An analysis of the warning letters issued by the FDA to pharmaceutical manufacturers regarding misleading health outcomes claims
Objective: To evaluate the number and type of warning letters issued by the US Food and Drug Administration (FDA) to pharmaceutical manufacturers for promotional violations.
Methods: Two reviewers downloaded, printed and independently evaluated warning letters issued by the FDA to pharmaceutical manufacturers from years 2003-2008. Misleading claims were broadly classified as clinical, Quality-of-Life (QoL), and economic claims. Clinical claims included claims regarding unsubstantiated efficacy, safety and tolerability, superiority, broadening of indication and/or omission of risk information. QoL claims included unsubstantiated quality of life and/or health-related quality of life claims. Economic claims included any form of claim made on behalf of the pharmaceutical companies related to cost superiority of or cost savings from the drug compared to other drugs in the market.
Results: In the 6-year study period, 65 warning letters were issued by FDA, which contained 144 clinical, three QoL, and one economic claim. On an average, 11 warning letters were issued per year. Omission of risk information was the most frequently violated claim (30.6%) followed by unsubstantiated efficacy claims (18.6%). Warning letters were primarily directed to manufacturers of cardiovascular (14.6%), anti-microbial (14.6%), and CNS (12.5%) drugs. Majority of the claims referenced in warning letters contained promotional materials directed to physicians (57%).
Conclusion: The study found that misleading clinical outcome claims formed the majority of the promotional violations, and majority of the claims were directed to physicians. Since inadequate promotion of medications may lead to irrational prescribing, the study emphasizes the importance of disseminating reliable, credible, and scientific information to patients, and more importantly, physicians to protect public health.
2. Kamal KM, Deselle SD, Rane P, Parekh R, Zacker C. Content Analysis of FDA warning letters to Manufacturers of Pharmaceuticals and Therapeutic Biologicals for Promotional Violations. Drug Inf J. 2009;43:385-393.
3. Benson EB, Alfors SN. Prescription drug advertising and promotion: learnings from recent Food and Drug Administration warning letters. Drug Inf J. 2007;41:281-289.
4. Berry IR, Martin RP. The Pharmaceutical Regulatory Process. Second Edition. Informa Health Care. 2008; 371-386.
5. Berry IR. The Pharmaceutical Regulatory Process. Taylor & Francis e-Library.2005; 609-651.
6. Borchers AT, Hagie F, Keen CL, Gershwin ME. The History and Contemporary Challenges of the US Food and Drug Administration. Clin Ther. 2007;29(1):1-16.
7. Center for Drug Evaluation and Research, Division of Drug, Marketing, Advertising and Communications. Description .Silver Spring (MD): US FDA. http://fda.gov/cder/ddmac/ [Accessed April 2009]
8. Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising and Communications. CDER Handbook: Warning Letter. Rockville (MD): US FDA. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/DrugMarketingAdvertisingandCommunications/ucm081617.htm [Accessed November 2009]
9. Mintzes B. Disease Mongering in Drug Promotion: Do Governments Have a Regulatory Role? PLoS Med. 2006;3(4):e198.
10. Center for Drug Evaluation and Research, Division of Drug, Marketing, Advertising and Communications. Description. Silver Spring, (MD): US FDA. http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090279.htm [Accessed November 2009]
11. United States Government Accountability Office. GAO-08-758T. Prescription Drugs: Trends in Oversight of Direct-to-Consumer Advertising. May 8, 2008.
12. Klaus Krippendorf. Content analysis: An Introduction to its methodology. Second edition. Thousand Oaks, CA: Sage Publications. 2008.
13. Gunter MJ. The role of the ECHO model in outcomes research and clinical practice improvement. Am J Manag Care. 1999;5(4 Suppl):S217-24.
14. Recent trends in DDMAC enforcement activity. (Aug 28, 2006) Food and Drug e-Alert. http://www.cov.com/files/Publication/0dd2bef8-c1d1-44a5-a7aa-9871458b0088/Presentation/PublicationAttachment/2b5fe504-baa4-4553-9db8-7f9505ed368a/665.pdf [Accessed October 2009]
15. The Best-Selling drugs In America. Pharmaceuticals. (Feb 26, 2006) http://www.forbes.com/2006/02/27/pfizer-merck-genentech-cx_mh_0224topsellingdrugs.html [Accessed April 2009]
16. Partnership to Fight Chronic Disease. http://www.fightchronicdisease.org/ [Accessed April 2009]
17. Trends in DDMAC Enforcement Activity During the Bush Administration. Food and Drug e-Alert; March 30, 2009. http://www.cov.com/files/Publication/6532be42-767e-4c2c-acc0-0c350eed5d8e/Presentation/PublicationAttachment/04b38cf7-655e-45d8-a98d-1cd0f595f212/Trends%20in%20DDMAC%20Enforcement%20Activity%20During%20the%20Bush%20Administration.pdf [Accessed November 2009]
18. Holmes ER, Desselle SP. Evaluating the balance of informative and persuasive content within product-specific print DTC ads. Drug Inf J. 2004;38:83-98.
19. Jackson J. FDAMA 1997 Section 114: Another Look. Value Health.2009;12(2):1-2.
20. Gellad ZF, Lyles KW. Direct-to-consumer advertising of pharmaceuticals. Am J Med. 2007;120(6):475-480.
21. Cardarelli R, Licciardone JC, Taylor LG. A cross-sectional evidence-based review of pharmaceutical promotional marketing brochures and their underlying studies: is what they tell us important and true? BMC Fam Pract. 2006;7:13.
22. Drug Promotion what we know, what we have yet to learn. (2004) http://apps.who.int/medicinedocs/pdf/s8109e/s8109e.pdf [Accessed July 2011]
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