As the result of the Prescription Drug User Fee Act Agreements in 2007, FDA promised to develop a draft guidance on the topic of NI Clinical Trials, the design used in many clinical studies when a placebo cannot ethically be used and an area of confusion among many that requires more clarity and direction. The draft guidance is being developed by a working group from CDER and CBER that includes clinicians and statisticians, as the issues are not strictly statistical in nature, but do involve clinical and regulatory consideration and some difficult and potentially controversial statistical approaches. This talk will present an outline of the considerations the guidance expects to cover, including some specifics on selected topics for NI margin determination, study design and analysis, and some of the types of examples that will be used in the guidance the concepts and recommendations.