Interval estimates for correlation coefficients corrected for within-person variation: implications for study design and hypothesis testing.

It is well known that random measurement error can attenuate the correlation coefficient between two variables. One possible solution to this problem is to estimate the correlation coefficient based on an average of a large number of replicates for each individual. As an alternative, several authors have proposed an unattenuated (or corrected) correlation coefficient which is an estimate of the true correlation between two variables after removing the effect of random measurement error. In this paper, the authors obtain an estimate of the standard error for the corrected correlation coefficient and an associated 100% x (1-alpha) confidence interval. The standard error takes into account the variability of the observed correlation coefficient as well as the estimated intraclass correlation coefficient between replicates for one or both variables. The standard error is useful in hypothesis testing for comparisons of correlation coefficients based on data with different degrees of random error. In addition, the standard error can be used to evaluate the relative efficiency of different study designs. Specifically, an investigator often has the option of obtaining either a few replicates on a large number of individuals, or many replicates on a small number of individuals. If one establishes the criterion of minimizing the standard error of the corrected coefficient while fixing the total number of measurements obtained, in almost all instances it is optimal to obtain no more than five replicates per individual. If the intraclass correlation is greater than or equal to 0.5, it is usually optimal to obtain no more than two replicates per individual.