Appropriate study populations must be used

EDITOR—Otto et al describe significant differences in the serum concentrations of S100 protein in patients with and without Creutzfeldt-Jakob disease.1 The population of patients studied is, however, not appropriate for assessing the usefulness of measuring serum concentrations of S100 protein as a diagnostic test, and Otto et al's calculations of positive and negative predictive values of the test are invalid as they fail to take into consideration the prevalence of Creutzfeldt-Jakob disease as a cause of dementia.

Patients with clinically evident disease do not need a diagnostic test. It is not informative to evaluate the potential of a blood test to distinguish those with clinically definite Creutzfeldt-Jakob disease from those without the disease on clinical grounds. The test is useful only if it helps to predict the likelihood of the disease in a population that does not meet the criteria for probable Creutzfeldt-Jakob disease, which is therefore the population in which it must be assessed.

Otto et al say that the primary use of serum concentrations of S100 protein will be in the differential diagnosis of diseases that cause dementia. At a cut off of 213 pg/ml they calculate a sensitivity of 77.8% and specificity of 81.1% for detecting Creutzfeldt-Jakob disease in a referred population of 108 patients with definite or probable …