Due to the special nature of medical device clinical studies, observational (non-randomized) studies play important roles in the pre-market safety/effectiveness evaluation of medical devices. When appropriate, existing data such as historical data or high quality registry data could be utilized for the evaluation of new medical devices. In this presentation, some of design challenges, such as prospective study design, control group selection from existing database and treatment group comparability will be discussed and illustrated with examples from a regulatory perspective.