Safety and Risk Benefit Analyses

In the past two decades more than 20 high-profile brand-name drugs including rofecoxib, troglitazone, cisapride, cerivastatin, natalizumab, gemtuzumab, and sibutramine were withdrawn from the market due to drug safety concerns related to severe adverse events. In 2005, the Food and Drug Administration (FDA) issued risk management guidance for the pharmaceutical industry. Subsequently the FDA Amendments Act in 2007 gave the FDA the authority to require pharmaceutical companies to develop and implement a Risk Evaluation and Mitigation Strategy (REMS) for specified prescription drugs and initiated the FDA Sentinel safety surveillance program in order to enhance the benefit-risk balance for pharmaceutical products. This chapter describes some basic concepts of drug safety, post-marketing surveillance, pharmacovigilance, and risk management. The safety signal detection algorithms and regulatory interventions will be also discussed. Finally some commonly used benefit-risk assessments (BRA) will be reviewed and discussed briefly in this chapter since the BRA methods are becoming critical tools for the life cycle of drug development and enhancing decision-making and regulatory interventions. The BRA is only one of unique analyses for clinical trials. Some concepts and methods of BRA may crossover with other analyses discussed in other chapters like “Intention to treat and alternative approaches,” “Cost effectiveness analyses,” and “Development and validation of risk prediction models” Bayesian adaptive designs.