Sequentially Determined Measures of Interobserver Agreement (Kappa) in Clinical Trials May Vary Independent of Changes in Observer Performance.

Background: Cohen's kappa is a statistic that estimates interobserver agreement. It was originally introduced to help develop diagnostic tests. Interpretative readings of 2 observers, for example, of a mammogram or other imaging, were compared at a single point in time. It is known that kappa depends on the prevalence of disease and that, therefore, kappas across different settings are hard to compare.

Methods: Using simulation, we examine an analogous situation, not previously described, that occurs in clinical trials where sequential measurements are obtained to evaluate disease progression or clinical improvement over time.

Results: We show that weighted kappa, used for multilevel outcomes, changes during the trial even if we keep the performance of the observer constant.

Conclusions: Kappa and closely related measures can therefore only be used with great difficulty, if at all, in quality assurance in clinical trials.