Unintended Effects of Communicating About Drug Safety Issues: A Critical Review of the Literature
Communications about the safety and effectiveness of human drugs can influence patients’ and prescribers’ perceptions and behaviors, which in turn can affect the public’s health more broadly. We conducted a critical review of the literature on the unintended effects from communicating information to the public about safety issues with prescription and over-the-counter drugs. We searched PubMed for peer-reviewed studies published from 1990 to 2017 where study authors reported probable unintended effects of communicating drug safety. The types of communications included in these studies were news reports, direct-to-consumer advertisements, and those released by government agencies. Among the 26 studies identified, the most commonly reported unintended effects were decreased drug use or discontinuation. Other unintended effects included spillover to populations not targeted by the communications (e.g., discontinuation of antidepressants among adults following communications concerning use among youth), shifts in clinical diagnoses (e.g., fewer diagnoses of depression), increased use of alternative therapies, and other undesirable behaviors (e.g., possible increased suicide attempts because antidepressants were discontinued). Limitations to the literature include the inability to establish causation or to isolate the effects of multiple communication sources and messages. Further, because the intended effect of many communications was not known, our study was limited by challenges in defining some effects as unintended. Most studies used health insurer claims data to identify unintended effects of communications, which provide an incomplete picture; few used self-reported or other methodologies that could help illuminate the reasons underlying the effects observed in the claims data. Best practices for communicating about the potential benefits and harms of drugs in a manner that minimizes negative unintended effects are needed to protect and improve public health.
Compliance with Ethical Standards
The US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Communications funded and participated in all phases of this project through a cooperative agreement with RTI International, award U18 FD004608-01. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the US Food and Drug Administration, Center for Drug Evaluation and Research or the US Department of Health and Human Services.
Conflict of interest
Jessica DeFrank, Lauren McCormack, Craig Lefebvre, Suzanne L. West, and Olivia Burrus have no conflicts of interest that are directly relevant to the content of this study.
- 6.Sobel RE, Bate A, Marshall J, Haynes K, Selvam N, Nair V, et al. Do FDA label changes work? Assessment of the 2010 class label change for proton pump inhibitors using the Sentinel System’s analytic tools. Pharmacoepidemiol Drug Saf. 2018;27(3):332–9. https://doi.org/10.1002/pds.4392.CrossRefGoogle Scholar
- 10.Gibbons RD, Brown CH, Hur K, Marcus SM, Bhaumik DK, Erkens JA, et al. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164(9):1356–63. https://doi.org/10.1176/appi.ajp.2007.07030454.CrossRefGoogle Scholar
- 16.Richardson LP, Lewis CW, Casey-Goldstein M, McCauley E, Katon W. Pediatric primary care providers and adolescent depression: a qualitative study of barriers to treatment and the effect of the black box warning. J Adolesc Health. 2007;40(5):433–9. https://doi.org/10.1016/j.jadohealth.2006.12.006.CrossRefGoogle Scholar
- 17.Singh T, Prakash A, Rais T, Kumari N. Decreased use of antidepressants in youth after US Food and Drug Administration black box warning. Psychiatry (Edgmont). 2009;6(10):30–4.Google Scholar
- 18.Valuck RJ, Libby AM, Orton HD, Morrato EH, Allen R, Baldessarini RJ. Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry. 2007;164(8):1198–205. https://doi.org/10.1176/appi.ajp.2007.07010007.CrossRefGoogle Scholar
- 19.Bobo WV, Epstein RA Jr, Hayes RM, Shelton RC, Hartert TV, Mitchel E, et al. The effect of regulatory advisories on maternal antidepressant prescribing, 1995–2007: an interrupted time series study of 228,876 pregnancies. Arch Womens Ment Health. 2014;17(1):17–26. https://doi.org/10.1007/s00737-013-0383-6.CrossRefGoogle Scholar
- 21.Wheeler BW, Gunnell D, Metcalfe C, Stephens P, Martin RM. The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18s in the United Kingdom: ecological study. BMJ. 2008;336(7643):542–5. https://doi.org/10.1136/bmj.39462.375613.BE.CrossRefGoogle Scholar
- 22.US Food and Drug Administration. Suicidality in children and adolescents being treated with antidepressant medications. Postmarket drug safety information for patients and providers. 2004. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm161679.htm. Accessed 6 Nov 2018.
- 23.Government of Canada. Archived: Health Canada advises of potential adverse effects of SSRIs and other anti-depressants on newborns. Recalls and safety alerts. 2004. http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2004/13187a-eng.php. Accessed 6 Nov 2018.
- 24.US Food and Drug Administration. Information for healthcare professionals rosiglitazone maleate (marketed as Avandia, Avandamet, and Avandaryl). Postmarket drug safety information for patients and providers. 2007. http://wayback.archive-it.org/7993/20170112032232/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm143406.htm. Accessed 6 Nov 2018.
- 26.Orrico KB, Lin JK, Wei A, Yue H. Clinical consequences of disseminating the rosiglitazone FDA safety warning. Am J Manag Care. 2010;16(5):e111–6.Google Scholar
- 29.Vetter VL, Elia J, Erickson C, Berger S, Blum N, Uzark K, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder [corrected]: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117(18):2407–23. https://doi.org/10.1161/CIRCULATIONAHA.107.189473.CrossRefGoogle Scholar
- 33.Paschall S, Kaunitz AM. Depo-Provera and skeletal health: a survey of Florida obstetrics and gynecologist physicians. Contraception. 2008;78(5):370–6. https://doi.org/10.1016/j.contraception.2008.07.022.CrossRefGoogle Scholar
- 35.US Food and Drug Administration. Early communication about an ongoing data review for ezetimibe/simvastatin (marketed as Vytorin), ezetimibe (marketed as Zetia), and simvastatin (marketed as Zocor). Postmarket drug safety information for patients and providers. 2008. https://wayback.archive-it.org/7993/20170722191107/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070779.htm. Accessed 6 Nov 2018.
- 36.US Food and Drug Administration. COX-2 selective (includes Bextra, Celebrex, and Vioxx) and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Postmarket drug safety information for patients and providers. 2005. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm429364.htm. Accessed 6 Nov 2018.
- 37.Pharmacia & Upjohn Company. Depo-Provera contraceptive injection: physician information. Kalamazoo (MI): Pharmacia & Upjohn Company; 2004. https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20246s025lbl.pdf. Accessed 27 May 2019.
- 39.McCormack L, Craig Lefebvre R, Bann C, Taylor O, Rausch P. Consumer understanding, preferences, and responses to different versions of drug safety messages in the United States: a randomized controlled trial. Drug Saf. 2016;39(2):171–84. https://doi.org/10.1007/s40264-015-0358-9.CrossRefGoogle Scholar
- 42.Fischhoff B, Bostrom A, Quadrel MJ. 8.9 Risk perception and communication. Cardiovasc Dis. 2011;3:49.Google Scholar
- 44.Institute of Medicine. Characterizing and communicating uncertainty in the assessment of benefits and risks of pharmaceutical products: workshop summary. Washington, DC: National Academies Press; 2014.Google Scholar
- 45.US Food and Drug Administration. Enhancing benefit-risk assessment in regulatory decision-making. 2015. http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm326192.htm. Accessed May 2015.