Analytic studies are increasingly important for understanding relationships between diseases and their causes. They usually take the form of observational investigations, but can also include randomized clinical trials. Risk factors are antecedents that are considered to be components of the disease pathway. Appropriate study design and consideration to systematic bias and confounding helps to establish association between the exposure and disease. The purpose for maintaining the principles of causal inference and eliminating chance, bias, and confounding is to establish validity. The most serious concern in analytic studies is maintaining validity. Confounders are extraneous factors that are related to the disease and to a risk factor or exposure related to the disease. The confounder usually predicts disease in the absence of any risk factor. Investigators have to consider cost and efficiency in their design as well as the potential public health impact of any observed association.