Market Insight - DTC advertising still a hot potato
This article was originally published in Scrip
It is now more than ten years since the US FDAfirst allowed the advertising of prescription medicines direct to the public. Since then, the US has been joined by just one other country, New Zealand, in allowing so-called direct-to-consumer (DTC) advertising, although there have been mutterings on the subject in some other countries. Despite its limited spread, DTC advertising remains a controversial issue.
DTC advertising recently came to the fore again in the wake of hearings in early May by the House Energy and Commerce Subcommittee on Oversight and Investigations. The purpose of the hearings was, in the words of the Subcommittee chairman Bart Stupak (D-Mich), "to examine the potentially misleading and deceptive tactics used in DTC advertisements for prescription pharmaceutical products". Mr Stupak's comment illustrates the polarisation that exists between supporters and critics of DTC advertising.
That increasing consumer awareness of new pharmaceutical products increases sales is beyond question: why else would the industry spend so much on DTC advertising? Spending rose from approximately $1.1 billion in 1997 to about $4.2 billion in 2005, according to Mr Stupak's figures. Every $1 spent on DTC advertising can lead to a sales increase of as much as $6, and one study has shown that every $1,000 spent on DTC advertising results in 24 new prescriptions for the product in question, the Congressman says. Other studies, it should be pointed out, have found that the ratio of sales increase to DTC advertising spend is somewhat less than these figures suggest.
three areas of concern
Critics of DTC advertising have concerns in three main areas: safety, cost and oversight. Concerns about safety relate to the fact that clinical trials required for drug approval are not designed to identify rare but significant side-effects, and that post-marketing surveillance techniques do not always detect adverse events that have a high background incidence. Previously unrecognised side-effects are most likely to appear during the first few years that a product is on the market, yet paradoxically this is usually the time when it receives the greatest marketing push. Opponents of DTC advertising point to products like Merck & Co's Vioxx (rofecoxib), which was heavily promoted to the US public before it emerged that it was associated with an increased risk of adverse cardiovascular events.
As far as cost is concerned, critics argue that advertising to consumers, particularly on television, not only increases demand but also encourages the inappropriate use of prescription medicines, both of which lead to increased costs. The introduction of Medicare Part D, a federal programme to subsidise the costs of prescription medicines for Medicare beneficiaries, in 2006, only served to increase the opportunity for costs to escalate.
Others of course argue that it is not DTC advertising that drives up overall drug costs but other factors, such as the introduction of newer, more expensive products, increased use of existing products, lower treatment thresholds, an ageing population and unit price rises. Indeed, a number of studies have shown no correlation, or even a negative correlation, between drug costs and the level of DTC advertising.
The third main concern is the extent to which the FDA exercises statutory control of DTC advertising; this was an issue that received much attention at the Oversight and Investigations Subcommittee meeting. The FDA, or more precisely its Division of Drug Marketing, Advertising, and Communications (DDMAC), is responsible for regulating the content of all prescription drug advertising, whether directed to consumers or to medical professionals. DTC advertising includes broadcast advertisements (such as those on television and radio), print advertisements (advertisements in magazines and newspapers), and internet advertisements (including consumer advertising on drug companies' websites). The FDA is also responsible for regulating "consumer-directed" materials, such as patient brochures designed to be given to patients in doctors' offices. If any violation of the regulations is identified, such as a false or misleading safety or efficacy claim, the FDA has the authority to issue a regulatory letter requiring the offending material to be withdrawn or a corrective advertisement to be issued.
In recent years, there have been growing misgivings about how the FDA was coping with the ever-increasing burden of advertising materials submitted to it and, in 2006, the Government Accountability Office(GAO) was asked to examine how the agency was overseeing DTC advertising and what actions it was taking when it identified violations of the regulations. The scale of the challenge facing the FDA was revealed in a GAO analysis of the number of materials directed to consumers submitted to the FDA.
The GAO released its findings in a report in November 2006. It found that the FDA reviewed only a small proportion of the DTC materials it received, and was unable to ensure that it was identifying for review those materials considered to be the highest priority. And, while the agency did prioritise the review of materials considered to have the greatest impact on public health, it had not documented the criteria on which it based these decisions.
In practice, the GAO found, the FDA applied informal criteria when identifying materials for review: for example, it reviewed all final and draft DTC television advertisements because they are likely to be widely disseminated to consumers. It also prioritised draft versions of other DTC materials because this provided it with an opportunity to identify problems before materials were released to consumers. But it did not systematically apply its informal criteria to all the DTC materials it received. Furthermore, it was unable to determine whether any particular material had been reviewed.
resource issue
The FDA was forced to adopt a selective approach to reviewing DTC materials because of limited resources: the DTC Review Group set up by DDMAC in 2002 consisted of just one group leader, four reviewers and two social scientists (by May 2008 it had grown to two group leaders, seven reviewers, and two social scientists). Its problems worsened in 2002 when a change in policy required all draft regulatory letters to be reviewed by the FDA's Office of Chief Counsel.
Whereas before the policy change it had taken an average of two weeks to issue a letter, afterwards it took an average of four months. The effect of this was that in many cases, companies had ceased to use the contentious advertising material long before the regulatory letter was received. For example, a warning letter to Roche about a radio advertisement for the anti-influenza drug Tamiflu was actually sent after the end of the influenza season, critics of the policy have claimed.
There have been suggestions that the change in policy was politically motivated, designed to inhibit the FDA's ability to reign in errant companies, although the then chief counsel Daniel Troy claimed that the intention was to avoid the FDA ever having to lose a case in court. Whatever the motivation, Representative Henry Waxman of California, a prominent critic of the pharmaceutical industry, claimed at the time that the Bush administration had presided over a 70% drop in FDA enforcement action relating to false and misleading drug advertisements.
In its 2006 report, the GAO made several recommendations aimed at improving the FDA's processes for identifying and reviewing final and draft DTC advertising materials. These were that it document its criteria for prioritising the materials it receives for review, systematically apply its documented criteria to all the materials it receives, and track which materials have been reviewed. The Oversight and Investigations Subcommittee hearings this May gave the GAO an opportunity to give a more up-to-date assessment of the FDA's performance in regulating DTC advertising.
According to testimony presented by Marcia Crosse, director for Health Care at the GAO, the FDA has now documented the criteria it uses to prioritise reviews of DTC advertising of pharmaceutical products. Its first priority is to review materials with "egregious" violations, such as those identified through complaints. It also places a high priority on reviewing television-advertising materials. And the agency continues to prioritise reviewing draft materials because they enable it to seek the correction of any problems before the materials are released to consumers.
However, the FDA still does not systematically apply its prioritisation criteria to all the DTC materials it receives for review. Furthermore, the agency still does not track which of the DTC materials submitted to it are actually reviewed, and consequently cannot be sure that it is identifying and reviewing the highest priority materials.
But the GAO reserved its greatest criticism for the delay in issuing regulatory letters that occurred after the 2002 policy change. The GAO said that the number of regulatory letters the FDA issues each year in respect of violative DTC materials decreased after the process for issuing letters was lengthened. Between 1997 and 2001, the FDA issued between 15 and 25 letters citing DTC materials each year. From 2002 to 2005, it issued between eight and 11 regulatory letters per year that cited DTC materials. The GAO cited an unnamed FDA official as blaming both the lengthened review time and staff turnover within the DTC Review Group for the decline in the number of regulatory letters issued. And since 2005 the number of letters issued that cite DTC materials has continued to decline, to four letters in 2006 and two in 2007.
Warning letters are issued for violations that may lead the FDA to pursue additional enforcement actions if not corrected; untitled letters are issued for violations that do not meet this threshold.
The GAO was not the only organisation dissatisfied with the status quo to testify at the hearings. In written testimony, the non-profit Consumers Union called for Congress to impose a three-year moratorium on DTC advertisements for new pharmaceutical products. Such a measure would permit doctors to get used to using a new drug and perform their own evaluation before patients start requesting it because of DTC advertising. It would also allow further safety evaluations and adverse event surveillance of new products in populations much larger than those used in clinical trials (typically a few hundred to a few thousand patients). And it would also help to minimise any overuse, the Union stated.
The Union also called on Congress to make more resources available to the FDA for reviewing DTC advertising, although it did not appear to address the delay caused to the issuance of regulatory letters caused by the need to have them pre-approved by the Office of Chief Counsel. The Union was particularly incensed by an advertisement for Lipitor (Pfizer's hypolipaemic atorvastatin calcium) featuring Dr Robert Jarvik, the inventor of the Jarvik artificial heart. Although no longer a practising physician, the Union claims he incorrectly stated that Lipitor was superior to generic alternatives and conveyed the impression that "leading doctors prefer Lipitor", yet the advertisement was used for several months before it was withdrawn. Such delays "result in windfalls for violating companies", according to the Union.
In addition, the Consumers Union alleged that the FDA had been slow to study whether the MedWatch toll-free telephone number and website address should be included in DTC television advertisements, as required for print advertisements by the FDA Amendments Act (FDAAA) (MedWatch is the FDA's programme for safety information and adverse event reporting.)
On the same day that the Oversight and Investigations Subcommittee was holding its hearings into DTC advertising, FDA Commissioner Andrew von Eschenbach was reporting to the Senate Committee on Health, Education, Labor, and Pensions and the House Committee on Energy and Commerce on what measures the FDA was planning to take to assess the appropriateness of the inclusion of MedWatch details in DTC television advertisements. This reporting is a requirement of Section 906 of the FDAAA. If this assessment were to find that the inclusion of such a statement is appropriate for television advertisements, FDAAA mandates that regulations be issued to implement this requirement, including a determination of what is a reasonable length of time for displaying the statement in television advertisements.
In his report, Dr von Eschenbach spelled out the steps needed to undertake such an assessment, some of which are a requirement of the Paperwork Reduction Act of 1995 and cannot be shortened. In the FDA's estimation, it could take up to two years to determine the appropriateness of including details of how to report suspected adverse events in DTC television advertisements. Unsurprisingly the Consumers Union, which recently filed a citizen's petition with the FDA asking that it require the information to be included in all DTC television advertisements, has declared two years to be too long.
The Lipitor advertisements featuring Dr Jarvik were among several that came under the spotlight at the Oversight and Investigations Subcommittee hearings. Others singled out by the Subcommittee included Merck & Co/Schering-Plough's "Food & Family" advertisements for the hypolipaemic Vytorin (ezetimibe plus simvastatin) and Johnson & Johnson's advertisements for the erythropoiesis-stimulating agent Procrit (epoetin alfa). Asked at the hearings to provide assurances about future business practices, representatives from these companies failed to provide any such promises on the grounds that they had insufficient authority to do so, although they did indicate that they followed PhRMA guidelines in this matter (see Box 1).
Box 1: PhRMA Guiding Principles for DTC advertisements DTC advertising should:
Full details of the Guiding Principles can be found on the PhRMA website at http://www.phrma.org/files/DTCGuidingprinciples.pdf |
Representative Stupak and Energy and Commerce Committee chairman John Dingell subsequently wrote to the CEOs of the four companies seeking assurances that their companies would act to reduce misleading and deceptive DTC advertisements. Specifically, they asked the companies to agree:
- to follow American Medical Association (AMA) guidelines on the use of actors and health professionals in DTC advertisements;
- not to market products in DTC advertisements until a valid outcomes study has been performed;
- to observe a two-year moratorium on the DTC advertising of new prescription drug products;
- not to market off-label uses of prescription products in DTC labelling;
- to add the FDA's toll-free MedWatch telephone number to all DTC advertising; and
- to add a "black box" warning in advertisements for products whose labelling includes a "black box" warning.
In response, there was broad agreement from the four companies to abide by the AMA guidelines over the use of actors and health professionals in advertisements, to incorporate "black box" warnings in broadcast materials (where appropriate) and not to promote off-label uses. But there was also unanimity that to delay DTC promotion pending the outcome of long-term studies was not workable. As to the other requests, the responses varied. Schering-Plough for example said that a two-year deferral of all broadcast advertising "might be appropriate in certain instances" although it agreed with the other companies that a blanket ban was unrealistic. And while there was some support for adding the MedWatch number to broadcast advertisements, Merck had reservations about adding another 1-800 number to the one it already includes for obtaining further information about a particular medication, and said it could not commit itself until the outcome of the FDA's Section 906 assessment was available.
PhRMA has invited the Committee leaders and their staff to discuss these issues and other concerns as part of its process of reviewing and updating its Guiding Principles, an invitation the Committee members have accepted. The outcome of those discussions is now awaited.
Dr Peter Charlish is a consultant editor to Scrip. He can be contacted at [email protected].