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Drug Safety

, Volume 42, Issue 10, pp 1125–1134 | Cite as

Unintended Effects of Communicating About Drug Safety Issues: A Critical Review of the Literature

  • Jessica T. DeFrankEmail author
  • Lauren McCormack
  • Suzanne L. West
  • Craig Lefebvre
  • Olivia Burrus
Review Article

Abstract

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.

Notes

Compliance with Ethical Standards

Funding

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.

Supplementary material

40264_2019_840_MOESM1_ESM.pdf (85 kb)
Supplementary material 1 (PDF 84 kb)
40264_2019_840_MOESM2_ESM.pdf (219 kb)
Supplementary material 2 (PDF 219 kb)
40264_2019_840_MOESM3_ESM.pdf (48 kb)
Supplementary material 3 (PDF 47 kb)

References

  1. 1.
    Kesselheim AS, Campbell EG, Schneeweiss S, Rausch P, Lappin BM, Zhou EH, et al. Methodological approaches to evaluate the impact of FDA drug safety communications. Drug Saf. 2015;38(6):565–75.  https://doi.org/10.1007/s40264-015-0291-y.CrossRefGoogle Scholar
  2. 2.
    Dusetzina SB, Higashi AS, Dorsey ER, Conti R, Huskamp HA, Zhu S, et al. Impact of FDA drug risk communications on health care utilization and health behaviors: a systematic review. Med Care. 2012;50(6):466–78.  https://doi.org/10.1097/MLR.0b013e318245a160.CrossRefGoogle Scholar
  3. 3.
    Piening S, Haaijer-Ruskamp FM, de Vries JT, van der Elst ME, de Graeff PA, Straus SM, et al. Impact of safety-related regulatory action on clinical practice: a systematic review. Drug Saf. 2012;35(5):373–85.  https://doi.org/10.2165/11599100-000000000-00000.CrossRefGoogle Scholar
  4. 4.
    Briesacher BA, Soumerai SB, Zhang F, Toh S, Andrade SE, Wagner JL, et al. A critical review of methods to evaluate the impact of FDA regulatory actions. Pharmacoepidemiol Drug Saf. 2013;22(9):986–94.  https://doi.org/10.1002/pds.3480.Google Scholar
  5. 5.
    Banerjee AK, Zomerdijk IM, Wooder S, Ingate S, Mayall SJ. Post-approval evaluation of effectiveness of risk minimisation: methods, challenges and interpretation. Drug Saf. 2014;37(1):33–42.  https://doi.org/10.1007/s40264-013-0126-7.CrossRefGoogle Scholar
  6. 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
  7. 7.
    Barry CL, Busch SH. News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics. 2010;125(1):88–95.  https://doi.org/10.1542/peds.2009-0792.CrossRefGoogle Scholar
  8. 8.
    Busch SH, Frank RG, Leslie DL, Martin A, Rosenheck RA, Martin EG, et al. Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns? Psychiatr Serv. 2010;61(1):11–6.  https://doi.org/10.1176/appi.ps.61.1.11.CrossRefGoogle Scholar
  9. 9.
    Bhatia SK, Rezac AJ, Vitiello B, Sitorius MA, Buehler BA, Kratochvil CJ. Antidepressant prescribing practices for the treatment of children and adolescents. J Child Adolesc Psychopharmacol. 2008;18(1):70–80.  https://doi.org/10.1089/cap.2007.0049.CrossRefGoogle Scholar
  10. 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
  11. 11.
    Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry. 2007;164(6):884–91.  https://doi.org/10.1176/ajp.2007.164.6.884.CrossRefGoogle Scholar
  12. 12.
    Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Arch Gen Psychiatry. 2009;66(6):633–9.  https://doi.org/10.1001/archgenpsychiatry.2009.46.CrossRefGoogle Scholar
  13. 13.
    Lu CY, Zhang F, Lakoma MD, Madden JM, Rusinak D, Penfold RB, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014;348:g3596.  https://doi.org/10.1136/bmj.g3596.CrossRefGoogle Scholar
  14. 14.
    Nemeroff CB, Kalali A, Keller MB, Charney DS, Lenderts SE, Cascade EF, et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiatry. 2007;64(4):466–72.  https://doi.org/10.1001/archpsyc.64.4.466.CrossRefGoogle Scholar
  15. 15.
    Olfson M, Marcus SC, Druss BG. Effects of Food and Drug Administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry. 2008;65(1):94–101.  https://doi.org/10.1001/archgenpsychiatry.2007.5.CrossRefGoogle Scholar
  16. 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. 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. 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. 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
  20. 20.
    Katz LY, Kozyrskyj AL, Prior HJ, Enns MW, Cox BJ, Sareen J. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. Can Med Assoc J. 2008;178(8):1005–11.CrossRefGoogle Scholar
  21. 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. 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. 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. 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.
  25. 25.
    Cohen A, Rabbani A, Shah N, Alexander GC. Changes in glitazone use among office-based physicians in the U.S., 2003–2009. Diabetes Care. 2010;33(4):823–5.  https://doi.org/10.2337/dc09-1834.CrossRefGoogle Scholar
  26. 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
  27. 27.
    Shi L, Zhao Y, Szymanski K, Yau L, Fonseca V. Impact of thiazolidinedione safety warnings on medication use patterns and glycemic control among veterans with diabetes mellitus. J Diabetes Complicat. 2011;25(3):143–50.  https://doi.org/10.1016/j.jdiacomp.2010.06.003.CrossRefGoogle Scholar
  28. 28.
    Garfield CF, Dorsey ER, Zhu S, Huskamp HA, Conti R, Dusetzina SB, et al. Trends in attention deficit hyperactivity disorder ambulatory diagnosis and medical treatment in the United States, 2000–2010. Acad Pediatr. 2012;12(2):110–6.  https://doi.org/10.1016/j.acap.2012.01.003.CrossRefGoogle Scholar
  29. 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
  30. 30.
    Dorsey ER, Rabbani A, Gallagher SA, Conti RM, Alexander GC. Impact of FDA black box advisory on antipsychotic medication use. Arch Intern Med. 2010;170(1):96–103.  https://doi.org/10.1001/archinternmed.2009.456.CrossRefGoogle Scholar
  31. 31.
    Gleason PP, Walters C, Heaton AH, Schafer JA. Telithromycin: the perils of hasty adoption and persistence of off-label prescribing. J Manag Care Pharm. 2007;13(5):420–5.  https://doi.org/10.18553/jmcp.2007.13.5.420.Google Scholar
  32. 32.
    Bradford WD, Kleit AN. Impact of FDA actions, DTCA, and public information on the market for pain medication. Health Econ. 2015;24(7):859–75.  https://doi.org/10.1002/hec.3067.CrossRefGoogle Scholar
  33. 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
  34. 34.
    Shrank WH, Choudhry NK, Tong A, Myers J, Fischer MA, Swanton K, et al. Warnings without guidance: patient responses to an FDA warning about ezetimibe. Med Care. 2012;50(6):479–84.  https://doi.org/10.1097/MLR.0b013e31825517b6.CrossRefGoogle Scholar
  35. 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. 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. 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.
  38. 38.
    Schwartz LM, Woloshin S, Welch HG. Using a drug facts box to communicate drug benefits and harms: two randomized trials. Ann Intern Med. 2009;150(8):516–27.CrossRefGoogle Scholar
  39. 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
  40. 40.
    Peters E, Klein W, Kaufman A, Meilleur L, Dixon A. More is not always better: intuitions about effective public policy can lead to unintended consequences. Soc Issues Policy Rev. 2013;7(1):114–48.  https://doi.org/10.1111/j.1751-2409.2012.01045.x.CrossRefGoogle Scholar
  41. 41.
    Cho H, Salmon CT. Unintended effects of health communication campaigns. J Commun. 2007;57(2):293–317.  https://doi.org/10.1111/j.1460-2466.2007.00344.x.CrossRefGoogle Scholar
  42. 42.
    Fischhoff B, Bostrom A, Quadrel MJ. 8.9 Risk perception and communication. Cardiovasc Dis. 2011;3:49.Google Scholar
  43. 43.
    Brewer NT, DeFrank JT, Gilkey MB. Anticipated regret and health behavior: a meta-analysis. Health Psychol Rev. 2016;35(11):1264–75.  https://doi.org/10.1037/hea0000294.CrossRefGoogle Scholar
  44. 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. 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.
  46. 46.
    Penfold RB, Zhang F. Use of interrupted time series analysis in evaluating health care quality improvements. Acad Pediatr. 2013;13(6):S38–44.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Communication ScienceRTI InternationalResearch Triangle ParkUSA

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