Prescription Drugs: Improvements Needed in FDA's Oversight of Direct-to-Consumer Advertising
Released: 2006-12-14T00:00:00

Letter

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.

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.

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. 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.

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. 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.

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. 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.

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. 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.

Since the 2002 Policy Change, FDA’s 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.

FDA’s 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. (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.

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. (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.

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 FDA’s 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. 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.

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. 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.

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. 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.

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. 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.

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: 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.

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 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.

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. 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.

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

Appendix III: GAO Contact and Staff Acknowledgments

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.