Delays in the post-marketing withdrawal of drugs to which deaths have been attributed: a systematic investigation and analysis.
Onakpoya IJ., Heneghan CJ., Aronson JK.
BACKGROUND: Post-marketing withdrawal of medicinal products because of deaths can be occasioned by evidence obtained from case reports, observational studies, randomized trials, or systematic reviews. There have been no studies of the pattern of withdrawals of medicinal products to which deaths have been specifically attributed and the evidence that affects such decisions. Our objectives were to identify medicinal products that were withdrawn after marketing in association with deaths, to search for the evidence on which withdrawal decisions were based, and to analyse the delays involved and the worldwide patterns of withdrawal. METHODS: We searched the World Health Organization's Consolidated List of [Medicinal] Products, drug regulatory authorities' websites, PubMed, Google Scholar, and textbooks on adverse drug reactions. We included medicinal products for which death was specifically mentioned as a reason for withdrawal from the market. Non-human medicines, herbal products, and non-prescription medicines were excluded. One reviewer extracted the data and a second reviewer verified them independently. RESULTS: We found 95 drugs for which death was documented as a reason for withdrawal between 1950 and 2013. All were withdrawn in at least one country, but at least 16 remained on the market in some countries. Withdrawals were more common in European countries; few were recorded in Africa (5.3%). The more recent the launch date, the sooner deaths were reported. However, in 47% of cases more than 2 years elapsed between the first report of a death and withdrawal of the drug, and the interval between the first report of a death attributed to a medicinal product and eventual withdrawal of the product has not improved over the last 60 years. CONCLUSIONS: These results suggest that some deaths associated with these products could have been avoided. Manufacturers and regulatory authorities should expedite investigations when deaths are reported as suspected adverse drug reactions and consider early suspensions. Increased transparency in the publication of clinical trials data and improved international co-ordination could shorten the delays in withdrawing dangerous medicinal products after reports of deaths and obviate discrepancies in drug withdrawals in different countries.