The medical history proves that clinical research has been a powerful weapon for disease control even when the etiology of the disease is unknown, as John Snow found the causal relationship between drinking water and cholera infection, and Kanehiro Takagi between nourishment and beriberi.

Medical science progresses along with the development of new medical technology such as new drugs and medical devices. In the history of hypertension, a great cohort study in Framingham in the USA has enhanced enormous scientific knowledge about the causal relationship between hypertension and cardiovascular diseases. The new sphygmomanometers and a lot of antihypertensive agents contributed to validation of the hypothesis generated from the Framingham study and development of hypertension practice guidelines. The modern data analyzing techniques like multivariable analysis were also produced in the struggle of the statisticians working for that study.

Every research method has strengths and weaknesses, even a randomized controlled trial is no exception. The important point is to use a method well suited to answer a question, whether it is randomized or not. Clinical research methods have been developed for solving several medical issues and will be developed with advances in medical science in the future. For example, “N–of–1 trial” method has rapidly become popular in these years, and CONSORT extension for reporting N–of–1 trials was published in 2015. We should contribute to development not only of new medical technologies but also of clinical research methods.