Research methodology is a set of methods, laws and procedures that guide research efforts towards solving scientific problems with maximum efficiency. The method is based on the development of different stages that lead to the establishment of a valid conclusion supported on the verification of a hypothesis and assumptions of the performed research. Thus, scientific research is not exempt from the errors, which can originate during the study issue, research design, establishment of eligibility criteria, sample size estimation, measurement process, during follow-up or due to lack of discussion of study limitations. In this context, one of the strategies to reduce potential errors in conducting a study lies in the proper development of a research project or protocol, which must be elaborated based on a research, design and method problem. This provides the researcher with a number of advantages associated with documented process planning, reproducibility of experimental protocols and facilitation of the results publication. This review aims to discuss the essential aspects regarding the scientific method in clinical research and to analyze the main problems, benefits and elements associated with the feasibility of developing a research protocol.