Safety risk-benefit balance

Although medical products are required to be safe, safety does not mean zero risk. A safe product is one that has reasonable risks, given the magnitude of the benefit expected and the alternatives available. All participants in the medical product development and delivery system have a role to play in maintaining this benefit-risk balance by making sure that products are developed, tested, manufactured, labeled, prescribed, dispensed, and used in a way that maximizes benefit and minimizes risk. ... 

Gordon AJ, editor. Benefit-risk balance for marketed drugs evaluating safety signals. Report of CIOMS Working Group IV. Geneva WHO Press 1998. 

CIOMS Working Group IV. 1999. Benefit-Risk Balance for Marketed Drugs. Evaluating Safety Signals. CIOMS Geneva. 

The chapter is organized along the risk management process and will discuss the topics of risk identification, risk characterization, benefit-risk balance, and risk minimization. Dependence on other regulatory documents with relevance to safety will be pointed out throughout all sections. 

Interest in subgroup analysis has intensified in recent years due to the development of targeted therapies under the broad theme of personalized medicine. While most of the attention on targeted therapies is currently focused on efficacy, safety will play an important role as the ultimate decision on a therapy is the balance between benefit and risk. While increasing benefit is one way to increase the benefit/risk balance, reducing adverse reaction could also lead to a more favorable benefit/risk profile for a subgroup of patients. 

The UK Committee of Safety of Medicines has previously warned that paroxetine appeared to be no more effective than placebo in the treatment of depression in adolescents and might be associated with a greater risk of self harm (SEDA-28, 16). In a meta-analysis of both published and unpublished placebo-controlled trials of SSRIs in childhood and adolescent depression, only fluoxetine seemed clearly to be associated with a positive benefit-harm balance (26). The evidence of efficacy for sertraline and citalopram was doubtful, while the risk of serious adverse events was significantly increased. Additionally, for both drugs the risk of suicidal behavior was numerically increased. In regard to venlafaxine, the risk of suicidal behavior was significantly greater than placebo. 

Clinical safety studies are conducted in human volunteers to determine the safety of chemicals, drugs, formulations, devices, or other products, which may come in contact with the human body. Clinical safety testing should always be conducted prior to efficacy investigations in order to determine the benefit/risk ratio of efficacy trials. When designing a study, benefits and risks shall be balanced and shown to be in a favorable ratio (The Belmont Report). The rights, safety and well-being of the trial subjects are the most important considerations. (ICH Guidelines 2.3). 

The legislative history of the original CPSA confirms the Congressional desire to balance a proposed standard s benefits to consumer safety against its drawbacks in other areas of consumer welfare. S. 3419, the Senate version of the Act, included an express definition of unreasonable risk of injury ... 

The book does not focus on occupational safety and health issues, although improved process safety can benefit these areas. Detailed engineering designs are outside the scope of this work. This book intends to identify issues and concerns in batch reaction systems and provide potential solutions to address these concerns. This should be of value to process design engineers, operators, maintenance personnel, as well as members of process hazards analysis teams. While this book offers potential solutions to specific issues/concerns, ultimately the user needs to make the case for the solutions that provide a balance between risk... 

A No. As the Chairman said in a recent interview-and I will repeat now-it is our intention to continually improve performance. However, it is unrealistic to believe that we could achieve a zero accident or emission standard tomorrow. Even if it were theoretically achievable, the cost would be so large that we would bankrupt the company. We must maintain a balance between the benefits we achieve and the cost of achieving them. Let me also remind you that as a company we have made a commitment to abandon any business or technology where we consider the safety and environmental risks to be intolerable. 

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