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A core set of clinical research designs have stood the test of time and are repeatedly used in most studies. No single research design is best to answer all research questions, and every research design has appropriate applications. This and the previous articles have described the most common designs. However, in the process of performing research, there are always other options (Table 2), and" hybrid" studies combining elements from different designs are not uncommon. This article does not have sufficient space to discuss subtypes and hybrid designs. Although it is a good practice to think of research designs in terms of degree of scientific integrity or rigor, it must be recognized that every design type has both advantages and disadvantages. In addition, usually many different ways are available to answer the same research question. Which design is most appropriate depends largely on a stage of evolution of the investigative process and the resources available. An understanding of the full breadth and spectrum of research study designs is necessary to select the model that is most appropriate for a given investigation. In general, the best approach is to use the most scientifically valid design that the circumstances will allow. However, the actual decision regarding the design usually represents a compromise between lofty scientific goals and the clinical or resource limitations of the research setting. Therefore, be realistic about the resources available, including the time frame and finances. Realize that research is done in incremental steps, and it is unusual to be able to answer an entire important research question in a single study. The …