• 1
    U.S. Food and Drug Administration. Guidance for industry development and use of risk minimization action plans. 2005; Available from:
  • 2
    European Medicines Agency. Guideline on risk management systems for medical products for human use. 2008; Incorporated into: Volume 9A of The Rules Governing Medicinal Products in the European Union, Guidelines on Pharmacovigilance for Medicinal Products for Human Use. Part I-3: Requirements for Risk Management Systems; Available from:
  • 3
    Regulation (EU) №1235/2010 amending, as regards pharmacovigilance of medicinal products for human use, Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products, (2010).
  • 4
    The European Parliment and the Council. Directive 2010/84/EU amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use, (2010).
  • 5
    Nkeng L, Cloutier AM, Craig C, Lelorier J, Moride Y. Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review. Drug Saf 2012;35(7):53546. Epub 2012/06/19.
  • 6
    European Medicines Agency. Guideline on good pharmacovigilance practices (GVP). Module XVI-risk monimisation measures: selection of tools and effectiveness indicators. 2013.
  • 7
    Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009: 339.
  • 8
    Cabana MD, Rand CS, Powe NR, et al. Why don't physicians follow clinical practice guidelines? JAMA 1999; 282(15): 14581465.
  • 9
    Hudon E, Beaulieu M-D, Roberge D. Integration of the recommendations of the Canadian Task Force on Preventive Health Care Obstacles perceived by a group of family physicians. Fam Pract 2004; 21(1): 1117.
  • 10
    Shadish WR, Cook TD, Campbell DT. Experimental and Quasi-experimental Designs for Generalized Causal Inference. 2002.
  • 11
    LaPointe NMA, Kramer JM, Weinfurt KP, Califf RM. Practitioner acceptance of the dofetilide risk-management program. Pharmacother: J Hum Pharmacol Drug Ther 2002; 22(8): 10411046.
  • 12
    Mayet S, Manning V, Williams A, Loaring J, Strang J. Impact of training for healthcare professionals on how to manage an opioid overdose with naloxone: effective, but dissemination is challenging. Intern J Drug Pol 2011; 22(1): 915.
  • 13
    Bensouda-Grimaldi L, Jonville-Béra AP, Mouret E, et al., editors. Isotrétinoïne: suivi de l'application des recommandations des prescriptions chez les femmes en âge de procréer. Annales de dermatologie et de vénéréologie; 2005: Elsevier.
  • 14
    Cheung A, Sacks D, Dewa CS, Pong J, Levitt A. Pediatric prescribing practices and the FDA black-box warning on antidepressants. J Dev Behav Pediatr 2008; 29(3): 213215.
  • 15
    Lledo A, Dellva MA, Strombom IM, et al. Awareness of potential valvulopathy risk with pergolide and changes in clinical practice after label change: a survey among European neurologists. Eur J Neurol 2007; 14(6): 644649.
  • 16
    Habib AS, Gan TJ. The use of droperidol before and after the Food and Drug Administration black box warning: a survey of the members of the Society of Ambulatory Anesthesia. J Clin Anesth 2008; 20(1): 3539.
  • 17
    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): 433439.
  • 18
    Schachter DC, Kleinman I. Psychiatrists' attitudes about and informed consent practices for antipsychotics and tardive dyskinesia. Psychiatr Serv 2004; 55(6): 714717.
  • 19
    Lee LY, Kortepeter CM, Willy ME, Nourjah P. Drug-risk communication to pharmacists: assessing the impact of risk-minimization strategies on the practice of pharmacy. J Am Pharm Assoc 2008; 48(4): 494500.
  • 20
    Kurian BT, Ray WA, Arbogast PG, Fuchs DC, Dudley JA, Cooper WO. Effect of regulatory warnings on antidepressant prescribing for children and adolescents. Arch Pediatr Adolesc Med 2007; 161(7): 690696.
  • 21
    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):884891. Epub 2007/06/02.
  • 22
    Valuck R, Libby A, Orton H, Morrato E, Allen R, Baldessarini R. Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psych 2007; 164(8): 11981205.
  • 23
    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): 94101.
  • 24
    Pamer CA, Hammad TA, et al. Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions. Pharmacoepidemiology and Drug Safety 2010; 19(2): 158174.
  • 25
    Smalley W, Shatin D, Wysowski DK, et al. Contraindicated use of cisapride. JAMA 2000; 284(23): 30363039.
  • 26
    Jones JK, Fife D, Curkendall S, Goehring E, Jr, Guo JJ, Shannon M. Coprescribing and codispensing of cisapride and contraindicated drugs. JAMA 2001; 286(13): 16071609.
  • 27
    Weatherby LB, Walker AM, Fife D, Vervaet P, Klausner MA. Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of ‘Dear Doctor’ letters. Pharmacoepidemiol Drug Saf 2001; 10(3): 211218.
  • 28
    Weatherby LB, Nordstrom BL, Fife D, Walker AM. The impact of wording in “Dear doctor” letters and in black box labels. Clin Pharmacol Therapeut-St Louis 2002; 72(6): 735742.
  • 29
    Guo JJ, Curkendall S, Jones JK, Fife D, Goehring E, She D. Impact of cisapride label changes on codispensing of contraindicated medications. Pharmacoepidemiol Drug Saf 2003; 12(4): 295301.
  • 30
    Wilkinson JJ, Force RW, Cady PS. Impact of safety warnings on drug utilization: marketplace life span of cisapride and troglitazone. Pharmacother: J Hum Pharmacol Drug Ther 2004; 24(8): 978986.
  • 31
    Feldstein AC, Smith DH, Perrin N, et al. Improved therapeutic monitoring with several interventions: a randomized trial. Arch Intern Med 2006; 166(17): 18481854.
  • 32
    Paulozzi LJ, Kilbourne EM, Desai HA. Prescription drug monitoring programs and death rates from drug overdose. Pain Med 2011; 12(5): 747754.
  • 33
    Lapane KL, Hughes CM, Daiello LA, Cameron KA, Feinberg J. Effect of a pharmacist-led multicomponent intervention focusing on the medication monitoring phase to prevent potential adverse drug events in nursing homes. J Am Geriatr Soc 2011; 59(7): 12381245.
  • 34
    Trivalle C, Cartier T, Verny C, et al. Identifying and preventing adverse drug events in elderly hospitalised patients: a randomised trial of a program to reduce adverse drug effects. J Nutr Health Aging 2010; 14(1): 5761.
  • 35
    Allen LaPointe NM, Chen A, Hammill B, DeLong E, Kramer JM, Califf RM. Evaluation of the dofetilide risk-management program. Am Heart J 2003; 146(5): 894901.
  • 36
    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): 10051011.
  • 37
    Brinker A, Kornegay C, Nourjah P. Trends in adherence to a revised risk management program designed to decrease or eliminate isotretinoin-exposed pregnancies: evaluation of the accutane SMART program. Arch Dermatol 2005; 141(5): 563.
  • 38
    Uhl K, Cox E, Rogan R, et al. Thalidomide use in the US: experience with pregnancy testing in the S.T.E.P.S. programme. Drug Saf 2006;29(4):321329. Epub 2006/03/30.
  • 39
    McCann L, Maguire R, Miller M, Kearney N. Patients' perceptions and experiences of using a mobile phone-based advanced symptom management system (ASyMS©) to monitor and manage chemotherapy related toxicity. Eur J Canc Care 2009; 18(2): 156164.
  • 40
    Kearney N, McCann L, Norrie J, et al. Evaluation of a mobile phone-based, advanced symptom management system (ASyMS©) in the management of chemotherapy-related toxicity. Support Care Canc 2009; 17(4): 437444.
  • 41
    Murray MD, Ritchey ME, Wu J, Tu W. Effect of a pharmacist on adverse drug events and medication errors in outpatients with cardiovascular disease. Arch Intern Med 2009; 169(8): 757763.
  • 42
    Mazor KM, Andrade SE, Auger J, Fish L, Gurwitz JH. Communicating safety information to physicians: an examination of dear doctor letters. Pharmacoepidemiol Drug Saf 2005; 14(12): 869875.
  • 43
    Melnikow J, Paterniti D, Azari R, et al. Preferences of Women Evaluating Risks of Tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction. Cancer 2005; 103(10): 19962005.
  • 44
    Wagner AK, Chan KA, Dashevsky I, et al. FDA drug prescribing warnings: is the black box half empty or half full? Pharmacoepidemiol Drug Saf 2006; 15(6): 369386.
  • 45
    Dorsey E, Rabbani A, Gallagher SA, Conti RM, Alexander GC. Impact of FDA black box advisory on antipsychotic medication use. Arch Intern Med 2010; 170(1): 96103.
  • 46
    Kurdyak PA, Juurlink DN, Mamdani MM. The effect of antidepressant warnings on prescribing trends in Ontario, Canada. J Inform 2007; 97(4): 750754.
  • 47
    Morrato E, Libby A, Orton H, Brent D, Allen R, Valuck R. Frequency of provider contact after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psych 2008; 165(1): 4250.
  • 48
    Schussel K, Schulz M. Prescribing of COX-2 inhibitors in Germany after safety warnings and market withdrawals. Die Pharmazie-An Intern J Pharmaceut Sci 2006; 61(10): 878886.
  • 49
    Valiyeva E, Herrmann N, Rochon PA, Gill SS, Anderson GM. Effect of regulatory warnings on antipsychotic prescription rates among elderly patients with dementia: a population-based time-series analysis. Can Med Assoc J 2008; 179(5): 438446.
  • 50
    Graham DJ, Drinkard CR, Shatin D, Tsong Y, Burgess MJ. Liver enzyme monitoring in patients treated with troglitazone. JAMA 2001; 286(7): 831833.
  • 51
    Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. JMCP 2008; 14(6): 523531.
  • 52
    Corry M, Bonner G, McEntee S, Dugan J, MacAuley D. Hospitals do not inform GPs about medication that should be monitored. Fam Pract 2000; 17(3): 268271.
  • 53
    Murray ML, Thompson M, Santosh PJ, Wong ICK. Effects of the Committee on Safety of Medicines advice on antidepressant prescribing to children and adolescents in the UK. Drug Safety 2005; 28(12): 11511157.
  • 54
    Jennings HR, Miller EC, Williams TS, Tichenor SS, Woods EA. Reducing anticoagulant medication adverse events and avoidable patient harm. Jt Comm J Qual Patient Saf 2008; 34(4): 196200.
  • 55
    Lederer J, Best D. Reduction in anticoagulation-related adverse drug events using a trigger-based methodology. Jt Comm J Qual Patient Saf 2005; 31(6): 313318.
  • 56
    Morrato EH, Staffa JA. Effectiveness of risk management plans: a case study of pemoline using pharmacy claims data. Pharmacoepidemiol Drug Saf 2007; 16(1): 104112.
  • 57
    Arana A, Allen S, Burkowitz J, et al. Infliximab paediatric Crohn's disease educational plan. Drug Saf 2010; 33(6): 489501.
  • 58
    De Bruin ML, Panneman MJ, Leufkens HG, Hoes AW, Herings RM. Use of cisapride with contraindicated drugs in The Netherlands. Ann Pharmacother 2002; 36(2): 338343.
  • 59
    Morrato EH, Druss B, Hartung DM, et al. Metabolic testing rates in 3 state Medicaid programs after FDA warnings and ADA/APA recommendations for second-generation antipsychotic drugs. Arch Gen Psychiatry 2010; 67(1): 1724.
  • 60
    Nuttall GA, Eckerman KM, Jacob KA, et al. Does low-dose droperidol administration increase the risk of drug-induced QT prolongation and torsade de pointes in the general surgical population? Anesthesiology 2007; 107(4): 531536.
  • 61
    Hetland ML, Unkerskov J, Ravn T, et al. Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO). Scand J Rheumatol 2005; 34(1): 4044.
  • 62
    Nemeroff CB, Kalali A, Keller MB, et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiatry 2007; 64(4): 466472.
  • 63
    Sanfélix-Gimeno G, Cervera-Casino P, Peiró S, López-Valcarcel BG, Blázquez A, Barbera T. Effectiveness of safety warnings in atypical antipsychotic drugs. Drug Saf 2009; 32(11): 10751087.
  • 64
    Trifiro G, Sini G, Sturkenboom MCJM, et al. Prescribing pattern of antipsychotic drugs in the Italian general population 2000–2005: a focus on elderly with dementia. Int Clin Psychopharmacol 2010; 25(1): 2228.
  • 65
    Unger MM, Reese JP, Oertel WH, Eggert KM. Real-life evaluations of compliance with mandatory drug safety monitoring exemplified with tolcapone in Parkinson's disease. Eur Neurol 2008; 60(3): 122126.
  • 66
    Staniscia T, Romano F, Festi D, Bilker WB, Macones GA, Strom BL. Co-dispensing of contraindicated medications in patients using cisapride in Italy. Pharmacoepidemiol Drug Saf 2006; 15(7): 469476.
  • 67
    Meagher DJ. Impact of an educational workshop upon attitudes towards pharmacotherapy for delirium. Int Psychogeriatr 2010; 22(6): 938946.
  • 68
    Shatin D, Gardner JS, Stergachis A, Blough D, Graham D. Impact of mailed warning to prescribers on the co-prescription of tramadol and antidepressants. Pharmacoepidemiol Drug Saf 2005; 14(3): 149154.
  • 69
    Al-Ghamdi SA, Mahmoud MA, Alammari MA, et al. The outcome of pharmacist counseling at the time of hospital discharge: an observational nonrandomized study. Ann Saudi Med 2012; 32(5): 492497.
  • 70
    Gibbons R, Brown C, Hur K, et al. Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatr 2007; 164(9): 13561363.
  • 71
    Lasser KE, Seger DL, Yu DT, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med 2006; 166(3): 338344.
  • 72
    Cluxton RJ, Li Z, Heaton PC, et al. Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio Medicaid program. Pharmacoepidemiol Drug Saf 2005; 14(1): 19.
  • 73
    Prieto L, Spooner A, Hidalgo-Simon A, Rubino A, Kurz X, Arlett P. Evaluation of the effectiveness of risk minimization measures. Pharmacoepidemiol Drug Saf.2012;21(8):896899. Epub 2012/06/26.
  • 74
    Office of Inspector General. FDA Lacks comprehensive data to determine whether risk evaluation and mitigation strategies improve drug safety. 2013.
  • 75
    Lawton K, Skjoet P. Assessment of three systems to empower the patient and decrease the risk of adverse drug events. Stud Health Technol Inform 2011; 166: 246253.
  • 76
    Shiffman S, Gerlach KK, Sembower MA, Rohay JM. Consumer understanding of prescription drug information: an illustration using an antidepressant medication. Ann Pharmacother 2011; 45(4): 452458.
  • 77
    Piening S, Reber KC, Wieringa JE, et al. Impact of safety-related regulatory action on drug use in ambulatory care in the Netherlands. Clin Pharmacol Therapeu 2012; 91(5): 838845.
  • 78
    Morrison P, Meehan T, Gaskill D, Lunney P, Collings P. Enhancing case managers' skills in the assessment and management of antipsychotic medication side-effects. Aust N Z J Psychiatry 2000;34(5):814821. Epub 2000/10/19.