Analysis of the Drugs Withdrawn from the US Market from 1976 to 2010 for Safety Reasons
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This study reviews the use of different study designs used to generate evidence to justify drug withdrawals for safety reasons in the United States (US). Secondarily it examines the most common reasons for withdrawing drugs, how long the withdrawn drugs were on the market and uses statistical modeling to estimate the risk of withdrawal over time.
A list of drugs withdrawn from the US market for safety reasons was generated, along with the corresponding period of time each drug was marketed. Evidence used to justify the withdrawal was obtained from searching Drugs@FDA and PubMed, and evidence was classified according to the study design used to generate the evidence. The number of drugs withdrawn was plotted as a function of how long they were marketed and a mathematical model was derived from this set of data to calculate the mean time the drugs were marketed before withdrawal.
A total of 34 drugs were withdrawn from the market for safety reasons in the US from 1976 to 2010. Nineteen of the 34 withdrawals relied only on case reports. Randomized and non-randomized studies were identified in 15 withdrawals and were increasingly used over the period of time examined. The median length of time that drugs were on the market was 3.4 years [interquartile range (IQR), 1.2, 10.4 years] with a mode at 1 year. The longest marketing period before withdrawal in the current data set was 53 years. Most drugs were withdrawn for either arrhythmias, hepato-renal failure or other cardiovascular problems.
The evidence used to justify safety withdrawals is dominated by case reports although there is an increased use of comparative studies.
KeywordsSibutramine Astemizole Safety Reason Tegaserod Phenylpropanolamine
The initial guidance for this project was provided by Professor Paul Glasziou, who made recommendations about defining and limiting the research focus. He also provided advice on how to select outcomes and present the results. Dr. Amanda Burls supervised Dr. Pierre La Rochelle throughout the entire research project.
Compliance with Ethical Standards
No sources of funding were used to assist in the preparation of this study.
Conflicts of interest
In 2015 and 2016 Joel Lexchin received payment for (a) participating in a panel discussion on the introduction of drug insurance in Canada; (b) being a consultant to a project looking at indication-based prescribing; and (c) being a consultant to a project that evaluated which drugs should be provided free of charge in a family practice setting. Pierre La Rochelle and David Simonyan have no conflicts of interest to declare.
No ethical approval was necessary as this study was based on publicly available data.
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