A Systematic Approach to Evaluating Benefit: Risk in Drug Development

We are all familiar with the tragedy of the use of thalidomide in pregnant women, which led to the passage of the Drug Amendments of 1962 to the Federal Food, Drug, and Cosmetic Act. Since then it has been a requirement to demonstrate the safety and efficacy of a drug for human use prior to approval for marketing. The terms "safe" and "effective" have been widely used. However, with the public translating FDA approval of a product almost as a guarantee that a drug will work in everyone, with no or limited side effects, the agency's interpretations of safe and effective have evolved. The situation is further complicated by the fact that safety and efficacy are usually demonstrated in a patient population, but the individual patient who experiences an adverse outcome is not always the same patient who experiences the benefit. More recently, there has been a shift to the use of the term "benefit:risk" to communicate more clearly the notion of inherent risk and existence of a balance between benefit and risk.