2003 年 24 巻 1 号 p. 17-41
Determination of a sample size of a clinical study is one of the essential design factors. This paper focuses on a problem of sample size determination of a clinical trial in the clinical development phase. Sample size calculation can be performed using a formula or simulation, once a set of conditions is given pertaining treatment effect, variability of observations, significance level and power. Contrary to calculation, determination of sample size is not an easy task. For example, formal application of a formula may result in a very large sample size. In designing a study, however, sample size calculation is affected by constraints from various design factors, amount of information at hand and feasibility of the study. I first present a principle for sample size calculation and stress on importance of assessment of risks of a given sample size. Next, I propose two conservative approaches to sample size calculation; double confidence limits method and effect size confidence limit method, and compare properties of these methods with an ordinary method for a two treatment parallel group study. A few actual examples of a conservative approach are presented and discussed. Further issues in and points to consider for sample size determination are also discussed. Several examples of approaches to sample size calculation in exploratory studies and dose-response studies are also presented.