A decade of direct-to-consumer advertising of prescription drugs

T h e n e w e ng l a n d j o u r na l o f m e dic i n e A Decade of Direct-to-Consumer Advertising Julie M. Donohue, Ph.D., Marisa Cevasco, B.A., and Meredith B. Rosenthal, Ph.D.
Evidence suggests that direct-to-consumer advertising of prescription drugs increases From the Department of Health Policy
and Management, University of Pittsburgh pharmaceutical sales and both helps to avert underuse of medicines and leads to Graduate School of Public Health, Pitts- potential overuse. Concern about such advertising has increased recently owing to burgh (J.M.D.); the Department of Health the withdrawal from the market of heavily advertised drugs found to carry serious Policy and Management, Harvard School of Public Health, Boston (M.C., M.B.R.); risks. Moreover, the Food and Drug Administration (FDA) has been criticized for its and Vanderbilt School of Medicine, Nash- weak enforcement of laws regulating such advertising.
ville (M.C.). Address reprint requests to Dr. Donohue at the Department of Health Policy and Management, University of We examined industry-wide trends in spending by pharmaceutical companies on di- Health, Crabtree Hal A613, 130 DeSoto St., rect-to-consumer advertising and promotion to physicians during the past decade. We Pittsburgh, PA 15261, or at jdonohue@ characterized the drugs for which such advertising is used and assessed the timing of advertising after a drug is introduced. Finally, we examined trends in the FDA’s N Engl J Med 2007;357:673-81.
Copyright 2007 Massachusetts Medical Society. Results
Total spending on pharmaceutical promotion grew from $11.4 billion in 1996 to $29.9
billion in 2005. Although during that time spending on direct-to-consumer advertis- ing increased by 330%, it made up only 14% of total promotional expenditures in 2005. Direct-to-consumer campaigns generally begin within a year after the approval of a product by the FDA. In the context of regulatory changes requiring legal review be- fore issuing letters, the number of letters sent by the FDA to pharmaceutical manu- facturers regarding violations of drug-advertising regulations fell from 142 in 1997 Conclusions
Spending on direct-to-consumer advertising has continued to increase in recent years
in spite of the criticisms leveled against it. Our findings suggest that calls for a mora- torium on such advertising for new drugs would represent a dramatic departure from n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e It has been 10 years since a change in a light on safety issues, and examined trends in the policy of the Food and Drug Administration FDA’s regulation of drug advertising during the (FDA) allowed direct-to-consumer advertising past decade.
of prescription drugs on television. Such advertis- ing has been criticized for encouraging inappro- priate use of medications and driving up drug spending.1,2 Concern that such advertising may Data Collection
lead to increased use of expensive medications was We obtained data on industry-wide and product- amplified by the introduction of a prescription- specific promotional expenditures from three mar- drug benefit in Medicare in 2006 (Part D). Studies ket-research firms that track advertising spend- of the effect of advertising on prescribing prac- ing and specialize in forms of promotion for the tices have shown that such advertising increases pharmaceutical industry; we also obtained infor- classwide sales, helps to avert underuse of medi- mation from researchers and staff members at the cines to treat chronic conditions, and leads to some FDA and other government agencies. These data have been widely used in studies of trends in and Direct-to-consumer advertising has also been the effects of direct-to-consumer advertising.3,5,11-14 controversial in light of postmarketing revelations Data on expenditures for such advertising were regarding problems with drug safety. Specifically, collected by TNS Media, which tracks local and clinical trials that are required for drug approval national advertising campaigns at 44 television are typically not designed to detect rare but sig- networks (including cable), 658 magazines, 202 nificant adverse effects, and contemporary meth- newspapers, the Internet, and several network and ods of postmarketing surveillance often fail to local radio stations. Data are representative of ma- connect adverse events that have a high rate of jor media markets.
background prevalence with the use of particu- We obtained publicly available data on promo- lar drugs. After the market withdrawal of Vioxx tion to health professionals from 1996 to 2005 (rofecoxib), a drug heavily promoted to consum- from IMS Health, an independent medical-infor- ers,6 critics called for the FDA to place limits on mation company. For the industry as a whole, we direct-to-consumer advertising, particularly for report on three major components of spending on new drugs,7 a view that was reiterated in a recent promotion to professionals: visits of pharmaceu- report by the Institute of Medicine on the safety tical sales representatives to physicians in office- based and hospital practices (“detailing”), free Finally, the Government Accountability Office samples dispensed to physicians, and advertising (GAO)9 and others10 have criticized the FDA’s en- in professional journals. IMS Health derives spend- forcement of regulations governing direct-to-con- ing estimates on detailing from a nationally rep- sumer advertising. Criticism has focused specifi- resentative panel of office-based physicians and cally on the adequacy of the FDA’s review of hospital pharmacy directors who track their con- pharmaceutical advertisements, as well as the level tacts with sales representatives. IMS Health ob- and speed of enforcement actions taken subse- tains data on spending on free samples from a panel of approximately 1200 office staff members Since direct-to-consumer advertising has a sig- in medical practices, sampled from the practices nificant effect on demand for prescription drugs, of the office-based physicians who are on the de- it is important to understand the evolution of such tailing panel. To estimate spending on advertising advertising and its regulation. Although one study in professional journals, IMS Health tracks adver- reported that spending for such advertising in- tisements placed in approximately 400 medical creased by a factor of 3 from 1996 to 2000,11 little journals and adds estimates of printing costs to is known about trends in spending and other the publisher’s charge for the advertisements.
forms of pharmaceutical promotion in recent We obtained data on industry-wide sales from years. In our study, we examined recent trends in published reports on the basis of an annual sur- the industry’s use of direct-to-consumer advertis- vey conducted by the Pharmaceutical Research and ing (as opposed to other forms of promotion), as- Manufacturers of America (PhRMA). We pur- sessed the timing of advertising campaigns rela- chased data on promotional expenditures in 2005 tive to the introduction of drugs in order to shed for products in specific classes from Verispan, n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. A decade of direct-to-consumer prescription-drug advertising another independent medical-information com- bution of promotional spending by type for the 10 pany, and from TNS Media. For the 10 therapeu- leading classes of drugs in terms of dollar sales in tic drug classes that had the highest U.S. sales in the United States. In addition, we examined the 2004, we obtained data on the five forms of phar- level and timing (relative to a drug’s FDA approval) maceutical promotion that are tracked by Verispan: of spending on advertising for the 20 drugs with direct-to-consumer advertising, detailing, advertis- the highest spending for direct-to-consumer ad- ing in professional journals, meetings and educa- vertising in 2005.
tional events for physicians, and online pharma- To characterize the nature of FDA enforcement ceutical promotion to physicians. Data regarding related to advertising spending over time, we ex- spending on advertising are collected by TNS Me- amined the numbers of enforcement letters related dia, as described previously. To track detailing, to promotion in each year and further calculated Verispan surveys approximately 13,000 office- the percentage of promotion-related enforcement based and hospital-based physicians and residents, actions that were for advertising campaigns (as nurse practitioners, and physician assistants who opposed to promotional materials aimed at health track their encounters with pharmaceutical sales professionals). Finally, we examined the content of representatives. The panel is geographically rep- the notices of violation to determine the type of resentative and includes members of 31 clinical violation (e.g., false or misleading claims about the effectiveness or risks of drugs) and calculated the Verispan produces estimates of industry ex- proportion related to each type.
penditures on professional meetings and events through a survey of more than 3500 office-based physicians representing 19 specialties who report on the events sponsored by pharmaceutical com- Industry-wide Trends in Promotion
panies that they attend. This panel of physicians Total real spending on promotion grew from $11.4 is also asked to report on online pharmaceutical- billion to $29.9 billion from 1996 to 2005, at an promotion activity, which includes digital (Inter- average annual rate of 10.6% (Table 1). The per- net and video) promotion and continuing medical centage of sales spent on promotion for the indus- education modules. Verispan audits approximate- try as a whole increased from 14.2% in 1996 to ly 600 medical journals and tabloids and calculates 18.2% in 2005. In the past 9 years, spending on spending on the basis of each journal’s rate-card direct-to-consumer advertising and free samples information and premium-factor costs.
has risen as a share of total promotion, whereas Finally, we obtained data on the number of FDA investments in detailing and advertising in profes- enforcement actions related to pharmaceutical sional journals have fallen as a share of the total.
promotion from 1997 to 2006 from the FDA, Real spending on direct-to-consumer adver- which posts the regulatory letters sent to pharma- tising increased by 330% from 1996 to 2005 (Table ceutical companies on its Web site (www.fda.gov/ 1). After a brief slowdown in spending on adver- cder/ddmac/lawsregs.htm). FDA approval dates for tising in 2000 and 2001, spending grew at an aver- specific products were obtained from the Orange age annual rate of 14.3% from 2002 to 2005. Yet, Book of approved drug products with therapeutic promotion to professionals still outweighs spend- equivalence evaluations.15 We obtained data on ing on direct-to-consumer advertising. In 2005, start dates for advertising campaigns through a only 14% of total industry expenditures on phar- series of Internet searches (with specific sources maceutical promotion were devoted to such adver- Data Analyses
Role of Advertising for Top-Selling Drugs
We conducted descriptive analyses. Data on pro- In 2005, 8 of the 10 top drug classes in terms of motional spending were adjusted to 2005 dollars dollar sales had at least one product with advertis- with the use of the Consumer Price Index. We ex- ing spending (Table 2). The importance of direct- amined spending on all forms of promotion rela- to-consumer advertising varied substantially across tive to sales to determine whether the intensity of the top classes. Manufacturers of proton-pump in- pharmaceutical promotional spending has changed hibitors, 3-hydroxy-3-methylglutaryl coenzyme A during the past decade. We examined the distri- (HMG-CoA) reductase inhibitors (statins), and n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e Table 1. Annual Spending on Direct-to-Consumer Advertising and Promotion to Health Professionals, 1996–2005.*
Annual Spending
Professional promotion
Free samples
Total promotion
* Data on promotional spending are from IMS Health (www.imshealth.com); data on sales are from PhRMA’s annual report. All data were adjusted to 2005 dollars, according to the Consumer Price Index. Spending on free samples for 2005 was estimated on the basis of growth and spending rates from the previous 3 years.
erythropoietin medications spent 34%, 34%, and Level and Timing of Expenditures
31% of their total marketing budget, respectively, Spending on direct-to-consumer advertising con- on direct-to-consumer advertising in 2005. The tinued to be concentrated among a relatively small manufacturers of several drugs in these classes number of brands. The 20 drugs with the highest invested in advertising campaigns (Table 2). Spend- spending made up 54.4% of total industry spend- ing for the advertising of antidepressant agents, ing on advertising in 2005 (Table 3). Drugs that are seizure-disorder medications, and antipsychotic advertised to consumers are predominantly new agents was lower than that for proton-pump in- drugs used to treat chronic conditions. Ten of the hibitors, statins, and erythropoietin medications top 20 drugs, as ranked by advertising spending, as a proportion of the total marketing budget. were introduced in 2000 or later. Notably, nearly The remaining 4 of the top 10 drug classes placed all (17 of 20) advertising campaigns for the most little emphasis on consumers in their promo- heavily advertised drugs began within a year after tional strategies. None of the angiotensin II an- FDA approval of the drug.
tagonists used direct-to-consumer advertising in 2005. Among manufacturers of calcium-channel FDA Enforcement of Regulations
blockers, only non–product-specific or “disease The number of letters sent by the FDA to pharma- awareness” ads were purchased. In 2005, manu- ceutical manufacturers notifying them that they facturers used direct-to-consumer advertising for had violated regulations for prescription-drug ad- only one of the cyclooxygenase-2 inhibitors (of vertising fell from 142 in 1997 to only 21 in 2006 which celecoxib was the only remaining product) (Fig. 1). During the same period, the proportion of and one of the angiotensin-converting–enzyme in- promotion-related regulatory letters citing prob- hibitors. Since data on the retail value of free sam- lems with direct-to-consumer advertisements (as ples that are dispensed for these drug classes were opposed to promotional material aimed at health not available, the overall promotion-to-sales ratios professionals) increased from 15.5% of all letters probably provide a conservative estimate.
in 1997 to 33.3% in 2006. And during the years n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. A decade of direct-to-consumer prescription-drug advertising Table 2. U.S. Sales Revenues and Promotional Spending for Leading Therapeutic Classes of Drugs, According to Dollar Sales in 2005.*
Class with
U.S. Sales Promotional Percentage
Type of Promotion
* Data on direct-to-consumer advertising are from TNS Media; data on detailing, professional meetings and events, journal advertising, and online promotions to physicians are from Verispan; and data on sales revenues are from IMS Health. Leading therapeutic classes of drugs were identified on the basis of publicly available IMS Health rankings of therapeutic classes according to spending for 2004. Values for se- lective serotonin-reuptake inhibitors (SSRIs) and selective norepinephrine-reuptake inhibitors (SNRIs) match the classification scheme used by Verispan, which was the source of our data on promotions. Values in the far right-hand column refer to product-specific advertising only. HMG-CoA denotes 3-hydroxy-3-methylglutaryl coenzyme A, ACE angiotensin-converting enzyme, and COX-2 cyclooxygenase-2.
2003–2004, nearly half of the FDA’s promotion- erratic camera movement, quick scene changes, related regulatory letters were focused on direct- and visual changes in point of view). In another to-consumer advertisements. From 1997 to 2006, case, the FDA said Pfizer’s print advertisement for nearly 84% of regulatory letters regarding direct- Zoloft (sertraline) was false or misleading because to-consumer advertising cited advertisements for it omitted important information relating to the either minimizing risks (e.g., minimizing or omit- risk of suicidality in patients, a risk stated on the ting information on side effects), exaggerating ef- product’s label at the time the advertisement ran.
fectiveness (e.g., portraying the indication too broadly or making unsubstantiated claims of su- periority over other drugs), or both.
For example, the FDA found that Eli Lilly’s tele- Spending on direct-to-consumer advertising has vision broadcast advertisement for Strattera (ato- continued to increase recently in absolute terms moxetine) was false or misleading because it in- and as a percentage of pharmaceutical sales in spite adequately communicated the indication for the of pressure on manufacturers to curtail such ad- drug (attention-deficit–hyperactivity disorder) by vertising.8 Promotion to physicians continues to be means of competing visuals, graphics, and music the dominant marketing strategy, but there are presented concurrently. Similarly, serious risk dis- some drugs in a majority of the top-selling classes closures were minimized for Strattera, the FDA that are promoted by such advertising. Driven by said, by the distracting visuals and graphics (e.g., increases in direct-to-consumer advertising, total n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e Table 3. Top 20 Pharmaceutical Products in Terms of Spending on Direct-to-Consumer Advertising in 2005.*
Year That
Approval Campaign
Therapeutic Category
Bristol-Myers Squibb/ Platelet-aggregation * HMG-CoA denotes 3-hydroxy-3-methylglutaryl coenzyme A, SNRI selective norepinephrine-reuptake inhibitor, 5-HT1 5-hydroxytryptamine 1, PDE5 phosphodiesterase type 5, and G-CSF granulocyte colony-stimulating factor.
‡ Approval dates are from the Electronic Orange Book.15 § Starting dates for direct-to-consumer campaigns were obtained through Internet searches. A detailed source list is promotion as a percentage of sales has increased sumers, physicians, and payers.17 Of course, it is substantially during the past 5 years, leading some possible that advertising reduces the price respon- observers to worry that consumers must bear these siveness of demand and thus leads manufactur- increased costs in the form of higher prices. Eco- ers to increase prices, but the empirical evidence nomic theory and evidence suggest that changes on this point is mixed.18,19 in marketing costs are unlikely to have a direct Advertising campaigns generally begin within effect on pharmaceutical prices, which largely a year after the introduction of a pharmaceutical reflect perceptions of product value held by con- product, which raises questions about the extent n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. A decade of direct-to-consumer prescription-drug advertising Letters related to direct-to-consumer advertising No. of Warning Letters
Related to Promotion
Percentage of Letters Related to
Direct-to-Consumer Advertising
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Figure 1. Trends in FDA Enforcement of Regulations Regarding Direct-to-Consumer Advertising, 1997–2006.
Data are from regulatory letters posted on the Web site of the Division of Drug Marketing Advertising and Commu- nication of the FDA (www.fda.gov/cder/ddmac/lawsregs.htm).
to which advertising increases the use of drugs AUTHOR, PLEASE NOTE: n 2002 the Secretary of Health and Hu-
with unknown safety profiles. At least one phar- man Services beg Figure has been redrawn and type has been reset.an requiring that all draft FDA
Please check carefully.
maceutical manufacturer (Bristol-Myers Squibb) regulatory letters, including letters related to ad- direct-to-consumer advertising for drugs in the the FDA’s Office of Chief Counsel before they are first year after FDA approval. And PhRMA, the issued. A GAO report found that this legal review industry trade group, has recommended that man- has led to a reduction in the number of letters is- ufacturers delay such campaigns for new drugs sued, as well as to delays such that FDA warning until after health professionals have been suffi- letters are frequently sent out long after the false ciently educated, although no details have been or misleading advertising campaign has run its provided on how long a period was deemed nec- course.22 Notably, the number of regulatory letters essary.20 Finally, in a recent study of drug safety, sent by the FDA in 2002 was less than half that the Institute of Medicine recommended that the in 2001 (28 vs. 68) (Fig. 1).
FDA restrict advertising for newer prescription A second indication of weakening FDA over- drugs.8 Our data show that a mandatory waiting sight of direct-to-consumer advertising in recent period on advertising for new drugs would rep- years is that the number of staff members who resent a dramatic departure from current indus- are dedicated to reviewing advertisements has re- mained relatively stable, whereas the use of such The number of regulatory actions taken by the advertising has grown substantially. In 2002, three FDA against companies marketing prescription FDA staff members were dedicated to reviewing drugs to consumers has fallen dramatically in re- direct-to-consumer advertisements.22 In 2004, four cent years. This decline may reflect either better staffers were reviewing such advertisements, even industry compliance with advertising regulations though spending on this form of advertising (and or a worsening of FDA oversight.21 Although a probably the volume of ads to review) had in- systematic assessment of the compliance of phar- creased by 45%, from $2.9 billion to $4.2 billion maceutical advertisers with advertising regulations (Table 1).23 is beyond the scope of this article, some insights Finally, consistent with the hypothesis that into this issue can be gained from examination of staffing has not kept pace with the number of policy changes and staffing levels within the FDA prescription-drug advertisements, the proportion over the period of our study. Three observations of broadcast advertisements that underwent FDA from such an examination suggest that the FDA’s review before airing declined from 64% in 1999 capacity to enforce advertising regulations has to only 32% in 2004.23 Thus, even if manufactur- ers were to increase submission of advertisements n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e to the FDA, the agency has said that “current FDA Since 2000, direct-to-consumer advertising of resourcing for this work would probably result in prescription drugs has continued to grow both in delayed reviews . . . and discourage [manufactur- absolute dollars and relative to other forms of pro- ers] from submitting the materials for prior FDA motion. Although the evidence base is growing, there are few data to support an assessment of the Our study has some key limitations. We ob- balance of the costs and benefits of such adver- tained data on industry sales from PhRMA, which tising.24 The debate over whether and how direct- includes in its annual reports sales data only for to-consumer advertising should be more tightly its members. Ideally, we would include sales of regulated takes place against a backdrop of grow- all branded drugs sold by prescription, including ing concern about the growth of health care pharmaceutical and biologic agents, and exclude spending, particularly in the Medicare program. sales of generic drugs (because generic drugs Gaining a better understanding of the effects of typically are not promoted). PhRMA sales data direct-to-consumer advertising for prescription may include some generic sales (if a member re- drugs has important public health implications ports both branded and generic sales) and typi- not only for the United States and New Zealand, cally exclude sales of biologic agents, which are where such advertising is also permitted, but also manufactured by companies that belong to an- for Canada and the European Union, where such other trade group (Biotechnology Industry Orga- advertising is banned but has been subject to re- nization). As a result, the sales figures may under- cent challenge.25,26 estimate total dollar sales for the industry. We Supported by a grant (KL2-RR024154-01, to Dr. Donohue) provide data on spending on free samples valued from the National Center for Research Resources, a component at their approximate retail price, which is how they of the National Institutes of Health (NIH); NIH Roadmap for typically are valued in industry promotional audits. Medical Research; and the Alfred P. Sloan Foundation (to Dr. Thus, the value of free samples we present prob- Dr. Donohue reports receiving consulting fees from Glaxo- ably overstates the opportunity cost to manufac- SmithKline and CanWest Global Communications. No other po- turers, which would lie somewhere between the tential conflict of interest relevant to this article was reported.
We thank Joseph Hanlon and Judith Lave for their helpful marginal cost of production and the retail value. comments on earlier drafts of this article.
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n engl j med 357;7 www.nejm.org august 16, 2007 Downloaded from www.nejm.org on December 5, 2010. For personal use only. No other uses without permission. Copyright 2007 Massachusetts Medical Society. All rights reserved.

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General introduction Homogeneous catalysis with metal phosphine complexes Tertiary organic phosphines (PR3; R= alkyl, aryl) were discoveredaround the middle of the 19th century. Their ability to combinewith heavy metal salts was noted almost immediately, but theapplication of the metal complexes in homogeneous catalysis is adevelopment which only started to flourish after the 1950s.1The firs

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