Dockets Management Branch

Food and Drug Administration

5630 Fishers Lane

Rockville, MD 20852

> Re: Comments on Submissions Concerning First Amendment Issues
>
> [Docket No. 02N-0209]{.underline}

Dear Sir or Madam:

This letter provides the comments of the Washington Legal Foundation
(WLF) on the submissions responding to the FDA's request for public
comment on First Amendment issues.[^1]

As a non-profit public interest law and policy center with many members
and supporters who wish to disseminate or receive truthful information
about FDA-regulated products, WLF has a long-standing interest in the
issues raised by FDA's request for comments. We want to commend FDA once
again for taking the initiative to harmonize its regulatory activities
with First Amendment mandates, and for inviting public comment on these
issues. FDA's request has prompted a remarkable outpouring of
thoughtful, often-provocative submissions on critical legal and public
health issues, which should be of great assistance to the Agency as it
goes about the task of evaluating and reforming its existing speech
restrictions. In this submission, we have addressed two of the principal
topics discussed in the initial set of comments to FDA: (1) the
dissemination of information about off-label uses of FDA-approved drugs
and devices;[^2] and (2) direct-to-consumer (DTC) advertising of
prescription drugs.

**\* \* \***

# [THE DISSEMINATION OF INFORMATION ON OFF-LABEL USES]{.underline}

By reducing barriers to the exchange of truthful scientific and medical
information on off-label uses of drugs and devices, FDA can advance two
important goals: facilitating physicians' access to information that may
help them to improve patient care, and honoring its obligation to
respect constitutionally-protected freedoms. While this does not require
FDA to lift all of its restrictions on speech by drug or device
manufacturers concerning off-label uses of their products, it plainly
does require some modest reforms in FDA's regulatory regime. In
particular, the First Amendment does not permit FDA to penalize
manufacturers for disseminating peer-reviewed journal articles or
reference textbooks on off-label uses to medical professionals, or for
suggesting content or speakers to independent CME providers for programs
discussing off-label uses (although FDA can require disclosures
concerning manufacturers' financial interests and the fact that the uses
are not FDA-approved, and can sanction [false or misleading]{.underline}
speech). The rationale for these principles was discussed in detail in
the [WLF I]{.underline} -- [WLF III]{.underline} decisions[^3] and in
our initial submission, and will not be repeated here.

While many of the parties responding to FDA's request for comments urged
FDA to recognize and uphold these principles, FDA spurred a robust
public debate that naturally produced a variety of dissenting views. We
address here the views expressed in September 13, 2002 comments
submitted by six members of Congress (Senator Kennedy, Senator Durbin,
Senator Schumer, Congressman Waxman, Congressman Brown, and
Congresswoman DeLauro).[^4]

While these comments are detailed, their principal argument is that
manufacturer-disseminated information about off-label uses can properly
be banned because it is "inherently misleading." More specifically, the
theory is that before the 1962 amendments to the Food, Drug and Cosmetic
Act (FDCA), drug manufacturers could market drugs without an FDA
determination concerning effectiveness; that Congress passed the 1962
amendments based on evidence that manufacturers were making false or
misleading claims that physicians found difficult to evaluate, and that
the pre-1962 regime was thus inadequate; and that the evidentiary record
underlying the 1962 amendments demonstrates that information on a
product's effectiveness for a particular use is "inherently misleading"
unless it has been vetted by FDA's rigorous approval process.[^5] As a
rationale for banning manufacturers' dissemination of information such
as peer-reviewed journal articles, this theory has two basic flaws.[^6]

[First]{.underline}, FDA and Congress have repeatedly recognized that
off-label use is an accepted part of the practice of medicine, and that
the exchange of off-label information between physicians and
manufacturers can be valuable in helping physicians to identify and
evaluate new treatment options that may benefit certain patients. For
example, FDA recently explained that:

> Congress . . . has generally refrained from providing . . . for the
> FDA to limit a physician, as part of the practice of medicine, from
> prescribing any legally available product for a particular
> patient . . . . Consistent with that background, the FDA has permitted
> physicians to prescribe approved drugs for \[off-label\] uses . . . .
> [That policy reflects the FDA's recognition that certain off-label
> uses perform an important therapeutic role in certain areas of medical
> practice, and that undue restrictions on such uses could have adverse
> health consequences]{.underline}.[^7]

Consistent with its recognition that off-label uses have an important
therapeutic role in certain areas, FDA has long acknowledged that
physicians need accurate scientific and medical information on off-label
uses, and that (in least in some circumstances) it is appropriate for
manufacturers to disseminate such information. For example, in 1996
Congressional testimony, an FDA official stated that:

> \[I\]n 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
> . . . .
>
> \* \* \*
>
> . . . 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 . . . . In addition, FDA does
> not prohibit a manufacturer from providing a physician information
> about off-label uses if the physician requests that
> information . . . . Drug companies \[also\] may distribute independent
> reference texts even if they contain certain information about
> off-label uses . . . so long as the texts do not have a significant
> focus on an off-label use of the manufacturer supporting dissemination
> of the text. . . . [\[A\]ll of these sources of information can be
> very important to good medical practice]{.underline}.[^8]

Similarly, the FDA stated in 1994 that there was a "need for reliable
scientific data and information on unapproved uses of approved products"
and that "because the agency recognizes the importance of dissemination
of reliable scientific information on . . . unapproved uses, it has
developed a number of policies related to dissemination of such
information."[^9] These include FDA's Final Guidance on
Industry-Supported Scientific and Educational Activities (which
explicitly provides that "most industry-supported scientific and
educational activities are not inherently misleading," and that the lack
of complete information on the risks of off-label uses "does not make
all discussions about unapproved uses misleading" provided that the
limitations on the data are disclosed);[^10] FDA's policy allowing
manufacturers to respond to unsolicited requests for information on
off-label uses;[^11] and FDA's acknowledgement that manufacturers must
be free to submit original research on off-label uses to peer-reviewed
journals given "[the need among health care professionals for peer
review and dissemination of the latest significant scientific data and
information on drugs and devices in scientific
journals]{.underline}."[^12]

Congress too has recognized that manufacturer-disseminated scientific
and medical information on off-label uses can be valuable to health care
professionals. In enacting Section 401 of FDAMA,[^13] Congress sought to
ensure "that health care practitioners can obtain important scientific
information about uses that are not included in the approved labeling of
drugs, biological products, and devices" while also encouraging
manufacturers to seek FDA approval for these uses.[^14]

Thus, FDA and Congress have both recognized that the off-label use of
drugs and devices is an accepted part of medical practice,[^15] and that
information on off-label uses [can be reliable and important to
physicians]{.underline} - - even though such information has not been
validated by the FDA, and even when it is disseminated by the product's
manufacturer. This contradicts the theory that information on off-label
uses (whether disseminated by manufacturers or other parties) is
"inherently misleading" simply because it lacks FDA's imprimatur. As the
First Amendment caselaw makes clear, a particular category of
information [cannot be valuable and inherently misleading at the same
time]{.underline}.

For example, in [Western States Medical Center v. Shalala]{.underline},
69 F. Supp.2d 1288 (D. Nev. 1999), [aff'd in part, rev'd in part on
other grounds]{.underline}, 238 F.3d 1090 (9^th^ Cir. 2001), [aff'd sub
nom. Thompson v. Western States Medical Center]{.underline}, 122 S. Ct.
1497 (2002), the Government argued that advertisements for compounded
drugs were "inherently misleading" since they suggested that compounded
drugs not approved by FDA have therapeutic value. The court disagreed,
observing that "Defendants themselves presumably believe that compounded
drugs have therapeutic value in some cases; otherwise, they would
prohibit the unapproved use of such drugs altogether." 69 F. Supp.2d at
1299. Similarly, the court rejected the claim that banning
advertisements for compounded drugs served the public health; noting
that the FDAMA provisions at issue allowed pharmacists to initiate
discussions about a compounded drug once a patient presented a
prescription for another drug, the court found it "difficult to see how
the communication of the same information can both serve and undermine
the public health, depending on which party initiates the contact or the
method used to communicate it." [Id.]{.underline}

In [WLF I]{.underline}, the court rejected the theory that
manufacturer-disseminated journal articles or textbooks discussing
off-label uses were inherently misleading. Among other things, the court
noted that FDA allows manufacturers to disseminate such materials in
response to unsolicited requests, holding that "the exact same journal
article or textbook reprint cannot be inherently conducive to
deception . . . when it is sent unsolicited, yet of significant clinical
value when mailed pursuant to a request." [WLF I]{.underline}, 13 F.
Supp.2d at 67.

In short, the Government's own statements and policies recognize that
information on off-label uses (including information disseminated by
manufacturers) can be valuable and important to good medical practice ‑‑
and the caselaw precludes speech prohibitions premised on the
conflicting theory that such information is inherently misleading.

[Second]{.underline}, an entire category of speech cannot be banned as
"inherently" misleading if the information can also be communicated in a
non-misleading fashion. Even where the speech at issue is potentially
misleading, a broad prophylactic ban cannot be justified if the
potential for deception is curable rather than [inherent]{.underline}.

In [In re R.M.J.]{.underline}, 455 U.S. 191 (1982), the Supreme Court
rejected the claim that certain forms of legal advertising could be
banned on prophylactic grounds, holding that:

> [Misleading advertising may be prohibited entirely, but the States may
> not place an absolute prohibition on certain types of potentially
> misleading information . . . if the information also may be presented
> in a way that is not deceptive]{.underline}. . . . \[T\]he remedy in
> the first instance is not necessarily a prohibition but preferably a
> requirement of disclaimers or explanation. . . . Although the
> potential for deception . . . is particularly strong in the context of
> advertising professional services, [restrictions upon such advertising
> may be no broader than reasonably necessary to prevent the
> deception]{.underline}.

[Id.]{.underline} at 203 (emphasis added). [See]{.underline}
[also]{.underline}, [e.g.]{.underline}, [Peel v. Attorney Registration
and Disciplinary Comm'n of Illinois]{.underline}, 496 U.S. 91, 111
(1990) ("\[t\]he Commission's concern about the possibility of deception
in hypothetical cases is not sufficient to rebut the constitutional
presumption favoring disclosure over concealment"); [Edenfield v.
Fane]{.underline}, 507 U.S. 761, 777 (1993) ("\[b\]road prophylactic
rules in the area of free expression are suspect") (quoting [NAACP v.
Button]{.underline}, 371 U.S. 415, 438 (1963)); [Revo v. Disciplinary
Bd. of the Supreme Ct. of New Mexico]{.underline}, 106 F.3d 929, 933
(10^th^ Cir. 1997) ("\[f\]or a particular mode of communication to be
inherently misleading, it must be incapable of being presented in a way
that is not deceptive"); [Pearson v. Shalala]{.underline}, 130 F.
Supp.2d 105, 118 (D.D.C. 2001) (where FDA failed to show that the
allegedly misleading aspects of a health claim could not be cured
through disclaimers, "its decision to classify the \[claim at issue\] as
inherently misleading is therefore erroneous"); [WLF I]{.underline}, 13
F. Supp.2d at 67 ("\[a\]lthough the Government argues that health claims
that have not been FDA approved are inherently misleading . . . at least
some can be presented in a non-misleading fashion") (quoting
[Nutritional Health Alliance v. Shalala]{.underline}, 953 F. Supp. 526,
529 (S.D. N.Y. 1997), [aff'd in part, vacated and dismissed in part on
other grounds]{.underline}, 144 F.3d 220 (2^nd^ Cir. 1998)); [Metpath,
Inc. v. Myers]{.underline}, 462 F. Supp. 1104, 1109 (N.D. Cal. 1978)
(advertisements for clinical laboratory services directed at the lay
public could not be banned as "inherently misleading" based on the
public's lack of technical expertise and the often-technical nature of
advertising by clinical labs, where the plaintiff's ads were not
technical and the court could "imagine an infinite number of
advertisements of equal simplicity" that would not mislead a lay
audience).

These principles preclude the position that information about off-label
uses can be banned as inherently misleading, as the Supreme Court's
[Western States]{.underline} decision illustrates. There, the Government
itself did not contend that advertisements for compounded
drugs - - which [have not been approved by FDA as safe and effective for
any use]{.underline} - - are inherently misleading.[^16] However, the
dissent suggested that the ban on advertising compounded drugs might be
justified by concerns that patients would be confused about their risks.
The majority disagreed, holding that:

> Even if the Government did argue that it had an interest in preventing
> misleading advertisements, [this interest could be satisfied by the
> far less restrictive means of requiring each compounded drug to be
> labeled with a warning that the drug had not undergone FDA testing and
> that its risks were unknown]{.underline}.
>
> [Western States]{.underline}, 122 S. Ct. at 1508.

If the potential for misleading patients by exposing them to
pharmacists' advertisements for unapproved drugs can be dealt with
through succinct disclaimers, any potentially misleading aspects of
professional publications or seminars directed to a professional
audience can plainly be dealt with through similar means. FDA itself has
recognized that this kind of scientific and medical information on
off-label uses can be reliable; that undue restrictions on this
information could have adverse health consequences to patients; and that
a manufacturer's involvement in disseminating such information does not
automatically taint the information and render it "inherently
misleading."

Few would advocate a repeal of the 1962 amendments to the FDCA, or a
wholesale deregulation of information about off-label uses of approved
products. But responsible reforms that promote the exchange of truthful
and non-misleading information on scientific and medical developments
are essential to align FDA's current policies with its legal obligations
and public health commitment.

# [DIRECT-TO-CONSUMER ADVERTISING]{.underline}

DTC advertising of prescription drugs has been a prominent topic in the
public debate initiated by FDA, which produced a wide variety of
comments on the legal issues surrounding DTC ads and the empirical
evidence regarding their effects. We have focused here on one discrete
aspect of the DTC debate. Several commentators emphasized the
possibility of DTC ads increasing health care costs ([i.e.]{.underline},
the potential for DTC ads to result in increased utilization of
high-cost drugs and/or price increases in the advertised drugs),[^17]
and FDA's Federal Register notice seemed to allude to this same issue
without using the word "cost," asking whether its current approach to
regulating advertising encourages "overprescription."[^18] Because FDA
may face pressure to use speech restrictions as a cost-containment
measure (and perhaps has some sympathy for this approach), we believe it
is important to address this strategy.

As an empirical matter, the evidence on whether DTC advertising
increases health care costs is inconclusive. This is partly because the
question involves a number of sub-issues. That is, DTC advertising might
increase or reduce health care spending: (1) because it results in price
increases; (2) because it increases drug utilization, or shifts
treatment toward more expensive or less expensive therapies; or
(3) because it prompts patients to discuss medical problems with their
physicians, or improves patient compliance, and thus avoids the costs
that might result from more delayed treatment or from noncompliance with
the prescribed treatment regimen.

Whether DTC advertising results in price increases is unclear. While
advertising could increase the prices of the advertised products (either
because companies raise prices to cover these advertising costs, or due
to increased demand) the empirical evidence on the issue is
sketchy,[^19] and advertising could also have the effect of reducing
prices generally due to increased competition.[^20] Whether DTC
advertising causes increased utilization of costly treatment
alternatives also is unclear. As a logical matter, one would not expect
a pharmaceutical company to expend resources on DTC ads unless it
believed they would increase sales, or to focus DTC ads on low-cost
products; on the other hand, new drug therapies may provide an
alternative treatment option for conditions that would otherwise require
more costly treatments or increase hospitalizations.[^21] Finally, the
evidence available from consumer surveys suggests that DTC advertising
can lead patients to ask their physicians about problems they had not
previously discussed, and encourage patient compliance;[^22] while both
of these factors could potentially produce long-term savings, the
magnitude of any such savings is speculative. In short, the question of
whether DTC advertising increases or reduces health care costs raises a
number of issues that undoubtedly will be the subject of further study,
but the existing research is not sufficient to suggest a clear answer.

By contrast, the situation on the legal front [is]{.underline} clear.
Even if the empirical evidence demonstrated that DTC ads increased
health care costs, FDA could not restrict speech in order to "protect"
patients from information that might lead them to seek high-cost or
"unnecessary" medications. The First Amendment "directs us to be
especially skeptical of regulations that seek to keep people in the dark
for what the government perceives to be their own good" - - a "teaching
\[that\] applies equally to state attempts to deprive consumers of
accurate information about their chosen products."[^23]

The principle that Government cannot suppress truthful speech to prevent
citizens from making the "wrong" decision has been recognized repeatedly
in the commercial speech cases, beginning with [Virginia State Bd. of
Pharmacy v. Virginia Citizens Consumer Council, Inc.]{.underline}, 425
U.S. 748, 769 (1976). There, the State of Virginia argued that a ban on
advertising prescription drug prices was necessary to prevent consumers
from selecting pharmacies offering lower prices but lower-quality
services. The Supreme Court rejected this rationale for the advertising
ban, holding that:

> There is . . . an alternative to this highly paternalistic approach.
> That alternative is to assume that . . . people will perceive their
> own best interest if only they are well enough informed, and that the
> best means to that end is to open the channels of communication rather
> than to close them . . . . Virginia is free to require whatever
> professional standards it wishes of its pharmacists . . . . But it may
> not do so by keeping the public in ignorance of the entirely lawful
> terms that competing pharmacists are offering . . .  \[T\]he
> justifications Virginia has offered for suppressing the flow of
> prescription drug price information, far from persuading us that the
> flow is not protected by the First Amendment, have reinforced our view
> that it is.

[Id.]{.underline} at 770.

Similarly, the court in [WLF I]{.underline} rejected paternalism as a
valid basis for restricting the dissemination of truthful information
about off-label uses, holding that "\[t\]o the extent that the FDA is
endeavoring to keep information from physicians out of concern that they
will misuse that information, the regulation is wholly and completely
insupportable." [WLF I]{.underline}, 13 F. Supp.2d at 69. "If there is
one fixed principle in the commercial speech arena," the court observed,
"it is that 'a State's paternalistic assumption that the public will use
truthful, nonmisleading commercial information unwisely cannot justify a
decision to suppress it.'" [Id.]{.underline} at 69-70 (quoting
[44 Liquormart, Inc. v. Rhode Island]{.underline}, 517 U.S. at 497).

The Supreme Court re-emphasized this principle in [Western
States]{.underline}, rejecting the theory that an interest in
"protecting" patients from truthful information could justify its
suppression. There, the Court addressed the argument that FDAMA's ban on
advertising compounded drugs could be sustained by an interest in
preventing patients who do not need compounded drugs from seeking them,
holding that:

> Even if . . . FDAMA's speech-related restrictions were motivated by a
> fear that advertising compounded drugs would put people who do not
> need such drugs at risk by causing them to convince their doctors to
> prescribe the drugs anyway, that fear would fail to justify the
> restrictions. Aside from the fact that this concern rests on the
> questionable assumption that doctors would prescribe unnecessary
> medications . . . \[it\] amounts to a fear that people would make bad
> decisions if given truthful information . . . . [We have previously
> rejected the notion that the Government has an interest in preventing
> the dissemination of truthful commercial information in order to
> prevent members of the public from making bad decisions with the
> information]{.underline}.

[Western States]{.underline}, 122 S. Ct. at 1507 (emphasis added).[^24]

Government agencies have a wide variety of tools to restrain health care
costs generally, or to combat the perceived "overutilization" of
specific products or services. For example, agencies that reimburse
health care costs use mechanisms such as copayment requirements,
coverage restrictions, and utilization reviews; agencies that purchase
or reimburse health care products engage in aggressive negotiations to
obtain discounts or rebates from product manufacturers; agencies often
carry out educational campaigns to promote lower-cost treatment
alternatives; and FDA itself has issued a series of public service
announcements encouraging the use of generic drugs. All of these
strategies are consistent with the First Amendment. What the First
Amendment caselaw [does]{.underline} preclude, however, is
"speech-containment" strategies aimed at cost containment. Preventing
citizens from asking their physicians about prescription drugs is not an
interest that can justify restrictions on truthful advertising.

\* \* \*

FDA's initiative to conform its regulatory activities to First Amendment
standards has the potential to produce legally-defensible policies that
facilitate the diffusion of valuable medical information and advance
FDA's public health objectives. We hope that FDA will be successful in
this important endeavor, and appreciate the opportunity to comment on
these issues.

Sincerely,

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Daniel J. Popeo

Chairman and General Counsel

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Richard A. Samp

Chief Counsel

[^1]: 67 Fed. Reg. 34942 (May 16, 2002).

[^2]: This issue is discussed in greater detail in WLF's initial
    comments of September 13, 2002.

[^3]: [See]{.underline} [Washington Legal Found. v.
    Friedman]{.underline}, 13 F. Supp.2d 51 (D.D.C. 1998)("[WLF
    I]{.underline}"); [Washington Legal Found. v. Friedman]{.underline},
    36 F. Supp.2d 16 (D.D.C. 1999)("[WLF II]{.underline}"); [Washington
    Legal Found. v. Henney]{.underline}, 56 F. Supp.2d 81 (D.D.C.
    1999)("[WLF III]{.underline}"); [Washington Legal Found. v.
    Henney]{.underline}, 202 F.3d 2000 (D.C. Cir. 2000)("[WLF
    IV]{.underline}"); [Washington Legal Found. v. Henney]{.underline},
    128 F. Supp.2d 11 (D.D.C. 2000)("[WLF V]{.underline}").

[^4]: These congressional comments were by no means the only comments
    FDA received expressing concerns about relaxing existing
    restrictions on speech about off-label uses. However, a number of
    comments expressed such concerns without focusing on a legal
    rationale that would assertedly permit FDA to retain its existing
    speech restrictions. For example, the September 13, 2002 comments
    submitted by Public Citizen Health Research Group argued that the
    information in peer-reviewed journals is not comparable to
    information vetted by FDA's drug approval process, discussed four
    instances in which manufacturers allegedly disseminated false or
    misleading information about off-label uses, and concluded that
    "[\[t\]o the extent that]{.underline} the FDA has authority under
    the law to regulate . . . off-label promotion, the agency should err
    on the side of public protection and not pander to . . . the
    pharmaceutical industry." (Emphasis added.) However, the extent to
    which FDA has authority under the law to regulate speech concerning
    off-label information is the key issue that FDA confronts.

[^5]: The argument is perhaps best encapsulated at page 16 of the
    comments (under the heading "Unsubstantiated Promotional Claims
    Shown to be Inherently Misleading"), which states that:

    > The evidence accumulated by Congress before passage of the 1962
    > Amendments to the FDCA demonstrated that, without benefit of
    > pre-market review of a drug's effectiveness by an objective body,
    > it simply was not possible for most physicians to discern which
    > products were effective and which were not. Three features of the
    > pre-1962 scheme caused promotional claims about unproven uses to
    > be inherently misleading: (1) physicians relied heavily on
    > promotional information from manufacturers, much of which was
    > misleading; (2) what reliable, objective evidence existed was
    > difficult or impossible for average physicians to find because
    > they were too busy to track down scattered, often unpublished data
    > on hundreds of new drugs; and (3) in the absence of required
    > testing, few . . . companies conducted . . . studies that would
    > provide reliable evidence of their products' effectiveness. . . .

    (Footnote omitted.)

[^6]: In addition to the points discussed below, it must be noted that
    the health care system has undergone a fundamental transformation in
    the 40 years since enactment of the 1962 FDCA amendments. In
    particular, the proposition that manufacturer-disseminated
    information on off-label uses is inherently misleading because it
    typically involves unsubstantiated assertions that physicians cannot
    evaluate in any meaningful way does not describe the current
    environment. Manufacturers today have many incentives to generate
    reliable, objective evidence concerning new uses of approved
    products: they can expand the market for a product by conducting the
    research necessary to seek FDA's approval for an off-label use; they
    can reduce product liability risks by obtaining FDA approval for new
    indications; and they operate in a marketplace where health care
    professionals and institutions, managed care organizations, and
    public and private insurers demand objective evidence of a product's
    benefits as a basis for making treatment and reimbursement
    decisions. Likewise, these various decisionmakers have the
    capability and motivation to evaluate the evidence concerning the
    benefits of competing therapies. In fact, even in the context of
    treatments that are [not]{.underline} subject to FDA approval
    (surgical procedures, for example) the demand for "evidence-based
    medicine" has grown increasingly powerful. [See]{.underline},
    [e.g.]{.underline}, [Evidence-Based Medicine: A New Approach to
    Teaching the Practice of Medicine]{.underline}, 268 JAMA 2420-25
    (1992) (although randomized clinical trials were rare in 1960,
    "\[i\]t is now accepted that virtually no drug can enter clinical
    practice without a demonstration of its efficacy in clinical trials"
    and "the same randomized clinical trial method increasingly is being
    applied to surgical therapies, and diagnostic tests") (footnotes
    omitted). Modest reforms allowing drug and device manufacturers to
    disseminate information such as peer-reviewed journal articles will
    not turn the clock back to 1962 or give manufacturers a mistaken
    impression that making unsubstantiated assertions about their
    products represents a sound business strategy.

[^7]: Brief for the Petitioners in [Thompson v. Western States Medical
    Center]{.underline}, 2001 WL 1605836, \*28 (emphasis added).

[^8]: February 22, 1996 testimony of William B. Schultz, FDA Deputy
    Commissioner for Policy, before the Senate Committee on Labor and
    Human Resources, <http://www.fda.gove/ola/1996/s/447.htm> (emphasis
    added).

[^9]: 59 Fed. Reg. 59820, 59822, 59825 (Nov. 18, 1994).

[^10]: 62 Fed. Reg. 64074, 64079 (Dec. 3, 1997).

[^11]: 59 Fed. Reg. at 59824. [See]{.underline} [also]{.underline} 63
    Fed. Reg. 64556, 64558 (Nov. 20, 1998) ("manufacturers who wish to
    furnish unapproved use information . . . may do so . . . in response
    to an unsolicited request. Otherwise, they must comply with the
    requirements set forth in section 401 of FDAMA \[the FDA
    Modernization Act of 1997\] and \[its implementing regulation\]").

[^12]: 59 Fed. Reg. at 59823 (emphasis added).

[^13]: 21 U.S.C. §§ 360aaa - 360aaa-6.

[^14]: H.R. Conf. Rep. No. 105-399 (Nov. 9, 1997), 1997 WL 703162 (Leg.
    Hist.), \*99.

[^15]: In fact, in Section 214 of FDAMA, "Practice of Medicine,"
    Congress explicitly provided that "\[n\]othing 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
    healthcare practitioner-patient relationship." As explained in the
    provision's legislative history, it was intended to "emphasize that
    the FDA should not interfere in the practice of medicine," since
    "the off-label use of a medical device by a physician using his or
    her best medical judgment in determining how and when to use the
    medical product for the care of a particular patient is not the
    province of the FDA." H.R. Conf. Rep. No. 105-399 (Nov. 9, 1997),
    1997 WL 703162 (Leg. Hist.), \*97.

[^16]: As noted earlier, the Government did advance this argument
    unsuccessfully in the district court; however, the argument was not
    pursued on appeal.

[^17]: [See]{.underline}, [e.g.]{.underline}, July 30, 2002 comments of
    Community Catalyst, Health Care For All and Health Law Advocates
    (stating that "\[a\]ided in part by direct-to-consumer advertising,
    our nationwide prescription drug market continues to grow at a
    phenomenal rate, burdening an increasing number of consumers with
    the astronomical costs of brand-name drugs" and that reminder ads
    for drugs should be eliminated partly because they "may help account
    for the fact that in 2001 the 50 drugs with the largest price
    increases were brand-name options, and they showed
    disproportionately high increases in sales")(footnotes omitted);
    May 29, 2002 comments of the National Organization for Rare
    Disorders (a recent editorial in [The Lancet]{.underline}
    "summarizes the negative effects of DTC advertising we have seen in
    the United States. Marketing expenses of pharmaceutical firms have
    risen from \$860 million in 1997 to \$2.5 billion in 2000. The
    impact of these expenses on drug costs to consumers is staggering");
    May 13, 2002 comments of the BlueCross BlueShield Association
    (stating that "increases in the sales of the 50 drugs most heavily
    advertised to consumers in 2000 were responsible for almost half of
    the \$20.8 billion (18.8%) one year increase in retail spending on
    prescription drugs" and that the "increased demand for prescription
    products raises the issue of whether patient requests for particular
    drugs represent the best available therapy. . . and whether DTC
    advertising may actually impair a physician's ability to prescribe
    the best available therapy by creating unrealistic consumer demands
    and preferences"); June 5, 2002 comments of Trigon BlueCross
    BlueShield (while DTC advertising has increased the use of
    prescription drug in appropriate patients, "it has also increased
    the use of expensive brand name drugs in place of more economical
    equivalent generic alternatives").

[^18]: 67 Fed. Reg. at 34943.

[^19]: As the FTC noted in its September 13, 2002 comments to FDA (at
    pp. 30-31):

    > Extensive studies investigating the effect of DTC advertising on
    > prices do not exist. In particular, the demand effects have not
    > been extensively studied. The available evidence, however,
    > suggests that any price effects from the costs of the advertising
    > itself are likely to be small. . . .

[^20]: For example, the FTC's January 11, 1996 comments to the FDA
    responding to its request for comments on DTC advertising noted
    that:

    > Although price effects cannot be definitively predicted
    > [a]{.underline} [priori]{.underline}, we believe that DTC
    > advertising may generally reduce drug prices. First . . .
    > advertising can trigger competition among alternative therapies,
    > which, in the long run, should result in lower average prices for
    > the therapeutic category, assuming all else (including quality)
    > remains constant . . . .

    http://www.ftc.gov/opp/advocacy/v960001.htm.

[^21]: [See]{.underline}, [e.g.]{.underline}, U.S. Department of Health
    and Human Services, Office of the Assistant Secretary for Planning
    and Evaluation, [Securing the Benefits of Medical Innovation for
    Seniors, The Role of Prescription Drugs and Drug
    Coverage]{.underline} (July 2002),
    http://aspe.hhs.gov/health/reports/medicalinnovation (noting that
    "\[i\]nnovations in medical science, especially pharmaceuticals,
    have shifted the focus of medicine from highly-invasive treatments
    and surgeries with potentially serious risks to less-invasive
    therapies focused on prevention and health maintenance. This shift
    has allowed many older Americans to . . . avoid\[ \] long hospital
    or nursing home stays").

[^22]: For example, FDA's consumer surveys showed that roughly 20% of
    patients (27% in 1999 and 18% in 2002) reported that DTC ads had
    caused them to ask their physicians about a medical condition or
    illness they had not previously discussed with their physicians.
    [Direct-to-Consumer Advertising of Prescription Drugs, Preliminary
    Patient Survey Results]{.underline}, Kathryn J. Aikin,
    http://www.fda.gov/cder/ddmac/ DTCnational2002a/sld001.htm. For a
    discussion of the survey evidence suggesting that DTC ads improve
    patient compliance, [see]{.underline}, [e.g.]{.underline}, John E.
    Calfee, [What Consumer Surveys Show About Direct-to-Consumer
    Advertising of Prescription Drugs]{.underline} (May 7, 2001) 19-20.

[^23]: [44 Liquormart, Inc. v. Rhode Island]{.underline}, 517 U.S. 484,
    503 (1996).

[^24]: [See]{.underline} [also]{.underline}, [e.g.]{.underline}, [Bates
    v. State Bar of Arizona]{.underline}, 433 U.S. 350, 374-75 (1977)
    ("\[t\]he argument assumes that the public is not sophisticated
    enough to realize the limitations of advertising and . . . is better
    kept in ignorance than trusted with correct but incomplete
    information. We suspect that the argument rests on an
    underestimation of the public. In any event, we view as dubious any
    justification that is based on the benefits of public ignorance");
    [Linmark Associates, Inc. v. Township of Willingboro]{.underline},
    431 U.S. 85, 96 (1977) (striking down a local ordinance because "the
    Council has sought to restrict the free flow of \[the information at
    issue\] because it fears that otherwise homeowners will make
    decisions inimical to what the Council views as the homeowners'
    self-interest and the corporate interest of the township").