceutical companies ‘to
promote off-label drug uses by disseminating peerreviewed articles from scientific or medical journals
or reference textbooks that include information about
a clinical investigation of the product to physicians.’46 The Act states that a drug manufacturer is
allowed to distribute ‘written information concerning the safety, effectiveness, or benefit of a use not
described in the approved labeling of a drug.’47 The
manufacturer can disseminate that information only
to certain parties as follows: ‘(1) a health care practitioner; (2) a pharmacy benefit manager; (3) a health
insurance issuer; (4) a group health plan; or (5)
a Federal or State governmental agency.’48
Although the manufacturer is allowed to disseminate this information to those parties, the 1997 Act
puts certain restrictions on the actual information
that is published.49 The manufacturer may distribute information on a new use if (1) a new drug
application has been filed;50 (2) the information
does not pose a significant risk to the public health
and is not abridged, false or misleading;51 (3) the
information is not from another manufacturer’s
clinical research unless permission was obtained
from that manufacturer to do so;52 (4) a copy of the
information was submitted to the FDA 60 days
before dissemination53 and (5) the manufacturer
submitted a supplemental application to the FDA or
qualified for an exemption to this requirement.54
Finally, the manufacturer must also include with
this information a ‘prominently displayed statement,’55 disclosing, among other things, that the
information is for a drug not approved by the FDA,56
the manufacturer is distributing the information at its
own cost57 and the official labeling with all updates.58
A manufacturer may not specifically request a
reference textbook to be published for the product.59
Of course, Congress has delegated the power to
regulate the distribution of this off-label information
to the FDA.60 The FDA requires that the information
supplied by the manufacturer must still be ‘a fair
balance of information between the effectiveness
and risks of a drug as well as any significant
limitations to the product’s use.’61
Although the FDA under the 1997 Act can ‘strictly
control any dissemination of information on a
product’s off-label use by its manufacturer,’62 the
Act is ‘not intended to restrict the full exchange of
scientific information concerning the drug, including dissemination of scientific findings in scientific
or lay media.’63 As such, the FDA is not able ‘to
regulate activities that are independent and nonpromotional,’64 such as ‘independent scientific
studies, conversations between doctors, etc.’65
137
The physician’s relationship with the drug
label
Learned Intermediary Doctrine
Products liability law typically requires a manufacturer ‘to warn consumers of danger[s] associated
with the use of its product to the extent the
manufacturer knew or should have known of the
International Journal of Impotence Research
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WA Meadows and BD Hollowell
138
danger[s].’66 There is an exception to this general
rule for pharmaceutical drug manufacturers, the
Learned Intermediary Doctrine.67 ‘The Learned
Intermediary Doctrine redirects the warning from
the consumer, as is typically required under products law, to the health care provider, who then is
expected to read, understand, and evaluate those
risks in applying pharmaceutical therapies in the
health care milieu.’68
‘The Learned Intermediary Doctrine does not
relieve the manufacturer of liability to the ultimate
user for an inadequate or misleading warning; it
only provides that the warning reaches the ultimate
user, the learned intermediary.’69
Thus, once the manufacturer has given the
prescribing physician an adequate warning and
appraisal of the drug, the manufacturer has fulfilled
its duty, and the Learned Intermediary Doctrine then
discharges the manufacturer from liability, making
the prescribing physician potentially liable.70
Although the Learned Intermediary Doctrine is
applied on a case-by-case basis, ‘it is applied almost
universally in cases involving prescriptions drugs
and medical devices because the doctrine takes into
account the complex role physicians play in the
treatment of patients.’71
The Learned Intermediary Doctrine absolves a
manufacturer from liability arising from its prescription drugs. Once the manufacturer sufficiently
reports the drug’s inherent risks and side effects to
the learned intermediary, the manufacturer is then
cloaked with the protection of the doctrine.72 Moreover, the manufacturer, while obligated to warn the
prescribing physicians, has no duty to warn the
drug’s user (the customer) about any risks related to
the product’s use.73 Further, a manufacturer needs
only to educate the physician about dangerous
qualities that are known or should be known to the
manufacturer.74
The manufacturer must still, however, monitor
the drug’s use for any new risks.75 The pharmaceutical company is still ‘held to a duty to only inform
the doctors [y].’76
The Learned Intermediary Doctrine, while pardoning the manufacturer, potentially places liability
upon the learned intermediary, the prescribing
physician.77 The prescribing doctor is the learned
intermediary because of his education, experience
and unique position as the interchange between
the company, its product and the end user (the
customer).
The manufacturer must, however, convey a sufficient warning to the physician. The manufacturer’s
warning to the learned intermediary should ‘convey
any risk or contraindication that the manufacturer
knows, or should know, is associated with the use of
the prescription drug.’78 This then invokes the
physician’s duty.
‘It is the physician’s duty to adequately weigh the
risks and rewards of a particular course of treatment
International Journal of Impotence Research
when prescribing medication.’79 ‘Whether the physician has met this duty depends not only on the
warnings provided by the manufacturer, but also the
prevailing knowledge of the field.’79 ‘An adequate
warning is one ‘that a reasonably prudent person in
the same or similar circumstances would have
provided with respect to the danger and that
communicates adequate information on the dangers
and safe use of the product... in the case of
prescription drugs, taking into account the characteristics of, and the ordinary knowledge common to,
the prescribing physician.’80 ‘[T]he adequacy of the
warnings becomes a question of law when the
warnings are clear and unambiguous.’81
The courts, rather than the legislature, created the
Learned Intermediary Doctrine on the basis that the
doctor is in the best position to evaluate the patient
and to assess and recommend the risks and benefits
of a particular course of treatment.82
Worth noting is that a few exceptions to the
Learned Intermediary Doctrine do exist. The exceptions are limited though and have been carved out
by the courts. The exceptions ‘includ[e] mass
immunizations,83 contraceptives,84 and the controversial ‘FDA-Mandate’ exception.’85
For the most part, ‘the manufacturer should not be
exposed to tort liability for any defect in labelling’
‘when a physician, as a learned intermediary, has
been provided with the indications for which a drug
is effective, but prescribes it for a non-indicated
use.’86 Further, ‘where a physician had independent
knowledge of the risks, and failed to communicate
them to the patient, then the manufacturer may not
be liable for its failure to disclose the same risks.’87
When a physician uses a product off-label, a
manufacturer is not subject to liability, even if the
manufacturer knows of the off-label use.88
Physicians’ potential liability for prescribing
medication off-label
‘The major thrust of the Learned Intermediary
Doctrine is to protect drug manufacturers from
liability for failure to warn and leave the injured
patient with only an action against the physician for
failure to obtain the patient’s informed consent.’89
Outside of the Learned Intermediary Doctrine,
physicians also engage in a common but often
publicly misunderstood practice of prescribing
drugs off-label. A drug is prescribed ‘off-label’ when
a physician administers the drug for a purpose that
is not indicated on the drug’s FDA-approved label.90
Since ‘over 125 000 patients die [every year] as a
direct result of using a prescription drug,’91 the
misunderstood nature of prescribing drugs off-label
and its implications raise serious issues. This
concern is heightened by the fact ‘that forty to sixty
percent of all drugs prescribed are for unapproved
uses.’92
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WA Meadows and BD Hollowell
As discussed above, the FDA does not prohibit
nor regulate a physician from prescribing a drug offlabel. The FDA’s intended mission is to regulate the
pharmaceutical industry without interfering with
the practice of medicine.93 As such, ‘[a]llowing
physicians to prescribe drugs for such ‘off-label’
usage ‘is an accepted and necessary corollary of the
FDA’s mission [y]’ ’94 and can be the standard of
care in many fields.95
Further, ‘[o]ff-label use is not only legal and
ethical but is a common and integral feature of
medical practice.’96 Prescribing drugs off-label ‘is
widespread in the medical community,’97 and
‘medical ethics, the FDA and most courts recognize’
that prescribing a drug off-label ‘is essential to
giving patients optimal medical care.’97 As such,
circumstances may mandate a physician to prescribe a drug in an off-label manner.
‘Prescriptions for off-label uses of drug products
‘may account for more than 25% of the approximately
1.6 billion prescriptions written each year, with some
recent estimates running as high as 60%.’98 In 1995,
the American Medical Association reported ‘that
approximately half of all prescriptions were written
for off-label uses.’99 ‘One estimate indicated off-label
use accounted for 40–50% of the $216 billion spent
on US prescription drugs in 2003.’100
A doctor’s need to prescribe drugs off-label stems
from science and medicine moving faster than the
FDA’s bureaucracy and regulation. ‘The pace of
medical discovery invariably runs far ahead of
FDA’s regulatory machinery, and off-label use is
frequently ‘state-of-the-art treatment.’ ’101 ‘[T]he editor of the Journal of the American Medical Association testified before Congress that
[y] For a product to have the most effective
potential benefits, law and regulation should
and must follow, not precede, science. There
are too many variations in clinical circumstances and too much time delay in regulations
to allow the government to impede the physician’s ability to practice in these regards when
it is medically appropriate.102
A doctor also has a need to prescribe drugs off-label
because of ‘orphan diseases,’ diseases that have
populations too small or that are too rare for a
manufacturer to ‘have the financial incentive to
spend the time or resources necessary to obtain FDA
approval for a drug treatment.’103 Manufacturers
may lack an incentive to get approved for the offlabel uses because ‘[s]eeking approval for [off-label]
uses would likely have little effect on drug sales, so
the benefit to drug manufacturers does not outweigh
the costs of the approval process.’104 Further, ‘when
new uses are discovered, less than the entire patent
term remains for the drug. Therefore, even with
extended patent terms, it is difficult for a drug
manufacturer to recover its investment in having an
off-label use approved.’105 Thus, prescribing a drug
off-label may be the standard, if not the only method
for treating a patient who has an orphan disease.
‘Examples of medical conditions whose standard
treatments involve or have involved extensive offlabel use include cancer, heart and circulatory
disease, AIDS, kidney diseases requiring dialysis,
osteoporosis, spinal fusion surgery, and various
uncommon diseases.’106 In these areas of medicine,
the percentage of drugs that are being prescribed offlabel is staggering. ‘Ninety-five percent of drugs
used in neonatology are used off-label.’107 The
National Organization for Rare Diseases reports that
for patients to have any treatment at all ‘90 percent
[of the patients] must rely on off-label uses.’108 ‘A
General Accounting Office study found that about
one-third of all drug treatment for cancer involved
off-label drug uses.’109 ‘The study also found that
[y] all major types of cancer studied had been
treated through off-label drug uses, and off-label
uses accounted for 85 percent of the prescriptions of
three popular cancer drugs.’110 In fact, ‘[m]ost
diseases afflicting fewer than 200 000 Americans
are totally without FDA-labeled treatment.’111
‘Since so few drugs are approved for use in
children, the use of off-label prescribing is especially prevalent in the realm of pediatric care.’112
According to the American Academy of Pediatrics,
‘80 percent of drugs prescribed for children are
administered for unindicated uses,’113 and another
study estimates that ‘80 percent to 90 percent of
pediatric patients are receiving off-label drug prescriptions.’114 Thus, ‘[p]ediatric uses also are mostly
off-label.’115 As such, a physician left with little to
no viable options for treating a patient with FDAapproved medication may, and sometimes must,
rely on off-label prescriptions.
‘[T]he availability of such off-label uses is critically important to saving hundreds of thousands of
lives each year.’116 Thus, physicians in an effort to
best serve their patients commonly prescribe drug’s
off-label.
Further, while attempting to comport with the
standard of care (and ultimately avoid liability), a
physician may actually commit malpractice by not
prescribing a drug off-label. ‘An officer of the
American Medical Association [stated] ‘in some
cases, if you didn’t use the drug in the off-label way,
you’d be guilty of malpractice.’ ’117 In some orphan
disease populations, such as with HIV patients,
‘[t]he off-label use [of drugs] represented the community standard of practice.’118 Further than just
meeting the standard of care, optimal patient care
oftentimes requires prescribing drugs off-label.119
139
Term ‘off-label’: an FDA regulatory term, not a
negative implication of its medical use
A lawyer defending a doctor in a case where the
doctor has prescribed the medication off-label may
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WA Meadows and BD Hollowell
140
have a difficult time convincing the jury that offlabel use is the norm and required by the standard of
care. A layperson on the jury could give great
deference to the fact the FDA did not approve of
the use for which the doctor prescribed the drug,
even though such use may be commonplace.
Whether the FDA has approved the off-label use
should be immaterial to considering a doctor’s
liability. A juror may have a difficult time understanding the distinction that ‘ ‘[o]ff-label’ is merely a
regulatory description of the use of a medical device
or drug—a legal status, not a medical fact.’120
‘Even if off-label connoted more than legal status,
it is (without more) medically neutral.’121 In fact,
‘[i]n many, if not most, cases, [the] FDA will have
made no determination, affirmative or negative,
about any given off-label use.’122 ‘Nor can it be
assumed that off-label uses are unproven or unsafe
because they have escaped FDA scrutiny.’123 ‘Thus,
it is not possible to draw any conclusion about the
safety or effectiveness of a particular use of a drug or
medical device from the administrative/legal status
of that use as off-label.’123
Therefore, ‘[o]ff-label thus only means ‘silent’
label.’121 ‘The term denotes nothing about health
risks or benefits, and therefore means nothing in the
medical context of informed consent.’121 ‘The only
certain conclusion is that FDA considers the
product generally safe enough to be on the market.’121 Admittedly, ‘[t]he status of the drug with the
FDA does not alter the relationship between drug
manufacturer, physician and patient.’124
Informed consent: a physician’s duty to disclose the
off-label status of a drug
Although a physician’s ‘[f]ailure to inform patients
that the treatment they are receiving is an off-label
application does not, in itself, constitute malpractice,’125 plaintiffs’ attorneys in medical malpractice
cases have tried to fashion informed consent cases
around the fact that a physician did not inform his
patient that the drug was prescribed in an off-label
manner from its FDA-approved use.
‘Examination of state informed consent laws thus
reveals that a physician’s duty is almost universally
limited to providing medical information.’126 ‘There
is no duty obligating a physician to discuss FDA
regulatory status of products being used for a
particular treatment because FDA regulatory status
is not a risk, benefit, or alternative of medical
treatment, nor does a product’s legal status affect the
nature of the treatment.’126 ‘Thus, the fact that FDA
has not approved labeling of a drug for a particular
use does not necessarily bear on those uses of the
drug that are established within the medical and
scientific community as medically appropriate.’127
Consequently, ‘[t]he mere fact that the FDA has
not cleared a product for a particular use does not
International Journal of Impotence Research
mean that the product is not in fact suitable for that
purpose; it simply means that the FDA has not
cleared it.’128 As such, ‘the fact that a medical
device[/drug] has not been approved by the FDA for
a particular use does not mean that the device is
unsafe, much less that the device is defective;’129 it
could simply mean that the ‘FDA lacked sufficient
information to make an affirmative finding of safety
or effectiveness’ or that ‘the manufacturer never
submitted an application concerning the use to the
FDA.’130
‘[T]he majority of reported cases hold that as a
matter of law doctors are not required to disclose the
FDA status of [a device] because such status is not a
medical risk of surgery.’131 The holding of these
cases are based on the premise that the FDA status of
a product ‘is not a ‘medical risk’ and thus need not
be disclosed in obtaining a patient’s informed
consent.’132 In fact, ‘[t]he FDA labels given to a
medical device do not speak directly to the medical
issues surrounding a particular surgery. They are
not, therefore, required to be disclosed pursuant to
the law of informed consent.’133
‘The New Jersey legislature found that off-label
use ‘is legal when prescribed in a medically
appropriate way,’ ‘conform[s] to the way in which
appropriate medical treatment is provided,’ and is
often ‘necessary and appropriate treatment.’ ’134
‘[P]hysicians’ prescribing a drug or device off-label
have a responsibility to be well-informed about the
drug or device.’135 A physician can be held liable in
a negligence claim if he prescribed the off-label drug
in that is a ‘sufficiently careless, imprudent or
unprofessional.’136
A doctor may be held liable based on an informed
consent theory. ‘Informed consent doctrine emerged
from the intentional tort battery.’137 ‘In order to
avoid the risk of liability for unlawfully intruding
into someone’s personal space, a healthcare professional would have to secure his or her patient’s
consent before performing a surgical or other
therapeutic intervention.’137 A claim based on
informed consent has moved from a battery and is
now ‘firmly rooted in the law of negligence.’137
‘[T]he duty to secure informed consent reflects a
commitment to patient autonomy and self-determination.’137
An informed consent claim may still be a viable
cause of action ‘in those jurisdictions defining
disclosure sufficient to obtain informed consent as
all information material to a reasonable person.’138
Even in those jurisdictions, the plaintiff would still
need to prove that had the patient known that the
drug prescribed was off-label, the patient would
have refused the treatment.138 Proving that might be
particularly difficult ‘given that off-label use is
frequently a treatment of last resort.’138
A state appellate court in Ohio has held that
a physician did not have a duty to disclose the
FDA status of a device when the device was used
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WA Meadows and BD Hollowell
off-label.139 In Klein v. Biscup, a patient sued her
physician claiming the physician failed to obtain
her informed consent since the doctor failed to
disclose that the devices used for her back surgery
were not approved by the FDA.140 The trial court
granted summary judgment for the defendant. The
court of appeals affirmed. The court of appeals held
that a physician’s failure to disclose the FDA status
of a product is not a breach of the physician’s duty to
obtain the patient’s informed consent.141
In Klein, although the FDA had twice denied the
manufacturing company’s application to market
the surgical screws as a device for spinal implants,
the FDA eventually approved the screws for use in
long and flat bones.140 The doctor, however, proposed to use the screws, not on the patient’s long or
flat bones but to stabilize the patient’s spine by
fusing several vertebrae.140 Before the first and
second surgeries, the patient signed consent forms
which acknowledged that the doctor had informed
her of the risks involved with the surgery. The
surgeon did not advise her about the FDA status of
the screws or that the screws were being employed
in an off-label use.140
The physician argued that he fully informed the
patient of the medical risks associated with the
procedure and that the FDA status of the screws was
not a medical risk.142 This argument was based on
the fact ‘that the FDA does not regulate the practice
of medicine, and therefore the FDA status of the
devices was wholly irrelevant to the issue of
informed consent.’142
The court of appeals found that the ‘[o]ff-label use
of a medical device is not a material risk inherently
involved in a proposed therapy which a physician
should disclose to a patient prior to the therapy.’143
Further, ‘the off-label use of a medical device is also
a matter of medical judgment and, as such, subjects
a physician to professional liability for exercising
professional medical judgment.’144 Thus, the court
held that, although a physician may be negligent in
his judgment to use a device, a physician has not
breached his duty to obtain a patient’s informed
consent by failing to disclose whether the device is
being used off-label or the FDA status of the device.
In a case similar to Klein, the Supreme Court of
Pennsylvania in Southard v. Temple University
Hospital held that a physician’s failure to inform
a patient of the FDA’s classification of a device
was not a failure to obtain a patient’s informed
consent.145
In Southard, the plaintiffs sued the defendant
doctors, alleging that the physicians were obligated
to advise patients of the FDA’s regulatory classification of a device.146 The trial court granted summary
judgment for the defendant doctors on plaintiff’s
informed consent claim.146 The appellate court
reversed the trial court’s granting of summary
judgment. The Supreme Court reversed the appellate court.
The appellate court found that summary judgment
was improper due to the FDA’s classification of the
device.147 The court found that the device had risks
because the FDA’s classification constituted a conclusion that the FDA believed the device had
unknown characteristics.148 Alternatively, the appellate court found that unknown characteristics, if
not risks, were at least facts directly related to the
surgical procedure and to medical issues involving
the surgery.148 Thus, the appellate court found that
‘a reasonable person, if adequately informed, might
opt for a more conventional FDA-approved mode of
treatment, and concluded that at the least, an issue
of fact remained for the jury.’148
The Pennsylvania Supreme Court disagreed.
The court found the FDA label ‘do[es] not speak
directly to the medical issues surrounding a particular surgery’149 and ‘does not constitute a material
fact, risk, complication or alternative to a surgical
procedure.’150 It found that the FDA’s classification
of a device relates to how the manufacturer
may market and label the device and ‘does not
enlighten the patient as to the nature or seriousness
of the proposed operation [y] or the possible
results.’150 The court also found that the FDA’s
finding that a device has ‘unknown characteristics’
does not ‘equate to ‘risks’ or ‘facts’ pertinent to
the informed consent inquiry.’150 Thus, the Supreme
Court held ‘that a physician need not inform
patients of the FDA classification of a medical
device.’151
A New York trial court has also found that
evidence about the FDA status of a drug is
admissible for an informed consent case if accompanied with expert testimony.152 In the case, the
plaintiff sued her doctor for malpractice for lack of
informed consent. Plaintiff claimed that the doctor
should have informed her that drug/injectable
substance had not been approved by the FDA for
any purpose. The defendant moved to preclude the
introduction of the FDA’s approval status of the
drug.
The trial court found that the admission of the
evidence related to the FDA’s lack of approval
‘would be entirely material and relevant to the
issues presented [y].’153 The court concluded that a
reasonable person, when considering the risks of the
drug, ‘would want information as to whether that
drug or substance has been tested and/or approved
by Federal authorities.’154 The court reasoned that
‘[i]t is a reasonable assumption that most patients,
confronted with a doctor’s recommendation for
injection of a foreign substance, presume that such
substance has been the subject of official testing,
consideration, and approval [y].’155 The court
continued: ‘[A]nd implicitly or explicitly [the
patient will] rely on this presumption as part of
the basis of their ‘consent’ to the treatment.’155 In
this case, however, the drug had not been approved
by the FDA for any purpose.155
141
International Journal of Impotence Research
Off-label drug use
WA Meadows and BD Hollowell
142
Courts have also allowed into evidence the fact
that a drug was prescribed for an off-label use. In
Richardson v. Miller,156 the plaintiff sued her doctor,
alleging that the administration of terbutaline during the plaintiff’s labor caused her to suffer a heart
attack resulting in permanent heart damage.157 The
trial court granted defendants’ motions in limine to
preclude reference to the drug’s package insert and
the Physicians’ Desk Reference, which would show
that the drug had not been approved by the FDA for
the manner prescribed and that it was prescribed
off-label. The Tennessee Court of Appeals reversed
the trial court on both accounts.
The Richardson court held that the drug’s
FDA-approved labeling and the Physicians’ Desk
Reference, when accompanied with other expert
evidence on the standard of care, was admissible ‘to
determine whether the drug presented an unacceptable risk to the patient.’158 The court did caution
that neither, ‘by themselves, are prima facie evidence of the prescribing physician’s standard of
care.’158 ‘Thus, proof of a departure from the
recommendations in a drug’s labeling or PDR
reference is not alone sufficient to prove a breach
of the standard of care.’158 The court did state that
the materials ‘can provide significant assistance in
identifying the standard of care.’158
The court of appeals overturned the trial court’s
‘wide latitude’ regarding the admissibility of evidence by overturning the trial court’s preclusion of
evidence showing that the drug was prescribed in an
off-label manner.158 The appellate court found that
allowing into evidence the absence of FDA-approved instructions regarding recommended dosage
levels and methods of administration was relevant
to show that the defendant doctor should not have
continued the treatment after the plaintiff had
experienced chest pain.159
Conclusion
Although claims for informed consent based on a
doctor’s failure to disclose the FDA’s status of a drug
is a new area, the FDA status of a drug/device is
simply not relevant to apprising a patient of the risks
involved in a procedure.
First, Congress has expressly represented that the
FDA’s regulations have no bearing on a physician’s
practice of medicine. The FDA status of a drug/
device is created by the FDA to enforce its regulations of approval and marketing. Second, the fact
that a drug has not been approved by the FDA could
be highly prejudicial to a doctor’s defense, even if
the drug is commonly prescribed for that reason.
The trial could lose focus on the critical issue:
whether the doctor committed malpractice by prescribing the treatment he did as opposed to why and
how the FDA approved the drug. Further, prescribing medication off-label is the norm in most
International Journal of Impotence Research
circumstances and constitutes the standard of care.
Also, prescribing medication off-label is required for
certain fields of practice.
Third, requiring a doctor to disclose that a drug is
being prescribed off-label would require the doctor
to understand the interworkings and regulations of
the FDA and keep abreast of its activity. This task is
unduly burdensome. The doctor is trained to
practice medicine, not to understanding the administrative ordeals of a large, bureaucratic government
agency. Additionally, the doctor would then have to
enlighten the patient of what the FDA status means
exactly. As such, the FDA’s approval process, which
is not related to the practice of medicine, is simply
irrelevant to the risks of a treatment plan or
procedure.
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102 Beck & Azari, supra note 4, at 79, quoting Promotion of Drugs
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M.D.).
103 Farley & Waters, supra note 103, at 1.
104 Hixson, supra note 79, at 214–215.
105 Hixson, supra note 79, at 215.
106 Beck & Azari, supra note 4, at 80.
107 Henry, supra note at 63, at 379.
108 Fox, supra note 27, at 1166, citing Off-Label Drug Use and
FDA Review of Supplemental Drug Applications, Hearing
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109 Stoffelmayr, supra note 17, at 278, citing United States
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Their Choice of Cancer Therapies 19 (1991).
110 Stoffelmayr, supra note 17, at 278, citing United States
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111 Beck & Azari, supra note 4, at 80 n.80.
112 Hixson, supra note 79, at 213, citing Gregory Hazard, Please,
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to Pediatric Testing Leaves Therapeutic Orphans Needing
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(2004).
113 Fox, supra note 27, at 1166, citing Robert Levine, Ethics and
Regulation of Clinical Research 241 (1986).
114 Farley & Waters, supra note 103, at 1, citing National Center
for Policy Analysis, ‘Speak No Good: The Tragedy of FDA
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(27 September 1996).
115 Beck & Azari, supra note 4, at 80.
116 Farley & Waters, supra note 103, at 1.
117 Stoffelmayr, supra note 17, at 278, citing Fran Kritz, FDA
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International Journal of Impotence Research
118 Henry, supra note 44, at 382.
119 Endejann, supra note 1, at 503.
120 Beck & Azari, supra note 4, at 83, citing Klein v. Biscup, 673
N.E.2d 225, 231 (Ct.App.Ohio 1996).
121 Beck & Azari, supra note 4, at 85.
122 Beck & Azari, supra note 4, at 84–85.
123 Beck & Azari, supra note 4, at 84.
124 Beck & Azari, supra note 4, at 83, citing Tracey, 569 N.E.2d at
880.
125 Salbu SR. Off-label use, prescription, and marketing of FDAapproved drugs: an assessment of legislative and regulatory
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126 Beck & Azari, supra note 4, at 100.
127 Beck & Azari, supra note 4, at 100, citing Weaver v. Reagen,
866 F.2d 194, 198 (8th Cir. 1989).
128 Holland v. Smith & Nephew Richards, Inc., 100 F.Supp.2d
53, 56 (D.Mass. 1999).
129 Minisan v. Danek Medical, Inc., 79 F.Supp.2d 970, 978
(N.D.Ind.1999), citing Sita v. Danek Medical, Inc., 43
F.Supp.2d 245, 247 (E.D.N.Y.1999).
130 Beck & Azari, supra note 4, at 84 n.103.
131 Alvarez v. Smith, 714 So.2d 652, 653 (Fla.Ct.App. 1998),
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1996); Weaver, 866 F.2d 194; Femrite v. Abbott Northwestern
Hosp., 568 N.W.2d 535 (Minn.Ct.App. 1997); Klein, 673
N.E.2d at 231; Staudt v. Froedtert Mem’l Lutheran Hosp., 580
N.W.2d 361 (Wis.Ct.App. 1998); Wyttenhove v. Fairview
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1914 (Philadelphia County Court of Common Pleas 1992).
132 Alvarez, 714 So.2d at 655.
133 . Orthopedic Bone Screw Products Liability Litigation, 1996
WL 107556.
134 Beck & Azari, supra note 4, at 77, quoting N.J. Stat.Ann.
y26:1A-36.9(d), (e), (g) (1997).
135 Richardson v. Miller, 44 S.W.3d 1, 15 (Tenn.Ct.App. 2000),
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136 Salbu, supra note 140, at 190.
137 Noah LA. Informed consent and the exclusive dichotomy
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138 Christopher WL. Off-label drug prescription: filling the
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139 Klein, 673 N.E.2d 225, 231 (Ct.App.Ohio 1996).
140 Klein, 673 N.E.2d at 227.
141 Klein, 673 N.E.2d at 231.
142 Klein, 673 N.E.2d at 230.
143 Klein, 673 N.E.2d at 231. [Citation omitted].
144 Klein, 673 N.E.2d at 230.
145 Southard, 781 A.2d 101 (Sup.Ct. 2001).
146 Southard, 781 A.2d at 103.
147 Southard, 781 A.2d at 105.
148 Southard, 781 A.2d at 106.
149 Southard, 781 A.2d at 107, citing Orthopedic Bone Screw
Litigation, 1996 WL 107556 at *3.
150 Southard, 781 A.2d at 107.
151 Southard, 781 A.2d at 108.
152 Retkwa, 584 N.Y.S. 710 (Sup.Ct.N.Y. 1992).
153 Retkwa, 584 N.Y.S. at 713.
154 Retkwa, 584 N.Y.S. at 712.
155 Retkwa, 584 N.Y.S. at 712 n.6.
156 Richardson, 44 S.W.3d at 15.
157 Richardson, 44 S.W.3d at 8.
158 Richardson, 44 S.W.3d at 17.
159 Richardson, 44 S.W.3d at 22.