Drug Safety

, Volume 37, Issue 1, pp 53–64

Comparing Time to Adverse Drug Reaction Signals in a Spontaneous Reporting Database and a Claims Database: A Case Study of Rofecoxib-Induced Myocardial Infarction and Rosiglitazone-Induced Heart Failure Signals in Australia

  • Izyan A.Wahab
  • Nicole L. Pratt
  • Lisa M. Kalisch
  • Elizabeth E. Roughead
Original Research Article

Abstract

Introduction

The objective of post-marketing surveillance of medicines is to rapidly detect adverse drug reactions (ADRs). Early ADR detection will enable policy makers and health professionals to recognise adverse events that may not have been identified in pre-marketing clinical trials. Multiple methods exist for ADR signal detection. Traditional quantitative methods employed in spontaneous reports data have include reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian techniques. With the development of administrative health claims databases, additional methods such as sequence symmetry analysis (SSA) may be able to be employed routinely to confirm ADR signals.

Objective and Method

We tested the time to signal detection of quantitative ADR signalling methods in a health claims database (SSA) and in a spontaneous reporting database (ROR, PRR, Bayesian confidence propagation neural network) for rofecoxib-induced myocardial infarction and rosiglitazone-induced heart failure.

Results

This study demonstrated that all four signalling methods detected safety signals within 1–3 years of market entry or subsidisation of the medicines, and for both cases the signals were detected before post-marketing clinical trial results. By contrast, the trial results and subsequent warning or withdrawal were published 5–7 years after first marketing of these medicines.

Conclusion

This case study highlights that a post-marketing quantitative method utilising administrative claims data can be a complementary tool to traditional quantitative methods employed in spontaneous reports that may help to verify safety signals detected in spontaneous reporting data.

References

  1. 1.
    Paludetto M-N, Olivier-Abbal P, Montastruc J-L. Is spontaneous reporting always the most important information supporting drug withdrawals for pharmacovigilance reasons in France? Pharmacoepidemiol Drug Saf. 2012;21(12):1289–94.PubMedCrossRefGoogle Scholar
  2. 2.
    Clarke A, Deeks JJ, Shakir SAW. An assessment of the publicly disseminated evidence of safety used in decisions to withdraw medicinal products from the UK and US markets. Drug Saf. 2006;29(2):175–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Wood AJJ. Thrombotic thrombocytopenic purpura and clopidogrel—a need for new approaches to drug safety. N Engl J Med. 2000;342(24):1824–6.PubMedCrossRefGoogle Scholar
  4. 4.
    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(17):2215–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Roughead E, Semple S. Medication safety in acute care in Australia: where are we now? Part 1: a review of the extent and causes of medication problems 2002–2008. Aust N Z Health Policy. 2009;6(1):18.CrossRefGoogle Scholar
  6. 6.
    Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Wu C, Bell CM, Wodchis WP. Incidence and economic burden of adverse drug reactions among elderly patients in Ontario emergency departments: a retrospective study. Drug Saf. 2012;35(9):769–81.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Vioxx (rofecoxib). Medicine recall. 2004. http://www.tga.gov.au/safety/recalls-medicine-vioxx-041001.htm. Accessed 10 Jul 2013.
  9. 9.
    Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365(9458):475–81.PubMedGoogle Scholar
  10. 10.
    United States Department of Health and Human Services, Food and Drug Administration. FDA news release: FDA adds boxed warning for heart-related risks to anti-diabetes drug Avandia. 2007. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109026.htm. Accessed 2 Dec 2012.
  11. 11.
    European Medicines Agency. European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim: anti-diabetes medication to be taken off the market. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2010/09/WC500096996.pdf. Accessed 20 Dec 2012.
  12. 12.
    Australian Government Department of Health and Ageing Therapeutic Goods Administration. Product information, Avandia (rosiglitazone). 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06879-3. Accessed 2 May 2013.
  13. 13.
    United States Department of Health and Human Services, Food and Drug Administration. Drugs@FDA. FDA approved drug products. AVANDIA (rosiglitazone maleate) tablets. 2007. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf. Accessed 2 May 2013.
  14. 14.
    Evans SJW, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf. 2001;10(6):483–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Egberts ACG, Meyboom RHB, Van Puijenbroek EP. Use of measures of disproportionality in pharmacovigilance: three Dutch examples. Drug Saf. 2002;25(6):453–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol. 1998;54(4):315–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Hallas J. Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis. Epidemiology. 1996;7(5):478–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Caughey GE, Roughead EE, Pratt N, Killer G, Gilbert AL. Stroke risk and NSAIDs: an Australian population-based study. Med J Aust. 2011;195(9):525–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Corrao G, Botteri E, Bagnardi V, Zambon A, Carobbio A, Falcone C, et al. Generating signals of drug-adverse effects from prescription databases and application to the risk of arrhythmia associated with antibacterials. Pharmacoepidemiol Drug Saf. 2005;14(1):31–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Bytzer P, Hallas J. Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions. Aliment Pharmacol Ther. 2000;14(11):1479–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Hallas J, Bytzer P. Screening for drug related dyspepsia: An analysis of prescription symmetry. Eur J Gastroenterol Hepatol. 1998;10(1):27–32.PubMedCrossRefGoogle Scholar
  22. 22.
    Hersom K, Neary MP, Levaux HP, Klaskala W, Strauss JS. Isotretinoin and antidepressant pharmacotherapy: a prescription sequence symmetry analysis. J Am Acad Dermatol. 2003;49(3):424–32.PubMedCrossRefGoogle Scholar
  23. 23.
    Lindberg G, Hallas J. Cholesterol-lowering drugs and antidepressants—a study of prescription symmetry. Pharmacoepidemiol Drug Saf. 1998;7(6):399–402.PubMedCrossRefGoogle Scholar
  24. 24.
    Silwer L, Petzold M, Hallas J, Lundborg CS. Statins and nonsteroidal anti-inflammatory drugs—an analysis of prescription symmetry. Pharmacoepidemiol Drug Saf. 2006;15(7):510–1.PubMedCrossRefGoogle Scholar
  25. 25.
    Tsiropoulos I, Andersen M, Hallas J. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis. Pharmacoepidemiol Drug Saf. 2009;18(6):483–91.PubMedCrossRefGoogle Scholar
  26. 26.
    Vegter S, De Jong-Van Den Berg LTW. Misdiagnosis and mistreatment of a common side-effect—angiotensin-converting enzyme inhibitor-induced cough. Brit J Clin Pharmacol. 2010;69(2):200–3.CrossRefGoogle Scholar
  27. 27.
    Wahab IA, Pratt NL, Wiese MD, Kalisch LM, Roughead EE. The validity of sequence symmetry analysis (SSA) for adverse drug reaction signal detection. Pharmacoepidemiol Drug Saf. 2013;22(5):496–502.PubMedCrossRefGoogle Scholar
  28. 28.
    Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Database of Adverse Event Notifications. 2012. http://www.tga.gov.au/daen/daen-report.aspx. Accessed 26 Nov 2012.
  29. 29.
    MedDRA MSSO (Medical Dictionary for Regulatory Activities, Maintenance and Support Services Organization). 2012. http://www.meddra.org/about-meddra/organisation/msso. Accessed 7 Apr 2013.
  30. 30.
    Australian Government Department of Health and Ageing Therapeutic Goods Administration. Medical Dictionary for Regulatory Activities-MedDRA. 2013. http://www.tga.gov.au/safety/daen-meddra.htm. Accessed 7 Apr 2013.
  31. 31.
    Gould AL. Practical pharmacovigilance analysis strategies. Pharmacoepidemiol Drug Saf. 2003;12(7):559–74.PubMedCrossRefGoogle Scholar
  32. 32.
    Hauben M, Madigan D, Gerrits CM, Walsh L, Van Puijenbroek EP. The role of data mining in pharmacovigilance. Expert Opin Drug Saf. 2005;4(5):929–48.PubMedCrossRefGoogle Scholar
  33. 33.
    Australian Government Department of Veterans’ Affairs. Treatment population statistics. Quarterly report—March 2011. 2011. http://www.dva.gov.au/aboutDVA/Statistics/Documents/TpopMar2011.pdf. Accessed 27 Jul 2011.
  34. 34.
    World Health Organization Collaborating Centre for Drug Statistics Methodology. Anatomical Therapeutic Chemical Code Classification/Defined Daily Dose Index. 2011. http://www.whocc.no/atc_ddd_index/. Accessed 28 Feb 2011.
  35. 35.
    Australian Government, Department of Health and Ageing. Schedule of pharmaceutical benefits. PBS for health professional. 2011. http://www.pbs.gov.au/info/healthpro/explanatory-notes/section1/Section_1_2_Explanatory_Notes. Accessed 28 Feb 2011.
  36. 36.
    National Centre for Classification in Health. International statistical classification of diseases and related health problems, tenth Revision, Australian modification (ICD-10-AM). Sydney: National Centre for Classification in Health, Faculty of Health Sciences, University of Sydney; 2004.Google Scholar
  37. 37.
    Australian Government. Department of Health and Ageing. Therapeutic Goods Administration. 2012. http://www.tga.gov.au/. Accessed 2 Dec 2012.
  38. 38.
    United States of Health and Human Services. Food and Drug Administration (FDA). Drugs@FDA. FDA approved drug products. 2012. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed 2 Dec 2012.
  39. 39.
    Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Australian adverse drug reactions bulletin. 2012. http://www.tga.gov.au/hp/aadrb.htm. Accessed 2 Dec 2012.
  40. 40.
    Australian Government. Medicare Australia. Medicare Australia statistics. 2013. https://www.medicareaustralia.gov.au/statistics/pbs_item.shtml. Accessed 3 April 2013.
  41. 41.
    Australian Government, Department of Health and Ageing. Australian statistics on medicines. 2012. http://www.pbs.gov.au/info/statistics/asm/asm-2009. Accessed 16 Apr 2013.
  42. 42.
    New drugs. Rofecoxib. Aust Prescr. 2000;23:137–9.Google Scholar
  43. 43.
    Langman MJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with nsaids. JAMA. 1999;282(20):1929–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Feldman M, McMahon AT. Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs, with less gastrointestinal toxicity? Ann Intern Med. 2000;132(2):134–43.PubMedCrossRefGoogle Scholar
  45. 45.
    United States Food and Drug Administration. Drug approval package. Voxx (rofecoxib) tablets. Company: Merck Research Laboratories. Application no.: 021042 & 021052. http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/021042_52_Vioxx.cfm. Accessed 17 May 2013.
  46. 46.
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343(21):1520–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Cheng JC, Siegel LB, Katari B, Traynoff SA, Ro JO. Nonsteroidal anti-inflammatory drugs and aspirin: a comparison of the antiplatelet effects. Am J Ther. 1997;4(2–3):62–5.PubMedCrossRefGoogle Scholar
  48. 48.
    United States Food and Drug Administration. Sequence of events with VIOXX, since opening of IND. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_04_E-FDA-TAB-C.htm. Accessed 17 May 2013.
  49. 49.
    United States Food and Drug Administration. NDA 21-042: VIOXX tablets. NDA 21-052: VIOXX oral suspension (rofecoxib). http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2_01_merck.pdf. Accessed 17 May 2013.
  50. 50.
    United States of America, Food and Drug Administration, Centre for Drug Evaluation and Research. Medical review (rofecoxib). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-042S007_Vioxx_medr_P1.pdf. Accessed 16 May 2013.
  51. 51.
    Konstam MA, Weir MR, Reicin A, Shapiro D, Sperling RS, Barr E, et al. Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. Circulation. 2001;104(19):2280–8.PubMedCrossRefGoogle Scholar
  52. 52.
    NDA 21-042/s007. Vioxx (rofecoxib). Cardiovascular data in Alzheimer’s studies. http://dida.library.ucsf.edu/pdf/oxx01l10. Accessed 16 May 2013.
  53. 53.
    United States Department of Health and Human Services, Food and Drug Administration. Vioxx (rofecoxib). 2002. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154520.htm. Accessed 26 Nov 2012.
  54. 54.
    Australian Adverse Drug Reactions Bulletin. 2003 Oct;22(5). http://www.tga.gov.au/pdf/aadrb-0310.pdf. Accessed 26 Nov 2012.
  55. 55.
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352(11):1092–102.PubMedCrossRefGoogle Scholar
  56. 56.
    United States Food and Drug Administration, Drugs@FDA, Label and Approval History. Avandia (rosiglitazone maleate). Label. http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21071lbl.pdf. Accessed 18 May 2013.
  57. 57.
    Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation. 2003;108(23):2941–8.PubMedCrossRefGoogle Scholar
  58. 58.
    United States Department of Health and Human Serviced, Food and Drug Administration. Drug approval package. Avandia (rosiglitazone maleate) tablets. Centre for Drug Evaluation and Research. Application number: 021071. Medical review. http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21071_Avandia_medr.pdf. Accessed 2 May 2013.
  59. 59.
    United States Department of Health and Human Services, Food and Drug Administration. Drugs@FDA, FDA approved drug products. Prescribing information Avandia. http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21071lbl.pdf. Accessed 26 Jun 2013.
  60. 60.
    Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Australian Register of Therapeutic Goods (ARTG). https://www.ebs.tga.gov.au/. Accessed 21 Dec 2012.
  61. 61.
    Australian Government, Department of Veterans’ Affairs, Veterans’ Affairs Pharmaceutical Advisory Centre (VAPAC). http://www.dva.gov.au/service_providers/pharmacy/Pages/vapac.aspx. Accessed 2 May 2013.
  62. 62.
    United States Department of Health and Human Services, Food and Drug Administration (FDA). Safety. Avandia (rosiglitazone) April 2002. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154468.htm. Accessed 2 Dec 2012.
  63. 63.
    United States Department of Health and Human Services. Food and Drug Administration (FDA). Safety: summary-FDA April 2002, ACTOS [pioglitazone HCl]; AVANDIA [rosiglitazone maleate]. http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM170872.pdf. Accessed 7 Dec 2012.
  64. 64.
    Felix B, editor. Australian medicines handbook 2002. Adelaide: Australian Medicines Handbook Pty Ltd; 2002.Google Scholar
  65. 65.
    Australian Government, Department of Health and Ageing, Therapeutic Goods and Administration. Australia adverse drug reactions bulletin, vol. 22, no. 2. http://www.tga.gov.au/hp/aadrb-0304.htm. Accessed 2 Dec 2012.
  66. 66.
  67. 67.
    National Prescribing Service Limited. Early use of insulin and oral antidiabetic agents. http://www.nps.org.au/__data/assets/pdf_file/0014/35231/PPR40_insulin_and_oral_antidiabetic_drugs_0308.pdf. Accessed 2 Dec 2012.
  68. 68.
    United States Department of Health and Human Services, Food and Drug Administration (FDA). Information for healthcare professionals rosiglitazone maleate (marketed as Avandia, Avandamet, and Avandaryl). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm143406.htm. Accessed 7 Dec 2012.
  69. 69.
    Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):1096–105.Google Scholar
  70. 70.
    Dormandy JA, Charbonnel B, Eckland DJA, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.PubMedCrossRefGoogle Scholar
  71. 71.
    Glaxo Smith Kline. Study no 049653/211 a 52 week double blind study of the effect of rosiglitazone on cardiovascular structure and function in subjects with type 2 diabetes and congestive heart failure. http://ctr.gsk.co.uk/Summary/Rosiglitazone/IV_49653_211.pdf. Accessed 2 May 2013.
  72. 72.
    Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care. 2007;29:2007.Google Scholar
  73. 73.
    Therapeutic Good Administration eBusiness Services. Product and consumer medicine information. Product information Avandia (rosiglitazone). https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06879-3. Accessed 2 May 2013.
  74. 74.
    Reicin AS, Shapiro D, Sperling RS, Barr E, Yu Q. Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone). Am J Cardiol. 2002;89(2):204–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Layton D, Riley J, Wilton LV, Shakir SAW. Safety profile of rofecoxib as used in general practice in England: results of a prescription-event monitoring study. Br J Clin Pharmacol. 2003;55(2):166–74.PubMedCrossRefGoogle Scholar
  76. 76.
    Mamdani MRPJDN, et al. Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med. 2003;163(4):481–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet. 2002;360(9339):1071–3.PubMedCrossRefGoogle Scholar
  78. 78.
    Thal LJ, Ferris SH, Kirby L, Block GA, Lines CR, Yuen E, et al. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology. 2005;30(6):1204–15.PubMedCrossRefGoogle Scholar
  79. 79.
    Reines SA, Block GA, Morris JC, Liu G, Nessly ML, Lines CR, et al. No effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology. 2004;62(1):66–71.PubMedCrossRefGoogle Scholar
  80. 80.
    United States Department of Health and Human Services. Drugs at FDA: FDA approved drug products. Vioxx (rofecoxib). NDA 21-042 (capsules) and NDA 21-052 (oral solution). http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/021042_52_vioxx_medr_P1.pdf. Accessed 10 Jul 2013.

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Izyan A.Wahab
    • 1
  • Nicole L. Pratt
    • 1
  • Lisa M. Kalisch
    • 1
  • Elizabeth E. Roughead
    • 1
  1. 1.School of Pharmacy and Medical Sciences, Quality Use of Medicines and Pharmacy Research Centre, Sansom InstituteUniversity of South AustraliaAdelaideAustralia

Personalised recommendations