An Assessment of the Publicly Disseminated Evidence of Safety Used in Decisions to Withdraw Medicinal Products from the UK and US Markets
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Methods: Medicinal products withdrawn from the UK and US markets for safety reasons were identified from websites of the UK Medicines Control Agency (now known as the Medicines and Healthcare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Results: Eleven products were withdrawn during 1999–2001.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Evidence from spontaneous reports supported the withdrawal of eight products (73%), with four products (36%) apparently withdrawn on the basis of spontaneous reports alone. Only two products (18%) were withdrawn on evidence for a patient relevant outcome from comparative studies.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.
KeywordsCisapride Troglitazone Spontaneous Report Astemizole Grepafloxacin
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.
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