Methodological Approaches to Evaluate the Impact of FDA Drug Safety Communications
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When the US FDA approves a new prescription drug there is still a great deal remaining to be learned about the safe and proper use of that product. When new information addressing these topics emerges post-approval, the FDA may issue a Drug Safety Communication (DSC) to alert patients and physicians. The effectiveness of the communication—how drug safety messaging conveyed in FDA DSCs changes patient or prescriber behavior—may depend on multiple factors, including the way physicians and patients learn about the information, their understanding of the issues conveyed, and their perception of the importance of the information. In 2013, the FDA issued two DSCs addressing critical new warnings related to products containing the sedative/hypnotic zolpidem.
In this article, we describe a core set of research initiatives that can be used to study how zolpidem-related DSCs affected subsequent physician and patient decision making.
These research initiatives include analyzing drug utilization patterns and related health outcomes; comparing zolpidem-containing products against a comparator with similar indications [eszopiclone (Lunesta)] not covered by the 2013 DSCs; and surveying patients and qualitatively evaluating the dissemination of information regarding these drugs in traditional and social-media channels.
Using an integrated, multidisciplinary approach, we can obtain information that can be used to optimize regulatory communications by seeking to understand the impact of the information contained in FDA risk communications.
KeywordsZolpidem Risk Communication News Story Eszopiclone Safety Message
The authors would like to thank the following persons: Lee Zwanziger, PhD, Office of Planning, Office of the Commissioner; Amy Ramanadham, PharmD, MS, Office of the Center Director, Center for Drug Evaluation and Research (CDER); and Solomon Iyasu, MD, MPH, Office of Surveillance and Epidemiology (OSE), CDER, for their scientific support. In addition, the authors would also like to thank Katrina Garry, Denise Jones, and Rita Noel, OSE Contracts Management Team, and Larry Russell, MS, OSE Regulatory Support Staff, for their administrative support.
Conflicts of interest
Sebastian Schneeweiss is a consultant to WHISCON LLC, a consulting company specializing in the conduct of drug safety database studies. He is also a consultant to, and owns some equities in, Aetion, Inc., a software company specializing in the analyses of healthcare databases. Paula Rausch, Brian M. Lappin, Esther H. Zhou, and Gerald J. Dal Pan are employed by the FDA, which commissioned this study. John D. Seeger is a consultant to both WHISCON LLC and Optum. John S. Brownstein owns shares in, and is employed as consultant to, Epidemico, Inc., a technology company that develops social-media mining tools for drug safety. Steven Woloshin and Lisa M. Schwartz were paid under a subcontract for work on this project and are co-founders of Informulary, Inc., a company that provides data regarding the benefit, harms, and uncertainties of prescription drugs. Aaron S. Kesselheim, Eric G. Campbell, Timothy Toomey, and Jerry Avorn have no conflicts of interest that are directly relevant to the content of this study.
Compliance with ethical standards
This study was funded by the Center for Drug Evaluation and Research at the FDA (Contract Number HHSF22301001T). Dr. Kesselheim is also supported by a Greenwall Faculty Scholarship in Bioethics.
- 1.Avorn J. Powerful medicines: the benefits, risks, and costs of prescription drugs. New York: Alfred A. Knopf; 2004.Google Scholar
- 4.Assche GV, Van Ranst M, Sciot R, Bénédicte D, et al. Progressive multifocal leukoencephalopathy after natalizumab for Crohn’s disease. N Engl J Med. 2005;353:363–8.Google Scholar
- 7.Food and Drug Administration. FDA drug safety communication: abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). http://www.fda.gov/drugs/drugsafety/ucm269086.htm (2011). Accessed 24 July 2014.
- 8.Food and Drug Administration. FDA drug safety communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. http://www.fda.gov/drugs/drugsafety/ucm256581.htm (2011). Accessed 24 July 2014.
- 10.Food and Drug Administration. Drug safety and availability. http://www.fda.gov/Drugs/DrugSafety/default.htm (2014). Accessed 24 July 2014.
- 11.Food and Drug Administration. Drug safety communications. http://www.fda.gov/Drugs/DrugSafety/ucm199082.htm (2014). Accessed 24 July 2014.
- 13.Food and Drug Administration. Drug details: Ambien. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed 27 Apr 2015.
- 14.Food and Drug Administration. Ambien approval letter(s) and printed labeling. http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/019908_S000_AP&AE_LTRS&FPL.pdf (2005). Accessed 13 July 2005.
- 15.Parker I. The big sleep. New Yorker. http://www.newyorker.com/magazine/2013/12/09/the-big-sleep-2 (2013). Accessed 9 Dec 2013.
- 17.Hoque R, Chesson AL Jr. Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem. J Clin Sleep Med. 2009;5(5):471–6.PubMedCentralPubMedGoogle Scholar
- 18.Food and Drug Administration. Drug safety communication: risk of next morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). http://www.fda.gov/downloads/Drugs/DrugSafety/UCM335007.pdf (2013). Accessed 24 July 2014.
- 19.Food and Drug Administration. Drug safety communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR. http://www.fda.gov/Drugs/DrugSafety/ucm352085.htm (2013). Accessed 24 July 2014.
- 25.Grilli R, Ramsay C, Minozzi S. Mass media interventions: effects on health services utilisation. Cochrane Database Syst Rev. 2002;2:CD000389.Google Scholar
- 26.Harrabin R, Coote A, Allen J. Health in the news: risk, reporting and media influence. London: King’s Fund Publications; 2003.Google Scholar
- 27.Kovach B, Rosenstiel T, Mitchell A. A first step to change: a commentary on the findings. Committee of Concerned Journalists and Pew Research Center for the People and the Press. http://people-press.org/reports/display.php3?PageID_616 (2003). Accessed 24 July 2014.
- 41.Eysenbach G, Kohler CH. What is the prevalence of health-related searches on the World Wide Web? Qualitative and quantitative analysis of search engine queries on the internet. AMIA Annu Symp Proc. 2003;225–9.Google Scholar
- 42.Food and Drug Administration. MedWatcher mobile app. http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/ucm385880.htm (2014). Accessed 24 July 2014.
- 44.Miles MB, Huberman AM. Qualitative data analysis: an expanded sourcebook. Thousand Oaks: Sage Publications; 1994.Google Scholar
- 45.Crabtree BF, Miller WL. Doing qualitative research. Thousand Oaks: Sage Publications; 1999.Google Scholar
- 46.Corbin J, Strauss AL. Basics of qualitative research: grounded theory procedures and techniques. 3rd ed. Thousand Oaks: Sage Publications; 2008.Google Scholar
- 49.Dillman DA. Mail and internet surveys: the tailored design method. 2nd ed. New York: Wiley; 2000.Google Scholar
- 50.Dykema J, Cyffka K, Jacques K, Ganci R, Elver K, Stevenson J. SHOW me the money? Effects of preincentives, differential incentives, and envelope messaging in an ABS mail survey. AAPOR J. 2012;5407–21. https://www.amstat.org/sections/SRMS/Proceedings/y2012/Files/400221_500635.pdf
- 54.Cook TD, Campbell DT. Quasi-experiments: interrupted time-series designs. In: Cook TD, Campbell DT, editors. Quasi-experimentation: design and analysis issues for field settings. Boston: Houghton-Mifflin Co.; 1979.Google Scholar