Prescription Drugs: Improvements Needed in FDA's Oversight of Direct-to-Consumer Advertising
Published: 2006-11-16T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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.
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: Spending on prescription drugs, which accounted for about 11 percent of  total health care spending in 2004, 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. The pharmaceutical  industry spent more than $4.2 billion in 2005 to advertise prescription  drugs to consumers. 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.
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. 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. FDA regulations require that drug companies submit final  advertising materials to FDA at the time they are first disseminated to the  public. 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.” 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. 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.”
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. 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.
subsections: section_title: Background
paragraphs: 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.
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). 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.
FDA requires that drug companies submit all final prescription drug  advertising materials to the agency when they are first disseminated to the  public. Drug companies are generally not required to submit advertising  materials to FDA before they are disseminated. However, drug  companies sometimes voluntarily submit draft DTC advertising materials  to FDA in order to obtain advisory comments from the agency.
Advertising materials must contain a “true statement” of information  including a brief summary of side effects, contraindications, and the  effectiveness of the drug. 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.
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.
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. 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.
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.” 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.
section_title: Drug Company Spending on DTC Advertising Has Increased More Rapidly Than Spending on Promotion to Physicians or Research and Development
paragraphs: 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. 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. 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 professionals to distribute to their patients has increased by about   15 percent annually. (See table 1.)
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. 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.
section_title: Research Suggests DTC Advertising Increases Drug Spending and Utilization
paragraphs: 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. 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. 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.
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,  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.
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. 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. 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. 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.
section_title: FDA Reviews a Small Portion of DTC Materials and Cannot Ensure It Is Reviewing the Highest-Priority Materials
paragraphs: 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.
subsections: section_title: FDA Reviews a Small Portion of DTC Advertising Materials
paragraphs: 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. 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.
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. 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.
section_title: FDA Cannot Ensure That It Is Reviewing the Highest-Priority DTC Advertising Materials
paragraphs: 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. In  addition, FDA officials told us that reviewers consider whether    a nonbroadcast material is likely to be widely disseminated to consumers;    a drug has been cited in previous regulatory letters;    a drug is being advertised to consumers for the first time;    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;   a drug is cited in a complaint submitted by a competitor, consumer, or    a drug has had recent labeling changes, such as the addition of new risk    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.
section_title: Since the 2002 Policy Change, FDA’s Process for Issuing Regulatory Letters Has Taken Longer and the Agency Has Issued Fewer Letters
paragraphs: 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.
subsections: section_title: FDA’s Process for Issuing Regulatory Letters Has Taken Longer Since the 2002 Policy Change
paragraphs: 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. (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.
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.  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. 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.
section_title: FDA Issued Fewer Regulatory Letters Citing Violative DTC Advertising Materials after Its 2002 Policy Change
paragraphs: 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. (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, 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.
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. 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. 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.
section_title: FDA Issues Regulatory Letters Only for DTC Advertising Materials It Considers Most Likely to Negatively Impact Consumers
paragraphs: 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.
section_title: Effectiveness of FDA Regulatory Letters at Halting Dissemination of Violative DTC Materials Has Been Limited
paragraphs: 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.
subsections: section_title: Lack of Timely Issuance of Regulatory Letters Limits FDA’s Effectiveness at Halting Violative DTC Advertising Materials
paragraphs: 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. However, by the time the letters were issued, these 14  materials had been disseminated for an average of about 7 months. See  figure 4 for information on the timeliness of the 19 regulatory letters  relative to the dissemination of the DTC advertising materials they cited.
section_title: FDA Regulatory Letters Led Drug Companies to Identify and Remove Materials Similar to the Violative DTC Advertising Materials
paragraphs: 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. 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.
section_title: Drug Companies Disseminated Corrective Advertising Materials 5 Months or More after FDA Issued the Regulatory Letter
paragraphs: 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. 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.
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.
section_title: FDA Regulatory Letters Do Not Always Prevent Subsequent Dissemination of Violative DTC Materials for the Same Drug
paragraphs: 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. 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. 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.
section_title: Conclusions
paragraphs: 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.
section_title: Recommendations for Executive Action
paragraphs: 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:    document criteria for prioritizing materials that it receives for review,    systematically apply its documented criteria to all of the materials it  track which materials have been reviewed.
section_title: Agency Comments and Our Evaluation
paragraphs: 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 http://www. ao. ov. gg If you or your staffs have any questions about this report, please contact  me at (202) 512-7119 or crossem@gao.gov. 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.
section_title: Appendix I: Scope and Methodology
paragraphs: 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. 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.
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.
section_title: Appendix II: Comments from the Department of Health and Human Services
section_title: Appendix III: GAO Contact and Staff Acknowledgments
subsections: section_title: Acknowledgments
paragraphs: 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.