Chapter 23: Assessing Drug Promotions

After completing this chapter, the reader will be able to

• Define drug promotions.

• List World Health Organization (WHO) recommendations for appropriate drug promotions.

• Describe the role of the Food and Drug Administration (FDA) Office of Prescription Drug Promotion (OPDP).

• Determine whether a piece of direct-to-consumer advertising (DTCA) has been cited in FDA warning letters to companies.

• Describe the allowed content for a specific type of DTCA.

• Evaluate a given piece of DTCA based on FDA and Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines.

• Report a drug promotion concern using the Bad Ad program.

• Evaluate the appropriateness of a piece of drug promotion designed for a health care professional.

• List system and individual strategies that may be used to combat proliferation of misinformation in drug promotions.

• Identify logical fallacies used in drug promotion, when given an interaction with a pharmaceutical industry representative.

• Describe the goals and design of academic detailing programs.

• Describe the clinical, economic, and humanistic effects of academic detailing.

1. Drug promotion is defined by the World Health Organization (WHO) as material or information provided by drug manufacturers with the ultimate goal of increasing prescribing or purchasing of medications.

2. The FDA currently recognizes and outlines appropriate content for three types of direct-to-consumer advertising (DTCA): help-seeking ads, reminder ads, and product claim ads.

3. The following information should be considered when validating appropriateness of DTCA: balance of risk and benefit information and inclusion of a brief summary of the risks listed in the labeling, a statement encouraging patients to seek information from their physicians, and references to other sources to find the full prescribing information.

4. Drug promotion to health care professionals makes up the majority of drug promotions activity in terms of financial expenditure on the part of the pharmaceutical industry; this information can be effective in eliciting changes in prescribing behavior.

5. All health care professionals, including pharmacists, should arm themselves using strategies of information mastery and vigilance for flawed reasoning when interacting with pharmaceutical sales representatives.

6. Health care professionals are encouraged to report drug promotion violations to the FDA’s Bad Ad program.

7. Academic detailing programs, often led by pharmacists, are designed to combat pharmaceutical industry detailing by providing evidence-based information in the form of one-on-one or small group interactions between a clinician and prescribers.

❶ Drug promotion is defined by the World Health Organization (WHO) as material or information provided by drug manufacturers with the ultimate goal of increasing prescribing or purchasing of medications. Every year, the pharmaceutical industry spends billions of dollars advertising their medications to the public and to health care professionals.^1-11 In 2012, about $27 billion was spent on drug promotion in the United States (U.S.) alone.¹² The channels companies use to promote their products include medical journals, newspapers, radio, television, magazines, Web sites, social media, search engine marketing, distributed promotional materials, billboards, direct mailings, medication samples, and sales representatives.^2,7,10,13-15

Health care professionals and consumers may not recognize the impact drug promotion can have on individual behavior.⁷ The literature has reported increased prescribing patterns, rapid implementation of new medications, and an increase in inappropriate prescribing among physicians who utilize promotional materials to obtain drug information.⁷ The effect of medication promotion on overall public health remains uncertain. WHO suggests clinical trials be conducted to assess the correlation of drug promotion with inappropriate prescribing and the occurrence of adverse events, to identify the public health outcomes of drug promotion.⁷ For these reasons, health care professionals must be prepared to critically interpret and evaluate verbal and written drug promotions. In particular, pharmacists play an important role as an interpreter of drug advertisements to their patients. The following section describes the full scope of drug promotion according to WHO.

In 1988, the WHO published criteria for the ethical promotion of medications.¹⁶ The guidelines state the promotion of drugs should comply with the national standards established by the country where the drugs are being promoted. These guidelines apply to both domestic and exported drug products. Overall, information presented for the purposes of promotion should be balanced, accurate, and current.

Advertisements targeted specifically to health care professionals should follow the approved product labeling and all writing should be clear and readable.¹⁶ A scientific summary is required when product claims are made within an advertisement directed at health care professionals. These advertisements should include generic name, brand name, amount of active ingredient per dosage form, other ingredients that can lead to allergies or adverse effects, indications, dosage form, adverse reactions, warnings and precautions, contraindications, drug interactions, additional notable interactions, manufacturer/distributor name and address, and scientific literature references. Detailed information about the scientific properties of a medication should be made available to health care professionals as appropriate.

The WHO criteria also provide information about direct-to-consumer advertising (DTCA).¹⁶ According to the WHO, DTCA should assist consumers in making decisions about nonprescription medications; however, the use of DTCA for prescription medications is not recommended. Scientific evidence must support all factual information provided. DTCA should not use fearful language or tactics and only information available in the approved labeling should be used, including the following: generic name, brand name, indications, major warnings and precautions, contraindications, and manufacturer/distributor name and address.

The WHO also outlines guidelines for pharmaceutical representatives.¹⁶ These personnel should be properly trained and retain adequate technical and medical knowledge. The information presented should only discuss the material from the approved labeling. The pharmaceutical industry is responsible for the statements made by their sales representatives and the salary of those representatives should not be influenced by the number of prescriptions written for the product they are promoting. The WHO recognizes that free samples of prescription medications can be given to prescribers in small quantities on request.

The WHO guidelines outline the proper features of drug promotion that are required to produce beneficial and accurate materials. These criteria provide the basis of drug promotion regulations and evaluative strategies, which will be discussed in more detail later in this chapter.

The U.S. FDA defines DTCA as any advertisement created by a pharmaceutical company to promote products to a general audience.¹⁵ The goal of such advertising is to encourage patients to discuss a medication with their prescribers, ultimately leading to a prescription.⁹

There are many methods pharmaceutical companies use to present DTCA to patients. The two most well known are print, through magazines or newspapers, and broadcast through television. The Pharmaceutical Research and Manufacturers of America (PhRMA) defines direct-to-consumer print advertisements as “space that is bought by a company in newspaper or magazine publications targeted to patients or consumers, or a direct mail communication paid for and disseminated by a company to patients or consumers, for the purpose of presenting information about one or more of the company’s medicines.”¹⁷ The PhRMA also defines direct-to-consumer television advertisements as, “portion of television air time on broadcast or cable television that is bought by a company for the purpose of presenting information about one or more of the company’s medicines.”¹⁷

DTCA has been known to increase prescription drug profit for the pharmaceutical industry.¹⁸ Specifically, for each dollar spent on DTCA the company makes about $4.20 in sales.^9,18 One study, assessing data from 1992 to 1997, found that 32 extra diagnoses and 41 additional prescriptions for statin medications were prescribed for every $1000 spent on DTCA.⁶ In 2002, the U.S. General Accounting Office (GAO) projected that each year eight million Americans requested and received prescriptions due to DTCA.⁶ A 2009 study found that there were an additional one million physician visits and 397,025 added Irritable Bowel Syndrome (IBS) diagnoses after the promotion of tegaserod (Zelnorm^®).¹⁸ In addition, 1796 prescriptions were written for every $1 million spent on tegaserod DTCA (1041-2529, 95% confidence interval).^6,18

Based on these reports, it is not surprising that between 1996 and 2005 spending on DTCA increased from $985 million to about $4 billion.^2-4 DTCA spending peaked at $5.4 billion in 2006, and spending decreased to $4.8 and $4.3 billion in 2007 and 2010, respectively.^2,8,10,11 These recent spending decreases could be due to loss of patent on highly advertised medications, fewer products being brought to the market, an increase in consumer doubt, and budget cuts due to the recent recession.² Some of the most highly marketed products in the United States in 2009 included atorvastatin (Lipitor^®) at $247.1 million and tadalafil (Cialis^®) at $179.2 million.² From January 2007 to March 2011, the highest DTCA marketed products were atorvastatin (Lipitor^®) at $917.70 million, duloxetine (Cymbalta^®) at $820.50 million, and fluticasone/salmeterol (Advair^®) at $766.3 million.⁶

Today, most of the DTCA spending is allotted for television advertisements, which results in the average American watching about 16 hours of televised drug advertisements per year.^6,10 Interestingly, smoking cessation products, impotence medications, and antidepressant television ads have the highest changing channel rates among viewing audiences.² The ads that retain most of the television audience through the commercial include overactive bladder treatments and osteoporosis medications.²

TYPES OF DTCA

❷ The FDA currently recognizes and outlines appropriate content for three types of DTCA: help-seeking advertisements, reminder advertisements, and product claim advertisements. The following describes each of these types of advertisements, including evaluative criteria, in detail.¹⁵

Help-seeking advertisements do not recommend a particular medication but provide information about a disease state or condition.^{6,10,15,18,19} The advertisement can describe particular symptoms, point patients to discuss their symptoms with their physicians, and offer a phone number for more information about the disease state.^19,20 These advertisements are regulated by the Federal Trade Commission (FTC) since a specific drug product is not mentioned.^19,20

Reminder advertisements do not describe the indication of a medication but do present the brand name.^{6,10,15,18,21} These particular advertisements are created with the assumption that patients are already familiar with the drug’s indication.¹⁹ Risk information is not included in these advertisements and, therefore, reminder advertisements of drugs with boxed warnings are illegal.^6,10,19,22 Any information or even implied information (through images or text) about a product’s benefits or risks is not permitted in reminder advertisements.¹⁹ For example, a medication for osteoporosis would not have an image of bones in the reminder advertisement as this implies the product’s indication.¹⁹

Product claim advertisements require more detail and should contain the drug name, the indication, as well as a balance between the risks and benefits associated with the product.^{6,10,15,18,19,21,} Specifically, printed product claim advertisements should include a brief summary that provides details about all of the risk information listed in the FDA-approved labeling.^10,19 Printed advertisements must also include a reference to the FDA MedWatch program for patients to report side effects to the medication.¹⁹ Product claim advertisements that are broadcasted either by television, radio, or phone are not required to include the brief summary of risk information.^2,15,19 Instead, television advertisements are required to contain a major statement of the main risks associated with the product, which can be presented verbally.^{8,10,19,21,23} In addition, when broadcast advertisements do not include all risk information listed in the labeling, the advertisement is expected to provide resources patients can consult to obtain the full prescribing information.¹⁹ For example, the advertisement can refer a patient to consult with their health care professional, call a toll-free number, visit the product Web site, or refer to a printed advertisement that contains more detailed information.^15,19,23 This is known as the adequate provision requirement.^3,10,19 Information DTCAs are not required to include is listed in Table 23–1.²⁴

Tone and themes of DTCA can vary.^21,23 Many advertisements only portray characters after successfully taking the product; similarly, advertisements tend to portray the product as a facilitator of healthy or recreational activities.²¹ Most advertisements rely on emotional, rather than logical appeals; these emotional appeals could be positive, negative, or both. One study used content analysis to describe major themes present in advertisements, finding that promotion, prevention, individualism, collectivism, cheerfulness, quiescence, dejection, agitation, fear, and affection were all prevalent.²³

DTCA LEGISLATION

Currently, among developed countries, DTCA is only permitted in the United States and New Zealand.^{6,10,15,18,21} New Zealand relies on self-regulation of DTCA by the pharmaceutical companies; however, in the United States the FDA is responsible for overseeing DTCA.⁶

The FDA’s authority over prescription drug advertising targeted to health care professionals was established in 1962 by the Kefauver-Harris Amendment.^3,10,25 Shortly after, in 1969, the FDA released regulations requiring drug advertisements to be accurate and not misleading; contain a brief summary of indications, adverse effects, warnings, and contraindications; be fair balanced; and include only factual information about the product’s advertised uses.^{7,10,23,26,27} Television advertisements were also required to contain the brief summary, which made these ads too lengthy for broadcast.²

The FDA first allowed companies to promote their products directly to consumers in 1985.^3,10,11 In 1997, the FDA released a draft guidance that stated television advertisements no longer required the brief summary; however, the guidance did require a major statement of the main safety risks and referral to a source for detailed information about the product.^{1,2,8,10,15,23} This guidance was finalized in 1999.^3,10 In addition, printed product claim advertisements were required to include the entire prescribing information prior to the release of 2004 regulations stating that only a simplified brief summary is required.¹⁰ However, patient mailings, brochures, and other drug company materials that promote a drug product still require the full FDA-approved prescribing information if any such materials mention the benefits of the medication.¹⁹ In 2007, the Food and Drug Administration Amendments Act (FDAAA) required the MedWatch reporting statement to be added to all printed advertisements, which states: “You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch, or call 1-800-FDA-1088.”^19,28 Today, prescription drug advertising regulations can be found in title 21, volume 4, part 202 of the Code of Federal Regulations (CFR).²⁷

To ensure that DTCAs are following FDA guidelines and to protect consumers from false information, the FDA maintains a surveillance and enforcement program through their Office of Prescription Drug Promotion (OPDP) division.¹⁵ It is important to remember that the FDA has the authority only over prescription medication DTCA.²⁴ Nonprescription DTCA and help-seeking ads are regulated by the FTC.^19,20,24 In addition, the FDA does not require pharmaceutical companies to submit DTCA prior to its distribution or being aired.²⁴ However, the FDA does require advertisements be submitted for review as soon as they are released to the public.^6,9,24

If the FDA discovers that a DTCA is not in compliance with the set of laws in place, warning letters can be issued to the pharmaceutical company, requesting the removal of the advertisement and to address the material that violates the law.^9,24 These letters are publically available on the FDA’s Warning Letters Web site.^24,29 If the advertisement has created a severe threat on public health, the FDA can also request the company to correct the advertisement and publish or broadcast the corrected version.²⁴ In rare cases, the FDA may bring criminal charges against the company in court and seize the company’s drug supply.²⁴ The FDA does not have authority to levy fines on pharmaceutical companies for DTCA violations.⁹

Recently there has been a decrease in the number of DTCA regulatory actions by the FDA.¹⁰ Critics say this could be the result of decreased FDA supervision or, in contrast, could be due to better compliance with DTCA laws.¹⁰ Another added factor is that all warning letters must be reviewed and approved by the FDA’s Office of Chief Counsel, which was mandated by the Secretary of Health and Human Services (HHS) in 2002.¹⁰ This action alone may have resulted in a decline in the number of promotional-related warning letters issued between 2001 and 2002, 68 and 28, respectively.¹⁰ In addition, the FDA has limited staff to review DTCA.¹⁰ Fewer than six FDA employees were assigned to review more than 15,000 brochures and DTCA in 2006.¹⁰ Since then, the OPDP staff has increased to accommodate the growing number of advertisements to review.

There is still a need for FDA guidelines in regard to online promotion of prescription medications.¹⁰ After warning letters issued from the FDA in 2009 stating that online search engine results need to include risk information since the drug name and indication is mentioned, the pharmaceutical companies now only include either the name of the drug or the indication in search engine links.¹⁰

Since studies have reported a lack of consumer awareness of the FDA role in DTCA oversight, it is vital for health care professionals to monitor and evaluate DTCA.^6,10

PhRMA GUIDING PRINCIPLES FOR DTCA

With the increasing role of DTCA in health care, the PhRMA established guiding principles for DTCA of prescription medications.¹⁷ These principles are voluntary, but do serve as guidance for pharmaceutical companies to create accurate, educational, and encouraging DTCAs that follow FDA regulations.¹⁷ See Table 23–2 for an overview of the PhRMA principles. A commitment to follow the PhRMA guiding principles and completion of an annual certification entitles the company to be identifiable as a signatory company and be recognized by PhRMA online.¹⁷

SUPPORT OF DTCA

Supporters of DTCA believe these advertisements serve a public health need.^6,15,17 Through DTCA patients become educated about different disease states, which can assist them in making better treatment decisions and create more knowledgeable patients in the health care environment.^{1,6,10,11,17,26} A related point is that DTCA can help improve the quality of patient–professional interactions and help patients identify meaningful questions to ask of their health care providers, as well as improve adherence to prescribed treatment.^6,10,15,17 DTCA provides patients with information about treatment options available early on, which can result in lower health care costs.¹⁰ Similarly, DTCA may also increase appropriate care for underdiagnosed diseases.^1,6,10,15,17 It has been asserted that if medication therapy is started sooner because of DTCA in a disease that could eventually lead to surgery if not treated, health care costs can be saved.¹⁰ However, there is limited data to support this claim.¹⁰ Supporters mention that DTCA can lower drug prices due to increased competition between products.¹⁰ DTCA also has been credited with reducing the stigma of certain diseases making them acceptable for discussion (e.g., psychiatric disorders).^6,10,11,15

OPPOSITION TO DTCA

In contrast, many who oppose DTCA express its potential threat to public health.¹⁵ DTCAs could contain inaccurate or misleading information in addition to inadequate information about adverse effects and risks.^1,15 Sixty-five percent of physicians reported that patients tend to underestimate the risks and overemphasize the benefits of a drug, mostly after viewing a television advertisement.⁹ Astudy analyzing television drug advertisements found that patients remembered the benefits of a drug more easily than the risks.⁹ This may be due to the dominance of visual messages over audio when presented jointly and the fact that much of the safety information is presented verbally in television advertisements.¹⁰ Patients may also overemphasize a product’s benefits because DTCA is known to exaggerate the happiness achieved with a medication.¹⁰

Opponents of DTCA state that FDA regulations are too lenient because the pharmaceutical companies are only held responsible for the information presented in DTCA if there is a violation.¹⁰ As a result, some advertisements presented have inappropriate information included. For example, in 1996 only 65% of newspaper and magazine DTCA were reported to be fair balanced.⁷ Unfortunately, consumers will remember the information presented in an ad even if there are violations.¹⁰ The PhRMA has released DTCA guidelines that suggest companies should submit DTCA to the FDA for review prior to distribution; however, these guidelines are optional and unenforceable.¹⁰

The content of DTCA is usually not written in lay person language (i.e., an eighth-grade reading level), making it challenging for consumers to understand the content.¹⁰ Along these lines the use of words such as usually, mild, may, etc., to describe safety information may lead to consumer confusion about the exact meaning of these terms.¹⁰

There have also been multiple reports of statistical overexaggeration of product benefits in advertisements.³⁰ Particularly, in DCTA, this paper points out that only two of 67 advertisements in U.S. magazines presented results of the promoted drug verses placebo as absolute rates of clinical outcomes. Other advertisements only presented data in the form of relative risk reduction (RRR); absolute risk reduction (ARR) was not included (see Chapters 5 and 8 for further information about RRR and ARR). Some provided references to clinical studies, but did not provide any data from the studies in the advertisements. One additional advertisement claimed that the promoted drug provided a clinical cure compared to competitors, but did not explain exactly what was defined as a clinical cure. In a study assessing 16 advertisements, only one ad provided adverse effect frequency using quantitative methods, two presented using comparative relationships, and the majority used a qualitative approach.³⁰ Prevalence of the disease state the product is treating is also rarely reported in advertisements. In a study from 2004, only three of 31 advertisements provided disease state prevalence information.³⁰

Due to DTCA, there has been an increase in patients requesting advertised medications during their provider visits.⁷ This can lead to the undermining of health care professional authority and hinder the provider–patient relationships.^3,6,10,11 This has been reported in the literature by 30% of patients and 39% of physicians who participated in a national survey.¹⁰ In particular, if a physician refuses to prescribe a medication that the patient is requesting, the patient is more likely to switch physicians.¹⁰ This pressure on prescribers from consumers can increase the risk of inappropriate prescribing.^{3,4,6,10,11,15} An FDA study reported about 50% of physicians felt some pressure to prescribe a particular medication after a patient reported seeing a DTCA for the product.^9,26 One study found that during physician visits, 40% of patients requested a medication they saw on a DTCA and about 50% of the requests were granted by the doctor.¹⁰ However, a study conducted in 2006 reported that of the patients who requested a medication due to a DTCA, only about 2% to 7% received a prescription for the product in the end.¹⁰ It has been reported that patients may try to fit the type of patient who is presented in the DTCA, which can also lead to inappropriate prescribing and diagnosis, and ultimately unnecessary side effects.^6,10 A study found that about half of physicians, participating in a focus group discussion, presumed that patients diagnosed themselves accurately based on DTCA.⁶ Also, this increase in unnecessary prescribing can lead to an increase in prescription drug spending.⁸

The added time for providers and patients to discuss DTCA during scheduled appointments could take away from other important aspects of the appointment and lead to negative patient outcomes.¹¹ DTCA can lead to unnecessary physician visits and make patients believe they have a particular disease.^1,8,10 For example, critics blame DTCA for converting menopause from a normal life process into an insufficient hormone disease.¹⁰

In addition, use of DTCA to advertise me-too drugs can increase health care costs since many patients will request the brand name drug when there may be inexpensive generic options available.^4,10,15 A study found that patients were more likely to switch from lansoprazole to omeprazole in areas that were more exposed to DTCA since omeprazole was advertised via DTCA and lansoprazole was not.⁶ The expense of DTCA may also drive up the consumer costs for the product as pharmaceutical companies increase prices to compensate for advertising costs.⁵ For example, one study found that the cost of clopidogrel increased by $0.40 (12%) per unit after the launch of the DTCA campaign.^5,6 In a study assessing television DTCA, the high-cost medications had longer air time for the ads (60 seconds) compared to medium cost medications (47.9 seconds).¹

Critics mention that the safety information required in the DTCA could cause patients to have concerns about the safety of a medication and may lead to issues with patient compliance.¹⁰ However, most of the time DTCA is released to the public before the majority of the safety information is collected (i.e., postmarketing surveillance).¹⁰ For example, rofecoxib (Vioxx^®), which was one of the most promoted medications in the United States. ($100 million/year spent on promotion), was not discovered to cause myocardial infarction (80,000 to 140,000 cases) or stroke until after the DTCA campaign.^6,10 This additional safety information led to its voluntary recall in 2004.^6,10 Another example of a highly marketed product whose side effects were not fully discovered until after DTCA was tegaserod (Zelnorm^®), which was later withdrawn from the market due to increased risk of cardiovascular-related adverse effects.^18,31

For the many reasons described above, information included in DTCA (in addition to advertisements intended for health care professionals) should be closely scrutinized for errors, promotional violations, and other misleading information.

SUGGESTIONS FOR IMPROVEMENT

Suggestions for the improvement of DTCA have been reported in the literature. One suggestion would eliminate the need for DTCA altogether. A group of representatives from industry, government, and academia would be tasked to create public service announcements discussing appropriate treatment for conditions that are known to cause morbidity or mortality, have effective and safe treatments available, and are identified as being undertreated and underdiagnosed.^8,10 This solution has not been implemented at this time. The U.S. Institute of Medicine (IOM) proposed enforcing a 2-year delay from the time a product is released to launching DTCA.^6,10 This can ensure that adequate time has passed for postmarketing data to be collected and allow physicians to become educated about the product.¹⁰ However, in 2011 the U.S. Congressional Budget Office stated that the benefits of providing information about new medications outweighed the risks and, therefore, the proposal was not supported.⁶ To have the FDA review all DTCA before being released to the public is another recommendation.¹⁰ However, this would only be achievable assuming additional user fees were paid to the FDA by the pharmaceutical industry. There was a proposal for such a program in 2008, but it was not funded by Congress and, therefore, could not be enforced by the FDA.

There have also been debates about the most appropriate DTCA format.³² A study assessing consumer preferences found that more patients preferred the drug facts box format, which is similar to the nonprescription labeling.³² In addition, more patients were able to recall risk information when presented in this matter. Other suggestions include listing adverse effects on drug advertisements in bullet form from the highest to the lowest possibility of occurring.¹¹ However, even with these findings, this format for DTCA has not been mandated.

Requiring quantitative data in the DTCAs, as well as mentioning if a generic alternative is available for the product, have also been described as possible solutions.¹⁰ The latter suggestion may not be well accepted by the pharmaceutical industry, but has been suggested in the literature. Another study suggested requirements to include specific information about the population at risk for the condition being advertised, describing nonpharmacologic treatment, and discuss the effectiveness of other therapies in the ads.²¹

With the solutions, suggestions, and continued evolvement, the hope for future DTCAs will be a greater emphasis on using medications appropriately, sustained use of medications, and medication adherence.²

EVALUATING DTCA

❸ The balance of risk and benefit information, inclusion of a brief summary of the risks listed in the labeling, a statement encouraging patients to seek information from their physicians, and references to other sources to find the full prescribing information should be included and considered essential content when validating DTCA.

In general, DTCA must present only accurate statements, maintain a balance of risk versus benefit information throughout, align with the information presented in the FDA-approved labeling, and only present content that is supported by robust evidence.^17,33 When evaluating DTCA, consider using the process outlined in Table 23–3.³⁴

The FDA also provides information for patients and health care professionals on how to determine if an advertisement is false or misleading based on the type.³⁵ FDA guidance for evaluating specific types of advertisements is provided in Table 23–4. The FDA encourages patients to report promotional violations to OPDP by calling 301-796-1200 or mailing a written complaint directly to the division.^24,36 Health care professionals are encouraged to report promotional violations using the Bad Ad program, described below.

❹ Drug promotion to health care professionals makes up the majority of drug promotions activity in terms of financial expenditure on the part of pharmaceutical industry; this information can be effective in eliciting changes in prescribing behavior. The following sections describe the scope and response to this issue.

Marketing of prescription medications differs from typical consumer products in that one individual—the prescriber—directly controls, to a large extent, purchasing decisions on behalf of the ultimate consumer.³⁷ For this reason, in addition to the very high expenditures of the pharmaceutical industry on DTCA, even greater financial resources are dedicated to promotions made directly to health care professionals, or detailing. Of the estimated $57.5 billion spent in pharmaceutical promotions in 2004, approximately 35.5% was spent on detailing along with approximately 27.7% and 3.5% spent on drug samples and professional meetings, respectively.³⁸ In contrast, only 7% was spent on DTCA. Detailing, like any type of marketing, combines use of scientific knowledge, logic, and reason with appeals to emotions through techniques such as slogans and use of wishful thinking.³⁷ Detailing may be defined as a one-on-one or group interaction in which a pharmaceutical industry representative, who might or might not have a clinical background, provides drug information and marketing materials to a prescriber or health care professional.^37,39 These activities could involve provision of product samples and continuing education. At its core, detailing is designed to produce a change in prescribing behavior. The extraordinary expenditures on detailing and related activities, as well as cases of illegal and unsupported drug promotion to health care professionals suggest that critically assessing the information delivered in these interactions is of vital importance.

LEGAL ISSUES

The same criteria described earlier for DTCA also apply to formal advertisements intended for health care professionals and information promotions such as detailing.⁴⁰ Briefly, the information provided must provide fair balance in addressing safety risks and efficacy benefits, describe factual information, and not be misleading. Additionally, information must be consistent with the FDA-approved product labeling (i.e., the package insert), including indications for which the medication may be used.⁴¹ Off-label information may be provided in scientific exchanges and at the request of a health care professional, but not in the context of promotion. The legality of off-label promotion is an often debated First Amendment issue.^41,42

FDA advertising rules also apply to industry-sponsored education programs that are, in actuality, promotional activities.⁴⁰ For a program to be considered independent and nonpromotional (and, thus, qualify as continuing education), the program must be conducted by a third party that controls the educational content. Additionally, all relevant relationships must be disclosed. PhRMA companies adhere to voluntary standards that prohibit direct speaker honorariums, entertainment (e.g., sporting event tickets), gifts, and noneducational practice-related items (e.g., coffee mugs, pens) at continuing education events and during detailing.⁴³ All programs must be conducted through an independent continuing education provider.

PROMOTION EFFECTIVENESS

The majority of scientific literature assessing health care professionals’ interactions with pharmaceutical industry centers around medical students, physicians, and nurse practitioners, and finds success on the part of industry in achieving their desired changes in attitudes and behaviors.^44-51 Little information is available regarding promotions targeted toward pharmacists. Two studies have attempted to quantify exposure to pharmaceutical promotion during medical training, with high proportions of medical students and residents reporting attending sponsored events and receiving gifts.^44,45 Studies vary in the degree to which medical residents and students value industry-sponsored information; however, survey responders perceive that they do not feel prepared to manage these types of interactions, but that drug promotions would not influence their prescribing habits. One survey of nurse practitioners found that this group does not prefer to receive drug information from pharmaceutical industry sources, but also found that approximately 36% have been offered paybacks in return for changes to prescribing habits.⁴⁶ Limited research describes which prescribers are more likely to meet with pharmaceutical industry representatives. One cross-sectional study found that factors of nonacademic affiliation, higher prescription volume, urban practice, small practice size, and specialization in primary care were positive correlations with this risk.⁴⁷

Several studies have assessed effects of detailing and related activities on prescribing patterns. Two studies found increased prescribing and loyalty to brand name prescription medications when physicians were exposed to detailing.^18,48 Similar results have been found in a study assessing effectiveness of industry-sponsored continuing education for physicians,⁴⁹ although it should be noted that it was conducted prior to publication of current industry guidelines.⁴³ One systematic review noted that 17 of 29 assessed articles found increased prescribing of a target medication as a result of one-on-one detailing; the remaining studies found no difference in practice.⁵⁰ Similarly, five out of eight articles assessing effectiveness of sponsored education events found the expected changes in practice (i.e., increased prescribing of the target medication). In the inpatient setting, one study found that physicians who request a medication to be added to formulary are more likely to have accepted payment from industry to attend or lead symposia or to have personally met with industry representatives from the company producing the medication.⁵¹

COMBATING MISINFORMATION

❺ All health care professionals, including pharmacists, should arm themselves using strategies of information mastery and vigilance for flawed reasoning when interacting with pharmaceutical sales representatives. Systematic and individual strategies for combating potential misinformation provided by the pharmaceutical industry are discussed in the following sections.

Both approaches are needed to ensure that undesired effects of drug promotions to health care professionals are minimized. This need is illustrated by several cases in which the pharmaceutical industry was fined for inappropriate promotion to health care professionals, including cases brought against the manufacturers of olanzapine (Zyprexa^®), gabapentin (Neurontin^®), and valdecoxib (Bextra^®) for off-label promotion and/or lack of fair balance.⁵²

A number of systematic strategies are active or have been proposed to decrease the potentially significant effect of promotions on prescribers and pharmacists at local, institutional, and national levels. Several of these strategies are described below:

• Academic detailing: Research has demonstrated the value of structured one-on-one visits between traveling clinicians, or academic detailers, and prescribers in terms of evidence-based prescribing habits and increased use of generic medications.³⁹ Applications of academic detailing are described later in the chapter.

• Conflict of interest policies: Conflict of interest policies have been used in residency programs, colleges of medicine, and health systems in order to decrease the effect of pharmaceutical promotions.^53,54 Many health systems have very specific policies regarding the allowed interactions with industry representatives. The policy may even be that such meetings are prohibited.

• Education: Several studies have assessed effectiveness of educational sessions focusing on pharmaceutical industry interactions with medical students and residents.^55-57 Study participants have generally expressed improved knowledge of the pharmaceutical industry and a greater ability to critically assess promotions, and identified potential behaviors they will change as a result of the program (e.g., stop seeing industry representatives).

• National initiatives: In the United States, OPDP is responsible for review of submitted promotional materials, monitoring at professional meetings for inappropriate promotion, and review of Internet sites related to prescription medications.⁵⁸

• Representative tracking: Health systems often use industry credentialing programs to enforce institutional policies regarding content, frequency, and length of meetings between clinicians and industry representatives.⁵⁹ These programs allow health systems administrators to know when representatives are on campus and with whom they are meeting.

Additionally, several professional organizations provide guidelines regarding information provided by the pharmaceutical industry. The American Society of Health-Systems Pharmacists (ASHP) guides members that a third party should control educational content of all industry-sponsored continuing education.⁶⁰ Similarly, the American Medical Association (AMA) recommends physicians select continuing education that is accredited and fair balanced. Promotional continuing education should be clearly denoted as such.⁶¹ Both organizations counsel members to limit interactions with the pharmaceutical industry to professional, scientific exchange of information and to avoid situations in which professional judgment is at risk and impropriety may be perceived.^60,61

Even in the presence of systematic approaches to preventing misinformation in drug promotions, the need for pharmacists, and other health care professionals, to critically evaluate specific information provided in drug promotions is clear. Considering the volume of medical information emerging every day, the task of analyzing, retaining, and synthesizing this information can be monumental.⁶² For this reason, health care professionals must develop skills and confidence in searching the medical literature and practicing evidence-based medicine (i.e., information mastery) using both patient-specific and general approaches (i.e., top down versus bottom up; see Chapter 7). It is recommended that health care professionals preferentially use tertiary drug information resources that are either FDA approved (i.e., the prescribing information) or prepared and published by unbiased sources (e.g., AHFS^® Drug Information, Micromedex 2.0). If health care professionals do meet with pharmaceutical industry representatives or use other promotional materials, they should be prepared to rigorously assess pharmaceutical promotions in the same way they would any tertiary resource (see Chapter 3). Additionally, health care professionals should evaluate any print pharmaceutical promotions distributed by industry representatives using strategies similar to DTCA, outlined in Tables 23–1 to 23–3.

Many pharmaceutical industry representatives use flawed logic in order to persuade prescribers and pharmacists that their product is the ideal choice for their patients.³⁷ Errors in reasoning can introduce self-doubt on the part of the health care professional and increase likelihood of a behavior change. It is important to identify when arguments are logical and when they are irrational. In particular, pharmacists who manage pharmacy and therapeutics committee initiatives should be vigilant in their awareness of flawed logic and misleading messages. One of the best methods for combating logical fallacies is reviewing relevant information prior to interacting with an industry representative. See Table 23–5 for examples of misleading strategies that industry representatives might use. See Table 23–6 for general recommendations for interacting with pharmaceutical industry representatives.

ADVERTISING TO HEALTH CARE PROFESSIONALS

❻ Health care professionals are encouraged to report advertising violations to the FDA’s Bad Ad program. All health care professionals have a responsibility to report inappropriate drug promotions using the process described below.

Health care professionals, particularly prescribers, are also targets of drug promotion in the form of print advertisements in medical journals.^63,64 One study found that approximately 16% of the pages in one oncology journal were devoted to drug promotion.⁶³ Advertisements appearing in medical journals are subject to the same standards as other print advertisements discussed earlier in the chapter, as well as ideally be in compliance with a journal’s advertising policy. Advertising policies should be robust and available to the reader. Advertisements in these journals should be assessed using the same methods described for DTCA.

The FDA’s Bad Ad program encourages prescribers to report misinforming or incorrect prescription drug advertising and promotion to FDA.^33,36 This assists OPDP in identifying and ceasing such advertisements.³³ Advertisements for products such as dietary supplements, medical devices, and nonprescription drugs should not be reported through the Bad Ad program since OPDP does not regulate the promotion of these products. In the past, OPDP obtained information about prescription drug promotion violations through complaints and comments about medication promotion, medical conference observations, review of company submitted promotional materials, and Internet searches.³⁶ Due to the absence of FDA employees at dinner programs, promotional speaker events, and prescribers’ offices, the FDA seeks the help of health care professionals to report promotional violations through this program.³⁶

If an ad is found to be in violation, the FDA can take enforcement action and/or continue to monitor additional advertisement activities.³³ Advertising methods that are assessed and can be reported through the Bad Ad program include information presented in printed or written drug promotional materials or by sales representatives, presentations by program speakers, as well as advertisements on radio or television.^33,36

Common violations identified in drug advertisements include inadequate risk information, overexaggeration of benefits, off-label or unapproved information, and false or deceiving comparisons with other medications.^33,36 For example, ads could say that the medication works in as little as 2 days, but in reality most patients might not see an effect for months.³⁶ Another example in reference to pharmaceutical representatives is statements that the adverse effects that occurred in clinical trials are not as likely to occur in practice.

Comments to the FDA through the Bad Ad program can be submitted anonymously; once received, they are analyzed by a member of the OPDP team.³³ FDA accepts comments from health care professionals via email: BadAd@FDA.gov, or by phone: 855-RX-BADAD (855-792-2323).

ACADEMIC DETAILING

❼ Academic detailing programs, often led by pharmacists, are designed to combat pharmaceutical industry detailing by providing evidence-based information in the form of one-on-one or small group interactions between a clinician and prescribers. The following sections address the design, effectiveness, and roles for pharmacists in academic detailing.

Academic detailing, also known as counterdetailing, prescriber outreach, and prescriber support and education is a proactive approach developed to combat proliferation of potentially biased information provided by pharmaceutical industry sales representatives in prescriber workplaces.^39,65,66 The goal of academic detailing is to provide objective, scientific evidence to prescribers in order to improve patient outcomes. While originally focused on increasing use of generic medications when the practice emerged in the 1980s, today’s academic detailing programs have expanded clinical roles including promotion of evidence-based medicine and dissemination of comparative effectiveness research. Although most commonly associated with outpatient settings, academic detailing programs have also been reported in inpatient and long-term care practices.^67,68 Pharmaceutical and academic detailing are similar in that both are designed to change prescribing behavior.^39,65,66,69

Program Design

The core process of an academic detailing program is outlined in Table 23–7.^66,67 At its heart is a one-on-one, face-to-face interaction between a traveling health care professional (e.g., physician, pharmacist, nurse) and a prescriber.^39,65,66,69 The academic detailer may also have a concurrent academic or clinical appointment.^65,66 While the original format for these interactions was inspired by the success of pharmaceutical detailing, a key difference is that academic detailing is intended to focus purely on evidence-based information without a promotional perspective.^39,65,66,69 Individuals providing academic detailing should have knowledge of clinical and information sciences as well as experience in providing direct patient care.⁶⁵ Interactions between the detailer and the prescriber should be nonjudgmental, empathetic, and professional.

The most accepted goal of academic detailing is promotion of rational prescribing.^39,65,66 One somewhat controversial aspect of academic detailing is whether improving cost savings–related outcomes should also be a core function of these initiatives.⁶⁵ Programs are occasionally accused of allowing pursuit of cost savings to supersede promotion of evidence-based medicine. While simply encouraging use of generic medications in place of branded product is a generally accepted aim, therapeutic substitution of a different medication in the same class is a more divisive issue. Differences in philosophy may vary depending on the organization sponsoring the program; for-profit and government organizations may be more likely than academic groups to acknowledge a cost savings goal.^39,65,66,69

For-profit, nonprofit, government, and academic organizations are all known to sponsor academic detailing programs.^39,65-71 Many of the most successful programs are collaborations among multiple groups. Large-scale academic detailing has been conducted by several Canadian provinces and at a national level in Australia; several states in the United States are considering or have developed programs modeled after the success of programs in these countries (where large scale academic detailing has a much longer history).^65,66 One of the most well-known academic detailing programs in the United States is the Independent Drug Information Service (iDiS), a division of the Pennsylvania Department of Aging’s Pharmaceutical Contract for the Elderly (PACE) program.⁷⁰ This program spends approximately $600 million annually to provide medication to over 300,000 elderly patients who are ineligible for Medicaid.^65,70 PACE reports that cost savings generated from improving prescribing of common chronic medications (e.g., antihypertensives, anti-inflammatories) more than cover the costs of this program.^65,66 The content for iDiS visits is developed by an independent group of physicians, the National Resource Center for Academic Detailing (NaRCAD), located at Harvard Medical School and Brigham and Women’s Hospital, and then provided by 10 academic detailers in approximately 1000 physician visits annually.

Another example of an American academic detailing collaboration is the South Carolina Medicaid Academic Detailing Program (SCORxE), a collaboration of the South Carolina Department of Health and Human Services and the South Carolina College of Pharmacy.^65,71 This program focuses on providing pharmacist-led academic detailing with prescribers who provide care for rural and urban Medicaid patients who have cancer, human immunodeficiency virus (HIV), or mental health disorders. These disease states were selected based on state law prohibiting legal prescribing restrictions in HIV and mental health. The programming is provided by four full-time pharmacists across at least nine counties.

Nationally, leadership in the area of academic detailing comes from NaRCAD, an Agency for Healthcare Research and Quality (AHRQ)-supported initiative.⁷² NaRCAD collaborates with states, including Pennsylvania and South Carolina, and private organizations to determine their specific needs in an academic detailing program, based on local medication use.^65,66,73 Additionally, the service translates important comparative effectiveness research into usable tools, conducts education on academic detailing best practices and implementation, and helps organizations develop an assessment plan for their programs.⁷³ A final key role of NaRCAD is enlarging the network of organizations providing academic detailing in order to encourage information exchange.

Effectiveness

While theoretical and observational data suggest huge potential for improvement in clinical and economic outcomes from academic detailing programs,^74,75 results from prospective, interventional studies assessing effectiveness of academic detailing programs have been mixed.^{65,66,68,76-81} The nationwide academic detailing program in Australia has demonstrated significant cost-effectiveness; however, less public information is available regarding tangible cost savings of such programs in the United States.⁷⁵ From a clinical perspective, some individual programs have demonstrated both improved prescribing practices in addition to some cost savings in areas such as control of vasodilator use, adherence to hypertension clinical practice guidelines and evidence-based treatment of gastrointestinal reflux disease (GERD) and related disorders.^76-78 Another study found improved prescribing practices regarding use of antipsychotics in long-term care.⁶⁸ Conversely, some studies have had only marginal clinical and economic results.^79,80 One study suggests academic detailing targeted toward resident physicians can be an effective strategy for improving rational prescribing.⁸¹ Most published studies have limited generalizability due to publication in past decades, conduct in a specific HMOs or institution, and interventions performed by a low number of individuals; however, these same limitations could signal good internal validity of individual programs and customizing based on local need, a key principle of academic detailing.^68,76-80 Another concern regarding effectiveness of academic detailing is that the resources dedicated to these programs are much less than the resources dedicated toward pharmaceutical detailing on the part of industry.^65,66,74 A meta-analysis of academic detailing studies found a consistent small benefit in terms of changes in targeted practice behavior, but did not assess pharmacoeconomic outcomes.⁸²

Pharmacy Role

With their strong academic background in drug information and drug literature evaluation, pharmacists can be ideally positioned to engage in academic detailing.^39,65,66 Indeed, many of the academic detailing programs described in clinical literature and the media are centered around a team of pharmacists.^{65-67,69,76,80,81} Pharmacists with postgraduate training in drug information may be particularly well equipped for these types of positions as a result of their special skills in drug information service management, evidence-based medicine, and communications.⁸³ Pharmacists seeking to engage in academic detailing should critically assess local demographics and prescribing patterns in order to identify a specific detailing target, network and collaborate with established programs through organizations such as NaRCAD and local key stakeholders, and strive to build strong interpersonal relationships with target prescribers. Finally, as with any novel clinical service, identifying and monitoring key metrics is vital to justify direct and indirect costs of the program. Considering the mixed results of published studies and their remote time of publication, pharmacists participating in academic detailing are encouraged to share more current effectiveness information.

Drug promotion, including DTCA and promotion to health care professionals, represents significant expenditure on the part of the pharmaceutical industry. The controversial issues surrounding DTCA, in particular, continue to raise concerns about the benefits and harms of providing this type of information to patients. Detailing and direct advertisement to health care professionals continues to be an effective method of promotion. The FDA calls on health care professionals to play a key role in reporting drug promotions violations related to advertising, detailing, and continuing education. As drug promotional methods evolve, pharmacists will continue to serve both health care professionals and the public as a valuable source in deciphering and evaluating materials distributed by the pharmaceutical industry. Academic detailing may be one avenue for drug information specialists and others to combat the influence of drug promotions on prescribing.