S. Lane* 1, E. Lynn1, 2, S. Shakir1, 2
Affiliations: 1 Drug Safety Research Unit 2 University of Portsmouth
Market withdrawal of a product affects patients, healthcare professionals, regulators and manufacturers, therefore these decisions should be based on the most robust evidence available. EU pharmacovigilance (PV) legislation was updated in 2012 and led to modernisation of PV systems in Europe. It is necessary to explore whether evolution of PV leads to changes in evidence supporting PV actions (e.g. withdrawals), and how the use of supporting evidence has adapted over time.
To evaluate changes in evidence supporting post-marketing product withdrawals from 1999-2016.
Using 3 previously published studies, it was possible to compare evidence used to support post-marketing PV actions in the EU, spanning the period 1999 to 2016.[1-3] The number of withdrawals per year was calculated. Study designs supporting post-marketing withdrawals in 1999-2016 were evaluated. Changes to evidence supporting product withdrawals were assessed.
A total of 31 market withdrawals occurred in the EU between 1999 and 2016 and were included in these publications, with an average of 1.72 per year. The number of withdrawals increased between 1999 to its peak in 2010 (5 withdrawals in 2010), and decreased from 2011 to 2016. In general the number of different study designs used to justify withdrawals increased between 1999 and 2016. Spontaneous and published case reports were the most common evidence source, involved in 29 withdrawals (93.5%). This evidence alone led to 4 (12.9%) withdrawals. The least common sources of supporting evidence were epidemiological studies (case-control n=6; cohort n=7). Other sources included randomised clinical trials (n=20), animal studies (n=13) and meta-analyses (n=7). The average number of distinct evidence types used was 3.1 per withdrawal. Six (19.4%) withdrawals were justified by just one source of evidence, with the remaining 25 (80.6%) withdrawals supported by at least 2 different types of evidence.
The number of products withdrawn from the EU market appears to have increased until 2010, and has since decreased. Although there is an apparent increase in different types of evidence being used to justify post-marketing withdrawals, spontaneous and published case reports remain a vital source of evidence for regulators.
- Clarke A, Deeks JJ, Shakir SA. An assessment of the publicly disseminated evidence of safety used in decisions to withdraw medicinal products from the UK and US markets. Drug Saf. 2006;29(2):175-81.
- Lane S, Lynn E, Shakir SAW. Measuring the Impact of Product Withdrawals and Other Major Pharmacovigilance Actions on Public Health Burden in the EU: Methodological Considerations. Drug Saf; 2017 Oct 15-18; Liverpool (UK): International Society of Parmacovigilance; 2017. p. 937-1045.
- McNaughton R, Huet G, Shakir S. An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making. BMJ Open. 2014;4(1):e004221.