The FDA now requires a sponsor to exclude a certain level of risk of certain safety concerns for select classes of compounds. For example, all diabetes treatments must exclude a certain level of risk of the compound versus all comparators for cardiovascular events and long acting beta agonists (LABAs) must exclude a certain level of risk for asthma exacerbations. The small event rates for certain safety events can make these outcome studies rather large. We will discuss the issues associated with these studies (sample size, non-inferiority margins, relative risk versus absolute risk, recruitment issues, cost, populations to be studied, choice of active or placebo control, etc.).

Key Questions: 1) What is your view of relative risk vs. absolute risk? 2) What recruitment issues do you foresee these studies? 3) What non-inferiority margins should be used for these studies?