Often the accuracy of a new diagnostic test must be assessed when a perfect gold standard does not exist. Use of an imperfect test biases the accuracy estimates of the new test. This paper reviews existing approaches to this problem including discrepant resolution and latent class analysis. Deficiencies with these approaches are identified. A new approach is proposed that combines the results of several imperfect reference tests to define a better reference standard. We call this the composite reference standard (CRS). Using the CRS, accuracy can be assessed using multistage sampling designs. Maximum likelihood estimates of accuracy and expressions for the variance of sensitivity and specificity are provided. Data from clinical literature on the detection of Chlamydia trachomatis are used to illustrate and compare the different approaches. Advantages of the CRS relative to other approaches include that the CRS reference is explicitly defined, does not depend on the results of the new test under investigation, and is easy to interpret.


Clinical Epidemiology | Design of Experiments and Sample Surveys | Epidemiology | Statistical Methodology | Statistical Theory