Prescription Drugs: Improvements Needed in FDA's Oversight of	 
Direct-to-Consumer Advertising (16-NOV-06, GAO-07-54).		 
                                                                 
The Food and Drug Administration (FDA) is responsible for	 
overseeing direct-to-consumer (DTC) advertising of prescription  
drugs. If FDA identifies a violation of laws or regulations in a 
DTC advertising material, the agency may issue a regulatory	 
letter asking the drug company to take specific actions. GAO was 
asked to discuss (1) trends in drug company spending on DTC	 
advertising and other activities; (2) what is known about the	 
relationship between DTC advertising and drug spending and	 
utilization; (3) the DTC advertising materials FDA reviews; (4)  
the number of regulatory letters that cited DTC materials and	 
FDA's process for issuing those letters; and (5) the		 
effectiveness of these letters at limiting the dissemination of  
violative DTC advertising. GAO reviewed research literature,	 
analyzed FDA's processes, and examined FDA documentation.	 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-07-54						        
    ACCNO:   A63508						        
  TITLE:     Prescription Drugs: Improvements Needed in FDA's	      
Oversight of Direct-to-Consumer Advertising			 
     DATE:   11/16/2006 
  SUBJECT:   Advertising					 
	     Consumer protection				 
	     Cost analysis					 
	     Pharmaceutical industry				 
	     Policy evaluation					 
	     Prescription drugs 				 
	     Regulatory agencies				 
	     Sales promotion					 
	     Surveys						 
	     Evaluation criteria				 
	     Public health					 
	     Policies and procedures				 

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GAO-07-54

   

     * [1]Results in Brief
     * [2]Background
     * [3]Drug Company Spending on DTC Advertising Has Increased More
     * [4]Research Suggests DTC Advertising Increases Drug Spending an
     * [5]FDA Reviews a Small Portion of DTC Materials and Cannot Ensu

          * [6]FDA Reviews a Small Portion of DTC Advertising Materials
          * [7]FDA Cannot Ensure That It Is Reviewing the Highest-Priority

     * [8]Since the 2002 Policy Change, FDA's Process for Issuing Regu

          * [9]FDA's Process for Issuing Regulatory Letters Has Taken Longe
          * [10]FDA Issued Fewer Regulatory Letters Citing Violative DTC Adv
          * [11]FDA Issues Regulatory Letters Only for DTC Advertising Mater

     * [12]Effectiveness of FDA Regulatory Letters at Halting Dissemina

          * [13]Lack of Timely Issuance of Regulatory Letters Limits FDA's E
          * [14]FDA Regulatory Letters Led Drug Companies to Identify and Re
          * [15]Drug Companies Disseminated Corrective Advertising Materials
          * [16]FDA Regulatory Letters Do Not Always Prevent Subsequent Diss

     * [17]Conclusions
     * [18]Recommendations for Executive Action
     * [19]Agency Comments and Our Evaluation
     * [20]GAO Contact
     * [21]Acknowledgments
     * [22]GAO's Mission
     * [23]Obtaining Copies of GAO Reports and Testimony

          * [24]Order by Mail or Phone

     * [25]To Report Fraud, Waste, and Abuse in Federal Programs
     * [26]Congressional Relations
     * [27]Public Affairs

Report to Congressional Requesters

United States Government Accountability Office

GAO

November 2006

PRESCRIPTION DRUGS

Improvements Needed in FDA's Oversight of Direct-to-Consumer Advertising

GAO-07-54

Contents

Letter 1

Results in Brief 5
Background 8
Drug Company Spending on DTC Advertising Has Increased More Rapidly Than
Spending on Promotion to Physicians or Research and Development 12
Research Suggests DTC Advertising Increases Drug Spending and Utilization
14
FDA Reviews a Small Portion of DTC Materials and Cannot Ensure It Is
Reviewing the Highest-Priority Materials 17
Since the 2002 Policy Change, FDA's Process for Issuing Regulatory Letters
Has Taken Longer and the Agency Has Issued Fewer Letters 21
Effectiveness of FDA Regulatory Letters at Halting Dissemination of
Violative DTC Materials Has Been Limited 27
Conclusions 34
Recommendations for Executive Action 34
Agency Comments and Our Evaluation 35
Appendix I Scope and Methodology 38
Appendix II Comments from the Department of Health and Human Services 43
Appendix III GAO Contact and Staff Acknowledgments 47

Tables

Table 1: Prescription Drug Promotion and Research and Development, 1997
through 2005 13
Table 2: Drugs for Which FDA Cited the Same Specific Violative Claim in
More Than One Regulatory Letter 33
Table 3: FDA Regulatory Letters Issued from 2004 through 2005 That Cited
DTC Materials 40

Figures

Figure 1: Number of Final DTC and Consumer-Directed Materials Submitted to
FDA, 1999 through 2005 18
Figure 2: Average Months to Issue Regulatory Letters Citing Violative DTC
Materials, 1997 through 2005 22
Figure 3: Number of Regulatory Letters FDA Issued That Cited DTC
Advertising Materials, 1997 through 2005 25
Figure 4: Timelines for 19 Regulatory Letters Issued from 2004 through
2005 and the Cited DTC Materials 29

Abbreviations

DDMAC Division of Drug Marketing, Advertising, and Communications DTC
direct-to-consumer FDA Food and Drug Administration HHS Department of
Health and Human Services OCC Office of the Chief Counsel PhRMA
Pharmaceutical Research and Manufacturers of America

This is a work of the U.S. government and is not subject to copyright
protection in the United States. It may be reproduced and distributed in
its entirety without further permission from GAO. However, because this
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copyright holder may be necessary if you wish to reproduce this material
separately.

United States Government Accountability Office

Washington, DC 20548

November 16, 2006

The Honorable Bill Frist Majority Leader United States Senate

The Honorable Charles E. Grassley Chairman Committee on Finance United
States Senate

The Honorable Herbert Kohl Ranking Minority Member Special Committee on
Aging United States Senate

Spending on prescription drugs, which accounted for about 11 percent of
total health care spending in 2004,1 has increased more rapidly since 1997
than any other component of health care spending in the United States. One
factor, among many, that has been cited as contributing to this trend is
the advertising of prescription drugs directly to consumers.
Direct-to-consumer (DTC) advertising includes a range of media, such as
television, radio, magazines, newspapers, and the Internet.2 The
pharmaceutical industry spent more than $4.2 billion in 2005 to advertise
prescription drugs to consumers.3 Supporters of DTC advertising maintain
that it educates consumers, helps to get patients into needed treatment,
and saves money by reducing spending on other medical care. Critics
contend that it can be misleading, encourages inappropriate increases in
prescription drug use, and creates unnecessary costs for the U.S. health
care system.

1Centers for Medicare & Medicaid Services, "Highlights," National Health
Expenditure Data, Historical (Baltimore, Md.: Centers for Medicare &
Medicaid Services, 2006), http://www.cms.hhs.gov/NationalHealthExpendData/
(accessed July 31, 2006).

2In addition to DTC advertising, drug companies promote their drugs
through other consumer-directed materials--such as informational videos or
brochures--that are intended to be given to consumers by medical
professionals. Drug companies also promote prescription drugs to medical
professionals, primarily by using sales representatives to provide
information about prescription drugs and by advertising in professional
journals. Further, drug companies provide free samples of prescription
drugs that medical professionals can give to their patients.

3IMS Health Inc., "Total U.S. Promotional Spend by Type, 2005," Top-Line
Industry Data (Fairfield, Conn.: IMS Health Inc., 2006),
http://www.imshealth.com/ (accessed Aug. 21, 2006).

The Department of Health and Human Services' (HHS) Food and Drug
Administration (FDA) regulates the promotion and advertising of
prescription drugs, including DTC materials and materials directed to
medical professionals, to ensure that they are not false or misleading and
otherwise comply with applicable laws and regulations.4 This oversight
function is carried out by the Division of Drug Marketing, Advertising,
and Communications (DDMAC) within FDA's Center for Drug Evaluation and
Research.5 FDA regulations require that drug companies submit final
advertising materials to FDA at the time they are first disseminated to
the public.6 In addition, drug companies sometimes voluntarily submit
draft versions of DTC advertising materials to FDA prior to their release
in order to obtain advisory comments from the agency.

If FDA identifies a violation in a disseminated DTC advertisement, such as
a false or misleading safety or effectiveness claim, the agency may issue
a regulatory letter. In these letters, FDA asks drug companies to take
specific actions such as stopping the dissemination of the advertisement
and, if FDA finds the violation to be particularly serious, running
another advertisement to correct misleading impressions left by the
violative advertisement. Regulatory letters for these violative
advertisements are drafted by DDMAC. Since January 31, 2002, at the
direction of HHS, all draft FDA regulatory letters, including the letters
drafted by DDMAC, are reviewed and approved by FDA's Office of the Chief
Counsel (OCC) before they are issued in order to ensure the letters'
"legal sufficiency and consistency with agency policy."7 In October 2002,
we reported that the 2002 policy change had adversely affected FDA's
ability to enforce compliance with its regulations by delaying the
issuance of regulatory letters and potentially allowing misleading
advertisements to continue to be disseminated.8 As we noted in that
report, issuing regulatory letters quickly after violative materials are
disseminated is a key component of FDA's oversight of DTC advertising
because any inaccurate impressions of a drug that are caused by a
misleading advertisement are minimized if the advertisement is quickly
removed. We recommended that FDA take action to reduce the amount of time
for internal review of draft regulatory letters citing violative DTC
materials. In its response to our recommendation, FDA wrote that it had
established a goal of issuing regulatory letters "within 15 working days
of review at OCC."9

4See 21 U.S.C. S 352(n), 21 C.F.R. S 202.1(e)(2006). FDA's authority does
not extend to "help-seeking" advertisements--those that do not identify
prescription drugs by name, but rather discuss a disease or condition and
advise the audience to "see your doctor" for possible treatments. In
addition, the Federal Trade Commission has primary oversight
responsibility for the regulation of advertising for over-the-counter
drugs.

5Other centers within FDA are responsible for overseeing promotion and
advertising of biologics--such as vaccines and blood products--and
electronic products emitting radiation.

621 C.F.R. S 314.81(b)(3)(i)(2006).

As a result of the increased spending on prescription drugs and concerns
about the effect of DTC advertising, you asked us to examine trends in DTC
advertising and FDA's regulation and oversight of this advertising. In
this report, we discuss (1) trends in pharmaceutical industry spending on
DTC advertising, as compared to promotion to medical professionals, and
research and development; (2) what is known about the relationship between
DTC advertising and prescription drug spending and utilization patterns;
(3) the DTC advertising materials FDA reviews; (4) the number of FDA
regulatory letters that cited DTC advertising materials and FDA's process
for issuing those letters; and (5) the effectiveness of FDA's regulatory
letters at limiting the dissemination of false or misleading DTC
advertising.

To examine trends in pharmaceutical industry spending on DTC advertising,
promotion to medical professionals, and research and development of new
drugs, we reviewed publicly reported data. For overall drug company
spending from 1997 through 2005 on DTC advertising and promotion to
medical professionals, we obtained data from IMS Health Inc. For 2005, we
reviewed detailed data from Neilsen Monitor-Plus on DTC advertising by
prescription drug. Some types of promotional spending on DTC advertising
and promotion to medical professionals--such as spending on professional
meetings and spending on promotion to nurse practitioners--are not
captured in the data we examined. In addition, we obtained data from the
Pharmaceutical Research and Manufacturers of America (PhRMA)--which
represents U.S. pharmaceutical research and biotechnology companies--on
drug company spending for the research and development of new drugs from
1997 through 2005. Based on our review of related documentation and our
discussions with the data providers, we determined that the data we
present were sufficiently reliable for our use. To examine the
relationship between DTC advertising and prescription drug spending and
utilization, we reviewed 64 peer-reviewed journal articles, dissertations,
and industry articles published from 1982 through 2006. To examine the DTC
advertising materials that FDA reviews, we obtained data from FDA on the
number and type of advertising materials that it received and reviewed
from 1997 through 2005. Based on interviews with FDA officials and
reviewers and our review of related documentation, we determined that
these data were sufficiently reliable for the purposes of this report. To
examine the number of FDA regulatory letters that cite violative DTC
advertising materials and FDA's process for issuing those letters, we
reviewed all regulatory letters issued by FDA from 1997 through 2005
citing prescription drug promotion. We identified 135 regulatory letters
issued during this period that cited one or more violative DTC advertising
materials.10 We also reviewed FDA documentation on the length of the
agency's process for issuing the 135 regulatory letters. Because FDA does
not track when the agency identifies a violation, we used the date on
which reviewers first began drafting a regulatory letter as the earliest
date in this process. To examine the effectiveness of the regulatory
letters FDA issued from 2004 through 2005 that cite violative DTC
advertising materials, we obtained additional details about the timeliness
of the letters and drug companies' compliance with any corrective action
requested by FDA. We reviewed the content of the regulatory letters FDA
issued from 1997 through 2005 to identify the violations cited; we did not
evaluate the appropriateness of cited violations or evaluate the legal
sufficiency of these letters. We also did not examine the effectiveness of
FDA's review of draft materials at preventing potentially violative
materials from being disseminated. Finally, our examination included only
DDMAC's oversight of prescription drug promotion and advertising; we did
not examine oversight by other parts of FDA of promotion for other types
of medical products. (For additional information on our methodology, see
app. I.) We conducted our work from January 2006 through November 2006 in
accordance with generally accepted government auditing standards.

7FDA issues regulatory letters on a variety of topics as a means of
bringing about voluntary compliance with applicable laws and regulations.
In a November 29, 2001, memo the Deputy Secretary of HHS instructed FDA
that no regulatory letters could be issued until FDA's OCC reviewed them.
According to FDA officials, OCC implemented this policy change on January
31, 2002. Prior to this policy change, OCC review and approval of draft
regulatory letters before their issuance was not required.

8GAO, Prescription Drugs: FDA Oversight of Direct-to-Consumer Advertising
Has Limitations, [28]GAO-03-177 (Washington, D.C.: Oct. 28, 2002).

9 [29]GAO-03-177 , p. 33.

10We excluded regulatory letters that cited only materials intended to be
given to consumers by medical professionals or that cited only materials
directed to medical professionals. FDA officials confirmed that the 135
letters included all letters that cited DTC materials.

Results in Brief

Drug company spending on DTC advertising has increased twice as fast as
spending on promotion to physicians or on the research and development of
new drugs. According to publicly reported data, from 1997 through 2005,
spending on DTC advertising increased almost 20 percent each year. Over
the same time period, spending on drug promotion to physicians and
spending on research and development each increased by about 9 percent
annually. Drug companies spent less in 2005 on DTC advertising ($4.2
billion) than on promotion to physicians ($7.2 billion) or research and
development ($31.4 billion).

Studies we reviewed suggest that while DTC advertising increases
prescription drug spending and utilization, it can have both positive and
negative effects on consumers. The studies we reviewed found that
increases in DTC advertising have contributed to overall increases in
spending on both the advertised drug itself and on other drugs that treat
the same conditions. For example, one study of 64 drugs found a median
increase in sales of $2.20 for every $1 spent on DTC advertising. Consumer
surveys suggest that DTC advertising increases utilization of drugs by
prompting some consumers to request the advertised drugs from their
physicians, who studies find are generally responsive to these requests.
The surveys we reviewed found that between 2 and 7 percent of consumers
who saw DTC advertising requested and ultimately received a prescription
for the advertised drug. Studies about DTC advertising and the increased
utilization of prescription drugs it can prompt suggest that its effect on
consumers can be both positive, such as encouraging them to talk to their
doctors about previously undiagnosed conditions, and negative, such as
encouraging increases in prescriptions for advertised drugs when
alternatives may be more appropriate.

FDA reviews a small portion of the DTC materials it receives, and the
agency cannot ensure that it is identifying for review the materials it
considers to be highest priority. Since FDA created a group in 2002--with
an initial staff allocation of one group leader, four reviewers, and two
social scientists--with specific responsibility for reviewing DTC
materials, the number of DTC materials FDA receives each year has almost
doubled. While FDA officials told us the agency prioritizes the review of
materials that have the greatest potential to impact public health, the
agency has not documented criteria to make this prioritization. FDA
officials identified informal criteria that reviewers consider when
identifying materials for review. For example, FDA officials told us that
they review all final and draft DTC television advertisements that FDA
receives because these materials are likely to be widely disseminated to
consumers. The agency also places a priority on draft versions of other
DTC materials because this provides the agency with an opportunity to
identify problems before the materials are disseminated to consumers.
However, FDA does not systematically apply its informal criteria to all of
the DTC materials it receives. Instead, the agency relies on reviewers to
be aware of the materials the agency has received and accurately apply the
various criteria to each of the materials. Furthermore, FDA cannot
determine whether a particular material has been reviewed. As a result,
the agency cannot ensure that it is identifying and reviewing the
highest-priority materials.

Since the 2002 policy change requiring legal review of all draft
regulatory letters, FDA's process for drafting and issuing letters has
taken longer and the agency has issued fewer letters per year. From 2002
through 2005, once the agency began drafting a regulatory letter for
violative DTC materials, it took an average of 4 months to issue the
letter, while it took an average of 2 weeks to issue a letter from 1997
through 2001. FDA officials told us that the policy change contributed to
the lengthened review by creating additional levels of review and making
it necessary for the DDMAC reviewers who draft the regulatory letters to
do substantially more work to prepare for and respond to comments from
OCC. Since the policy change, FDA has issued about half as many regulatory
letters citing violative DTC advertisements per year--between 8 and 11
letters annually from 2002 through 2005, compared with 15 to 25 letters
annually from 1997 through 2001. FDA's regulatory letters sometimes cited
more than one DTC material and more than one violation per material.
Commonly cited violations included failure of the material to accurately
communicate information about the safety of the drug, overstatement of the
drug's effectiveness, and use of misleading comparative claims. FDA
officials told us that the agency issues letters only for the violative
DTC materials that it considers the most serious and most likely to impact
consumers' health.

The effectiveness of FDA's regulatory letters at halting the dissemination
of violative DTC materials has been limited. The 19 regulatory letters FDA
issued from 2004 through 2005 were issued an average of 8 months after the
violative materials were first disseminated to consumers. By the time
these regulatory letters were issued, drug companies had already
discontinued use of more than half of the violative advertising materials.
When cited materials were still being disseminated, drug companies
complied with FDA's requests to remove the materials in response to FDA's
letters. In addition, as requested in the regulatory letters, drug
companies identified and removed additional materials with similar claims.
Further, for the 6 letters in which FDA requested that drug companies
issue new advertising materials to correct the misimpressions left by the
violative materials cited in the letters, drug companies disseminated the
corrective materials. These corrections were not disseminated to consumers
until 5 months or more after FDA issued the regulatory letter. Despite
halting the dissemination of both cited and other violative materials at
the time a letter was issued, FDA's issuance of regulatory letters has not
always prevented drug companies from later disseminating similar violative
materials for the same drugs. We found that of the 89 drugs for which FDA
cited violative DTC materials from 1997 through 2005, 25 drugs had DTC
materials cited in more than one regulatory letter, sometimes for similar
types of violations. In our 2002 report, we expressed similar concerns
about the length of time it takes FDA to issue regulatory letters and
recommended that HHS take steps to reduce the time that FDA's DTC draft
regulatory letters are under review. HHS agreed in its written response to
that report that letters needed to be issued more quickly and established
a goal of issuing the letters "within 15 working days of review at OCC."
Given our findings in this report, we continue to believe that letters
must be issued more quickly in order to limit consumers' exposure to false
or misleading claims.

To improve FDA's processes for identifying and reviewing final and draft
DTC advertising materials, we are making recommendations to the Acting
Commissioner of FDA. Specifically, we recommend that FDA (1) document
criteria for prioritizing materials that it receives for review, (2)
systematically apply its documented criteria to all of the materials it
receives, and (3) track which materials have been reviewed.

In its comments on a draft of this report, HHS generally agreed with our
description of FDA's oversight of DTC advertising but disagreed with our
recommendations and some aspects of our conclusions. Specifically, HHS
commented that implementing our recommendations would require vastly
increased staff. HHS also expressed concern that our draft report
criticized the length of time it takes to issue regulatory letters since
the policy change requiring legal review, without adequately addressing
the underlying purpose of that review. We believe it is important for FDA
to develop a more complete and systematic process for screening the
materials it receives, in order to ensure that FDA is reviewing the
highest-priority materials. We do not agree that such a process would
require that every DTC material be reviewed in detail, as HHS contends.
Instead, we believe that FDA should apply its criteria as a screening
mechanism to all submitted materials to determine the priority of
materials for review. Furthermore, FDA already has most of the information
that would be necessary to establish a system to screen submitted
materials against these criteria. Additionally, we agree with HHS that it
is important to ensure that FDA's regulatory letters are legally
supportable. As FDA agreed in its response to our 2002 report, however, it
is also important for letters to be issued quickly. We believe that it is
important for letters to be issued in a timely manner if they are to have
an impact on halting the dissemination of the violative materials that the
letters cite and reducing consumers' exposure to false or misleading
advertising.

Background

The practice of advertising prescription drugs to consumers has been
controversial. The United States is one of only two nations that allow DTC
advertising (the other is New Zealand). In the United States, there have
been concerns about the impact of DTC advertising on prescription drug
spending and about potential safety issues, particularly with regard to
the advertising of new drugs. These concerns have led to calls to restrict
DTC advertising. For example, the Institute of Medicine recently
recommended that DTC advertising be restricted during the first two years
a new drug is marketed because some of the health risks of new drugs are
not fully understood.11

FDA regulates the content of all prescription drug advertising, whether
directed to consumers or medical professionals. Advertising that is
targeted to consumers includes both DTC and "consumer-directed" materials.
DTC advertising includes, for example, broadcast advertisements (such as
those on television and radio), print advertisements (such as those in
magazines and newspapers), and Internet advertisements (such as consumer
advertising on drug companies' Web sites).12 In contrast,
consumer-directed advertisements are designed to be given by medical
professionals to consumers and include, for example, patient brochures
provided in doctors' offices.

11Institute of Medicine, The Future of Drug Safety: Promoting and
Protecting the Health of the Public (Washington, D.C.: The National
Academies Press, September 2006).

12A drug company Web site may contain advertising directed to consumers,
advertising directed to medical professionals, and product labeling.

FDA requires that drug companies submit all final prescription drug
advertising materials to the agency when they are first disseminated to
the public.13 Drug companies are generally not required to submit
advertising materials to FDA before they are disseminated.14 However, drug
companies sometimes voluntarily submit draft DTC advertising materials to
FDA in order to obtain advisory comments from the agency.15

Advertising materials must contain a "true statement" of information
including a brief summary of side effects, contraindications, and the
effectiveness of the drug.16 To meet this requirement, advertising
materials must not be false or misleading, must present a fair balance of
the risks and benefits of the drug, and must present any facts that are
material to the use of the drug or claims made in the advertising. With
the exception of broadcast advertisements, materials must present all of
the risks described in the drug's approved labeling. Broadcast materials
may present only the major side effects and contraindications, provided
the materials make "adequate provision" to give consumers access to the
information in the drug's approved or permitted package labeling.17

1321 C.F.R. S 314.81(b)(3)(2006).

14See 21 U.S.C. S 352(n)(3)(A) (providing that FDA generally may not
require advertisements to be submitted for approval prior to
dissemination). Advertising and promotional materials must be submitted to
FDA before they are disseminated for drugs approved under FDA's
accelerated approval process, which is for drugs that treat serious or
life-threatening illnesses, and for drugs approved based on animal studies
where human efficacy studies are not ethical or feasible. 21 C.F.R. SS
314.550, 314.640(2006).

15PhRMA issued guidance effective January 2006 that states that "[drug]
companies should submit all new DTC television advertisements to the FDA
before releasing these advertisements for broadcast." PhRMA, PhRMA Guiding
Principles: Direct to Consumer Advertisements about Prescription Medicines
(Washington, D.C.: PhRMA, November 2005),
http://www.phrma.org/files/DTCGuidingprinciples.pdf (last accessed July
31, 2006).

1621 C.F.R. S 202.1(e)(1)(2006). Those advertising materials that call
attention to the name of the drug but do not include indication or dosage
recommendations for use of the drug are exempt from these brief summary
requirements.

Within FDA, DDMAC is responsible for implementing the laws and regulations
that apply to prescription drug advertising. The division, which had 41
staff as of July 2006, is responsible for the oversight of both
advertising directed to consumers and advertising directed to medical
professionals. In March 2002, DDMAC created a DTC Review Group, which is
responsible for oversight of advertising materials that are directed to
consumers. Four Professional Review groups are responsible for oversight
of promotional materials targeted to medical professionals. The DTC Review
Group was allocated a group leader, four reviewers, and two social
scientists when it was created. This group's responsibilities include
reviewing final DTC materials and reviewing and providing advisory
comments on draft DTC materials. The group also monitors television,
magazines, and consumer advertising on drug companies' Web sites to
identify advertising materials that were not submitted to FDA at the time
they were first disseminated and reviews advertising materials cited in
complaints submitted by competitors, consumers, and others. The two social
scientists support reviewers in both the DTC and professional groups in
their assessment of the content of advertising materials and conduct
research related to DTC advertising, such as surveys of consumer and
physician attitudes toward DTC advertising.

Once submitted to FDA, final and draft DTC advertising materials are
distributed to a reviewer in the DTC Review Group. For final materials, if
the reviewer identifies a concern, the agency determines whether it
represents a violation and merits a regulatory letter. For draft materials
submitted by drug companies, FDA may provide the drug company with
advisory comments to consider before the materials are disseminated to
consumers if, for example, the reviewers identify claims in materials that
could violate applicable laws and regulations.18

17FDA published draft guidance for DTC broadcast advertisements in 1997,
and final guidance in 1999, that described an approach drug companies
could use to meet the regulatory requirement for making adequate provision
of key information. The outlined approach provides that drug companies
disseminate complete information included in a drug's approved package
labeling through four alternative sources--including a toll-free number
and a drug company Web site. See FDA, Guidance for Industry:
Consumer-Directed Broadcast Advertisements (Rockville, Md.: FDA, August
1999). For other guidance related to DTC advertising, see FDA, Draft
Guidance for Industry: Brief Summary: Disclosing Risk Information in
Consumer-Directed Print Advertisements (Rockville, Md.: FDA, January
2004), and FDA, Draft Guidance for Industry: Help-Seeking and Other
Disease Awareness Communications by or on Behalf of Drug and Device Firms
(Rockville, Md.: FDA, January 2004).

If FDA identifies violations in disseminated DTC materials, the agency can
issue two types of regulatory letters--either a "warning letter" or an
"untitled letter." Warning letters are typically issued for violations
that may lead FDA to pursue enforcement action if not corrected; untitled
letters are issued for violations that do not meet this threshold. FDA
generally posts issued letters on its Web site within several days of
issuance.19 Both types of letters--which ranged from 2 to 9 pages, from
1997 through 2005--cite the type of violation identified in the company's
advertising material, request that the company submit a written response
to FDA within 14 days, and request that the company take specific actions.
Untitled letters request that companies stop disseminating the cited
advertising materials and other advertising materials with the same or
similar claims. In addition, warning letters further request that the
company issue advertising materials to correct the misleading impressions
left by the violative advertising materials. While FDA does not have
explicit authority to require companies to act upon these letters, if the
companies continue to violate applicable laws or regulations, the agency
has other administrative and judicial enforcement avenues that could
encourage compliance or result in the product being taken off the market.
For example, FDA, through the Department of Justice, may seek additional
remedies in the courts resulting in the seizure of drugs deemed to be
misbranded because their advertising is false or misleading.

As reviewers from the DTC Review Group draft the regulatory letters, they
sometimes obtain consultations from other FDA experts. For example, they
may consult with the social scientists in the DTC Review Group about how
consumers might interpret the violative materials, with the regulatory
counsel in DDMAC about regulatory issues, or with a medical officer in
FDA's Office of New Drugs who has knowledge of a drug's clinical testing
and approval history. The reviewers may also consult with reviewers in
DDMAC's Professional Review groups.

18If FDA notifies the drug company that a draft material is not in
violation and, at some subsequent time, changes its opinion, the agency is
to notify the drug company in writing and is to provide it with a
reasonable amount of time for correction before any regulatory action is
taken. 21 C.F.R. S 202.1(j)(4)(2006).

19FDA, Center for Drug Evaluation and Research, Warning Letters and Notice
of Violation Letters to Pharmaceutical Companies (Rockville, Md.: FDA,
2006), http://www.fda.gov/cder/warn/ (last accessed Sept. 26, 2006).

The draft regulatory letters are subsequently reviewed by officials in
DDMAC, FDA's Office of Medical Policy (which oversees DDMAC), and OCC. In
January 2002, at the direction of the Deputy Secretary of HHS, FDA
implemented a policy change requiring OCC to review and approve all
regulatory letters prior to their issuance, including letters drafted by
the DTC Review Group, to ensure "legal sufficiency and consistency with
agency policy."20 In its written comments on a draft of our 2002 report,
FDA stated that, prior to the policy change, there had been complaints
that FDA would not follow up on many of its regulatory letters, and that
the goal of the policy change was to promote voluntary compliance by
ensuring that drug companies who receive a regulatory letter understand
that the letter has undergone legal review and the agency is prepared to
go to court if necessary.21

Drug Company Spending on DTC Advertising Has Increased More Rapidly Than
Spending on Promotion to Physicians or Research and Development

The amount that drug companies spend on DTC advertising increased twice as
fast as spending on promotion to physicians or on research and
development. IMS Health estimated that, from 1997 through 2005, spending
on DTC advertising in the United States increased from $1.1 billion to
$4.2 billion--an average annual increase of almost 20 percent.22 In
contrast, over the same time period, IMS Health estimated that spending on
drug promotion to physicians increased by 9 percent annually. Further,
PhRMA reported that spending on the research and development of new drugs
increased by about 9 percent annually during the same period.23 While
spending on DTC advertising has grown rapidly, companies continue to spend
more on promotion to physicians and on research and development. In
addition, IMS Health reports that the retail value of the free drug
samples that companies provide to medical

20Prior to the January 2002 policy change, OCC review and approval of
draft regulatory letters before their issuance was not required. DDMAC
officials told us, however, that prior to the policy change they routinely
obtained feedback from OCC on draft warning letters.

21 [30]GAO-03-177 , p. 32.

22IMS Health Inc., "Total U.S. Promotional Spend, by Type," Top-Line
Industry Data (Fairfield, Conn.: IMS Health Inc., 2006),
http://www.imshealth.com/ (last accessed Aug. 21, 2006).

23PhRMA, Pharmaceutical Industry Profile 2006 (Washington, D.C.: PhRMA,
March 2006).

professionals to distribute to their patients has increased by about 15
percent annually.24 (See table 1.)

Table 1: Prescription Drug Promotion and Research and Development, 1997
through 2005

Dollars in                                                                       
billions                                                                         
                                                              Average      Total 
                                                               annual percentage 
                                                           percentage  increase, 
             1997 1998 1999 2000 2001 2002 2003 2004  2005   increase  1997-2005 
Promotion                                                                        
Spending on                                                                      
DTC                                                                              
advertisinga $1.1 $1.3 $1.8 $2.5 $2.7 $2.6 $3.3 $4.0  $4.2       19.6      296.4 
Spending on                                                                      
promotion to                                                                     
physiciansb   3.9  4.6  4.8  5.6  5.9  6.6  7.4  7.8   7.2        9.0       86.0 
Retail value                                                                     
of samplesc   6.0  6.6  7.2  8.5 10.5 11.9 13.5 15.9  n.a.      14.9d     162.4d 
Research and                                                                     
Development                                                                      
Spending on                                                                      
research and                                                                     
developmente 15.5 17.1 18.5 21.4 23.5 25.7 27.1 29.6 31.4f        9.3      103.3 

Sources: GAO analysis of IMS Health and PhRMA data.

Legend: n.a. = not available.

aIncludes estimated spending on DTC advertising on television, in
magazines and newspapers, on radio, and outdoors (such as on billboards).
The estimates do not include other spending, such as spending to develop
and maintain drug companies' Web sites or spending on sponsorship of
sporting events.

bIncludes estimated spending on office- and hospital-based promotion to
physicians and journal advertising. These estimates do not include other
spending, such as drug company spending on meetings and events, or
spending on promotion that targets medical professionals other than
physicians, such as nurse practitioners and physicians assistants.

cWe used the retail value of drug samples as a measure of the volume of
drug samples provided to physicians, but the retail value of samples does
not directly reflect the amount spent by drug companies to manufacture and
provide these samples.

dRepresents data from 1997 through 2004.

eIncludes spending on research and development reported by PhRMA member
companies, as reported in PhRMA's annual industry review. Although not all
drug companies are members of PhRMA, its member companies account for
almost all spending on prescription drug promotion.

fThis figure represents an estimate by PhRMA of spending for this year.

24We used the retail value of drug samples as a measure of the volume of
drug samples provided to physicians, but the retail value of samples does
not directly reflect the amount spent by drug companies to manufacture and
provide these samples.

Some types of promotional spending are not captured in the data we report.
For example, figures for spending on DTC advertising do not include
spending to develop and maintain drug companies' Web sites or spending on
sponsorship of sporting events. In addition, some spending on promotion to
medical professionals is not captured. For example, the data do not
include drug company spending on meetings and events, or spending on
promotion that targets medical professionals other than physicians, such
as nurse practitioners and physicians assistants.

Drug companies concentrate their spending on DTC advertising in specific
forms of media and on relatively few drugs. Television and magazine
advertising represented about 94 percent of all spending on DTC
advertising in 2005. DTC advertising also tends to be concentrated on
relatively few brand name prescription drugs--in 2005, the top 20 DTC
advertised drugs accounted for more than 50 percent of all spending on DTC
advertising.25 Many of the drugs most heavily advertised to consumers in
2005 were for the treatment of chronic conditions, such as high
cholesterol, asthma, and allergies. Several of the drugs that have high
levels of DTC advertising are also often promoted to physicians, and the
drug companies often provide physicians with free samples of these drugs
to be given to consumers.

Research Suggests DTC Advertising Increases Drug Spending and Utilization

Studies we reviewed suggest that DTC advertising increases prescription
drug spending and utilization. It increases utilization by prompting some
consumers to request the drugs from their physicians and for some
physicians to prescribe the requested drugs. Evidence about increased
utilization prompted by DTC advertising suggests it can have both positive
and negative effects on consumers.

Studies we reviewed suggest that DTC advertising can increase drug
spending for both the advertised drug and for other drugs that are used to
treat the same condition. Studies have found that, for many drugs, DTC
advertising increases sales of the drug itself, though the amount varies
substantially. Across the studies we examined, estimates for certain drugs
range from little change in sales to an increase of more than $6 for every
$1 spent to advertise the specific drug. For example, one study of 64
drugs found a median increase in sales of $2.20 for every $1 spent on DTC
advertising.26 The impact of DTC advertising on the sales of an individual
drug depends on many factors. For example, one study found that, for the
63 drugs with the largest revenues in 2000, DTC advertising for newer
drugs--launched in 1998 or 1999--increased sales more than DTC advertising
for drugs launched from 1994 through 1997.27 Further, research suggests
that the sales of a specific drug may be affected by DTC advertising for
other drugs that treat the same condition. For example, one study found
that every $1,000 spent on advertising for allergy drugs was associated
with 24 new prescriptions for one specific allergy drug.28

25Med Ad News staff, "DTC Takes a Back Seat," Med Ad News, vol. 25, no. 5
(May 2006).

The studies we reviewed also suggest that DTC advertising increases
prescribing by prompting some consumers to request the drugs from their
physicians, and that physicians are generally responsive to the patient
requests. Across the consumer and physician surveys that we reviewed,29
about 90 percent of consumers report having seen a DTC advertisement.
Studies have found that about 30 percent (ranging from 18 to 44 percent)
of consumers who have seen DTC advertising reported discussing with their
physician either the condition seen in an advertisement or an advertised
drug. Of consumers who reported discussing an advertised condition or
drug, about one quarter (ranging from 7 to 35 percent) reported requesting
a prescription for the advertised drug. Surveys have found that of
consumers who requested a drug they saw advertised, generally more than
half (ranging from 21 to 84 percent) reported receiving a prescription for
the requested drug. The surveys we reviewed found that between 2 and 7
percent of consumers who see a DTC advertisement requested and ultimately
received a prescription for the advertised drug. Studies suggest that
physicians are generally responsive to consumers' requests, and that
decisions to prescribe a drug are influenced by a variety of factors in
addition to a patient's medical condition. For example, studies have found
that advertising in medical journals and visits from drug sales
representatives may influence physician prescribing to a greater degree
than DTC advertising.

26David Gascoigne and John Busbice for IMS, DTC ROI: The Latest Findings
(presented at the DTC National Conference, Washington, D.C., Apr. 26,
2006).

27Dick Wittink, Analysis of ROI for Pharmaceutical Promotion (ARPP)
(Westfield, N.J.: The Association of Medical Publications, Inc., September
2002), http://www.rxpromoroi.org/arpp/media/arpp9_18dwittink.ppt (accessed
May 19, 2006).

28Woodie M. Zachry III et al., "Relationship between Direct-to-Consumer
Advertising and Physician Diagnosing and Prescribing," American Journal of
Health-Systems Pharmacy, vol. 59, no. 1 (2002).

29Because the precise questions each survey asked and the resulting
responses varied, we present general findings along with the relevant
range of responses. The studies surveyed U.S. adults, but were not always
representative of the general U.S. population. The surveys of consumer and
physician behaviors that we reviewed included Prevention Magazine's Eighth
Annual Survey of Consumer Reaction to Direct-to-Consumer Advertising of
Prescription Medicines (Emmaus, Pa.: Prevention Magazine, 2005); Kathryn
J. Aikin, John L. Swasy, and Amie C. Braman, Patient and Physician
Attitudes and Behaviors Associated With DTC Promotion of Prescription
Drugs--Summary of FDA Survey Research Results (Rockville, Md.: FDA, Nov.
19, 2004); Barbara Mintzes et al., "How Does Direct-to-Consumer
Advertising (DTCA) Affect Prescribing? A Survey in Primary Care
Environments with and without Legal DTCA," Canadian Medical Association
Journal, vol. 169, no. 5 (2003); Sharon Allison-Ottey, Karen Ruffin, and
Kimberly Allison, "Assessing the Impact of Direct-to-Consumer
Advertisements on the AA Patient: A Multisite Survey of Patients During
the Office Visit," Journal of the National Medical Association, vol. 95,
no. 2 (2003); Balaji Datti and Mary W. Carter, "The Effect of
Direct-to-Consumer Advertising on Prescription Drug Use by Older Adults,"
Drugs & Aging, vol. 23, no. 1 (2006); Stephen E. Everett, "Lay Audience
Response to Prescription Drug Advertising," Journal of Advertising
Research, vol. 31, no. 2 (1991); The NewsHour with Jim Lehrer/Kaiser
Family Foundation/Harvard School of Public Health, "National Survey on
Prescription Drugs," (Menlo Park, Calif.: Kaiser Family Foundation, Sept.
2000), http://www.pbs.org/newshour/health/prescriptions/full_survey.pdf
(accessed May 25, 2006).

Studies about DTC advertising and the increased utilization of
prescription drugs it can prompt suggest that its effect on consumers can
be both positive and negative. Some research suggests that DTC advertising
can have benefits for consumers, such as encouraging them to talk to their
doctors about previously undiagnosed conditions. For example, one study
found that DTC advertising is associated with the diagnosis and treatment
of high cholesterol with prescription drugs.30 Similarly, another study
found that DTC advertising for antidepressant drugs was associated with an
increase in the number of people diagnosed with depression and who
initiated drug therapy, as well as with a small increase in patients who
received the appropriate duration of therapy.31 In contrast, other
research suggests that DTC advertising can have negative effects, such as
encouraging increases in prescriptions for advertised drugs when
alternatives may be more appropriate. For example, one study found that
consumers who requested a pain medication as a result of DTC advertising
were more likely to get the requested drug than a drug more appropriate
for those consumers.32 Another study, using actors posing as patients,
found that 55 percent of those who presented with symptoms of adjustment
disorder and requested a specific antidepressant received an
antidepressant, even though treatment with drugs may not have been
appropriate given their symptoms.33

30Woodie M. Zachry III et al., "Relationship between Direct-to-Consumer
Advertising and Physician Diagnosing and Prescribing."

31Julie M. Donohue et al., "Effects of Pharmaceutical Promotion on
Adherence to the Treatment Guidelines for Depression," Medical Care, vol.
42, no. 12 (2004).

FDA Reviews a Small Portion of DTC Materials and Cannot Ensure It Is Reviewing
the Highest-Priority Materials

FDA reviews a small portion of the increasingly large number of DTC
materials it receives. FDA attempts to target available resources by
focusing its reviews on the DTC advertising materials that have the
greatest potential to impact public health, but the agency has not
documented criteria for prioritizing the materials it receives for review.
FDA officials told us that agency reviewers consider several informal
criteria when prioritizing the materials. However, FDA does not apply
these criteria systematically to the materials it receives. Instead, FDA
relies on each of the reviewers to be aware of the materials the agency
has received and accurately apply the criteria to determine the specific
materials to review. Further, the agency does not document if a particular
DTC material was reviewed. As a result, the agency cannot ensure that it
is identifying or reviewing the materials that are the highest priority.

FDA Reviews a Small Portion of DTC Advertising Materials

FDA reviews a small portion of the increasingly large number of DTC
materials submitted to the agency by drug companies. In 2005, FDA received
4,600 final DTC materials (excluding Internet materials) and 6,168 final
Internet materials.34 FDA also received 4,690 final consumer-directed
materials--such as brochures given to consumers by medical professionals.
As shown in figure 1, FDA has received a steadily increasing number of
final materials from 1999 through 2005. We could not determine whether
there has been a similar increase in the number of draft DTC materials FDA
has received because the agency does not track this information.35

32Michele M. Spence et al. "Direct-to-Consumer Advertising of COX-2
Inhibitors: Effect on Appropriateness of Prescribing," Medical Care
Research and Review, vol. 62, no. 5 (2005). This study evaluated the
appropriateness of a prescription by determining whether it was consistent
with a patient's risk of gastrointestinal bleeding, which was assessed
according to three evidence-based risk assessment guidelines.

33Richard L. Kravitz et al., "Influence of Patients' Requests for
Direct-to-Consumer Advertised Antidepressants," Journal of the American
Medical Association, vol. 293, no. 16 (2005). This study used actors
trained to present a standard set of symptoms to office-based physicians
and to make standard requests for treatment in accordance with the
established study protocol.

34We present Internet materials separately from other DTC materials
because FDA's count of submitted materials does not distinguish between
Internet materials targeted to consumers and those targeted to medical
professionals. However, FDA officials told us that most Internet
materials, such as drug companies' Web sites, include both a consumer and
a professional component.

Figure 1: Number of Final DTC and Consumer-Directed Materials Submitted to
FDA, 1999 through 2005

Notes: We do not include final DTC materials submitted to FDA in 1997 and
1998 because FDA changed the way it categorized submitted materials in
1999. We present Internet materials separately from DTC materials because
FDA's data do not distinguish between Internet materials that are targeted
to consumers and those targeted to professionals. However, FDA officials
told us that most Internet materials contain a consumer component.

35FDA tracks the number of submissions of draft DTC materials, rather than
the actual number of draft materials. These submissions can include both
materials directed to consumers and materials targeted to medical
professionals, and FDA officials estimated that each submission could
contain as few as 1 or as many as 60 separate draft materials. As a
result, we were unable to determine the number of draft DTC materials
submitted to FDA in a given year.

FDA officials told us that the agency receives substantially more final
and draft materials than the DTC Review Group can review. The total number
of final materials has almost doubled since FDA formed its DTC Review
Group in March 2002. FDA officials told us that the group was not fully
staffed until September 2003 and that turnover has been a problem,
temporarily reducing the number of reviewers in the group from four to one
in late summer 2005. FDA has since filled all of the positions in the
group and it added a fifth reviewer in September 2006.36 Officials told us
that it can take 6 months to a year for new reviewers to become fully
productive.

FDA officials estimate that reviewers spend the majority of their time
reviewing and commenting on draft materials. However, we were unable to
determine the number of final or draft materials FDA reviews, because FDA
does not track this information. In the case of final and draft broadcast
materials, FDA officials told us that the DTC group reviews all of the
materials it receives; in 2005, it received 337 final and 146 draft
broadcast materials. However, FDA does not document whether these or other
materials it receives have been reviewed. As a result, FDA cannot
determine how many materials it reviews in a given year.

FDA Cannot Ensure That It Is Reviewing the Highest-Priority DTC Advertising
Materials

FDA cannot ensure that it is identifying and reviewing the
highest-priority DTC materials because it does not have documented
criteria that it systematically uses to select DTC materials for review.
FDA officials told us that, to target available resources, the agency
prioritizes the review of the DTC advertising materials that have the
greatest potential to impact public health. However, FDA has not
documented criteria for reviewers in the DTC Review Group to consider when
prioritizing materials for review. Instead, FDA officials identified
informal criteria that reviewers use to prioritize their reviews. For
example, FDA officials told us that the DTC Review Group reviews all final
and draft broadcast DTC advertising materials because they are likely to
be disseminated to a large number of people. In addition, FDA officials
told us that the agency places a high priority on reviewing other draft
materials because they provide the agency with an opportunity to identify
problems and ask drug companies to correct them before the materials are
disseminated to consumers.37 In addition, FDA officials told us that
reviewers consider whether

36FDA officials told us that DDMAC has been approved to hire two
additional full-time employees, whom DDMAC plans to hire for the DTC
Review Group.

           o a nonbroadcast material is likely to be widely disseminated to
           consumers;

           o a drug has been cited in previous regulatory letters;

           o a drug is being advertised to consumers for the first time;

           o a drug is one of several drugs that can be used to treat the
           same condition, which FDA believes increases the likelihood that
           advertising will use comparative claims that may not be supported
           by available scientific evidence;

           o a drug is cited in a complaint submitted by a competitor,
           consumer, or other stakeholder;

           o a drug has had recent labeling changes, such as the addition of
           new risk information; or

           o a drug was approved under FDA's accelerated approval process.

           FDA officials indicated that the agency does not systematically
           apply its informal criteria to all of the materials that it
           receives. Specifically, at the time FDA receives the materials,
           the agency does not identify the materials that meet its various
           criteria. FDA officials told us that the agency does identify all
           final and draft broadcast materials that it receives, but does not
           have a system for identifying any other high-priority materials.
           Absent such a system for all materials, FDA relies on each of the
           reviewers--in consultation with other DDMAC officials--to be aware
           of the materials that have been submitted and to accurately apply
           the criteria to determine the specific materials to review. This
           creates the potential for reviewers to miss materials that the
           agency would consider to be a high priority for review.
           Furthermore, because FDA does not track information on its
           reviews, the agency cannot determine whether a particular material
           has been reviewed. As a result, the agency cannot ensure that it
           is identifying and reviewing the highest-priority materials.
			  
			  Since the 2002 Policy Change, FDAï¿½s Process for Issuing Regulatory
			  Letters Has Taken Longer and the Agency Has Issued Fewer Letters
			  
           Since the 2002 policy change requiring legal review by OCC of all
           draft regulatory letters, the agency's process for drafting and
           issuing letters has taken longer and FDA has issued fewer
           regulatory letters per year. As a result of the policy change,
           draft regulatory letters receive additional levels of review and
           the DTC reviewers who draft the letters must do substantially more
           work to prepare for and respond to comments resulting from review
           by OCC. Since the policy change, FDA has issued fewer regulatory
           letters per year than it did in any year prior to the change. FDA
           officials told us that the agency issues letters for only the
           violative DTC materials that it considers the most serious and
           most likely to impact consumers' health.
			  			  
			  FDAï¿½s Process for Issuing Regulatory Letters Has Taken Longer
			  Since the 2002 Policy Change

           Since the 2002 policy change requiring legal review of all draft
           regulatory letters, FDA's process for issuing letters has taken
           longer. Once FDA identifies a violation in a DTC advertising
           material and determines that it merits a regulatory letter, FDA
           takes several months to draft and issue a letter.38 (See fig. 2.)
           For letters issued from 2002 through 2005, once DDMAC began
           drafting a letter for violative DTC materials it took an average
           of about 4 months to issue the letter. The length of this process
           varied substantially across these regulatory letters--one letter
           took around 3 weeks from drafting to issuance, while another took
           almost 19 months. In comparison, for regulatory letters issued
           from 1997 through 2001, it took an average of 2 weeks from
           drafting to issuance. During this earlier time period, 11 letters
           were issued the day they were drafted, and the longest time from
           drafting to issuance was slightly more than 6 months.

           Figure 2: Average Months to Issue Regulatory Letters Citing
           Violative DTC Materials, 1997 through 2005

           Note: For each letter, we determined the number of months from the
           date on which a reviewer first began drafting a regulatory letter
           to the date the letter was issued. FDA does not track the date a
           violation was identified or the date it was determined that the
           violation merited a regulatory letter.

           The primary factor contributing to the increase in the length of
           FDA's process for issuing regulatory letters is the additional
           work that resulted from the 2002 policy change. In addition to the
           time required of OCC, DDMAC officials told us that the policy
           change has created the need for substantially more work on their
           part to prepare the necessary documentation for legal review.
           According to DDMAC officials, to prepare for initial meetings with
           OCC on draft regulatory letters reviewers prepare extensive
           background information describing the violations as well as the
           drug and its promotional history. As a part of this process, DDMAC
           reviewers sometimes seek consultations with regulatory and
           clinical experts within FDA. For example, reviewers may request
           consultations with the medical officers in FDA's Office of New
           Drugs in order to determine whether available data from the drug
           approval process are sufficient to support the advertising claims
           being made in DTC materials.39 After incorporating comments from
           the requested consultations, DDMAC reviewers hold their initial
           meeting with OCC and subsequently revise the draft regulatory
           letter to reflect the comments from OCC. Once these initial
           revisions are complete, DDMAC formally submits a draft regulatory
           letter to OCC for legal review and approval. All DDMAC regulatory
           letters are reviewed by both OCC staff and OCC's Chief Counsel.
           OCC often requires additional revisions to the draft regulatory
           letter before OCC will concur that a letter is legally supportable
           and can be issued. Depending on comments provided by OCC, the
           DDMAC reviewers may request additional consultations with FDA
           experts at each stage of review.

           OCC officials told us that the office has given regulatory letters
           that cite violative DTC materials higher priority than other types
           of regulatory letters, but that the attorneys have many other
           responsibilities. Prior to 2005, OCC had two staff attorneys and
           one supervising attorney assigned to review all of the regulatory
           letters submitted by DDMAC, including the letters that cite DTC
           materials. However, OCC officials told us that the review of
           DDMAC's draft regulatory letters is a small portion of their total
           responsibilities and must be balanced with other requests, such as
           the examination of legal issues surrounding the approval of a new
           drug. OCC officials told us that, in 2005, the office assigned two
           additional attorneys in an attempt to help issue the DDMAC
           regulatory letters more quickly.

           Prior to September 2005, OCC had a goal of providing initial
           comments to DDMAC within 15 business days from the date that a
           letter citing DTC materials was formally submitted.40 Based on our
           review of DDMAC's and OCC's documentation for the 19 letters
           issued from 2004 through 2005, we estimated that OCC generally met
           its 15-day goal for providing initial comments. However, the goal
           OCC established is not directly relevant to the total amount of
           time it takes FDA to issue the regulatory letter once it has been
           formally submitted to OCC because DDMAC must make changes to the
           letters to respond to OCC's comments and OCC may review letters
           more than once. For regulatory letters issued from 2004 through
           2005 that cited violative DTC materials, we found that, once DDMAC
           had formally submitted a draft letter to OCC, it took an average
           of about 3 months for the letter to receive final OCC concurrence
           and be issued. FDA does not have a goal for how long it should
           take the agency to issue a letter from the time that OCC first
           formally receives a draft of the letter.41
			  
			  FDA Issued Fewer Regulatory Letters Citing Violative DTC
			  Advertising Materials after Its 2002 Policy Change

           The number of regulatory letters FDA issued per year for violative
           DTC materials decreased after the 2002 policy change lengthened
           the agency's process for issuing letters. From 2002 to 2005, the
           agency issued between 8 and 11 regulatory letters per year that
           cited DTC materials.42 (See fig. 3.) Prior to the policy change,
           the agency issued about twice as many such regulatory letters per
           year. From 1997 through 2001, FDA issued between 15 and 25 letters
           citing DTC materials per year. An FDA official told us that both
           the lengthened review time resulting from the 2002 policy change
           and staff turnover within the DTC Review Group contributed to the
           decline in the number of issued regulatory letters. In addition,
           from 2002 through 2005,43 FDA did not ultimately issue 10 draft
           regulatory letters citing DTC materials that DDMAC had submitted
           to OCC for the required legal review. For 5 letters, OCC
           determined that there was insufficient legal support for issuing
           the letters and, therefore, did not concur with DDMAC. DDMAC
           withdrew the other 5 letters from OCC's consideration but could
           not provide us with information on why it withdrew these letters.

           Figure 3: Number of Regulatory Letters FDA Issued That Cited DTC
           Advertising Materials, 1997 through 2005

           Although the total number of regulatory letters FDA issued for
           violative DTC materials decreased, the agency issued relatively
           more warning letters--which cite violations FDA considers to be
           more serious--in recent years. Historically, almost all of the
           regulatory letters that FDA issued for DTC materials were untitled
           letters for less serious violations. From 1997 through 2001, FDA
           issued 98 regulatory letters, 6 of which were warning letters.
           From 2002 through 2005, 8 of the 37 regulatory letters were
           warning letters.

           FDA regulatory letters may cite more than one DTC material or type
           of violation for a given drug.44 Of the 19 regulatory letters FDA
           issued from 2004 through 2005, 7 cited more than 1 DTC material,
           for a total of 31 different materials.45 These 31 materials
           appeared in a range of media, including television, radio, print,
           direct mail, and Internet. Further, FDA identified multiple
           violations in 21 of the 31 DTC materials cited in the letters. The
           most commonly cited violations related to a failure of the
           material to accurately communicate information about the safety of
           the drug. For example, FDA wrote in 5 letters that distracting
           visuals in cited television advertisements minimized important
           information about the risk of the drug. The letters also often
           cited materials for overstating the effectiveness of the drug or
           using misleading comparative claims.
			  
			  FDA Issues Regulatory Letters Only for DTC Advertising Materials
			  It Considers Most Likely to Negatively Impact Consumers

           FDA officials told us that the agency issues regulatory letters
           for DTC materials that it believes are the most likely to
           negatively impact consumers and does not act on all of the
           concerns that its reviewers identify. When reviewers have concerns
           about DTC materials, they discuss them with others in DDMAC and
           may meet with OCC and medical officers in FDA's Office of New
           Drugs to determine whether a regulatory letter is warranted or on
           the content of the letter itself. FDA officials told us that the
           agency issues regulatory letters only for the violative materials
           that it considers the most likely to negatively impact public
           health. For example, they said the agency may be more likely to
           issue a letter when a false or misleading material was broadly
           disseminated to a large number of consumers. In addition, FDA
           officials told us that they are more likely to issue a regulatory
           letter when the drug is one of several drugs that can be used to
           treat the same condition; they said that the issuance of a
           regulatory letter in this situation may enhance future voluntary
           compliance by promoters of the competing drugs. However, because
           FDA does not document decisions made at the various stages of its
           review process about whether to pursue a violation, officials were
           unable to provide us with an estimate of the number of materials
           about which concerns were raised but the agency did not issue a
           letter.
			  
			  Effectiveness of FDA Regulatory Letters at Halting Dissemination
			  of Violative DTC Materials Has Been Limited

           FDA regulatory letters have been limited in their effectiveness at
           halting the dissemination of false and misleading DTC advertising
           materials. We found that, from 2004 through 2005, FDA issued
           regulatory letters an average of about 8 months after the
           violative DTC materials they cited were first disseminated. By the
           time these letters were issued, drug companies had already
           discontinued more than half of the cited materials. For the
           materials that were still being disseminated, drug companies
           removed the cited materials in response to FDA's letter. Drug
           companies also identified and removed other materials with claims
           similar to the materials cited in the regulatory letters. Although
           drug companies complied with FDA's requests to create materials
           that correct the misimpressions left by the cited materials, these
           corrections were not disseminated until 5 months or more after FDA
           issued the regulatory letter. Despite halting the dissemination of
           both cited and other violative materials at the time the letter
           was issued, FDA's issuance of these letters did not always prevent
           drug companies from later disseminating similar violative
           materials for the same drugs.
			  
			  Lack of Timely Issuance of Regulatory Letters Limits FDAï¿½s
			  Effectiveness at Halting Violative DTC Advertising Materials
			  
           FDA's regulatory letters have been limited in their effectiveness
           at halting the dissemination of the violative DTC materials they
           cite. Because of the length of time it took FDA to issue these
           letters, violative advertisements were often disseminated for
           several months before the letters were issued. From 2004 through
           2005, FDA issued regulatory letters citing DTC materials an
           average of about 8 months after the violative materials were first
           disseminated. FDA issued one letter less than 1 month after the
           material was first disseminated, while another letter took over 3
           years. The cited materials were usually disseminated for 3 or more
           months, though there was substantial variability across materials.
           Of the 31 violative DTC materials cited in these letters, 16 were
           no longer being disseminated by the time the letter was issued. On
           average, these letters were issued more than 4 months after the
           drug company stopped disseminating these materials, and therefore
           had no impact on their dissemination. For the 14 DTC materials
           that were still in use when FDA issued the letter, the drug
           companies complied with FDA's request to stop disseminating the
           violative materials.46 However, by the time the letters were
           issued, these 14 materials had been disseminated for an average of
           about 7 months.47 See figure 4 for information on the timeliness
           of the 19 regulatory letters relative to the dissemination of the
           DTC advertising materials they cited.

37We did not examine the effectiveness of FDA's review of draft materials
in preventing the dissemination of violative DTC materials because FDA
does not track whether the draft materials it reviews are later cited in a
regulatory letter.

38FDA does not track when it identifies a violation in a DTC material and
determines that it merits a regulatory letter. Because the agency does,
however, document the date on which reviewers first began drafting a
letter, we examined the amount of time it took for FDA to draft and issue
a letter.

39Of the 19 regulatory letters FDA issued from 2004 through 2005,
reviewers obtained a consultation from the social scientists in the DTC
Review Group for 5 letters and from medical officers in the Office of New
Drugs for 9 letters. FDA officials told us that some of these
consultations were due to increasingly complex advertising claims--for
example, claims that the drug is more effective than other drugs--and DTC
advertising for more complex drugs--for example, drugs that treat the
human immunodeficiency virus or diabetes. We did not examine the numbers
of consultations obtained in prior years because FDA officials told us
that its documentation of consultations in earlier years was not reliable.

40OCC officials indicated that OCC changed this goal in September 2005 and
now has a goal of providing initial comments to DDMAC within 10 business
days from the date that a letter is formally submitted. We used the 15-day
goal in our analysis because each of the 19 regulatory letters issued from
2004 through 2005 were submitted to OCC prior to September 2005.

41HHS indicated in its written comments on a draft of our October 2002
report that it had "established a goal of issuing regulatory letters
within 15 working days of review at OCC" ( [31]GAO-03-177 , p. 33).
However, FDA officials have subsequently told us that there is no set goal
for issuing regulatory letters and, instead, OCC had agreed to provide
DDMAC with initial comments within 15 business days from the date draft
regulatory letters citing DTC materials were formally submitted to OCC.

42From January through September 2006, FDA issued three regulatory letters
citing violative DTC materials, one of which was a warning letter.

43FDA officials indicated that OCC began tracking information on its
reviews of draft regulatory letters in April 2002.

44Of the 19 regulatory letters issued from 2004 through 2005, 18 cited
violative advertising materials for only one drug. One letter cited
materials for two drugs promoted by a single company.

45Of the 19 regulatory letters citing DTC materials, 2 also cited
materials intended to be provided to consumers by medical professionals
and 5 also cited materials targeted directly to medical professionals.

46For one violative advertising material, we were unable to determine from
FDA's case files when the violative advertising material ended.

47This average is based on 12 of 14 advertising materials for which we
were able to determine the length of time the materials were disseminated.

Figure 4: Timelines for 19 Regulatory Letters Issued from 2004 through
2005 and the Cited DTC Materials

Note: Of these 19 regulatory letters, 18 cited violative advertising
materials for a single drug. In one instance, the letter cited materials
promoting two drugs promoted by a single company.

aThe drug company started disseminating the violative DTC material about
36 months before FDA issued the regulatory letter.

bWe were unable to determine from FDA's documentation the date the drug
company first disseminated the violative material. However, the drug
company indicated in correspondence with FDA that it stopped disseminating
the material when it received the regulatory letter.

cThe drug company started disseminating the violative material about 31
months before FDA issued the regulatory letter.

dFDA started drafting the regulatory letter about 19 months before the
letter was issued. This letter, which was drafted about 9 months before
the violative DTC material was first disseminated, also cited materials
directed to medical professionals, and those materials are not represented
in this figure. In addition, we were unable to determine from FDA's
documentation the date the drug company stopped disseminating the
violative material. However, the drug company indicated that the material
was no longer being disseminated when it initially responded to FDA's
regulatory letter.

FDA Regulatory Letters Led Drug Companies to Identify and Remove Materials
Similar to the Violative DTC Advertising Materials

As requested by FDA in the regulatory letters, drug companies often
identified and stopped disseminating other materials with claims similar
to those in the violative materials. For 18 of the 19 regulatory letters
issued from 2004 through 2005, the drug companies indicated to FDA that
they had either identified additional similar materials or that they were
reviewing all materials to ensure compliance.48 Some of these drug
companies indicated in their correspondence with FDA which similar
materials they had identified. Specifically, drug companies responding to
13 letters indicated that they had identified and stopped disseminating
between 1 and 27 similar DTC and other materials directed to consumers
that had not been cited in the regulatory letter. In addition to halting
materials directed to consumers, companies responding to 11 letters also
stopped disseminating materials with similar claims that were targeted
directly to medical professionals.49

Drug Companies Disseminated Corrective Advertising Materials 5 Months or More
after FDA Issued the Regulatory Letter

Drug companies disseminated the corrective advertising materials requested
in FDA warning letters, but took 5 months or more to do so. In each of the
six warning letters FDA issued in 2004 and 2005 that cited DTC materials,
the agency asked the drug company to disseminate truthful, nonmisleading,
and complete corrective messages about the issues discussed in the
regulatory letter to the audiences that received the violative promotional
materials. In each case, the drug company complied with this request by
disseminating corrective advertising materials. For four warning letters
we were able to examine the resulting corrective materials and found that
they each contained an explicit reference to the regulatory letter and a
message intended to correct misleading impressions created by the
violative claim.50 In addition, the drug companies provided evidence to
FDA that the materials would be disseminated to a consumer population
similar to the one that received the original violative advertising
materials. For example, one drug company provided FDA with the broadcast
schedule for the violative television advertisement and the planned
schedule for the corrective advertising material to demonstrate that it
would run on similar channels, at similar times, and with similar
frequency.

48For one letter, the FDA documentation we reviewed did not contain the
drug company's written response.

49In their responses, the drug companies identified between 1 and 18
materials directed to medical professionals.

For the six warning letters FDA issued in 2004 and 2005 that cited DTC
materials, the corrective advertising materials were initially
disseminated more than 5 to almost 12 months after FDA issued the letter.
For example, for one allergy medication, the violative advertisements ran
from April through October 2004, FDA issued the regulatory letter in April
2005, and the corrective advertisement was not issued until January 2006.
FDA officials told us that the process of issuing a corrective
advertisement is lengthy because the agency and the drug company negotiate
the content and format of the corrective advertisements. They also said
that, in some cases, FDA reviewers work closely with the drug company to
develop, and sometimes suggest specific content for, the corrective
advertisement. See figure 4 for more detail on the dissemination of the
corrective advertisements.

FDA Regulatory Letters Do Not Always Prevent Subsequent Dissemination of
Violative DTC Materials for the Same Drug

FDA regulatory letters do not always prevent the same drug companies from
later disseminating violative DTC materials for the same drug, sometimes
using the same or similar claims. From 1997 through 2005, FDA issued
regulatory letters for violative DTC materials used to promote 89
different drugs.51 Of these 89 drugs, 25 had DTC materials that FDA cited
in more than one regulatory letter, and one drug had DTC materials cited
in eight regulatory letters. For 15 of the 25 drugs, FDA cited similar
broad categories of violations in multiple regulatory letters.52 For
example, FDA issued regulatory letters citing DTC materials for a
particular drug in 2000 and again in 2005 for "overstating the
effectiveness of the drug." However, the specific claims cited in each of
these regulatory letters differed. In 2000, FDA wrote in its regulatory
letter that the "totality of the image, the music, and the audio
statements" in a television advertisement overstated the effectiveness of
the drug. The 2005 letter stated that a different television advertisement
overstated effectiveness by suggesting that the drug was effective for
"preventing or modifying the progression of arthritis" when the drug was
approved for the "relief of the signs and symptoms" of arthritis. For 4 of
the 15 drugs, FDA cited the same specific violative claim for the same
drug in more than one regulatory letter. (See table 2.) For example, in
1999 FDA cited a DTC direct mail piece for failing to convey important
information about the limitations of the studies used to approve the
promoted drug. In 2001, FDA cited a DTC broadcast advertisement for the
same drug for failing to include that same information.

50For two regulatory letters, the FDA documentation that we reviewed did
not contain a copy of the corrective material that had been disseminated
by the drug company.

51When multiple drugs contained the same active ingredient, we considered
them to be the same drug for the purposes of this analysis. For example,
we considered the tablet and syrup versions of a drug to be a single drug
product because they contained the same active ingredient.

52We did not examine how many of the drugs that were cited for violative
DTC materials had also been cited for violative materials directed to
medical professionals. However, during our review of the regulatory
letters, we noted that some drugs have had both types of materials cited,
and that FDA sometimes cited the same or similar violative claims in both
types of materials. In addition, the regulatory letters we reviewed
sometimes stated that FDA, based on its review of draft versions of
advertising materials, had previously issued advisory comment letters
expressing its concern about drug companies' use of the claims cited in
the regulatory letter.

Table 2: Drugs for Which FDA Cited the Same Specific Violative Claim in
More Than One Regulatory Letter

                                        Material cited  
Drug product                          in FDA letter  
(company)         Condition          First letter    Subsequent letter     
Ditropan XL (Alza Overactive bladder Letter cited a  Letter cited a DTC    
Corporation)                         DTC direct mail broadcast             
                                        letter for      advertisement and a   
                                        failing to      DTC print             
                                        convey that the advertisement for     
                                        clinical        failing to            
                                        studies were    prominently disclose  
                                        set up to       important             
                                        include only    facts--specifically,  
                                        patients whom   that the clinical     
                                        the company     trials for Ditropan   
                                        knows would     XL were set up to     
                                        have improved   include only patients 
                                        symptoms on     who were known to     
                                        Ditropan XL     have had improved     
                                        because they    symptoms on           
                                        were known to   oxybutynin, or other  
                                        have had        similar medications   
                                        improved        used to treat         
                                        symptoms on     overactive bladder.   
                                        oxybutynin, the (July 12, 2001)       
                                        active                                
                                        ingredient in                         
                                        Ditropan XL, or                       
                                        other similar                         
                                        medications                           
                                        used to treat                         
                                        overactive                            
                                        bladder. (Apr.                        
                                        2, 1999)                              
                                        Letter cited a  Letter cited a DTC    
                                        DTC direct mail print advertisement   
                                        letter for      for failing to        
                                        failing to      prominently disclose  
                                        disclose that   that patients         
                                        patients        randomized to placebo 
                                        randomized to   experienced a 51%     
                                        the placebo arm reduction in the      
                                        experienced a   number of wetting     
                                        51% reduction   accidents. (July 12,  
                                        in the number   2001)                 
                                        of wetting                            
                                        accidents.                            
                                        (Apr. 2, 1999)                        
MUSE (VIVUS Inc.) Erectile           Letter cited a  Letter cited a DTC    
                     dysfunction        DTC print       print advertisement   
                                        advertisement   for not displaying a  
                                        for not         qualifying subhead    
                                        providing       with the prominence   
                                        qualifying      necessary to provide  
                                        information     the context needed    
                                        with sufficient for the headline      
                                        prominence to   "Impotence is         
                                        balance out the Optional." (Apr. 1,   
                                        headline claim  1998)                 
                                        "Impotence is                         
                                        Optional."                            
                                        (Feb. 19, 1998)                       
                                        Letter cited a  Letter cited a DTC    
                                        DTC print       television            
                                        advertisement   advertisement for     
                                        for failing to  failing to adequately 
                                        communicate an  disclose how the drug 
                                        important       is used; FDA's letter 
                                        material        specifically          
                                        characteristic  references the        
                                        of the drug     related citation from 
                                        because FDA     its April 1, 1998     
                                        considers the   letter. (May 25,      
                                        term "urethral  2004)                 
                                        suppository" to                       
                                        be an                                 
                                        unfamiliar                            
                                        medical term                          
                                        for the average                       
                                        consumer that                         
                                        does not                              
                                        disclose how                          
                                        the drug is                           
                                        used. (Apr. 1,                        
                                        1998)                                 
Nolvadex          Breast cancer      Letter cited a  Letter cited a DTC    
(AstraZeneca                         DTC direct mail print advertisement   
Pharmaceuticals                      advertisement   for not providing     
LP)                                  for not         adequate context for  
                                        providing       a risk reduction      
                                        adequate        claim. Without        
                                        context for a   additional context,   
                                        risk reduction  the use of this claim 
                                        claim. Without  overstates the        
                                        additional      efficacy of the drug  
                                        context, the    at reducing           
                                        use of this     occurrence of new     
                                        claim           cancers. (Dec. 14,    
                                        overstates the  2001)                 
                                        efficacy of the                       
                                        drug at                               
                                        reducing                              
                                        incidence of                          
                                        breast cancer                         
                                        in women at                           
                                        high risk.                            
                                        (July 20, 2000)                       
Prevacid (TAP     Gastro-esophageal  Letter cited a  Letter cited a DTC    
Pharmaceutical    reflux disease     DTC television  television            
Products Inc.)                       advertisement   advertisement for     
                                        for not clearly failing to clearly    
                                        communicating   communicate           
                                        the indication, limitations of the    
                                        which implies   approved indication   
                                        that the drug   because communication 
                                        may be used in  of the indication is  
                                        a broader range interfered with by    
                                        of conditions   competing visual,     
                                        because         graphic, and auditory 
                                        disclosed       distractions that     
                                        limitations to  combine to interfere  
                                        the indication  with, and undermine,  
                                        are             a typical consumer's  
                                        nonprominent,   reading and           
                                        hard to         comprehension. (Aug.  
                                        comprehend, and 2, 2002)              
                                        displayed                             
                                        against                               
                                        distracting                           
                                        visual                                
                                        backgrounds.                          
                                        (Mar. 15, 2000)                       

Source: GAO analysis of FDA regulatory letters.

Conclusions

Given substantial increases in drug company spending on DTC advertising in
recent years, and evidence that DTC advertising can influence consumers'
behavior, it is important to develop a full understanding of its impact on
the U.S. health care system. It is also important that FDA effectively
limit the dissemination of DTC advertising that is false or misleading.
Because FDA reviews a small portion of the final and draft DTC materials
that it receives, it is important that the agency have a process to
identify and review the materials that are the highest priority. However,
FDA lacks documented criteria for identifying and prioritizing DTC
materials for review, a process to ensure that criteria are applied
systematically to all materials received, and a system for tracking
whether materials have been reviewed. As a result, FDA cannot be assured
that the highest-priority materials have been identified or reviewed.

Given the length of time it takes FDA to issue regulatory letters and the
potential for repeated use of violative claims, we are concerned about
FDA's effectiveness at limiting consumers' exposure to false or misleading
DTC advertising. In our 2002 report, we recommended that HHS take steps to
reduce the time that FDA's DTC draft regulatory letters are under review.
In its written response to the recommendation in that report, HHS agreed
that it needs to issue DTC regulatory letters more quickly and established
a goal of issuing the letters "within 15 working days of review at OCC."
However, we have now found that it takes FDA months to complete the
process of drafting and reviewing the letters. As we previously
recommended, we believe that regulatory letters must be issued more
quickly.

Recommendations for Executive Action

To improve FDA's processes for identifying and reviewing final and draft
DTC advertising materials, we recommend that the Acting Commissioner of
the Food and Drug Administration take the following three actions:

           o document criteria for prioritizing materials that it receives
           for review,

           o systematically apply its documented criteria to all of the
           materials it receives, and

           o track which materials have been reviewed.
			  
			  Agency Comments and Our Evaluation

           HHS reviewed a draft of this report and provided comments, which
           are reprinted in appendix II.

           In its comments, HHS generally agreed with our description of
           FDA's oversight of DTC advertising, but disagreed with our
           recommendations and some aspects of our conclusions. First, HHS
           disagreed with our recommendations that it systematically
           prioritize and track the DTC advertising materials it reviews. HHS
           stated that DDMAC now reviews all of some types of high priority
           DTC materials, especially final and draft broadcast
           advertisements. HHS also commented that, although DDMAC has not
           documented its selection criteria, those criteria are
           systematically applied by its reviewers to determine workload
           priorities. HHS also noted that reviewing each DTC material
           received according to selection criteria and tracking the reviews
           that DDMAC conducts would require DDMAC's staff to be vastly
           increased.

           We recognize that, with current staffing, DDMAC's DTC Review Group
           cannot review in detail the more than 10,000 DTC materials that
           are submitted to the agency each year and that DDMAC now focuses
           its review efforts specifically on broadcast materials and draft
           materials. However, it is because DDMAC's reviewers are only able
           to review selected materials that we believe it is important for
           FDA to develop a more complete and systematic process for
           screening the materials the agency receives. To do so, the
           informal criteria that reviewers now consider when prioritizing
           reviews should be formalized to help ensure consistent
           application. Contrary to HHS's comments, we do not agree that
           systematically applying these criteria would require that every
           DTC material be reviewed in detail. Instead, FDA should apply the
           criteria as a screening mechanism to all materials it receives.
           Furthermore, FDA already has most of the information that would be
           necessary to establish a system to screen submitted materials
           against these criteria. For instance, when drug companies submit
           DTC materials to FDA, the agency records information about the
           drug being advertised and the type of material submitted.
           Additionally, for most of the priority criteria described in our
           report, FDA already has information--such as whether the drug has
           been the subject of a previous regulatory letter or a recent label
           change--needed to determine how the criteria would apply to
           materials used to promote a given drug.

           Second, HHS also expressed concern that our draft report
           criticized the agency for the length of time it takes to issue
           regulatory letters and declines in the number of letters issued
           since the policy change requiring review by OCC, without
           adequately addressing the underlying purpose of that review. HHS
           commented that its policy change has led to more defensible
           regulatory letters and better compliance after issuance. We agree
           with HHS that it is important to ensure that FDA's regulatory
           letters are legally supportable, and, as HHS noted, we did not
           examine the effect of the policy change on the legal sufficiency
           of the letters in this report. However, we also believe that it is
           important for letters to be issued in a timely manner if they are
           to have an impact on halting the dissemination of the violative
           materials that the letters cite. In 2002, HHS agreed with the
           recommendation of our earlier report that DTC regulatory letters
           be issued more quickly. Nonetheless, as we noted in the draft of
           this report, we found that violative advertisements had often been
           disseminated for several months before letters were issued in 2004
           and 2005. More than half of the violative DTC materials cited in
           the 2004 and 2005 letters were no longer being disseminated by the
           time the letter was issued. Delays in issuing regulatory letters
           limit FDA's effectiveness in overseeing DTC advertising and in
           reducing consumers' exposure to false or misleading advertising.

           Finally, HHS commented that our discussion of research on DTC
           advertising implies that we statistically aggregated data from
           different studies to generate summary figures on the impact of DTC
           advertising on various types of consumer requests to their
           physicians. We have revised the report to clarify that the
           information we present is from the studies we reviewed and that we
           did not aggregate data across studies. HHS also provided technical
           comments which we incorporated as appropriate.

           As agreed with your offices, unless you publicly announce the
           contents of this report earlier, we plan no further distribution
           of it until 30 days from the date of this letter. We will then
           send copies of this report to the Secretary of Health and Human
           Services, the Acting Commissioner of the Food and Drug
           Administration, and other interested parties. We will also make
           copies available to others who request them. In addition, the
           report will be available at no charge on GAO's Web site at
           [32]http://www.ao.ovgg .

           If you or your staffs have any questions about this report, please
           contact me at (202) 512-7119 or [email protected]. Contact points
           for our Offices of Congressional Relations and Public Affairs may
           be found on the last page of this report. GAO staff who made major
           contributions to this report are listed in appendix III.

           Marcia Crosse
			  Director, Health Care
			  
			  Appendix I: Scope and Methodology

           To examine trends in pharmaceutical industry spending on
           direct-to-consumer (DTC) advertising, promotion to medical
           professionals, and research and development of new drugs, we
           reviewed publicly reported data. For overall drug company spending
           from 1997 through 2005 on DTC advertising and promotion to medical
           professionals, we obtained data from IMS Health.1 We interviewed
           knowledgeable IMS Health officials to verify the data's accuracy
           and the methodologies used for collecting them and reviewed
           related documentation and determined that the data were
           sufficiently reliable for the purposes of this report. In
           addition, we obtained data on drug company spending from 1997
           through 2005 on research and development of new drugs from the
           Pharmaceutical Research and Manufacturers of America (PhRMA),
           which represents U.S. pharmaceutical research and biotechnology
           companies. For 2005, we reviewed more detailed data on DTC
           advertising by prescription drug from Neilsen Monitor-Plus, which
           were reported in the May 2006 edition of Med Ad News, a
           publication targeted to the pharmaceutical industry. For the PhRMA
           and Neilsen Monitor-Plus data, we reviewed related documentation
           and determined that the data were sufficiently reliable for the
           purposes of this report. The scope of our analysis focuses on
           trends since 1997 because in that year the Food and Drug
           Administration (FDA) issued its draft guidance clarifying the
           requirements for broadcast advertising.

           To examine the relationship between DTC advertising and
           prescription drug spending and utilization, we conducted a
           literature review. We conducted a structured search of 33
           databases that included peer-reviewed journal articles,
           dissertations, and industry articles issued from January 2000
           through February 2006. We searched these databases for articles
           with key words in their title or abstract related to DTC
           advertising, such as various versions of the word "advertising,"
           "consumer," "patient," "physician," "doctor," and "return on
           investment." We supplemented this list with searches of the
           references in articles identified through the database search. We
           also included articles cited during our interviews with
           representatives from advocacy organizations--Consumers Union and
           Public Citizen--and industry representatives from PhRMA,
           AstraZeneca Pharmaceuticals LP, and Pfizer Inc. From all of these
           sources, we identified over 600 articles published from 1982
           through 2006. Within the more than 600 articles, we identified for
           detailed review 64 journal articles and dissertations that were
           original research and had subject matter directly relevant to the
           relationship between DTC advertising and prescription drug
           spending and utilization.

           To examine the DTC advertising materials that FDA reviews, we
           reviewed applicable laws and regulations and data from FDA on the
           number and type of advertising materials that the agency receives
           and reviews. For materials submitted from 1997 through 2005, we
           obtained data from FDA's Advertising Management Information System
           database, which tracks the number of final advertising materials
           the drug companies submit to FDA at the time of their
           dissemination to the public. FDA officials told us that these data
           may contain errors because drug companies do not always properly
           identify the type of advertising material in their submission to
           FDA. For example, a DTC material may be incorrectly coded as a
           material directed to professionals. Although FDA officials do not
           know the extent to which such errors are entered into the
           database, based on our review of their data collection methods and
           our interviews with knowledgeable agency officials, we determined
           that these data were sufficiently reliable for reporting on trends
           in the volume of materials submitted to FDA. We also obtained data
           from FDA's Marketing, Advertising, and Communications Management
           Information System database--which tracks correspondence between
           the agency and drug companies--to determine the number of
           submissions of draft materials received by FDA from 1997 through
           2005. We discussed these data with the responsible FDA official,
           and determined that they were sufficiently reliable for their use
           in this report. We also interviewed FDA officials, including staff
           who are directly responsible for reviewing DTC materials, about
           their processes for reviewing advertising materials. We did not
           examine the effectiveness of FDA's review of draft materials at
           preventing potentially violative materials from being
           disseminated.

           To examine the number of FDA regulatory letters that cited DTC
           materials and FDA's process for issuing regulatory letters, we
           reviewed all letters issued by FDA from 1997 through 2005 citing
           prescription drug promotion and identified those that cited DTC
           advertising materials. We excluded regulatory letters that cited
           only materials intended to be given to consumers by medical
           professionals or that cited only materials directed to medical
           professionals. We then asked FDA officials to review our list and
           add letters we had not identified and remove letters that did not
           specifically cite DTC materials. As a result of this process, we
           identified 135 regulatory letters--citing materials promoting 89
           different drugs--that cited a violative DTC material. In our
           review of the regulatory letters, we did not evaluate the
           appropriateness of the cited violations or evaluate the legal
           sufficiency of the letters. We examined the content of FDA's most
           recent regulatory letters--the 19 regulatory letters, 6 warning
           letters and 13 untitled letters, FDA issued from 2004 through
           2005--in order to determine the types of violations that FDA
           identified and the actions that the agency requested the drug
           companies to take. (See table 3.) Of these 19 regulatory letters,
           18 cited violative materials for a single drug. In one instance,
           the letter cited materials promoting two drugs promoted by a
           single company.

1IMS Health data for spending on DTC advertising do not include spending
to develop and maintain drug companies' Web sites or spending on
sponsorship of sporting events. In addition, the data for spending on
promotion to medical professionals do not include drug company spending on
meetings and events, or spending on promotion that targets medical
professionals other than physicians, such as nurse practitioners and
physicians assistants.

Table 3: FDA Regulatory Letters Issued from 2004 through 2005 That Cited
DTC Materials

                                                                Type of each  
              Date of                                           cited         
Drug cited lettera    Condition              Drug company    advertisement 
2004                                                                       
Warning                                                                    
letters                                                                    
MUSE       5/25/2004  Erectile dysfunction   VIVUS Inc.      Television    
                                                                Web site      
Norvir     6/10/2004  Human immunodeficiency Abbott          Web site      
                         virus                  Laboratories                  
Pamine     11/9/2004  Peptic ulcer           Bradley         Web site      
                                                Pharmaceuticals               
                                                Inc.                          
Untitled                                                                   
letters                                                                    
Crestor    12/21/2004 Cholesterol            AstraZeneca     Print         
                                                Pharmaceuticals               
                                                LP                            
Effexor    3/18/2004  Depression             Wyeth           Radio         
                                                Pharmaceuticals               
Kaletra    10/29/2004 Human immunodeficiency Abbott          Print         
                         virus                  Laboratories                  
                                                                Restroom      
                                                                poster        
Paxil CR   6/9/2004   Social anxiety         GlaxoSmithKline Television    
                         disorder                                             
Seasonale  12/29/2004 Contraceptive          Barr Research   Television    
                                                Inc.                          
Viagra     11/10/2004 Erectile dysfunction   Pfizer Inc.     Television 1  
                                                                Television 2  
Viramune   9/22/2004  Human immunodeficiency Boehringer      Print         
                         virus                  Ingelheim                     
                                                Pharmaceuticals               
                                                Inc.                          
Zyrtec-D   4/22/2004  Allergies              Pfizer Inc.     Web site      
12hr                                                                       
2005                                                                       
Warning                                                                    
letters                                                                    
Enbrel     2/18/2005  Plaque psoriasis       Amgen Inc       Television    
Quadramet  7/18/2005  Pain associated with   Cytogen         Radio         
                         cancer                 Corporation                   
                                                                Web site      
Zyrtec     4/13/2005  Allergies              Pfizer Inc.     Print 1       
                                                                Print 2       
                                                                Print 3       
Untitled                                                                   
letters                                                                    
Celebrex   1/10/2005  Osteoarthritis,        Pfizer Inc.     Television 1  
and Bextra            rheumatoid arthritis,                                
                         painful menstruation                   Television 2  
                                                                Television 3  
                                                                Direct mail   
Crestor    3/8/2005   Cholesterol            AstraZeneca     Television    
                                                Pharmaceuticals               
                                                LP              Print 1       
                                                                Print 2       
                                                                Print 3       
Levitra    4/13/2005  Erectile dysfunction   Bayer           Television    
                                                Pharmaceuticals               
                                                Corporation                   
Strattera  6/14/2005  Attention deficit      Eli Lilly and   Television    
                         hyperactivity disorder Company                       
Zoloft     5/6/2005   Major depressive       Pfizer Inc.     Print         
                         disorder                                             

Source: GAO analysis of FDA regulatory letters.

aRegulatory letters are available online from FDA, Center for Drug
Evaluation and Research, Warning Letters and Notice of Violation Letters
to Pharmaceutical Companies, http://www.fda.gov/cder/warn/ (last accessed
on Sept. 26, 2006).

We also reviewed FDA documentation to determine how long it took the
agency to draft and issue the 135 regulatory letters it issued from
January 1997 through December 2005. We used information from FDA records
to obtain the date on which reviewers first began drafting a regulatory
letter. These records also contained information about key meetings that
occurred, internal consultations requested by FDA's Division of Drug
Marketing, Advertising, and Communications (DDMAC), and the comments
obtained during the drafting and review of each regulatory letter. Because
FDA does not track when the agency identifies a violation, we considered
the date on which reviewers first began drafting a regulatory letter as
the earliest date in the letter drafting and review process. For each of
the 19 regulatory letters issued from 2004 through 2005, we obtained the
date DDMAC formally submitted the draft letter to the Office of the Chief
Counsel (OCC) from FDA's Agency Information Management System database.
This system is designed to document the dates of key interactions between
OCC and other FDA offices. OCC officials told us that the date DDMAC
submitted draft regulatory letters to OCC was consistently documented in
the system. Based on our discussions with OCC officials and our review of
similar dates recorded in DDMAC's case files, we determined that these
data were sufficiently reliable for the purposes of this report.

To examine the effectiveness of FDA's regulatory letters, we focused on
the 19 regulatory letters issued from 2004 through 2005 that cited DTC
materials. We reviewed the files that FDA maintains for each advertised
drug cited in these letters. These files contain correspondence from the
drug companies, copies of advertising materials, and documentation of FDA
actions. We reviewed FDA's correspondence with the drug companies to
obtain information regarding the regulatory letters, the dates the
violative advertisements started and ended, and the drug companies'
compliance with any corrective action requested by FDA. The information we
collected is based both on what drug companies reported in correspondence
with FDA and, in some cases, what we obtained directly from the sponsoring
drug company. We did not confirm the accuracy of the information drug
companies reported to FDA or to us. We also identified the violations
cited in the 135 regulatory letters FDA issued from 1997 through 2005.

We conducted our work from January 2006 through November 2006 in
accordance with generally accepted government auditing standards.

Appendix II: Comments from the Department of Health and Human Services

Appendix III: GAO Contact and Staff Acknowledgments

GAO Contact

Marcia Crosse, (202) 512-7119 or [email protected]

Acknowledgments

In addition to the contact named above, Martin T. Gahart, Assistant
Director; Chad Davenport; William Hadley; Cathy Hamann; Julian Klazkin;
and Eden Savino made key contributions to this report.

(290510)

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www.gao.gov/cgi-bin/getrpt?GAO-07-54 .

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For more information, contact Marcia Crosse at (202) 512-7119 or
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Highlights of [40]GAO-07-54 , a report to congressional requesters

November 2006

PRESCRIPTION DRUGS

Improvements Needed in FDA's Oversight of Direct-to-Consumer Advertising

The Food and Drug Administration (FDA) is responsible for overseeing
direct-to-consumer (DTC) advertising of prescription drugs. If FDA
identifies a violation of laws or regulations in a DTC advertising
material, the agency may issue a regulatory letter asking the drug company
to take specific actions. GAO was asked to discuss (1) trends in drug
company spending on DTC advertising and other activities; (2) what is
known about the relationship between DTC advertising and drug spending and
utilization; (3) the DTC advertising materials FDA reviews; (4) the number
of regulatory letters that cited DTC materials and FDA's process for
issuing those letters; and (5) the effectiveness of these letters at
limiting the dissemination of violative DTC advertising. GAO reviewed
research literature, analyzed FDA's processes, and examined FDA
documentation.

[41]What GAO Recommends

GAO recommends that FDA (1) document criteria for prioritizing DTC
materials for review, (2) systematically apply its criteria to materials
it receives, and (3) track which materials it reviews. In its comments on
a draft of this report, HHS disagreed with the recommendations, stating
that they would require vastly increased staff. GAO believes that FDA
already has most of the information that would be required to establish a
systematic process for screening DTC materials.

Drug company spending on DTC advertising--such as that on television and
in magazines--of prescription drugs increased twice as fast from 1997
through 2005 as spending on promotion to physicians or on research and
development. Over this period, drug companies spent less each year on DTC
advertising ($4.2 billion in 2005) than on promotion to physicians ($7.2
billion in 2005) or research and development ($31.4 billion in 2005).

Studies GAO reviewed suggest that DTC advertising has contributed to
increases in drug spending and utilization, for example, by prompting
consumers to request the advertised drugs from their physicians, who are
generally responsive to these requests. Evidence suggests that the effect
of DTC advertising on consumers can be both positive, such as encouraging
them to talk to their doctors, and negative, such as increased use of
advertised drugs when alternatives may be more appropriate.

FDA reviews a small portion of the DTC materials it receives. To identify
materials that have the greatest potential to impact public health, FDA
has informal criteria to prioritize materials for review. However, FDA has
not documented these criteria, does not apply them systematically to all
of the materials it receives, and does not track information on its
reviews. As a result, the agency cannot ensure that it is identifying or
reviewing those materials that it would consider to be the highest
priority.

FDA has taken longer to draft and review regulatory letters and the agency
has issued fewer letters per year since 2002, when legal review of all
draft regulatory letters was first required. From 2002 through 2005, from
the time FDA began drafting a regulatory letter for a violative DTC
material, it took the agency an average of 4 months to issue a regulatory
letter, compared with an average of 2 weeks from 1997 through 2001. FDA
has issued about half as many regulatory letters per year since the 2002
policy change.

The effectiveness of FDA's regulatory letters at halting the dissemination
of violative DTC materials has been limited. The 19 regulatory letters FDA
issued in 2004 and 2005 were issued an average of 8 months after the
materials were first disseminated. By the time FDA issued these letters,
companies had already discontinued use of more than half of the violative
materials. When the cited materials were still being disseminated, drug
companies complied with FDA's requests to remove the materials, and
identified and removed other materials with similar claims. FDA's issuance
of regulatory letters did not always prevent drug companies from later
disseminating similar violative materials for the same drugs. These issues
are not new. In 2002, GAO reported that, by delaying the issuance of
regulatory letters, the 2002 policy change had adversely affected FDA's
ability to enforce compliance. At that time, GAO recommended, and FDA
agreed, that letters be issued more quickly. GAO continues to believe this
is necessary in order to limit consumers' exposure to false or misleading
advertising.

References

Visible links
  28. http://www.gao.gov/cgi-bin/getrpt?GAO-03-177
  29. http://www.gao.gov/cgi-bin/getrpt?GAO-03-177
  30. http://www.gao.gov/cgi-bin/getrpt?GAO-03-177
  31. http://www.gao.gov/cgi-bin/getrpt?GAO-03-177
  32. http://www.gao.gov/
 
  39. http://www.gao.gov/cgi-bin/getrpt?GAO-07-54
  40. http://www.gao.gov/cgi-bin/getrpt?GAO-07-54
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