Determination and Selection of the Optimum Number of Sites and Patients for Clinical Studies

Abstract

Calculating required sample sizes is a critical step in the design of any study. For dental studies, the sample size needs to be specified at two levels: (1) the number of patients (n) enrolled in the study, and (2) the average number of sites (m) examined per patient. In general, m and n should be selected in such a way that the precision of the research findings is maximized, while the cost of the study is minimized. This objective can be realized by taking stock of the components of variation and the costs involved with enrolling patients and examining sites. The research cost for n patients ($C₁/ patient), at an average of m sites per patient ($C₂/site), can usually be approximated by n C₁ + nm C2. The precision varies as a function of the variance components, m, and n. To optimize precision for a fixed cost, the average number of sites examined per patient (m_opt) should be approximately equal towhere p is the within-patient correlation coefficient of the site-specific variable measured. When m_opt is approximately equal to or in excess of the average number of sites availableper patient, whole-mouth examinations are indicated. When m_opt is considerably smaller than the average number of sites available, the sample of optimum size should be obtained by some random mechanism. Examination of a number of sites considerably different from m_opt results in a waste of resources, regardless of the number of patients studied. Standard statistical analyses for determination of the patient sample size required to obtain a pre-specified precision or power are discussed.