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“There Is No Free Lunch”: Strategies to Prevent Industry Influence
CONTINUING EDUCATION
“There Is No Free Lunch”: Strategies to Prevent Industry Influence Robyn Panther Gleason, PhD, FNP-BC, and Susan D. Schaffer, PhD, FNP-BC
ABSTRACT Nurse practitioners (NPs) are frequently exposed to industry influences, particularly that of pharmaceutical companies. These exposures occur in practices or at NP organization meetings and conferences. It is important to adopt meaningful methods to overcome industry influence. NPs should be equipped to avoid prescribing practices that are not evidence-based and provided with tools that enable them to apply evidence-based practice principles to combat biased industry influence. Protocols such as the STEPS mnemonic can help NPs to evaluate new medications and industry information. It is the ongoing responsibility of NPs to inform and educate colleagues on this issue. Keywords: evidence-based practice, industry influence, nurse practitioners, pharmaceutical representatives, prescribing, STEPS mnemonic Ó 2013 Elsevier, Inc. All rights reserved. Both authors are employed at the University of Florida’s College of Nursing in Gainesville. Robyn Panther Gleason, PhD, MPH, ARNP, FNP-BC, is a clinical assistant professor and can be reached at rgleason@ufl.edu. Susan D. Schaffer, PhD, ARNP, FNP-BC, is an associate professor and department chair of women’s, children’s, and family nursing.
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urse practitioners (NPs) are frequently exposed to industry influence, particularly that of pharmaceutical companies, as described by Dr. Elissa Ladd in this journal in February 2011.1 Building on Ladd’s research, this article will provide NPs with tools that enable them to apply evidence-based practice principles to combat biased industry influence.
These exposures occur in outpatient practices when industry representatives bring lunch and present a short informational program, or during more formal presentations at local, state, or national NP organization meetings and conferences. Attendees at such presentations may or may not receive continuing education credits, but they do generally receive free food.2 In a study by Ladd, Mahoney, and
This CE learning activity is designed to augment the knowledge, skills, and attitudes of nurse practitioners and assist in their understanding of the pros and cons of information supplied by pharmaceutical/device companies about their products. At the conclusion of this activity, the participant will be able to: A. Critique information and materials provided by industry sales representatives B. Integrate strategies that prevent adoption of non-evidence-based, industry-influenced prescribing practices C. Access nonindustry information for clinical decision making The authors, reviewers, editors, nurse planners, and pilot testers all report no financial relationships that would pose a conflict of interest. The authors do not present any off-label or non-FDA-approved recommendations for treatment. This activity has been awarded 1.0 contact hours for nurses and advanced practice nurses. The activity is valid for CE credit until March 1, 2015. Readers may receive the 1.0 CE credit free by reading the article and answering each question online at www.npjournal.org, or they may mail the test answers and evaluation, along with a processing fee check for $10 made out to Elsevier, to PO Box 540, Ellicott City, MD 21041-0540. Required minimum passing score is 70%. This educational activity is provided by Nurse Practitioner AlternativesÔ. NPAÔ is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Accreditation does not imply endorsement by NPA, JNP, Elsevier, or ANCC of recommendations or any commercial products displayed or discussed in conjunction with the educational activity.
www.npjournal.org
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Emani, most NP participants (91%) reported rating the information provided at such events as reliable, and many (48%) reported that the events influenced them to prescribe brand name drugs.3 Thus, encounters with industry representatives may result in changes in prescribing behaviors among NPs in current practice, the NP students they precept, and in nurse educators responsible for building a competent advanced practice nurse workforce. In addition, NP practice is affected by the influence that pharmaceutical companies exert on drug and device research, since clinical trials are heavily supported by the pharmaceutical industry. Numerous studies have examined this relationship and found associations between the amount of funding and positive trial results, as well as the publication of results.4,5 This support differs from simply providing funding to researchers following a promising research track that may lead to a new or “improved” drug, in that the publication strategy is planned in advance by the pharmaceutical company.4-6 The studies are reported in a systematic manner to build a case for drug approval and subsequent marketing.4,5 This results in multiple studies designed to produce positive results, rather than studies that seek new knowledge or compare outcomes between drugs with similar indications.4-6 The issue of pharmaceutical company influence was addressed in the Institute of Medicine 2009 report Conflict Of Interest in Medical Research, Education, and Practice.7 As the same issues affect NPs and NP education, it is important to adopt meaningful methods to overcome industry influence of NPs and NP students.3 Health care professionals, including NPs, have a fiduciary responsibility to their patients, because of their higher level of knowledge, their position of power in the relationship, and the patient’s trust in the provider.8 This obligation requires NPs to use their advanced knowledge to provide the highest standard of quality care for patients, while avoiding conflicts of interest.3 Failure to use treatments with the best riskto-benefit ratio violates the principles of fiduciary duty implicit in this trust-based relationship.9 In order to equip NPs to avoid adoption of prescribing practices based on industry influence, strategies that empower NPs to make informed 72
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prescribing decisions must be adopted and incorporated into practice and throughout NP education programs. A first step in this process is recognizing the marketing techniques used by pharmaceutical companies. PHARMACEUTICAL MARKETING TECHNIQUES
Since January 1, 2009, signatory companies (currently numbering 58) to the Pharmaceutical Research and Manufacturers of America’s Code on Interactions with Healthcare Professionals have ceased providing low-cost items such as pens and scratchpads to prescribers, resulting in the need to establish less tangible connections when interacting with health care providers. The code does not discourage provision of food, however.10 It is therefore important for prescribers to identify the methods underlying seemingly friendly interactions that take place with pharmaceutical representatives during “drug lunches” and other encounters. Detailing
One such method used by the pharmaceutical industry since at least the 1940s is the technique of “detailing” or presenting drug information in a structured format.11 Since pharmaceutical representatives receive intensive sales training, detailing sessions include more than information about the scientific merits of the drug they are selling. Representatives also attempt to determine the provider’s perceived need for the drug or objections to it, resulting in a presentation targeted to meet that need or overcome any objections. The goal of each interaction with a provider is to leave with an assurance that the provider will prescribe the drug.12,13 In order to secure this commitment, representatives use many methods to appeal to providers’ emotions, often presenting information that is scientifically relevant, without being clinically relevant or is based on a logical fallacy. Use of Scientific Findings Unrelated to Patient Outcomes
Scientific drug comparisons may show differences on a molecular level or changes in certain lab values. However, these differences may have no effect on patient outcomes. A current example of this type of difference is found among the HMG-CoA Volume 9, Issue 2, February 2013
reductase inhibitors (statins). Although clinical evidence demonstrates that the lowest effective dose of a generic statin should be prescribed for most patients, 2 of the top 10 selling drugs in the United States in 2010 (by sales totaling $11 billion) were LipitorÔ (atorvastatin) and CrestorÔ (rosuvastatin calcium), both among the highest priced statins on the market and both highly marketed to providers and consumers.14-17 Another example is the proton pump inhibitor (PPI) NexiumÔ (esomeprazole magnesium). This drug came to market in 2001, with an intensive marketing campaign.18 It was developed by AstraZeneca to replace PrilosecÔ (omeprazole) when its patent expired. Nexium consists of 1 of the 2 “mirror” molecules that make up omeprazole. Even though equivalent doses of other PPIs demonstrate comparable therapeutic effects in most patients, with the exception of CYP2C19 rapid metabolizers, Nexium was the second highest seller of all drugs in 2010 ($6.3 billion).15,19 In the case of the aforementioned statins and PPIs, similar generics are available in place of the highly expensive brand names. The average cost of 30 Nexium capsules is approximately 4-14 times that of the same dose/quantity of generic omeprazole, which is often less costly than the amount paid for Nexium by a patient with health insurance. The same situation exists with generic statins, some of which are available on the $4 discount prescription lists of national pharmacy chains.20-22 Evidence demonstrating the equivalent efficacy of generic statins and PPIs versus the brand name drugs is readily available.14,16,19,23,24 However, Lipitor, Crestor, and Nexium have been marketed as possessing significant therapeutic advantages over their competitors, with print advertising, pharmaceutical representative detailing, and direct-to-consumer advertising flaunting benefits that either have little clinical significance or apply only to small cohorts of potential patients.19,23 It can therefore be inferred that use of these brand name drugs is the result of such influence on prescribers, as there is insufficient clinically relevant evidence that the brand name drugs improve patient outcomes.3,14,19,23-25 To combat this lack of evidence, common logical fallacies are used to influence prescribers, including www.npjournal.org
those that NPs are familiar with, such as the “red herring” (ie, stating that a drug lowers a certain lab value by 10% over another drug, when lowering the value by 10% is clinically irrelevant, as it will not affect any patient outcome).26 Clinical trial articles referenced by pharmaceutical companies may be from studies where non-equivalent doses of comparison drugs were used in the trial or conclusions by the authors are at odds with actual trial results.5 Use of Opinion/Thought Leaders
Use of the “appeal to authority” fallacy is frequently not obvious to providers, such as when locally respected providers, also called “thought leaders,” make paid drug-focused presentations at in-office lunches, restaurant dinners, and organizational meetings.26 Thought leaders generally do not provide their own expert knowledge about the product e instead they use materials and presentations provided by the company. In fact, most companies do not allow speakers to alter the provided presentation in any way.27 This use of local providers is no longer focused on physicians alone: NPs are also paid to provide these sessions. Strategies are needed to encourage NPs to make informed treatment decisions (as well as career decisions) based on unbiased evidence, rather than decisions that are unduly influenced by vendors. STRATEGIES TO PREVENT UNDUE INFLUENCE
Many providers find the search for unbiased evidencebased information to be a daunting task in a health care environment where over 30,000 biomedical journals are published, some on a weekly basis.28 Over the past 20 years, several groups have developed strategies to prevent providers from succumbing to easily available, subjective sales pitches from industry. Key information incorporated into such strategies includes the differentiation between useful and nonrelevant clinical information, the importance of patient outcomes over disease outcomes, and emphasis on clinical rather than statistical significance. Use of structured protocols to evaluate new medications and industry information has been shown to improve providers’ understanding of these key elements.9,29,30 In the 1990s, the concept of “patient-oriented evidence that matters” (POEMS) was introduced by The Journal for Nurse Practitioners - JNP
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Slawson and Shaughnessy to encourage providers to focus on clinical information relating to effects on morbidity, mortality, and quality of life, rather than minutiae that do not affect patient outcomes.31 Daily POEMS, a subscription service that provides “synopses of new evidence carefully filtered for relevance to patient care and evaluated for validity,”32 is available at http://www.essentialevidenceplus.com/ content/poems. STEPS MNEMONIC
A practical application of these concepts, the STEPS mnemonic, was first described by Preskorn33 in 1994 and further defined by Pegler and Underhill25 in a series of articles in Lancet in 2005. The STEPS mnemonic addresses safety, tolerability, effectiveness, price, and simplicity. Comparing differences between competing medications in these 5 areas can assist providers as they examine new drugs and attempt to decide between available generics and brand name drugs. Providers should ask themselves the following questions. How safe will the drug be in my patient population? In addition to adverse effects reported in clinical trials, after-market comparison studies should be examined to determine the safety of the drug in populations similar to those of the provider. Recent safety alerts from the Food and Drug Administration (FDA) that have been issued for older drugs (citalopram and other selective serotonin reuptake inhibitor antidepressants, simvastatin and other statins, PPIs, thiazolidinediones) demonstrate that long-term effects may not be evident in the clinical trial process that takes place before drugs come to market. Will my patients tolerate the drug well and continue to take it? Peglar and Underhill25 state, “A more reliable indicator than trying to compare lists of side effects is to compare dropout rates from clinical trials.” This will provide a more accurate preview of what will happen in practice. Will the drug be effective for my patients? Was there a difference in effectiveness when the drugs were compared at therapeutic doses? Pay close attention to the doses used in the trials and determine if they are the same as doses used in common practice. The patient population is 74
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also important in terms of efficacy and must be compared to that in your practice. How will the price of the drug affect adherence? Is the price appropriate for the benefits expected from the drug? All costs must be considered, including the need for additional diagnostics and office visits to monitor treatment. Is an equivalent cheaper drug available? This consideration is important for patients of all income levels, with or without insurance, because unnecessarily expensive drugs affect overall US health care costs. Will addition of this drug be simple or difficult for my patients? Will it fit well with the patient’s current drug regimen/routine? Dose frequency, route, timing of administration, and delivery method must all be considered. The STEPS mnemonic can be used in many formats, including application at practice locations, local organizational meetings, and conferences. Utilization of this or a similar method to examine new products in a structured, evidence-based manner will help NPs to fulfill their ongoing responsibility to inform and educate themselves and their colleagues on treatment advances and prevent inappropriate use in practice. Use in the Practice Setting
In the practice setting, Peglar, Williams, and Evans26 suggest requiring pharmaceutical representatives to present their products via a time-limited structured approach using the STEPS mnemonic, followed by a guided critique among the providers after the company representatives have left. They also suggest calling these sessions by a name that implies education or information, rather than “drug lunches.”26 When possible, inclusion of a local pharmacist in such meetings could provide expert interpretation of evidence and enhance interprofessional relations among health care providers. Use at Local NP Meetings
For organizational meetings that include a presentation by a pharmaceutical company, requiring the presenter to use the STEPS format may present problems, as many companies require paid presenters to use only industry-prepared materials.27 Instead, NP organizations can follow the company Volume 9, Issue 2, February 2013
presentation with a guided critique of the drug using the STEPS mnemonic in a more generalized format: How safe is the drug for various patient populations? Is the drug well tolerated or do its adverse effects cause patients to stop taking it? Has the drug been shown to be effective for various patient populations? How will the price of the drug affect adherence? Will addition of this drug be simple or difficult for various patient populations? Discussion facilitators should have advanced education that enables them to guide this type of critique (eg, a nurse educator or pharmacist). In addition, NP organizations should strongly consider forgoing the “free” dinners provided by pharmaceutical and device companies and instead develop nonsponsored meetings that include new product reviews using a structured format, guided by a facilitator. Either of these approaches requires prior research by facilitators in order to critique the industry presentation or develop an independent STEPS analysis. Many non-industry resources provide this type of information online, such as: Prescriber’s Letter, available in an online format or by mail for less than $200 per year: http:// www.prescribersletter.com Up-to-date, available by individual subscription, approximately $500 per year: https://www. uptodate.com/store American Family Physician journal includes STEPS information on new drugs on a regular basis; their site contains free links to over 60 STEPS reviews dating back to 2003 (on the journal website, click on “Department Collections,” then choose “STEPS”): http://www. aafp.org/online/en/home/publications/ journals/afp.html FDA’s Center for Drug Evaluation and Research provides E-mail alerts, continuing education, and other online resources: http:// www.accessdata.fda.gov/scripts/cder/drugsatfda Use at NP Conferences
State and national conferences of NP groups generally rely on industry sponsors to reduce the www.npjournal.org
cost of conference attendance. In addition to displays in sponsor exposition areas, industry sponsors often provide free lunch or dinner events that include presentations on their products by opinion/thought leaders. As a beginning effort, industry-sponsored presentations at conferences should be followed by a guided critique using the STEPS (or other) structured format. Conference planners should also include presentations/panel discussions on the issue of industry influence. Another topic that should be addressed in NP meetings and conferences is the presence or absence of bias in new clinical guidelines. Ladd1 and others34,35 have reported the influence of industry on federal advisory committees and the effect of political action on policy adoption. Given such influences, careful examination of the evidence used in guideline preparation is warranted. Graduate-prepared NPs have the ability to carry out this type of critique, including examination of potential conflicts of interest of advisory panels and similarity of the studied population to that seen in NP practice. Panel discussions or workshops at NP meetings/conferences could assist NPs to make appropriate decisions for their patients regarding guideline adoption into practice. CONCLUSION
NPs are frequently exposed to industry influence, particularly that of pharmaceutical companies. Research demonstrates that this sort of influence results in inappropriate prescribing behaviors by NPs and other providers. Therefore, NPs should be equipped with strategies to avoid adoption of industry-influenced prescribing practices and provided with tools that enable them to apply impartial evidence-based practice principles to combat biased industry influence. Strategies such as the STEPS mnemonic can help NPs to differentiate relevant clinical information from that provided by industry, identify treatments that improve patient outcomes, and overcome sales techniques used by industry representatives to influence providers. In addition, NPs must be adept at accessing nonindustry information for clinical decision-making. The Journal for Nurse Practitioners - JNP
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NP groups need to consider the ethical implications of allowing industry to subsidize local, state, and national NP meetings. We must determine the best approaches to reduce such influence, as ample evidence exists to demonstrate its effect on NP prescribing practices. Dialogue should ensue at the local, state, and national levels to put an end to or, at the very least, counteract biased presentations to NP groups. References 1. Ladd E. Pharmaceutical industry sponsorship and the np prescriber: policy and practice implications. J Nurs Pract. 2011;7(2):102-108. 2. American Academy of Nurse Practitioners. Registration Brochure 27th National Conference. Orlando FL. Austin, TX: Author; 2012. 3. Ladd EC, Mahoney DF, Emani S. “Under the radar”: nurse practitioner prescribers and pharmaceutical industry promotions. Am J Manag Care. 2010;16(12):e358-e362. 4. Sismondo S. How pharmaceutical industry funding affects trial outcomes: causal structures and responses. Soc Sci Med. 2008;66(9):1909-1914. 5. Lexchin J. Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications. Sci Eng Ethics. 2012;18(2):247-261. 6. Sufrin CB, Ross JS. Pharmaceutical industry marketing: understanding its impact on women’s health. Obstet Gynecol Surg. 2008;63(9):585-596. 7. Institute of Medicine. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009. 8. Hill G, Hill KT. The People’s Law Dictionary. 2002. http://biotech.law.lsu.edu/ Books/lbb/x236.htm Accessed April 5, 2012. 9. Crigger N, Holcomb L. Improving nurse practitioner practice through rational prescribing. J Nurs Pract. 2008;4(2):120-125. 10. Pharmaceutical Research and Manufacturers of America. Code on Interactions with Healthcare Professionals. Washington, DC: Author; 2008. 11. Greene JA. Attention to “details”: etiquette and the pharmaceutical salesman in Postwar American [sic]. Soc Stud Sci. 2004;34(2):271-292. 12. Integrity Solutions LLC. Integrity selling for pharmaceutical sales. http://www. integrityservices.com/sales/pharmaceutical_sales.aspx. Accessed November 29, 2012. 13. Odette WS, Horveath B, Fullowan D, Green J, Kauffman S. The Rx Advantage TM. 2nd ed. Somerset, NJ: InVentiv Health; 2006. 14. Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21):2514-2526. 15. IMS Health. Top U.S. Pharmaceutical Products by Spending. 2011. http:// www.imshealth.com. 16. Weng TC, Kao Yang YH, Lan SJ, Tai SH. A systematic review and metaanalysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010;35(2):139-151.
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17. Lavelle E. AstraZeneca ads help Crestor outpace pfizer’s lipitor (Update 5). http://www.bloomberg.com/apps/news?pid¼newsarchive&sid¼a_ viUgO8pHv0&refer¼uk. Accessed November 29, 2012. 18. Bazell R. The costly side effects of Nexium’s ad blitz. http://www.msnbc.msn. com/id/20249591/ns/health-second_opinion/t/costly-side-effects-nexiums-adblitz/#.T19eBXl6jYg. Accessed November 29, 2012. 19. Miehlke S, Lobe A, Madisch A, et al. Intragastric acidity during administration of generic omeprazole or esomeprazole—a randomised, two-way crossover study including CYP2C19 genotyping. Aliment Pharmacol Ther. 2011;33(4):471-476. 20. drugstore.com. Search. http://www.drugstore.com 21. Walgreen Co. Prescription savings club pricing calculator for common properties. http://www.walgreens.com/pharmacy/psc/psc_overview_page. jsp. Accessed November 29, 2012. 22. Walmart Stores I. Walmart $4 Prescriptions. http://www.walmart.com/cp/ 1078664?povid¼cat1088607-env458327-moduleB063012lLinkSavingsPrograms1FourDollarPrescriptions. Accessed November 29, 2012. 23. Lazar LD, Pletcher MJ, Coxson PG, Bibbins-Domingo K, Goldman L. Cost-effectiveness of statin therapy for primary prevention in a low-cost statin era. Circulation. 2011;124:146-153. 24. McDonagh MS, Carson S, Thakurta S. Proton Pump Inhibitors, Final Report Update 5. Portland, OR: Oregon Evidence-based Practice Center; 2009. 25. Pegler S, Underhill J. Evaluating promotional material from industry: an evidence-based approach. Pharm J. 2005;274:271-274. 26. Pegler S, Williams R, Evans SJ. Whatever the appeal of drug lunches, take STEPS to avoid indigestion! Pharm J. 2007;278:612-614. 27. Carlat D. Dr. drug rep. http://www.nytimes.com/2007/11/25/magazine/ 25memoir-t.html. Accessed November 29, 2012. 28. Harrison JP, Radcliffe K. Evidence based medicine as a strategy for quality improvement. Int J Public Policy. 2010;5(2):133-142. 29. Dolan JG. Multi-criteria clinical decision support: a primer on the use of multiple-criteria decision-making methods to promote evidence-based, patient-centered healthcare. Patient. 2010;3(4):229-248. 30. Houle TT, Stump DA. Statistical significance versus clinical significance. Semin Cardiothorac Vasc Anesth. 2008;12(1):5-6. 31. Bennett JH, Shaughnessy AF, Slawson DC. Becoming a medical information master: feeling good about not knowing everything. J Fam Pract. 1994;38(5):505-513. 32. Essential Evidence Plus. Daily POEMS. http://www.essentialevidenceplus. com/content/poems. Accessed November 29, 2012. 33. Preskorn SH. Antidepressant drug selection: criteria and options. J Clin Psychiatry. 1994;55(Supplement A):6-22-24, 98-100. 34. Lux S, Crook TR, Woehr DJ. Mixing business with politics: a meta-analysis of the antecedents and outcomes of corporate political activity. J Manag. 2011;37(1):223-247. 35. Steinbrook R. Controlling conflict of interest—proposals from the Institute of Medicine. N Engl J Med. 2009;360(21):2160-2163.
1555-4155/13/$ see front matter © 2013 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2012.12.009
Volume 9, Issue 2, February 2013
“There Is No Free Lunch”: Strategies to Prevent Industry Influence Robyn Panther Gleason, PhD, FNP-BC, and Susan D. Schaffer, PhD, FNP-BC
ABSTRACT Nurse practitioners (NPs) are frequently exposed to industry influences, particularly that of pharmaceutical companies. These exposures occur in practices or at NP organization meetings and conferences. It is important to adopt meaningful methods to overcome industry influence. NPs should be equipped to avoid prescribing practices that are not evidence-based and provided with tools that enable them to apply evidence-based practice principles to combat biased industry influence. Protocols such as the STEPS mnemonic can help NPs to evaluate new medications and industry information. It is the ongoing responsibility of NPs to inform and educate colleagues on this issue. Keywords: evidence-based practice, industry influence, nurse practitioners, pharmaceutical representatives, prescribing, STEPS mnemonic Ó 2013 Elsevier, Inc. All rights reserved. Both authors are employed at the University of Florida’s College of Nursing in Gainesville. Robyn Panther Gleason, PhD, MPH, ARNP, FNP-BC, is a clinical assistant professor and can be reached at rgleason@ufl.edu. Susan D. Schaffer, PhD, ARNP, FNP-BC, is an associate professor and department chair of women’s, children’s, and family nursing.
N
urse practitioners (NPs) are frequently exposed to industry influence, particularly that of pharmaceutical companies, as described by Dr. Elissa Ladd in this journal in February 2011.1 Building on Ladd’s research, this article will provide NPs with tools that enable them to apply evidence-based practice principles to combat biased industry influence.
These exposures occur in outpatient practices when industry representatives bring lunch and present a short informational program, or during more formal presentations at local, state, or national NP organization meetings and conferences. Attendees at such presentations may or may not receive continuing education credits, but they do generally receive free food.2 In a study by Ladd, Mahoney, and
This CE learning activity is designed to augment the knowledge, skills, and attitudes of nurse practitioners and assist in their understanding of the pros and cons of information supplied by pharmaceutical/device companies about their products. At the conclusion of this activity, the participant will be able to: A. Critique information and materials provided by industry sales representatives B. Integrate strategies that prevent adoption of non-evidence-based, industry-influenced prescribing practices C. Access nonindustry information for clinical decision making The authors, reviewers, editors, nurse planners, and pilot testers all report no financial relationships that would pose a conflict of interest. The authors do not present any off-label or non-FDA-approved recommendations for treatment. This activity has been awarded 1.0 contact hours for nurses and advanced practice nurses. The activity is valid for CE credit until March 1, 2015. Readers may receive the 1.0 CE credit free by reading the article and answering each question online at www.npjournal.org, or they may mail the test answers and evaluation, along with a processing fee check for $10 made out to Elsevier, to PO Box 540, Ellicott City, MD 21041-0540. Required minimum passing score is 70%. This educational activity is provided by Nurse Practitioner AlternativesÔ. NPAÔ is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Accreditation does not imply endorsement by NPA, JNP, Elsevier, or ANCC of recommendations or any commercial products displayed or discussed in conjunction with the educational activity.
www.npjournal.org
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Emani, most NP participants (91%) reported rating the information provided at such events as reliable, and many (48%) reported that the events influenced them to prescribe brand name drugs.3 Thus, encounters with industry representatives may result in changes in prescribing behaviors among NPs in current practice, the NP students they precept, and in nurse educators responsible for building a competent advanced practice nurse workforce. In addition, NP practice is affected by the influence that pharmaceutical companies exert on drug and device research, since clinical trials are heavily supported by the pharmaceutical industry. Numerous studies have examined this relationship and found associations between the amount of funding and positive trial results, as well as the publication of results.4,5 This support differs from simply providing funding to researchers following a promising research track that may lead to a new or “improved” drug, in that the publication strategy is planned in advance by the pharmaceutical company.4-6 The studies are reported in a systematic manner to build a case for drug approval and subsequent marketing.4,5 This results in multiple studies designed to produce positive results, rather than studies that seek new knowledge or compare outcomes between drugs with similar indications.4-6 The issue of pharmaceutical company influence was addressed in the Institute of Medicine 2009 report Conflict Of Interest in Medical Research, Education, and Practice.7 As the same issues affect NPs and NP education, it is important to adopt meaningful methods to overcome industry influence of NPs and NP students.3 Health care professionals, including NPs, have a fiduciary responsibility to their patients, because of their higher level of knowledge, their position of power in the relationship, and the patient’s trust in the provider.8 This obligation requires NPs to use their advanced knowledge to provide the highest standard of quality care for patients, while avoiding conflicts of interest.3 Failure to use treatments with the best riskto-benefit ratio violates the principles of fiduciary duty implicit in this trust-based relationship.9 In order to equip NPs to avoid adoption of prescribing practices based on industry influence, strategies that empower NPs to make informed 72
The Journal for Nurse Practitioners - JNP
prescribing decisions must be adopted and incorporated into practice and throughout NP education programs. A first step in this process is recognizing the marketing techniques used by pharmaceutical companies. PHARMACEUTICAL MARKETING TECHNIQUES
Since January 1, 2009, signatory companies (currently numbering 58) to the Pharmaceutical Research and Manufacturers of America’s Code on Interactions with Healthcare Professionals have ceased providing low-cost items such as pens and scratchpads to prescribers, resulting in the need to establish less tangible connections when interacting with health care providers. The code does not discourage provision of food, however.10 It is therefore important for prescribers to identify the methods underlying seemingly friendly interactions that take place with pharmaceutical representatives during “drug lunches” and other encounters. Detailing
One such method used by the pharmaceutical industry since at least the 1940s is the technique of “detailing” or presenting drug information in a structured format.11 Since pharmaceutical representatives receive intensive sales training, detailing sessions include more than information about the scientific merits of the drug they are selling. Representatives also attempt to determine the provider’s perceived need for the drug or objections to it, resulting in a presentation targeted to meet that need or overcome any objections. The goal of each interaction with a provider is to leave with an assurance that the provider will prescribe the drug.12,13 In order to secure this commitment, representatives use many methods to appeal to providers’ emotions, often presenting information that is scientifically relevant, without being clinically relevant or is based on a logical fallacy. Use of Scientific Findings Unrelated to Patient Outcomes
Scientific drug comparisons may show differences on a molecular level or changes in certain lab values. However, these differences may have no effect on patient outcomes. A current example of this type of difference is found among the HMG-CoA Volume 9, Issue 2, February 2013
reductase inhibitors (statins). Although clinical evidence demonstrates that the lowest effective dose of a generic statin should be prescribed for most patients, 2 of the top 10 selling drugs in the United States in 2010 (by sales totaling $11 billion) were LipitorÔ (atorvastatin) and CrestorÔ (rosuvastatin calcium), both among the highest priced statins on the market and both highly marketed to providers and consumers.14-17 Another example is the proton pump inhibitor (PPI) NexiumÔ (esomeprazole magnesium). This drug came to market in 2001, with an intensive marketing campaign.18 It was developed by AstraZeneca to replace PrilosecÔ (omeprazole) when its patent expired. Nexium consists of 1 of the 2 “mirror” molecules that make up omeprazole. Even though equivalent doses of other PPIs demonstrate comparable therapeutic effects in most patients, with the exception of CYP2C19 rapid metabolizers, Nexium was the second highest seller of all drugs in 2010 ($6.3 billion).15,19 In the case of the aforementioned statins and PPIs, similar generics are available in place of the highly expensive brand names. The average cost of 30 Nexium capsules is approximately 4-14 times that of the same dose/quantity of generic omeprazole, which is often less costly than the amount paid for Nexium by a patient with health insurance. The same situation exists with generic statins, some of which are available on the $4 discount prescription lists of national pharmacy chains.20-22 Evidence demonstrating the equivalent efficacy of generic statins and PPIs versus the brand name drugs is readily available.14,16,19,23,24 However, Lipitor, Crestor, and Nexium have been marketed as possessing significant therapeutic advantages over their competitors, with print advertising, pharmaceutical representative detailing, and direct-to-consumer advertising flaunting benefits that either have little clinical significance or apply only to small cohorts of potential patients.19,23 It can therefore be inferred that use of these brand name drugs is the result of such influence on prescribers, as there is insufficient clinically relevant evidence that the brand name drugs improve patient outcomes.3,14,19,23-25 To combat this lack of evidence, common logical fallacies are used to influence prescribers, including www.npjournal.org
those that NPs are familiar with, such as the “red herring” (ie, stating that a drug lowers a certain lab value by 10% over another drug, when lowering the value by 10% is clinically irrelevant, as it will not affect any patient outcome).26 Clinical trial articles referenced by pharmaceutical companies may be from studies where non-equivalent doses of comparison drugs were used in the trial or conclusions by the authors are at odds with actual trial results.5 Use of Opinion/Thought Leaders
Use of the “appeal to authority” fallacy is frequently not obvious to providers, such as when locally respected providers, also called “thought leaders,” make paid drug-focused presentations at in-office lunches, restaurant dinners, and organizational meetings.26 Thought leaders generally do not provide their own expert knowledge about the product e instead they use materials and presentations provided by the company. In fact, most companies do not allow speakers to alter the provided presentation in any way.27 This use of local providers is no longer focused on physicians alone: NPs are also paid to provide these sessions. Strategies are needed to encourage NPs to make informed treatment decisions (as well as career decisions) based on unbiased evidence, rather than decisions that are unduly influenced by vendors. STRATEGIES TO PREVENT UNDUE INFLUENCE
Many providers find the search for unbiased evidencebased information to be a daunting task in a health care environment where over 30,000 biomedical journals are published, some on a weekly basis.28 Over the past 20 years, several groups have developed strategies to prevent providers from succumbing to easily available, subjective sales pitches from industry. Key information incorporated into such strategies includes the differentiation between useful and nonrelevant clinical information, the importance of patient outcomes over disease outcomes, and emphasis on clinical rather than statistical significance. Use of structured protocols to evaluate new medications and industry information has been shown to improve providers’ understanding of these key elements.9,29,30 In the 1990s, the concept of “patient-oriented evidence that matters” (POEMS) was introduced by The Journal for Nurse Practitioners - JNP
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Slawson and Shaughnessy to encourage providers to focus on clinical information relating to effects on morbidity, mortality, and quality of life, rather than minutiae that do not affect patient outcomes.31 Daily POEMS, a subscription service that provides “synopses of new evidence carefully filtered for relevance to patient care and evaluated for validity,”32 is available at http://www.essentialevidenceplus.com/ content/poems. STEPS MNEMONIC
A practical application of these concepts, the STEPS mnemonic, was first described by Preskorn33 in 1994 and further defined by Pegler and Underhill25 in a series of articles in Lancet in 2005. The STEPS mnemonic addresses safety, tolerability, effectiveness, price, and simplicity. Comparing differences between competing medications in these 5 areas can assist providers as they examine new drugs and attempt to decide between available generics and brand name drugs. Providers should ask themselves the following questions. How safe will the drug be in my patient population? In addition to adverse effects reported in clinical trials, after-market comparison studies should be examined to determine the safety of the drug in populations similar to those of the provider. Recent safety alerts from the Food and Drug Administration (FDA) that have been issued for older drugs (citalopram and other selective serotonin reuptake inhibitor antidepressants, simvastatin and other statins, PPIs, thiazolidinediones) demonstrate that long-term effects may not be evident in the clinical trial process that takes place before drugs come to market. Will my patients tolerate the drug well and continue to take it? Peglar and Underhill25 state, “A more reliable indicator than trying to compare lists of side effects is to compare dropout rates from clinical trials.” This will provide a more accurate preview of what will happen in practice. Will the drug be effective for my patients? Was there a difference in effectiveness when the drugs were compared at therapeutic doses? Pay close attention to the doses used in the trials and determine if they are the same as doses used in common practice. The patient population is 74
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also important in terms of efficacy and must be compared to that in your practice. How will the price of the drug affect adherence? Is the price appropriate for the benefits expected from the drug? All costs must be considered, including the need for additional diagnostics and office visits to monitor treatment. Is an equivalent cheaper drug available? This consideration is important for patients of all income levels, with or without insurance, because unnecessarily expensive drugs affect overall US health care costs. Will addition of this drug be simple or difficult for my patients? Will it fit well with the patient’s current drug regimen/routine? Dose frequency, route, timing of administration, and delivery method must all be considered. The STEPS mnemonic can be used in many formats, including application at practice locations, local organizational meetings, and conferences. Utilization of this or a similar method to examine new products in a structured, evidence-based manner will help NPs to fulfill their ongoing responsibility to inform and educate themselves and their colleagues on treatment advances and prevent inappropriate use in practice. Use in the Practice Setting
In the practice setting, Peglar, Williams, and Evans26 suggest requiring pharmaceutical representatives to present their products via a time-limited structured approach using the STEPS mnemonic, followed by a guided critique among the providers after the company representatives have left. They also suggest calling these sessions by a name that implies education or information, rather than “drug lunches.”26 When possible, inclusion of a local pharmacist in such meetings could provide expert interpretation of evidence and enhance interprofessional relations among health care providers. Use at Local NP Meetings
For organizational meetings that include a presentation by a pharmaceutical company, requiring the presenter to use the STEPS format may present problems, as many companies require paid presenters to use only industry-prepared materials.27 Instead, NP organizations can follow the company Volume 9, Issue 2, February 2013
presentation with a guided critique of the drug using the STEPS mnemonic in a more generalized format: How safe is the drug for various patient populations? Is the drug well tolerated or do its adverse effects cause patients to stop taking it? Has the drug been shown to be effective for various patient populations? How will the price of the drug affect adherence? Will addition of this drug be simple or difficult for various patient populations? Discussion facilitators should have advanced education that enables them to guide this type of critique (eg, a nurse educator or pharmacist). In addition, NP organizations should strongly consider forgoing the “free” dinners provided by pharmaceutical and device companies and instead develop nonsponsored meetings that include new product reviews using a structured format, guided by a facilitator. Either of these approaches requires prior research by facilitators in order to critique the industry presentation or develop an independent STEPS analysis. Many non-industry resources provide this type of information online, such as: Prescriber’s Letter, available in an online format or by mail for less than $200 per year: http:// www.prescribersletter.com Up-to-date, available by individual subscription, approximately $500 per year: https://www. uptodate.com/store American Family Physician journal includes STEPS information on new drugs on a regular basis; their site contains free links to over 60 STEPS reviews dating back to 2003 (on the journal website, click on “Department Collections,” then choose “STEPS”): http://www. aafp.org/online/en/home/publications/ journals/afp.html FDA’s Center for Drug Evaluation and Research provides E-mail alerts, continuing education, and other online resources: http:// www.accessdata.fda.gov/scripts/cder/drugsatfda Use at NP Conferences
State and national conferences of NP groups generally rely on industry sponsors to reduce the www.npjournal.org
cost of conference attendance. In addition to displays in sponsor exposition areas, industry sponsors often provide free lunch or dinner events that include presentations on their products by opinion/thought leaders. As a beginning effort, industry-sponsored presentations at conferences should be followed by a guided critique using the STEPS (or other) structured format. Conference planners should also include presentations/panel discussions on the issue of industry influence. Another topic that should be addressed in NP meetings and conferences is the presence or absence of bias in new clinical guidelines. Ladd1 and others34,35 have reported the influence of industry on federal advisory committees and the effect of political action on policy adoption. Given such influences, careful examination of the evidence used in guideline preparation is warranted. Graduate-prepared NPs have the ability to carry out this type of critique, including examination of potential conflicts of interest of advisory panels and similarity of the studied population to that seen in NP practice. Panel discussions or workshops at NP meetings/conferences could assist NPs to make appropriate decisions for their patients regarding guideline adoption into practice. CONCLUSION
NPs are frequently exposed to industry influence, particularly that of pharmaceutical companies. Research demonstrates that this sort of influence results in inappropriate prescribing behaviors by NPs and other providers. Therefore, NPs should be equipped with strategies to avoid adoption of industry-influenced prescribing practices and provided with tools that enable them to apply impartial evidence-based practice principles to combat biased industry influence. Strategies such as the STEPS mnemonic can help NPs to differentiate relevant clinical information from that provided by industry, identify treatments that improve patient outcomes, and overcome sales techniques used by industry representatives to influence providers. In addition, NPs must be adept at accessing nonindustry information for clinical decision-making. The Journal for Nurse Practitioners - JNP
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NP groups need to consider the ethical implications of allowing industry to subsidize local, state, and national NP meetings. We must determine the best approaches to reduce such influence, as ample evidence exists to demonstrate its effect on NP prescribing practices. Dialogue should ensue at the local, state, and national levels to put an end to or, at the very least, counteract biased presentations to NP groups. References 1. Ladd E. Pharmaceutical industry sponsorship and the np prescriber: policy and practice implications. J Nurs Pract. 2011;7(2):102-108. 2. American Academy of Nurse Practitioners. Registration Brochure 27th National Conference. Orlando FL. Austin, TX: Author; 2012. 3. Ladd EC, Mahoney DF, Emani S. “Under the radar”: nurse practitioner prescribers and pharmaceutical industry promotions. Am J Manag Care. 2010;16(12):e358-e362. 4. Sismondo S. How pharmaceutical industry funding affects trial outcomes: causal structures and responses. Soc Sci Med. 2008;66(9):1909-1914. 5. Lexchin J. Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications. Sci Eng Ethics. 2012;18(2):247-261. 6. Sufrin CB, Ross JS. Pharmaceutical industry marketing: understanding its impact on women’s health. Obstet Gynecol Surg. 2008;63(9):585-596. 7. Institute of Medicine. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009. 8. Hill G, Hill KT. The People’s Law Dictionary. 2002. http://biotech.law.lsu.edu/ Books/lbb/x236.htm Accessed April 5, 2012. 9. Crigger N, Holcomb L. Improving nurse practitioner practice through rational prescribing. J Nurs Pract. 2008;4(2):120-125. 10. Pharmaceutical Research and Manufacturers of America. Code on Interactions with Healthcare Professionals. Washington, DC: Author; 2008. 11. Greene JA. Attention to “details”: etiquette and the pharmaceutical salesman in Postwar American [sic]. Soc Stud Sci. 2004;34(2):271-292. 12. Integrity Solutions LLC. Integrity selling for pharmaceutical sales. http://www. integrityservices.com/sales/pharmaceutical_sales.aspx. Accessed November 29, 2012. 13. Odette WS, Horveath B, Fullowan D, Green J, Kauffman S. The Rx Advantage TM. 2nd ed. Somerset, NJ: InVentiv Health; 2006. 14. Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21):2514-2526. 15. IMS Health. Top U.S. Pharmaceutical Products by Spending. 2011. http:// www.imshealth.com. 16. Weng TC, Kao Yang YH, Lan SJ, Tai SH. A systematic review and metaanalysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010;35(2):139-151.
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17. Lavelle E. AstraZeneca ads help Crestor outpace pfizer’s lipitor (Update 5). http://www.bloomberg.com/apps/news?pid¼newsarchive&sid¼a_ viUgO8pHv0&refer¼uk. Accessed November 29, 2012. 18. Bazell R. The costly side effects of Nexium’s ad blitz. http://www.msnbc.msn. com/id/20249591/ns/health-second_opinion/t/costly-side-effects-nexiums-adblitz/#.T19eBXl6jYg. Accessed November 29, 2012. 19. Miehlke S, Lobe A, Madisch A, et al. Intragastric acidity during administration of generic omeprazole or esomeprazole—a randomised, two-way crossover study including CYP2C19 genotyping. Aliment Pharmacol Ther. 2011;33(4):471-476. 20. drugstore.com. Search. http://www.drugstore.com 21. Walgreen Co. Prescription savings club pricing calculator for common properties. http://www.walgreens.com/pharmacy/psc/psc_overview_page. jsp. Accessed November 29, 2012. 22. Walmart Stores I. Walmart $4 Prescriptions. http://www.walmart.com/cp/ 1078664?povid¼cat1088607-env458327-moduleB063012lLinkSavingsPrograms1FourDollarPrescriptions. Accessed November 29, 2012. 23. Lazar LD, Pletcher MJ, Coxson PG, Bibbins-Domingo K, Goldman L. Cost-effectiveness of statin therapy for primary prevention in a low-cost statin era. Circulation. 2011;124:146-153. 24. McDonagh MS, Carson S, Thakurta S. Proton Pump Inhibitors, Final Report Update 5. Portland, OR: Oregon Evidence-based Practice Center; 2009. 25. Pegler S, Underhill J. Evaluating promotional material from industry: an evidence-based approach. Pharm J. 2005;274:271-274. 26. Pegler S, Williams R, Evans SJ. Whatever the appeal of drug lunches, take STEPS to avoid indigestion! Pharm J. 2007;278:612-614. 27. Carlat D. Dr. drug rep. http://www.nytimes.com/2007/11/25/magazine/ 25memoir-t.html. Accessed November 29, 2012. 28. Harrison JP, Radcliffe K. Evidence based medicine as a strategy for quality improvement. Int J Public Policy. 2010;5(2):133-142. 29. Dolan JG. Multi-criteria clinical decision support: a primer on the use of multiple-criteria decision-making methods to promote evidence-based, patient-centered healthcare. Patient. 2010;3(4):229-248. 30. Houle TT, Stump DA. Statistical significance versus clinical significance. Semin Cardiothorac Vasc Anesth. 2008;12(1):5-6. 31. Bennett JH, Shaughnessy AF, Slawson DC. Becoming a medical information master: feeling good about not knowing everything. J Fam Pract. 1994;38(5):505-513. 32. Essential Evidence Plus. Daily POEMS. http://www.essentialevidenceplus. com/content/poems. Accessed November 29, 2012. 33. Preskorn SH. Antidepressant drug selection: criteria and options. J Clin Psychiatry. 1994;55(Supplement A):6-22-24, 98-100. 34. Lux S, Crook TR, Woehr DJ. Mixing business with politics: a meta-analysis of the antecedents and outcomes of corporate political activity. J Manag. 2011;37(1):223-247. 35. Steinbrook R. Controlling conflict of interest—proposals from the Institute of Medicine. N Engl J Med. 2009;360(21):2160-2163.
1555-4155/13/$ see front matter © 2013 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2012.12.009
Volume 9, Issue 2, February 2013