Drug Safety

, Volume 29, Issue 2, pp 175–181 | Cite as

An Assessment of the Publicly Disseminated Evidence of Safety Used in Decisions to Withdraw Medicinal Products from the UK and US Markets

  • Andrea Clarke
  • Jonathan J. Deeks
  • Saad A.W. ShakirEmail author
Original Research Article


Background: The objective of this study was to assess the publicly disseminated evidence used to support decisions to withdraw medicinal products for safety reasons, and related implications for the conduct of systematic reviews of harm.

Methods: Medicinal products withdrawn from the UK and US markets for safety reasons were identified from websites of the UK Medicines Control Agency (now known as the Medicines and Healthcare products Regulatory Agency) and the US FDA. Related scientific evidence was identified from communications made to the public and healthcare professionals at the time of each product withdrawal. Evidence for each product withdrawal decision was classified according to study design and outcome.

Results: Eleven products were withdrawn during 1999–2001. Randomised trial evidence was cited for two products (18%) and comparative observational studies for two products (18%). Evidence from spontaneous reports supported the withdrawal of eight products (73%), with four products (36%) apparently withdrawn on the basis of spontaneous reports alone. Only two products (18%) were withdrawn on evidence for a patient relevant outcome from comparative studies.

Conclusions: It is rare that evidence other than spontaneous reports is cited in support of drug withdrawals. The serious implications of product withdrawal mandate the elevation of the level of evidence that supports such public health decisions. Once suspicions of important safety hazards have emerged, prospective studies may be unfeasible and may be seen as unethical. Prospective studies can strengthen the evidence base and should be planned to commence when every drug is first marketed. Systematic reviews are unlikely to elicit evidence of harm associated with a drug unless they include spontaneous reports and surrogate outcomes.


Cisapride Troglitazone Spontaneous Report Astemizole Grepafloxacin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The Drug Safety Research Unit (DSRU) is a registered independent charity (No. 327206) associated with the University of Portsmouth.

The DSRU receives unconditional donations from pharmaceutical companies. The companies have no control on the conduct or the publication of its studies. The DSRU has received such funds from the manufacturers of products included in this study.

The research fellowship for Andrea Clarke was supported by the Astra Foundation.


  1. 1.
    Carne X, Arnaiz JA. Methodological and political issues in clinical pharmacology research by the year 2000. Eur J Clin Pharmacol 2000; 55: 781–5PubMedCrossRefGoogle Scholar
  2. 2.
    Skegg DC. Pitfalls of pharmacoepidemiology. BMJ 2000; 321: 1171–2PubMedCrossRefGoogle Scholar
  3. 3.
    Jefferys DB, Leakey D, Lewis JA, et al. New active substances authorized in the United Kingdom between 1972 and 1994. Br J Clin Pharmacol 1998; 45: 151–6PubMedCrossRefGoogle Scholar
  4. 4.
    Cuervo LG, Clarke M. Balancing benefits and harms in health care. BMJ 2003; 327: 65–6PubMedCrossRefGoogle Scholar
  5. 5.
    Arnaiz JA, Carne X, Riba N, et al. The use of evidence in pharmacovigilance: case reports as the reference source for drug withdrawals. Eur J Clin Pharmacol 2001; 57: 89–91PubMedCrossRefGoogle Scholar
  6. 6.
    US Food and Drug Administration. Safety-based drug withdrawals (1997–2001) [online]. Available from URL: [Accessed 2002 Jul 25]Google Scholar
  7. 7.
    UK Medicines Control Agency (MCA) [online]. Available from URL: [Accessed 2002 May 10]Google Scholar
  8. 8.
    European Agency for the Evaluation of Medicinal Products (EMEA) [online]. Available from URL: [Accessed 2002 May 10]Google Scholar
  9. 9.
    US Food and Drug Administration [online]. Available from URL: [Accessed 2002 Jul 25]Google Scholar
  10. 10.
    Ross-Degnan D, Soumerai SB, Fortess EE, et al. Examining product risk in context: market withdrawal of zomepirac as a case study. JAMA 1993; 270: 1937–42PubMedCrossRefGoogle Scholar
  11. 11.
    Sackett DL, Straus ES, Richardson WS, et al. Evidence-based medicine: how to practice and teach EBM. London: Churchill Livingstone, 2000: 169–82Google Scholar
  12. 12.
    Shakir SA. PEM in the UK. In: Mann RD, Andrews EB, editors. Pharmacovigilance. Chichester: John Wiley & Sons Ltd, 2002: 333–44CrossRefGoogle Scholar
  13. 13.
    Heeley E, Riley J, Layton D, et al. Prescription-event monitoring and reporting of adverse drug reactions. Lancet 2001; 358: 1872–3PubMedCrossRefGoogle Scholar
  14. 14.
    Martin RM, Kapoor KV, Wilton LV, et al. Underreporting of suspected adverse drug reactions to newly marketed (‘black triangle’) drugs in general practice: observational study. BMJ 1998; 317: 119–20PubMedCrossRefGoogle Scholar
  15. 15.
    Glasser DB, Dieck GS. A view from industry. In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons Ltd, 2000: 91–108CrossRefGoogle Scholar
  16. 16.
    Wiholm BE, Olsson S, Moore N, et al. Spontaneous reporting systems outside the US. In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons Ltd, 2000: 175–92CrossRefGoogle Scholar
  17. 17.
    Strom B. What is pharmacoepidemiology? In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons, 2000: 4–15CrossRefGoogle Scholar
  18. 18.
    Mann R. Prescription-event monitoring. In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons, 2000: 231–46CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Andrea Clarke
    • 1
  • Jonathan J. Deeks
    • 2
  • Saad A.W. Shakir
    • 1
    • 3
    Email author
  1. 1.Drug Safety Research UnitSouthamptonUK
  2. 2.Centre for Statistics in MedicineOxfordUK
  3. 3.University of PortsmouthPortsmouthUK

Personalised recommendations