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C O M M E N T A R Y : D R U G  A D S
W E B  E X C L U S I V E   

26 February 2003  
  

Pharmaceutical Promotion: 
Don’t Throw The Baby Out With The Bathwater

Preliminary evidence supports the possible benefit of pharmaceutical promotion.


Robert W. Dubois

ABSTRACT:

Spending on prescription drugs and promotion by the pharmaceutical industry grew substantially during the past ten years. Does the greater exposure offered by promotion fill a needed educational gap, or does it merely promote inappropriate use? This paper uses two recent studies to explore this question, presenting a framework in which the impact of promotion depends upon the level of evidence and consensus on drug use.

As one of health care’s fastest-growing components, prescription drugs command much attention. Spending on prescription drugs exceeded $150 billion in 2001, almost double the $79 billion spent in 1997.¹ Alongside and perhaps underlying this trend, promotion by the pharmaceutical industry also grew substantially, rising 70 percent from 1996 to 2000.² In 2000 the industry spent more than $15 billion in promotional activities (85 percent directed toward providers and 15 percent, toward consumers).³

Promotional spending translates into exposure, getting messages about prescription drugs to physicians and patients. Physician-oriented marketing consists primarily of detailing (in-person visits by drug company representatives), advertising in journals, and continuing medical education events. Patient-oriented marketing has thus far focused on advertising in various media, including print, broadcast, and online. Does the exposure fill a needed educational gap, or does it merely promote inappropriate use?

Proponents of drug promotion say that it leads to increased disease awareness by both physicians and patients and to greater detection, diagnosis, and treatment. Critics counter that promotion has fueled the rise in drug spending, chiefly in the form of inappropriate prescribing caused by ad-induced patient demand or incomplete information influencing physicians’ decisions, or both. As a recent medical journal editorial stated, “The education of patients—or physicians—is too important to be left to the pharmaceutical industry.”⁴ Is this a valid conclusion or a misguided assertion? And how should policymakers react to this controversy?

Research Into The Issue Of Drug-Use Variation

The pharmaceutical industry has allocated substantial resources to detailing, or visits during which information about drugs is conveyed and drug samples provided, and is spending more to convey information to patients. These resources far exceed those of nonprofit or governmental agencies. Does the potential benefit of educating physicians and consumers outweigh the potential clinical and economic harm of overuse?⁵

Several studies have shown that consumer-directed advertising raises awareness of diseases, treatment, and specific drugs—and that patients who are exposed to this information are more likely to request specific drugs.⁶ Although drug promotion is regulated through oversight by the U.S. Food and Drug Administration (FDA), many critics assert that current regulation does not ensure that physicians and patients react appropriately or that they make the right decisions. This has led to calls for greater limitations on how the industry promotes its products, perhaps even the cessation of direct-to-consumer (DTC) advertising. Is this a step in the right direction, or are we “throwing the baby out with the bathwater”?

It would enlighten the discussion to know whether—on balance—pharmaceutical promotion educates or misleads. Although there have been reports that pharmaceutical sales representatives occasionally make inaccurate statements to prescribing physicians, there are no objective data showing that drug promotion (in general) or DTC advertising (in particular) results in the inappropriate use of drugs.⁷ And although a definitive answer is not available, recent studies provide a framework for considering further research and for public discussion. These studies have addressed the following questions: How much variation is there in the use of pharmaceutical therapies? Has the relative proportion of appropriate and inappropriate drug use changed over time?

Variation in procedures. As evidence-based medicine has emerged, there is a growing consensus that the sizable geographic variation in health services cannot be explained simply by differences in patient demographics or the prevalence of disease, but rather results from inconsistencies in how physicians (and patients) make medical care decisions. It has been shown many times that rates of various surgical and medical procedures vary four- to tenfold from town to town or state to state.⁸ For the surgical treatment of common diseases, in 1995 there was a 3.5-fold range of variation from the highest to lowest hospital referral regions for coronary artery bypass graft (CABG), 6.5-fold for back surgery, and 7.8-fold for radical prostatectomy.⁹ For the evaluation and treatment of common medical conditions, the range in variation in use of coronary angiography has been shown to vary more than twelvefold, and the use of upper gastrointestinal endoscopy, almost fourfold.¹⁰ These findings have formed the basis of continuous quality improvement efforts whose goal is that similar patients should generally receive similar interventions. Patients should receive interventions that have proven clinical benefit and represent a cost-effective option.

Variation in medication use. Variation in use of medications has been assumed to mirror the geographic findings for other health care services. This turns out, perhaps, not to be true. In a recent study of medication use in eleven geographic regions in California, rather than finding the four- to tenfold variability as noted above, we found only 1.3- to 1.4-fold variability (that is, the difference between the highest- and lowest-use areas amounted to only 30–40 percent for many drugs). This study used administrative claims data from three California health plans (Blue Cross of California, Blue Shield of California, and PacifiCare of California) during 1998–1999; the data represented 638,188 patients who had received services (drugs or otherwise) and thus might represent a group of people who were somewhat more ill than a randomly selected population would be. Of these people, 39 percent were enrolled in a health maintenance organization (HMO), 60 percent in a preferred provider organization (PPO), and 1 percent in a point-of-service (POS) plan. This analysis examined drug use for patients with specific diagnoses and determined the percentage of patients with that diagnosis who filled at least one prescription for the specified class of medication.

As examples of variability, 62 percent of patients with sinusitis on antibiotics received a brand-name rather than a generic medication. This proportion varied from 53 percent in the state’s lowest-use region to 72 percent in the highest-use region. Similarly, 49 percent of asthmatics overall used inhaled corticosteroids, with results ranging from 40 percent to 59 percent. On average, for all medications examined, the ratio of highest- to lowest-use areas was 1.77.¹¹

Since variability of proportions may appear lower because the range can vary only from zero to 100 percent, variability was also examined on a population level (that is, rate of use of a medication per 100 members), a method more closely mirroring that published for procedures. This methodology similarly showed much lower variability in the use of drugs than in the use of procedures; thus, the results did not merely reflect the characteristics of the study design.

The large pharmacy benefit manager (PBM) Express Scripts observed similar findings in a nationwide study of its covered population in 2000. The investigators found a 1.55-fold variation in overall use of medications between the highest- and lowest-use states (11.9 versus 7.65 prescriptions per member per year, respectively) and for each of twenty-four key medication classes, typically a twofold variability from highest- to lowest-use states, after differences in age and sex were controlled for using direct standardization.¹²

There are multiple possible explanations for the relatively lower variation in these two studies that will require further research, including whether these results are generalizable to the US population or reflect unique aspects of the managed care/PBM environment, or whether the required clinical trials for drugs create more data on which to base clinical decision making. The higher variability in use of procedures also could reflect that a relatively small number of specialists in any given geographic area, who might be either enthusiasts or nihilists and could have trained together, control the use of procedures and thus could have a large impact on local use. In contrast, medications are prescribed by a larger number of physicians whose practice patterns might have less influence upon one another.

The Effect Of Promotion

The above results of lower geographic variability in the use of medications should be viewed as exploratory and certainly not conclusively linked to greater promotion of pharmaceuticals. The ideal study has yet to be performed, in which changes in variation are linked directly to marketing activities: Variation in use falls commensurate with substantial physician and patient promotional activities. In the absence of these definitive data, many potential explanations can be raised.

However, an important or perhaps overlooked explanation for the uniformity of drug use relates to the potential influence of pharmaceutical promotion. In contrast to surgical or medical procedures, for which no concerted educational effort conveys evidence for what does and does not work, the pharmaceutical industry has the resources to disseminate these types of messages and routinely does so. Based on information approved by the FDA (Division of Drug Marketing, Advertising, and Communications), journal advertisements, visits to physicians, and convening of continuing education seminars convey coherent information about a drug’s characteristics and its potential role in therapy. Thus, physicians (and patients) see and hear the evidence frequently. This repeated and consistent “education” can promote a more uniform approach and reduce variation.

We also do not know the relative impact of promotional efforts on influencing overall use (that is, the number of patients using a particular therapy) versus their impact on market share (that is, shifting usage from one drug to another). The former would influence aggregate number of prescriptions per patient, and the latter would influence relative market share (“business stealing”), as they focus on a specific brand. Both influences of promotion could affect cost and patient outcomes.

However, assuming that variation is reduced by promotional activities, is this reduction desirable? As discussed above, quality improvement attempts to reduce variability. But is the greater uniformity in use of medications based around the right or the wrong amount? Given the economic incentives, pharmaceutical companies may provide a more than optimal amount of advertising, from a societal perspective.¹³ Annual spending on DTC advertising rose gradually in the 1990s and then tripled between 1996 and 2000, when it reached $2.5 billion.¹⁴ Although DTC spending had been increasing prior to 1997, the FDA guidelines issued in that year (which clarified and relaxed the quantity of “balanced” information that was required in each broadcast advertisement) seem to correspond with the rapid increases that were observed thereafter.

Excessive promotion could lead to excessive product use, albeit with a more uniform distribution. This should be the subject of future research, but there is some evidence now that supports the contention that promotion is not accompanied by excessive use, at least in some circumstances. A recently published study examined whether the relative proportion of appropriate use and misuse of lipid-lowering therapies (statins) changed between 1997 and 1999, a period during which there was sizable growth in DTC advertising in general and advertising of this drug class in particular.¹⁵ Moreover, the number of patients using these drugs increased by 60 percent during this time period. Those concerned about the effects of promotion would posit that DTC advertising causes greater use of various therapies by more “marginal” candidates. Thus, in the case of statins, they would assert that the clinical characteristics of typical users of the therapy would shift to a less “at risk” population.

The study mentioned above examined the use of statins in managed care plans in twenty-two states and found that the proportion of the population using these drugs rose from 5 percent to 8 percent, a substantial increase. To assess the appropriateness of that use and to determine whether the appropriateness fell as usage increased, patients were assigned to one of seven categories representing cardiovascular risk based on documentation of comorbid diseases or risk factors. These categories were based on elements of the National Cholesterol Education Program guidelines. Two findings have relevance. First, even after several years of DTC advertising, almost 95 percent of patients on lipid-lowering therapy had some documented objective level of cardiovascular risk (coronary artery disease, diabetes, or cardiac risk factors). Second, despite the 60 percent increase in number of treated patients, that large growth in use did not affect the underlying high rate of appropriateness. The proportion of patients in the categories of highest cardiovascular risk (secondary prevention) did not change from 1997 to 1999. In essence, the group of patients on therapy grew by the addition of candidates with a similar need for therapy. If promotion had led to the addition of more marginal candidates, then the profile of cardiovascular risk would have changed to a less severe patient mix (that is, more patients seeking primary prevention and having few if any cardiovascular risk factors).

Admittedly, this study was limited by its examination of just one drug class. For this class, at least, growth in use, which corresponded to a time period of much pharmaceutical promotion, was associated not with inappropriate use or overuse, but rather with the identification of additional patients in need of lipid-lowering therapy—especially given the general awareness and scientific consensus of the importance of high blood cholesterol levels as a risk factor for cardiovascular disease. Perhaps the use of statins remained appropriate because of the unique circumstances of high-profile clinical practice guidelines and an increasing number of studies showing improved outcomes with statin use. This study represents just an initial set of data, not a definitive assessment. Studies of rates of appropriateness over time are needed for additional drug classes.

Framing The Debate

The current public discussion about the value and propriety of pharmaceutical promotion in general and DTC advertising in particular has looked at this activity as having a uniform impact. Thus, those who advocate for greater regulation would want that restriction uniformly applied to all classes of medications. This improperly frames the discussion, since pharmaceutical promotion is most likely variable in its impact, depending on the degree of consensus regarding the role of a specific medication in treatment. Those who look at established and accepted therapies could reasonably argue that promotion’s main intent is to raise awareness and that therefore it provides a societal “good” as currently regulated. By contrast, those who look at new therapies whose roles in treatment are still evolving argue that promotion may stimulate inappropriate use and therefore that promotional activities should be subject to stricter regulation.

This reformulation of the debate can be simply stated: The efficiency of any particular pharmaceutical promotional effort, from a societal perspective, depends upon the available scientific evidence and clinical consensus regarding the place of a new medication within a clinical area. If there is consensus (and good evidence) about proper use, then the impact will likely be to increase use among patients with high benefit-cost ratios. If consensus does not exist (good evidence is limited) about appropriate use, then the impact will be to increase use among not only patients who have high benefit-cost ratios, but also those with lower ratios. This means that some patients may receive added clinical benefit, but perhaps at a higher-than-desirable cost, which is less efficient from a societal perspective.

For areas where there is ample evidence that a particular therapy works (by published literature or consensus guidelines) and underuse exists, any means to educate, promote, or get the word out is probably beneficial. Does it matter whether the Centers for Medicare and Medicaid Services (CMS); the National Committee for Quality Assurance (NCQA); the National Heart, Lung, and Blood Institute (NHLBI); or manufacturers of inhaled corticosteroids, angiotensin-converting enzyme (ACE) inhibitors, or beta-blockers promote the merits of more complete treatment of asthma, congestive heart failure (CHF), or post–myocardial infarction (MI) prophylaxis? It is known that relatively few asthmatics receive an anti-inflammatory controller medication as recommended, that ACE inhibitors in CHF reduce mortality by 16 percent with $9,000 reduction in per patient hospital costs over three years, and that post-MI beta-blockers reduce mortality by 40 percent in two years.¹⁶ Should society care who promotes this evidence, when that promotion has the capability to greatly improve patient outcomes? The new National Cholesterol Education Program II guidelines broaden the indication for lipid treatment.¹⁷ If makers of statins, who have the resources to do so, promote this consensus, is wrong done?

Perhaps the concern about promotion relates to its use in the absence of consensus or strong evidence for proper use. Most would agree that proton pump inhibitors have a role in the management of acid disorders and that Cox-2 inhibitors greatly help some patients with arthritis and pain. However, less costly alternatives are available for the broader population of people with these conditions, and consensus is not clear regarding their use. Here, promotion might provide patients with added clinical benefit, but perhaps at a higher-than-desired cost.

Where clinical consensus exists, variability in pharmaceutical use is the lowest. For example, in the Express Scripts study, the lowest variability occurred in the use of penicillins, lipid-lowering medications, macrolides, and asthma medications (1.7- to 1.9-fold variation from the highest- to lowest-use states). Where there is more controversy regarding appropriate use, variability is highest. The highest variability was for calcium channel blockers and estrogens (3.1- to 4.1-fold variation). In the California study, variability was generally lower, ranging from 1.2- to 2-fold variation, but the data were also generally consistent with this hypothesis; less variation was observed with ACE inhibitors and antidepressants (1.5- to 1.6-fold variation) in comparison with that observed for digoxin or methotrexate (twofold variation).

The impact of promotion is neither uniformly efficient nor inefficient from a societal perspective. Those who view this area simplistically will have a tendency to “throw the baby out with the bathwater”—that is, to eliminate something of benefit while removing something that is perceived to be useless. There is no obvious regulatory change that would selectively limit “relatively inefficient” promotional efforts. Proposals for stricter regulation should consider their potential impact on the desirable outcomes that accrue from pharmaceutical promotion. Perhaps the framework introduced here can help enlighten further dialogues and assist in the design of future studies and policies.

This research was funded by internal sources (Zynx Health Inc., a subsidiary of the Cerner Corporation), as well as an unrestricted educational grant from Merck and Company Inc.

NOTES

1. National Institute for Health Care Management, “Prescription Drug Expenditures in 2001: Another Year of Escalating Costs,” 6 May 2002, www.nihcm.org/spending2001.pdf (6 January 2003).
2. M.B. Rosenthal et al., “Promotion of Prescription Drugs to Consumers,” New England Journal of Medicine 346, no. 7 (2002): 498–505.
3. S.M. Wolfe, “Direct-to-Consumer Advertising—Education or Emotion Promotion?” New England Journal of Medicine 346, no. 7 (2002): 524–526; and J.M. Drazen, “The Consumer and the Learned Intermediary in Health Care,” New England Journal of Medicine 346, no. 7 (2002): 523–524.
4. Wolfe, “Direct-to-Consumer Advertising.”
5. R.L. Kravitz, “Direct-to-Consumer Advertising of Prescription Drugs,”Western Journal of Medicine 173, no. 4 (2000): 221–222.
6. See, for example, R.A. Bell, R.L. Kravitz, and M.S. Wilkes, “Direct-to-Consumer Prescription Drug Advertising and the Public,” Journal of General Internal Medicine 14, no. 11 (1999): 651–657.
7. M.G. Ziegler, P. Lew, and B.D. Singer, “The Accuracy of Drug Information from Pharmaceutical Sales Representatives,” Journal of the American Medical Association 273, no. 5 (1995): 1296–1298.
8. R.W. Dubois, E. Batchlor, and S. Wade, “Geographic Variation in the Use of Medications: Is Uniformity Good News or Bad?” Health Affairs (Jan/Feb 2002): 240–250; and J.E. Wennberg and M.M. Cooper, The Dartmouth Atlas of Health Care in the United States (Chicago: American Hospital Publishing, 1998).
9. J.D. Birkmeyer et al., “Variation Profiles of Common Surgical Procedures,” Surgery 124, no. 5 (1998): 917–923.
10. L.L. Leape et al., “Does Inappropriate Use Explain Small-Area Variations in the Use of Health Care Services?” Journal of the American Medical Association 263, no. 5 (1990): 669–672.
11. Dubois et al., “Geographic Variation in the Use of Medications.”
12. B. Motheral, “Trend Management: How Important Are Demographics, Plan Design, and Region?”
www.express-scripts.com/other/news_views/outcomes2001/outcomes_conf_2001_summary.htm (22 October 2002).
13. D.W. Carlton and J.M. Perloff, “Advertising and Disclosure,” in Modern Industrial Organization, 3d ed. (Reading, Mass.: Addison Wesley Longman, 2000).
14. Rosenthal et al., “Promotion of Prescription Drugs to Consumers.”
15. Ibid.; and R.W. Dubois et al., “Growth in Use of Lipid Lowering Therapies: Are We Targeting the Right Patients?” American Journal of Managed Care 8, no. 10 (2002): 81–86.
16. S.S. Gottlieb, R.J. McCarter, and R.A. Vogel, “Effect of Beta-Blockade on Mortality among High-Risk and Low-Risk Patients after Myocardial Infarction,” New England Journal of Medicine 339, no. 8 (1998): 489–497.
17. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, “Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III),” Journal of the American Medical Association 285, no. 19 (2001): 2486–2497.

Bobby Dubois, a physician, is senior vice president of Zynx Health Inc., in Beverly Hills, California.

Related papers on this topic are available by clicking the author's name below:
Joel S. Weissman et al • Robert W. Dubois • Thomas Bodenheimer • Elaine Batchlor and Marianne Laouri •
Jerry Avorn • John E. Calfee • Martin T. Gahart et al.

©2003 Project HOPE–The People-to-People Health Foundation, Inc.