Drug Safety

, Volume 35, Issue 7, pp 535–546

Impact of Regulatory Guidances and Drug Regulation on Risk Minimization Interventions in Drug Safety

A Systematic Review
  • Lenhangmbong Nkeng
  • Anne-Marie Cloutier
  • Camille Craig
  • Jacques Lelorier
  • Yola Moride
Systematic Review

Abstract

Background: Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored.

Objective: The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions.

Methods: Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. ‘drug toxicity’) and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK’s Medicines and Healthcare products Regulatory Agency, Japan’s Pharmaceutical and Medical Devices Agency and Australia’s Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication.

Results: A total of 119 unique interventions were identified in the literature (54 published in 2000–4 and 65 published in 2005–9). Interventions included educational material (n = 37; 31%), black-box warnings (n = 22; 19%) and therapeutic drug monitoring (n = 11; 9%). The website review produced a total of 1112 interventions: 326 posted between the years 2000 and 2004, and 786 between the years 2005 and 2009. The main interventions observed were: educational material (n = 956; 86%), black-box warnings (n = 45; 4%) and withdrawals (n = 39; 4%).

Limitations: Additional regulatory resource websites were available in the post-guidances periods that were not available in the earlier years of the pre-guidances periods, and may bias the post-guidances results. Also, not all global regulatory websites were searched. Finally, only English-language websites were searched, limiting the variation of RMIs observed. Classification and categorizing for this particular review may not be consistent with future reviews by other researchers.

Conclusion: The US is the sole region with a substantial increase in published RMIs during the post-guidances period, while the EU, Japan and the US all indicated an increase in the number of interventions on their websites.

References

  1. 1.
    US Food and Drug Administration. Guidance for industry: development and use of risk minimization action plans [online]. Available from URL: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126830.pdf [Accessed 2010 Oct 1]
  2. 2.
    Health Canada. Guidance for industry: issuance of health professional communications and public communications by market authorization holders [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/pubs/medeff/_guide/2010-guid-dir_indust_hppc-cpsp/index-eng.php [Accessed 2011 Sep 28]
  3. 3.
    Touw DJ, Neef C, Thomson AH, et al. Cost effectiveness of therapeutic drug monitoring: an update. EJHP Science 2007; 4(13): 83–91Google Scholar
  4. 4.
    European Medicines Agency. Guideline on risk management systems for medical products for human use. Incorporated into: Volume 9A of the rules governing medicinal products in the European Union. Guidelines on pharma-covigilance for medicinal products for human use. Part I-3: requirements for risk management systems [online]. Available from URL: http://ec.europa.eu/health/files/eudralex/vol-9/pdf/vol9a_09-2008_en.pdf [Accessed 2012 May 27]
  5. 5.
    Leiderman DB. Risk management of drug products and the U.S. FoodandDrugAdministration: evolution and context. Drug Alcohol Depend 2009; 105 Suppl. 1: S9–13PubMedCrossRefGoogle Scholar
  6. 6.
    Wise L, Parkinson J, Raine J, et al. New approaches to drug safety: a pharmacovigilance tool kit. Nat Rev Drug Discov 2009; 8(10): 779–82PubMedGoogle Scholar
  7. 7.
    Hirst C, Cook S, Wanju D. A call for international harmonization in therapeutic risk management. Pharmacoepidemiol Drug Saf 2006; 15: 839–49PubMedCrossRefGoogle Scholar
  8. 8.
    Nicholson SC, Peterson J, Yektashenas B. Risk Evaluation and Mitigation Strategies (REMS): educating the prescriber. Drug Saf 2012; 35(2): 91–104PubMedCrossRefGoogle Scholar
  9. 9.
    Zomerdijk IM, Sayed-Tabatabaei FA, Gianluca T, et al. Risk minimisation activities of centrally authorized products in the EU: a descriptive study. Drug Saf 2012; 35(4): 299–314PubMedCrossRefGoogle Scholar
  10. 10.
    Liberati A, Altman G, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009; 6(7): 1–29CrossRefGoogle Scholar
  11. 11.
    Health Canada, MedEffect™ Canada. Advisories, warnings and recalls [online]. Available from URL: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/index-eng.php [Accessed 2012 May 28]
  12. 12.
    European Medicines Agency. European public assessment reports [online]. Available from URL: http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&murl=menus/medicines/medicines.jsp&mid=WC0b01ac058001d124 [Accessed 2012 May 22]
  13. 13.
    US FDA. Approved risk evaluation and mitigation strategies [REMS; online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm [Accessed 2012 May 28]
  14. 14.
    US FDA. Approved medication guides [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm [Accessed 2012 May 28]
  15. 15.
    US FDA. MedWatch safety alerts for human medical products [online]. Available from URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ [Accessed 2012 May 22]
  16. 16.
    Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Alerts [online]. Available from URL: http://www.tga.gov.au/safety/alerts.htm [Accessed 2012 May 28]
  17. 17.
    Medicines and Healthcare products Regulatory Agency. Safety warnings and messages for medicines [online]. Available from URL: http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/index.htm [Accessed 2012 May 22]
  18. 18.
    Pharmaceuticals and Medical Devices Agency, Japan. MHLW pharmaceuticals and medical devices safety information [online]. Available from URL: http://www.pmda.go.jp/english/service/precautions.html [Accessed 2012 May 22]

Copyright information

© Adis Springer International Publishing AG 2012

Authors and Affiliations

  • Lenhangmbong Nkeng
    • 1
    • 2
  • Anne-Marie Cloutier
    • 1
    • 2
  • Camille Craig
    • 1
    • 2
  • Jacques Lelorier
    • 2
  • Yola Moride
    • 1
    • 2
  1. 1.Faculty of PharmacyUniversité de MontréalMontrealCanada
  2. 2.Research CenterUniversity of Montreal Hospital Center (CRCHUM)MontrealCanada

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