Skip to main content

Advertisement

SpringerLink
Log in

Sources of information used by regulatory agencies on the generation of drug safety alerts

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The study of the grounds on which data regulatory authorities base their decisions on drug safety evaluations is an important clinical and public health issue. The aim of this study was to review the type and publication status of data sources supporting benefit/risk ratio re-evaluations conducted by the major regulatory authorities on safety issues.

Methods

A website search was carried out to identify all safety alerts published by the U.S Food and Drugs Administration, Health Canada, European Medicines Agency and the Australian Therapeutics Goods Administration. Safety alerts were included if the causal relation between a suspected drug exposure and the occurrence of an adverse event was evaluated for the first time between 2010 and 2012. Type of data sources evaluated by these regulatory authorities, publication status of the data sources and status of the drug label section with respect to updating were evaluated.

Results

A total of 59 safety alerts were included in this study. Of these, 33 (56%) were supported by post-marketing spontaneous reports, 24 (41%) evaluated randomized clinical trials, 16 evaluated cohort studies (27%), 13 were case–control studies (22%) and 11 evaluated case report/case series (17%). Twenty-three safety alerts (39%) were issued based. on unpublished evidence, corresponding mainly to post-marketing spontaneous reports. The “Warnings and precautions section” was the drug label section most frequently updated (n = 40; 68%).

Conclusion

Despite the different lengths of time taken by the different regulatory authorities to come to similar decisions on the same issues—an issue which would seem to deserve further harmonization—post-marketing spontaneous reports have supported most of the benefit/risk ratio re-evaluations, thereby confirming the value of such re-evaluations in detecting unknown adverse events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. US Food and Drug Administration (2012) Centre for Drug Evaluation and Research. Guidance drug safety information – FDA’s Communication to Public. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM295217.pdf. Accessed 22 May, 2013

  2. Madre LK, Califf RM, Reynolds RF et al (2006) Views from Academia, Industry, and Regulatory Agencies. In: Strom BL, Kimmel SE (eds) Textbook of pharmacoepidemiology. John Wiley & Sons, Chichester, pp 63–88

    Google Scholar 

  3. Wysowski DK, Swartz L (2005) Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reported suspected reactions. Arch Inter Med 165(12):1363–1369

    Article  Google Scholar 

  4. Moore TJ, Singh S, Furberg CD (2012) The FDA and new safety warnings. Arch Intern Med 172(1):78–80

    Article  PubMed  Google Scholar 

  5. Ahamd SR, Marks NS, Goetsch RA (2006) Spontaneous reporting in the United States. In: Strom BL, Kimmel SE (eds) Textobook of pharmacoepidemiology. John Wiley & Sons, Chichester, pp 91–116

    Google Scholar 

  6. Edwards IR, Olsson S, Lindquist M, Hugman B (2006) Global Drug Surveillance: The WHO Programme for International Drug Monitoring. In: Strom BL, Kimmel SE (eds) Textobook of pharmacoepidemiology. John Wiley & Sons, Chichester, pp 117–136

    Google Scholar 

  7. US Food and Drug Administration (2008) Department of Health and Human Services. The Sentinel Initiative: National Strategy for Monitoring Medical Product Safety. Available at: http://www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf. Accessed 22 May 2013

  8. Rothwell PM (2005) External validity of randomised controlled trials:“ to whom do the results of this trial apply?”. Lancet 365(9453):82–93

    Article  PubMed  Google Scholar 

  9. Papanikolaou PN, Christidi GD, Ioannidis JPA (2006) Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies. CMAJ 174(5):635–641

    Article  PubMed  Google Scholar 

  10. Edwards IR, Biriell C (1994) Harmonisation in Pharmacovigilance. Drug Saf 10(2):93–102

    Article  PubMed  CAS  Google Scholar 

  11. Bull J (2007) US activities in risk management of pharmaceutical products. In: Mann RD, Andrews EB (eds) Pharmacovigilance, 2nd edn. John Wiley & Sons, Chichester, pp 535–552

    Google Scholar 

  12. US Food and Drug Administration (2011) Guidance for Industry. US Food and Drug Administration. Warnings and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products. Available at: http://www.fda.gov/downloads/Drugs/Guidances/ucm075096.pdf. Accessed 22 May 2013

  13. US Food and Drug Administration (2013) Drug Safety Communications. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm199082.htm. Accessed 22 May 2013

  14. Health Canada (2013) Advisories, warnings and recalls. Available at: http://www.hc-sc.gc.ca/dhp-mps/advisories-avis/index-eng.php. Accessed 22 May 2013

  15. European Medicines Agency (2013) News and events. News, and press release archive. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/landing/news_search_landing_page.jsp&mid=WC0b01ac058004d5c1. Accessed 22 May 2013

  16. European Medicines Agency (2012) Working parties and other groups. Retired working parties. CHMP Pharmacovigilance Working Party. Monthly reports. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/document_listing/document_listing_000198.jsp&mid=WC0b01ac05805a8fd3. Accessed 22 May 2013

  17. Australian Government (2013) Department of Health and Ageing. Therapeutic Goods Administration. Safety information. Alerts. Available at: http://www.tga.gov.au/safety/alerts-all-date.htm. Accessed 22 May 2013

  18. Australian Government (2013) Department of Health and Ageing. Therapeutic Goods Administration. Safety information. Product recalls. Available at: http://www.tga.gov.au/safety/recalls-all-date.htm. Accessed 22 May 2013

  19. WHO Collaboration Centre for Drug Statistics Methodology (2013) ATC/DDD Index 2013. Available at: http://www.whocc.no/atc_ddd_index/. Accessed 22 May 2013

  20. Lester J, Neyarapally GA, Lipowski E, Graham CF, Hall M, Dal Pan G (2013) Evaluation of FDA safety-related drug label changes in 2010. Pharmacoepidemiol Drug Saf 22(3):302–305

    Article  PubMed  Google Scholar 

  21. Byetta (exenatide) injection-detailed view: safety labeling changes approved by FDA Centre for Drug Evaluation and Research (2009) FDA/MedWatch the FDA Safety Information and Adverse Event Reporting Program. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm190571.htm. Accessed 22 May 2013

  22. Dore DD, Seeger JD, Chan KA (2009) Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin 25(4):1019–1027

    Article  PubMed  CAS  Google Scholar 

  23. Garg R, Chen W, Pendergrass M (2010) Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care 33(11):2349–2354

    Article  PubMed  CAS  Google Scholar 

  24. Dore DD, Bloomgren GL, Wenten M et al (2011) A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 13(6):559–566

    Article  PubMed  CAS  Google Scholar 

  25. Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336(7650):924–926

    Article  PubMed  Google Scholar 

  26. Vandenbroucke JP, Psaty BC (2008) Benefits and risks of drug treatments: how combine the best evidence on benefits with the best data about adverse effects. JAMA 300(20):2417–2419

    Article  PubMed  CAS  Google Scholar 

  27. Wolfe SM (2012) Early signals of harmful drugs. Arch Intern Med 172(1):73–74

    PubMed  Google Scholar 

  28. Dal Pan GJ, Temple R (2012) Balancing transparency and uncertainty. Arch Intern Med 172(1):74–75

    PubMed  Google Scholar 

  29. Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E (2004) Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet 363(9418):1341–1345

    Article  PubMed  CAS  Google Scholar 

  30. Powers A, Cook GE (2012) Potential safety signals and their significance. Arch Intern Med 172(1):72–73

    Article  PubMed  Google Scholar 

  31. Hirst C, Cook S, Dai W, Perez-Gutthann S, Andrews E (2006) A call for international harmonization in therapeutic risk management. Pharmacoepidemiol Drug Saf 15(12):839–849

    Article  PubMed  Google Scholar 

  32. US Food and Drug Administration (2013) Guidance, Comp-liance & Regulatory Information. International Conference on Harmonisation—Safety. Available at: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065007.htm. Accessed 22 May 2013

  33. Pfistermeister B, Schenk C, Kornhuber J, Bürkle T, Fromm MF, Maas R (2013) Different indications, warnings and precautions, and contraindications for the same drug—an international comparison of prescribing information for commonly used psychiatric drugs. Pharmacoepidemiol Drug Saf 22(3):329–333

    Article  PubMed  Google Scholar 

  34. European Medicines Agency (2013) Partners & Networks. Regulators outside the EU. United States. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/partners_and_networks/document_listing/document_listing_000228.jsp&mid=WC0b01ac058003176e. Accessed 22 May 2013

  35. European Medicines Agency (2013) Partners & Networks. Regulators outside the EU. Canada. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/partners_and_networks/document_listing/document_listing_000230.jsp&mid=WC0b01ac0580034f00. Accessed 22 May 2013

  36. Stang M, Wysowski DK, Butler-Jones D (1999) Incidence of lactic acidosis in metformin users. Diabetes Care 22(6):925–927

    Article  PubMed  CAS  Google Scholar 

  37. Furberg CD (2007) Decisions by regulatory agencies: are they evidence-based? Trials 8:13

    Article  PubMed  Google Scholar 

  38. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH (2002) Timing for new black box warnings and withdrawals for prescription medications. JAMA 287(17):2215–2220

    Article  PubMed  Google Scholar 

  39. Temple RJ, Himmel MH (2002) Safety of newly approved drugs: implications for prescribing. JAMA 287(17):2273–2275

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Carlos Alves is supported by a research grant from Foundation for Science and Technology, Portugal, reference: SFRH/BD/64957/2009. Ana Filipa Macedo and Francisco Batel Marques did not receive any financial support for conducting this study.

Author information

Authors and Affiliations

  1. Centre for Health Technology Assessment and Drug Research (CHAD), Association for Innovation and Biomedical Research on Light and Image (AIBILI), Azinhaga de Santa Comba, Celas, Coimbra, 3000-548, Portugal

    Carlos Alves & Francisco Batel Marques

  2. School of Pharmacy, University of Coimbra, Coimbra, Portugal

    Carlos Alves & Francisco Batel Marques

  3. Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

    Carlos Alves & Ana Filipa Macedo

Authors
  1. Carlos Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Filipa Macedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco Batel Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos Alves.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 25 kb)

ESM 2

(DOCX 57 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alves, C., Macedo, A.F. & Marques, F.B. Sources of information used by regulatory agencies on the generation of drug safety alerts. Eur J Clin Pharmacol 69, 2083–2094 (2013). https://doi.org/10.1007/s00228-013-1564-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-013-1564-y

Keywords

Search

Navigation