Top

Published in:

01-02-2006 | Original Research Article

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

Authors: Andrea Clarke, Jonathan J. Deeks, Professor Saad A.W. Shakir

Published in: Drug Safety | Issue 2/2006

Abstract

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Methods: Medicinal products withdrawn from the UK and US markets for safety reasons were identified from websites of the UK Medicines Control Agency (now known as the Medicines and Healthcare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Results: Eleven products were withdrawn during 1999–2001.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Evidence from spontaneous reports supported the withdrawal of eight products (73%), with four products (36%) apparently withdrawn on the basis of spontaneous reports alone. Only two products (18%) were withdrawn on evidence for a patient relevant outcome from comparative studies.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.

Carne X, Arnaiz JA. Methodological and political issues in clinical pharmacology research by the year 2000. Eur J Clin Pharmacol 2000; 55: 781–5PubMedCrossRef

Skegg DC. Pitfalls of pharmacoepidemiology. BMJ 2000; 321: 1171–2PubMedCrossRef

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: 151–6PubMedCrossRef

Cuervo LG, Clarke M. Balancing benefits and harms in health care. BMJ 2003; 327: 65–6PubMedCrossRef

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: 89–91PubMedCrossRef

US Food and Drug Administration. Safety-based drug withdrawals (1997–2001) [online]. Available from URL: http://www.fda.gov/fdac/features/2002/chrtWithdrawals.html [Accessed 2002 Jul 25]

UK Medicines Control Agency (MCA) [online]. Available from URL: http://www.mca.gov [Accessed 2002 May 10]

European Agency for the Evaluation of Medicinal Products (EMEA) [online]. Available from URL: http://www.emea.eu.int [Accessed 2002 May 10]

US Food and Drug Administration [online]. Available from URL: http://www.fda.gov [Accessed 2002 Jul 25]

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: 1937–42PubMedCrossRef

11.

Sackett DL, Straus ES, Richardson WS, et al. Evidence-based medicine: how to practice and teach EBM. London: Churchill Livingstone, 2000: 169–82

12.

Shakir SA. PEM in the UK. In: Mann RD, Andrews EB, editors. Pharmacovigilance. Chichester: John Wiley & Sons Ltd, 2002: 333–44CrossRef

13.

Heeley E, Riley J, Layton D, et al. Prescription-event monitoring and reporting of adverse drug reactions. Lancet 2001; 358: 1872–3PubMedCrossRef

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: 119–20PubMedCrossRef

15.

Glasser DB, Dieck GS. A view from industry. In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons Ltd, 2000: 91–108CrossRef

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: 175–92CrossRef

17.

Strom B. What is pharmacoepidemiology? In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons, 2000: 4–15CrossRef

18.

Mann R. Prescription-event monitoring. In: Strom B, editor. Pharmacoepidemiology. Chichester: John Wiley & Sons, 2000: 231–46CrossRef

Title: An Assessment of the Publicly Disseminated Evidence of Safety Used in Decisions to Withdraw Medicinal Products from the UK and US Markets
Authors: Andrea Clarke
Jonathan J. Deeks
Professor Saad A.W. Shakir
Publication date: 01-02-2006
Publisher: Springer International Publishing
Published in: Drug Safety / Issue 2/2006
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI: https://doi.org/10.2165/00002018-200629020-00008

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2006

Current Understanding of Contrast Media Reactions and Implications for Clinical Management

Interactions between Antiepileptic and Antipsychotic Drugs

Ophthalmological Events in Patients Receiving Risedronate

Adverse Drug Reaction-Related Hospitalisations

NSAID-Associated Adverse Effects and Acid Control Aids to Prevent Them

The Effect of Detection Approaches on the Reported Incidence of Tenfold Errors