An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making

Abstract

ObjectivesThe objective of this study was to determine the nature of evidence used to support the withdrawal of marketing authorisations of drug products for safety reasons throughout the European Union (EU) between 2002 and 2011.SettingProducts withdrawn, either by a medicines agency or a marketing authorisation holder, during the period 2002–2011 were identified by conducting detailed searches of the WHO, the European Medicines Agency (EMA) and national medicines agency websites throughout the EU plus Norway, Iceland and Liechtenstein. The scientific evidence used to support the decision was identified from a search within PubMed, the EMA and national medicines agencies websites. Information about spontaneous case reports entered into EudraVigilance and unavailable on the EMA website was received by email from the EMA.Results19 drugs were withdrawn from the market, throughout the EU, for safety reasons from 2002 to 2011. Case reports were cited in 95% of withdrawals (18/19) and case–control studies (4/19), cohort studies (4/19), randomised controlled trials (RCTs) (12/19) or meta-analysis (5/19) were cited in 63% of withdrawals (12/19). Cardiovascular events or disorders were the main reason for withdrawal (9/19), followed by hepatic disorders (4/19) and neurological or psychiatric disorders (4/19).ConclusionsThis study has shown that the level of evidence used to support drug withdrawal has improved during the past 10 years, with an increased use of case–control studies, cohort studies, RCTs and meta-analyses. This research has demonstrated that such studies have contributed to decision-making in almost two-thirds of cases.

Farmacovigilância em Portugal: Atividade da Unidade Regional do Centro

“…53 A maioria das decisões regulamentares levadas a cabo pelas autoridades reguladoras acerca da segurança de medicamentos, incluindo a retirada de medicamentos do mercado e a geração de alertas de segurança, tem sido maioritariamente baseada em notificação espontânea. 49,[53][54][55][56][57][58] Mais de metade dos alertas de segurança gerados pelas autoridades reguladoras entre 2010 e 2012 tiveram por base notificações espontâneas, dos quais 20% exclusivamente através desta fonte de evidência. 49 Estes resultados sugerem a importância da notificação espontânea na geração de novo conhecimento acerca da segurança de medicamentos.…”

Chronic drug‐induced effects on contractile motion properties and cardiac biomarkers in human induced pluripotent stem cell‐derived cardiomyocytes

“…hERG inhibition) to detect liabilities that might translate into QT-prolongation and cardiac arrhythmias in humans. However, less attention is paid to the delayed cardiac liabilities that are currently identified in the more costly, late-phase toxicity studies using in vivo models, or in the worst cases within clinical development or on the market (Laverty et al, 2011;McNaughton et al, 2014). Furthermore, it is believed that one of the major factors contributing to the limited success of predicting clinical toxicities is the translatability across preclinical (animal) models into humans.…”

Adverse Event of Drug Therapy (The First Results of the Study According to the Profile Outpatient Register)

“…по требованию EMЕA с фармацевтическо-го рынка Евросоюза отозвали 19 лекарственных пре-паратов [23]. Авторы подчеркивают, что за последнее десятилетие существенно улучшилась доказательная база, на основании которой и были выявлены НЯ, по-служившие причиной изъятия препаратов с рынка.…”

“…По-мимо данных РКИ и мета-анализов сбору этих сведе-ний помогли наблюдательные исследования (случай-контроль, когортные и др.) [23].…”