Drug Safety and Risk

FDA has also formed a Drug Safety and Risk Management Advisory Committee during this time, provided specific training for the members and has subsequently placed selected members on Advisory Committee Panels to consider various risks or to review existing risk management programs. 

It is clear that pharmacovigilance (the study of clinical drug safety and benefit-to-risk analysis) should have four major goals ... 

The requirements for the format and content of the IND application, as well as the requirements governing the use of the IND, are provided in Title 21 of the Code of Federal Regulations (21 CFR), Section 312. Unlike an NDA, the FDA does not formally approve an IND submission. If the FDA reviewers believe that the proposed clinical trial(s) submitted in the IND are acceptable from a safety and risk versus benefit viewpoint, the IND is in effect, and the compound that is the subject of that IND may be shipped in interstate commerce for the purpose of conducting specific clinical trials. Drugs shipped under an IND have specific labeling requirements, and false or misleading statements, as well as any claims regarding safety and efficacy, are prohibited. 

In the past decade there has been increased emphasis on drug safety, and more public visibility of safety problems. The volume of reports now exceeds 250 000 spontaneous reports per year, and adverse events have been highlighted in the medical sector and also in the media. In parallel, the FDA has focused more intently on this area in both NDA reviews and in the postmarketing period. This has accompanied withdrawals of a number of products, such as cisapride, phenylpropanolamine and terfenadine, and special scrutiny of products associated with particular adverse events, such as cardiac arrhythmias (torsades de Pointes ) and hepatic necrosis. The result has been an emphasis on the concept of risk management of a product. This concept, which is due to be described in forthcoming FDA recommendations, stresses the need to identify potential... 

Through each of these steps, the drug is evaluated for its efficacy, safety, and risk/benefit ratio (406). The French equivalent of the U.S. FDA reviews drugs for marketing approval. This process is completed relatively quickly the government has 120 days to make a decision after an application for marketing authorization is filed, with a 90-day extension available (406). 

Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk-benefit methodologies for assessing drug safety and efficacy—Report of the ISPOR risk-benefit management working group. Value Health August 2010 13(5) 657-666. 

Covers several Bayesian approaches, including a meta-experimental design for evaluating cardiovascular risk, adaptive trials for drug safety, and network meta-analysis for safety evaluation... 

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