A cross-sectional evidence-based review of pharmaceutical promotional marketing brochures and their underlying studies: Is what they tell us important and true?
© Cardarelli et al; licensee BioMed Central Ltd. 2006
Received: 25 October 2005
Accepted: 03 March 2006
Published: 03 March 2006
A major marketing technique used by pharmaceutical companies is direct-to-physician marketing. This form of marketing frequently employs promotional marketing brochures, based on clinical research, which may influence how a physician prescribes medicines. This study's objective was to investigate whether or not the information in promotional brochures presented to physicians by pharmaceutical representatives is accurate, consistent, and valid with respect to the actual studies upon which the promotional brochures are based.
Physicians in five clinics were asked to consecutively collect pharmaceutical promotional brochures and to send them all to a centralized location. The brochures for any class of medication were collected on a continuous basis until 20 distinct promotional brochures were received by a central location. Once the brochure was received, the corresponding original study was obtained. Two blinded reviewers performed an evidence-based review of the article, comparing data that was printed on the brochure to what was found in the original study.
Among the 20 studies, 75% of the studies were found to be valid, 80% were funded by the pharmaceutical company, 60% of the studies and the corresponding brochures presented patient-oriented outcomes, and 40% were compared to another treatment regimen. Of the 19 brochures that presented the data as graphs, 4 brochures presented a relative risk reduction while only 1 brochure presented an absolute risk reduction. 15% of the promotional marketing brochures presented data that was different from what was in the original published study.
Given the present findings, physicians should be cautious about drawing conclusions regarding a medication based on the marketing brochures provided by pharmaceutical companies.
The pharmaceutical industry spent over $11 billion in pharmaceutical marketing, excluding medication samples, in 2004, with more than $7 billion directed to clinicians . This creates the potential for an ethical dilemma because such marketing may influence physician prescribing behavior without necessarily benefiting the patient [2–6]. Such marketing also creates the potential for inappropriate prescribing practices, which contribute to escalating national health care costs.
There is an ongoing debate on the effects of pharmaceutical marketing on health care delivery. For example, while diuretic and beta-blocker medications are considered the first line antihypertensive therapies (both medications being relatively inexpensive and available in generic forms), extensive marketing campaigns by pharmaceutical companies to promote calcium channel blockers (CCBs) resulted in the largest growth in revenues for this class of anti-hypertension drugs during the 1990s . The percentage of CCB advertisements increased from 4.6% in 1986 to 26.9% in 1996, while advertisements for beta-blockers and diuretics decreased from 12.4% to 0% and from 4.2% to 0%, respectively, during the same time period . It was also noted that CCBs accounted for 38% of antihypertensive prescriptions written in 1995, while diuretics and beta-blockers combined accounted for only 19% . This, in essence, affected the standard of care in the management of hypertension,  even though CCBs may increase the risk of fatal and nonfatal myocardial infarction by 18% . Lack of compliance with antihypertensive guidelines, by using second-line medications over first-line medications, was associated with potential increases in health care expenditures in the range of $2.6 billion to $3.2 billion in 1996 .
Direct-to-physician (DTP) marketing is one important facet of the promotion of pharmaceuticals. DTP includes verbal in-office presentations which are usually accompanied by promotional advertising brochures, free medication samples, and possibly gifts such as meals or other promotional items. These in-office presentations by pharmaceutical representatives (PRs) are an important method of promotion for pharmaceutical companies. Their impact is undeniable, as PRs are most frequently reported by physicians as their source of primary information about new medications . While direct-to consumer (DTC) pharmaceutical marketing has increased dramatically in the last decade, DTP marketing expenditures remain 48% greater than for DTC marketing .
There is concern about the influence of DTP marketing on physician prescribing practices and its consequences, such as the physician's ethical obligation to the patient and health care costs. Studies have repeatedly shown that pharmaceutical promotion influences physician behavior [3, 12–14]. The more physicians are encountered by PRs, the more likely they are to deny that they are influenced by pharmaceutical gifts and PR interactions . Some information provided by PRs to physicians has been found to be misleading or biased [5, 16–21]. Eleven percent of the verbal statements about drugs made by pharmaceutical representatives to physicians has been found to be inaccurate . Further, a majority of journal advertisements have been found to be based on studies of poor methodological quality .
While studies have investigated the accuracy and influence of promotional information provided by PRs to physicians, [3, 5, 8, 12–14, 16–21] no study has assessed the visual nature and accuracy of the data that are presented in the promotional brochures. The accuracy and validity of the visual displays and data presented in promotional brochures is important because physicians who rely more on promotional information tend to be heavier prescribers and more willing to try new medications [13, 23–28, 28–31]. The objective of this study was to review the data that is visually presented on advertisement brochures for its accuracy, consistency, and validity.
1. Was the assignment of patients to treatments randomized?
2. Were all patients who entered the trial accounted for at its conclusion?
3. Were the patients analyzed in the groups to which they were randomized?
1. Were patients and clinicians kept "blind" to which treatment was being received?
2. Aside from the experimental treatment, were the groups treated equally?
3. Were the groups similar at the start of the trial?
A Cohen's kappa and a prevalence-adjusted bias-adjusted kappa (PABAK)  were calculated on validity assessments to obtain an index of inter-rater reliability. While under most circumstances a Cohen's kappa value would suffice, we believe that both prevalence (the unequal distribution of "Yes" vs. "No" validity decisions between the reviewers) and bias (from the reviewers' differing assessments of the frequency of study validity) may have yielded misleading results given our high percentage of crude agreement. This concept has been explained in greater detail by Feinstein and Cicchetti and Byrt et al. . Thus a PABAK value may better measure agreement between the two reviewers as it adjusts for factors (prevalence, bias, and agreement) present in an unbalanced 2 × 2 agreement table.
(N = 20)
1. Was the study valid?
2. Was the study funded by a pharmaceutical company?
3. What was the study outcome?
4. What was the study therapy compared to?
Another medication or therapy
5. Was a graphic* used on the brochure?
6. Of the brochures with graphics, how was the data presented?
Relative risk reduction
Absolute risk reduction
7. Was the outcome of interest statistically significant?***
8. Did the data on the brochure differ from the underlying study?
A value of .41 was calculated for Cohen's kappa, and the PABAK value was .60, indicating a moderate level of agreement between the two reviewers . The crude level of overall agreement, unadjusted for chance, was 80%.
Seventy five percent of the reviewed articles were considered valid. This supports findings from a previous study that assessed whether the quality of a study was influenced by sponsorship . The authors found that the majority of the studies sponsored by pharmaceutical companies were of good quality. However, they also found that published studies that were sponsored by pharmaceutical companies were four times more likely to have outcomes favoring the sponsor's product than were studies that had other types of sponsors. One potential solution to reducing the skepticism resulting from industry-funded research is to have pharmaceutical companies improve access to their original data. Another possible solution is for academia to have funding available to independently conduct studies without the influence of the pharmaceutical companies. Although pharmaceutical companies exert control over their clinical trials, clinical outcome studies conducted at academic health science centers may have a role in complementing the post-marketing surveillance of new drugs following FDA approval.
A large majority of the brochures presented data that were based on underlying studies funded by the pharmaceutical company. However, a recent study by Cooper and Schriger found that only 58% of the original research cited in advertisements was sponsored by a pharmaceutical company or had a company affiliated author . This deviation from our results may be due to differences in methods for ascertaining funding source and product mix analyzed (e.g., brochures vs journal advertisements). Alternatively, it may also reflect our study's small sample size. There has been concern that industry-supported manuscripts may selectively report study data that make a medication or therapy appear more efficacious than it actually is [39–41]. The clinician's dilemma becomes, "Are the results from this 'valid study' truly valid?"
Although a majority of the outcomes in the reviewed studies were patient-oriented, a substantial number were not. It is important to present data that reflects the outcome of the patient, such as mortality, quality of life changes, and symptom reduction. Thus, while a CCB may reduce blood pressure just as effectively as a diuretic, patient outcomes (e.g., mortality) may prevail in the long term [11, 42].
While 95% of the brochures presented a visual graphic, only 1 brochure presented an absolute risk reduction and 4 brochures presented relative risk reductions. This "framing effect" may mislead physicians to conclude that a large difference in outcome occurs with the use of the promoted medication or therapy . Moreover, as the consistency of outcomes was being assessed in the underlying study and its subsequent promotional brochure, the reviewers noted that the overwhelming majority of data selected for the brochure were based on a desired visual impact. Although it was not a part of this study's objectives, it appeared that pharmaceutical companies often selected the outcome with the greatest relative risk reduction or percent-change from baseline in lieu of more clinically important findings in the original manuscript. This is an area for further research and scrutiny.
A minority of the studies (eight of 20) compared the medication to another medication or treatment strategy. When a medication has already been approved by the Food and Drug Administration, subsequent studies that compare that medication to placebo have limited value to practicing physicians, as efficacy has already been established. It is of more value to physicians for studies to compare new medications to generic and inexpensive medications that are currently used in practice to determine if a change in disease management is indicated.
Although three of the 20 brochures presented data that were different from the original study, the differences were small and most likely would not have affected the clinician's prescribing behavior.
This study had several limitations. Only two blinded reviewers were available and any discrepancies were resolved by consensus rather than adjudication by a third reviewer. The method in which the reviewers deemed the underlying studies valid has not been validated in previous studies. The sample size may have been too small to detect clinically important findings. Because brochures were collected only in selected family medicine clinics in one city, these findings may not be generalized to other specialties, settings (i.e. hospital), or geographic regions. Only brochures were studied, therefore these findings may not be generalized to other types of promotional products or advertisements, such as journal advertisements. We believe that successful drug marketing to physicians entails more than simply presenting a brochure to the physician and this study only assessed one aspect of drug marketing tactics. There may be seasonal variations in drug marketing that further limit generalizability, although this may have been mitigated to some degree by the wide range of drugs included in the study.
Given the present findings, physicians should be cautious about drawing conclusions based on data presented on brochures provided by pharmaceutical companies. It would be prudent for physicians to review the original study prior to changing prescribing behavior based on promotional brochures only. Further, physicians should be familiar with and utilize the principles of evidence-based medicine in assessing the validity of published studies. As our study was a descriptive cross-sectional study with the primary purpose of using a semi-objective methodology to review pharmaceutical brochures and their corresponding published studies, future research needs to determine not only how the promotional brochure plays in overall DTP marketing and how pharmaceutical brochures affect physician prescribing behaviors, but also if patient outcomes are associated with such changes.
We would like to acknowledge the participating physicians in the Department of Family Medicine, University of North Texas Health Science Center who made this study possible.
- Health IMS: Total U.S. promotional spend by type, 2004. 2005, [http://www.imshealth.com/ims/portal/front/articleC/0,2777,6599_49695992_75406357,00.html]Google Scholar
- Brody H: The company we keep: why physicians should refuse to see pharmaceutical representatives. Ann Fam Med. 2005, 3: 82-85. 10.1370/afm.259.View ArticlePubMedPubMed CentralGoogle Scholar
- Orlowski JP, Wateska L: The effects of pharmaceutical firm enticements on physician prescribing patterns. There's no such thing as a free lunch. Chest. 1992, 102: 270-273.View ArticlePubMedGoogle Scholar
- Figueiras A, Caamano F, Gestal-Otero JJ: Influence of physician's education, drug information and medical-care settings on the quality of drugs prescribed. Eur J Clin Pharmacol. 2000, 56: 747-753. 10.1007/s002280000217.View ArticlePubMedGoogle Scholar
- Wazana A: Physicians and the pharmaceutical industry: is a gift ever just a gift?. JAMA. 2000, 283: 373-380. 10.1001/jama.283.3.373.View ArticlePubMedGoogle Scholar
- Chew LD, O'Young TS, Hazlet TK, Bradley KA, Maynard C, Lessler DS: A physician survey of the effect of drug sample availability on physicians' behavior. J Gen Intern Med. 2000, 15: 478-483. 10.1046/j.1525-1497.2000.08014.x.View ArticlePubMedPubMed CentralGoogle Scholar
- Xu KT, Moloney M, Phillips S: Economics of suboptimal drug use: cost-savings of using JNC-recommended medications for management of uncomplicated essential hypertension. Am J Manag Care. 2003, 9: 529-536.PubMedGoogle Scholar
- Siegel D, Lopez J: Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? Fifth Joint National Commission on the Detection, Evaluation, and Treatment of High Blood Pressure. JAMA. 1997, 278: 1745-1748. 10.1001/jama.278.21.1745.View ArticlePubMedGoogle Scholar
- Wang TJ, Ausiello JC, Stafford RS: Trends in antihypertensive drug advertising, 1985-1996. Circulation. 1999, 99: 2055-2057.View ArticlePubMedGoogle Scholar
- Zweifler J, Hughes S, Schafer S, Garcia B, Grasser A, Salazar L: Are sample medicines hurting the uninsured?. J Am Board Fam Pract. 2002, 15: 361-366.PubMedGoogle Scholar
- Opie LH, Schall R: Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy. J Am Coll Cardiol. 2002, 39: 315-322. 10.1016/S0735-1097(01)01728-4.View ArticlePubMedGoogle Scholar
- Peay MY, Peay ER: Innovation in high risk drug therapy. Soc Sci Med. 1994, 39: 39-52. 10.1016/0277-9536(94)90164-3.View ArticlePubMedGoogle Scholar
- The Drug Promotion Database. 2002, [http://www.drugpromo.info]
- Gonul F: Promotion of prescription drugs and its impact on physicians' choice behavior. Journal of Marketing. 2001, 216: 79-90.View ArticleGoogle Scholar
- Hodges B: Interactions with the pharmaceutical industry: experiences and attitudes of psychiatry residents, interns and clerks. CMAJ. 1995, 153: 553-559.PubMedPubMed CentralGoogle Scholar
- Ziegler MG, Lew P, Singer BC: The accuracy of drug information from pharmaceutical sales representatives. JAMA. 1995, 273: 1296-1298. 10.1001/jama.273.16.1296.View ArticlePubMedGoogle Scholar
- Katz D, Caplan AL, Merz JF: All gifts large and small: toward an understanding of the ethics of pharmaceutical industry gift-giving. Am J Bioeth. 2003, 3: 39-46. 10.1162/15265160360706552.View ArticlePubMedGoogle Scholar
- Avorn J, Chren M, Hartley R: Scientific versus commercial sources of influence on the prescribing behavior of physicians. Am J Med. 1982, 73: 4-8. 10.1016/0002-9343(82)90911-1.View ArticlePubMedGoogle Scholar
- Lexchin J: Doctors and detailers: therapeutic education or pharmaceutical promotion?. Int J Health Serv. 1989, 19: 663-679.View ArticlePubMedGoogle Scholar
- Lexchin J: Interactions between physicians and the pharmaceutical industry: what does the literature say?. CMAJ. 1993, 149: 1401-1407.PubMedPubMed CentralGoogle Scholar
- Lexchin J: What information do physicians receive from pharmaceutical representatives?. Can Fam Physician. 1997, 43: 941-945.PubMedPubMed CentralGoogle Scholar
- Lexchin J, Holbrook A: Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal. CMAJ. 1994, 151: 47-54.PubMedPubMed CentralGoogle Scholar
- Mapes R: Aspects of British general practitioners' prescribing. Medical Care. 1977, 15: 371-381.View ArticlePubMedGoogle Scholar
- Bower AD, Burkett GL: Family physicians and generic drugs: a study of recognition, information sources, prescribing attitudes, and practices. Journal of Family Practice. 1987, 24: 612-616.PubMedGoogle Scholar
- Caudill TS, Lurie N, Rich EC: The influence of pharmaceutical industry advertising on physician prescribing. J Drug Issues. 1992, 22: 331-338.View ArticleGoogle Scholar
- Becker MH, Stolley PD, Lasagna L, McEvilla JD, Sloane LM: Differential education concerning therapeutics and resultant physician prescribing patterns. Journal of Medical Education. 1972, 47: 118-127.PubMedGoogle Scholar
- Stolley PD, Becker MH, Lasagna L, McEvilla JD, Sloane LM: The relationship between physicians characteristics and prescribing appropriateness. Medical Care. 1972, 10: 17-28.View ArticlePubMedGoogle Scholar
- Haayer F: Rational prescribing and sources of information. Soc Sci Med. 1982, 16: 2017-2023. 10.1016/0277-9536(82)90158-7.View ArticlePubMedGoogle Scholar
- Cormack MA, Howells E: Factors linked to the prescribing of benzodiazepines by general practice principals and trainees. Family Practice. 1992, 9: 466-471.View ArticlePubMedGoogle Scholar
- Stross JK: Information sources and clinical decisions. Journal of General Internal Medicine. 1987, 2: 155-159.View ArticlePubMedGoogle Scholar
- Strickland-Hodge B, Jepson MH: Identification and characterization of early and late prescribers in general practice. Journal of the Royal Society of Medicine. 1982, 75: 341-345.PubMedPubMed CentralGoogle Scholar
- DL S, al : Evidence-Based Medicine: How to practice and teach EBM. 2000, Edinburgh London, Churchill Livingstone, 2ndGoogle Scholar
- SPSS, Inc. 2002, Chicago, Il.
- Byrt T, Bishop J, Carlin JB: Bias, prevalence and kappa. J Clin Epidemiol. 1993, 46: 423-429. 10.1016/0895-4356(93)90018-V.View ArticlePubMedGoogle Scholar
- Feinstein AR, Cicchetti DV: High agreement but low kappa: I. The problems of two paradoxes. J Clin Epidemiol. 1990, 43: 543-549. 10.1016/0895-4356(90)90158-L.View ArticlePubMedGoogle Scholar
- RJ L, GC K: The measurement of onserver agreement for categorical data. Biometrics. 1977, 33: 159-174.View ArticleGoogle Scholar
- Lexchin J, Bero LA, Djulbegovic B, Clark O: Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ. 2003, 326: 1167-1170. 10.1136/bmj.326.7400.1167.View ArticlePubMedPubMed CentralGoogle Scholar
- Cooper RJ, Schriger DL: The availability of references and the sponsorship of original research cited in pharmaceutical advertisements. CMAJ. 2005, 172: 487-491.View ArticlePubMedPubMed CentralGoogle Scholar
- Djulbegovic B, Lacevic M, Cantor A, Fields KK, Bennett CL, Adams JR, Kuderer NM, Lyman GH: The uncertainty principle and industry-sponsored research. Lancet. 2000, 356: 635-638. 10.1016/S0140-6736(00)02605-2.View ArticlePubMedGoogle Scholar
- Rochon PA, Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, Chalmers TC: A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med. 1994, 154: 157-163. 10.1001/archinte.154.2.157.View ArticlePubMedGoogle Scholar
- Moher D, Cook DJ, Jadad AR, Tugwell P, Moher M, Jones A, Pham B, Klassen TP: Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses. Health Technol Assess. 1999, 3: i-98.PubMedGoogle Scholar
- Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002, 288: 2981-2997. 10.1001/jama.288.23.2981.
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/7/13/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.