Adverse Events: The More You Search, the More You Find

Editorials21 February 2006Adverse Events: The More You Search, the More You FindJohn P.A. Ioannidis, MD, Cynthia D. Mulrow, MD, MSc, Deputy Editor, and Steven N. Goodman, MD, PhDJohn P.A. Ioannidis, MDFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205., Cynthia D. Mulrow, MD, MSc, Deputy EditorFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205., and Steven N. Goodman, MD, PhDFrom the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-4-200602210-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail People want reliable information about potential harms of medications. Concerns about possible adverse effects guide therapy selections, and unpleasant surprises about unsuspected harms cause anxiety and make headlines (1). We often rely on compendia and product inserts for information about such effects. These materials offer litanies of possible adverse events, sometimes accompanied by an estimate of how often those events might occur. From whence are these estimates derived? What do they really mean? How can we better measure and understand how many and what kinds of harms may be caused by medications?Sources of Evidence about Medication-Related HarmsWe can ...References1. Topol EJ. Failing the public health—rofecoxib, Merck, and the FDA. N Engl J Med. 2004;351:1707-9. [PMID: 15470193] CrossrefMedlineGoogle Scholar2. Kaufman DW, Shapiro S. Epidemiological assessment of drug-induced disease. Lancet. 2000;356:1339-43. [PMID: 11073036] CrossrefMedlineGoogle Scholar3. Papanikolaopu PN, Christidi G, Ioannidis JPA. Large-scale evidence on harms of medical interventions: randomized, controlled trials versus observational studies. CMAJ [In press]. Google Scholar4. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215-20. [PMID: 11980521] CrossrefMedlineGoogle Scholar5. Bent S, Padula A, Avins AL. Brief communication: better ways to question patients about adverse medical events. A randomized, controlled trial. Ann Intern Med. 2006;144:257-61. LinkGoogle Scholar6. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337:725-33. [PMID: 9287227] CrossrefMedlineGoogle Scholar7. Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999;341:1865-73. [PMID: 10601505] CrossrefMedlineGoogle Scholar8. Götzsche PC. Non-steroidal anti-inflammatory drugs. BMJ. 2000;320:1058-61. [PMID: 10764369] CrossrefMedlineGoogle Scholar9. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA. 2001;285:437-43. [PMID: 11242428] CrossrefMedlineGoogle Scholar10. Ioannidis JP, Evans SJ, Götzsche PC, O'Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781-8. [PMID: 15545678] LinkGoogle Scholar11. Jonville-Béra AP, Giraudeau B, Autret-Leca E. Reporting of drug tolerance in randomized clinical trials: when data conflict with authors' conclusions. Ann Intern Med. 2006;144:306-7. LinkGoogle Scholar12. Papanikolaou PN, Ioannidis JP. Availability of large-scale evidence on specific harms from systematic reviews of randomized trials. Am J Med. 2004;117:582-9. [PMID: 15465507] CrossrefMedlineGoogle Scholar13. Strand CV, Simon LS, Tugwell P, Brooks P, Boers M. OMERACT 7 International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials. Introduction. Accessed at jrheum.com/archives/oct05.html on 10 January 2006. Google Scholar14. Bonhoeffer J, Kohl K, Chen R, Duclos P, Heijbel H, Heininger U, et al. The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI). Vaccine. 2002;21:298-302. [PMID: 12450705] CrossrefMedlineGoogle Scholar15. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176-81. [PMID: 12903007] CrossrefMedlineGoogle Scholar16. Venning GR. Identification of adverse reactions to new drugs. II—How were 18 important adverse reactions discovered and with what delays? Br Med J (Clin Res Ed). 1983;286:289-92. [PMID: 6218859] CrossrefMedlineGoogle Scholar17. Centers for Education and Research on Therapeutics Risk Assessment Workshop. Risk assessment of drugs, biologics and therapeutic devices: present and future issues. Pharmacoepidemiol Drug Saf. 2003;12:653-62. [PMID: 14762981] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the University of Ioannina School of Medicine, Ioannina 45110, Greece; American College of Physicians, Philadelphia, PA 19106; and Johns Hopkins School of Medicine, Baltimore, MD 21205.Disclosures: None disclosed.Corresponding Author: John P.A. Ioannidis, MD, Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece; e-mail, [email protected]uoi.gr.Current Author Addresses: Dr. Ioannidis: Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.Dr. Mulrow: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.Dr. Goodman: Division of Biostatistics, Johns Hopkins Sidney Kimmel Cancer Center, Suite 1103, 550 North Broadway, Baltimore, MD 21205. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBrief Communication: Better Ways To Question Patients about Adverse Medical Events Stephen Bent , Amy Padula , and Andrew L. 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Some Dilemmas of Data Monitoring in Clinical TrialsSteven N. Goodman, MD, MHS, PhDThe safety of etanercept for the treatment of plaque psoriasisAdverse-event rates: journals versus databasesAntimicrobial-Associated QT Interval Prolongation: Pointes of InterestCurrent awareness: Pharmacoepidemiology and drug safetyHypothyroidism Associated with Quetiapine Therapy; Paradoxical Bronchospasm Associated with Albuterol; Alcohol Cravings with Paroxetine Therapy?; Lamotrigine-Induced Toxic Epidermal Necrolysis – Three Cases; Acute Lung Injury with Vinorelbine; Adverse Events Related to Epinephrine Use in Asthma Patients Seen in the Emergency Department; Collecting Information from Patients Having Adverse Events; New Anticonvulsants – New Adverse EffectsRecent Publications on Medications and PharmacySystemic Therapy for Breast Cancer: Using Toxicity Data to Inform Decisions 21 February 2006Volume 144, Issue 4Page: 298-300KeywordsAdverse eventsAdverse reactionsClinical epidemiologyClinical trialsDrugsEvidence based medicineObservational studiesToxicity ePublished: 21 February 2006 Issue Published: 21 February 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. 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