Standardizing diagnostic markers to evaluate and compare their performance.
BACKGROUND
Markers that purport to distinguish subjects with a condition from those without a condition must be evaluated rigorously for their classification accuracy. A single approach for statistical evaluation and comparison of markers is not yet established.


METHODS
We suggest a standardization that uses the marker distribution in unaffected subjects as a reference. For an affected subject with marker value Y, the standardized placement value is the proportion of unaffected subjects with marker values that exceed Y.


RESULTS
We applied the standardization to 2 illustrative datasets. As a marker for pancreatic cancer, the CA-19-9 marker had smaller placement values than the CA-125 marker, indicating that CA-19-9 was the better marker. For detecting hearing impairment, the placement values for the test output (the marker) were smaller when the input sound stimulus was of lower intensity, which indicates that the test better distinguishes hearing-impaired from unimpaired ears when a lower intensity sound stimulus is used. Explicit connections are drawn between the distribution of standardized marker values and the receiver operating characteristic curve, one established statistical technique for evaluating classifiers.


CONCLUSIONS
The standardization is an intuitive procedure for evaluating markers. It facilitates direct and meaningful comparisons between markers. It also provides a new view of receiver operating characteristic analysis that may render it more accessible to those as yet unfamiliar with it. The general approach provides a statistical tool to address important questions that are typically not addressed in current marker research, such as quantifying and controlling for covariate effects.
Pepe
Margaret Sullivan
MS
Department of Biostatistics, University of Washington, Seattle, WA, USA. mspepe@u.washington.edu
Longton
Gary
G
D014408:Biomarkers, Tumor / Q000097:blood*; D001699:Biometry; D018394:CA-125 Antigen / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006311:Hearing Disorders / Q000175:diagnosis*; D006320:Hearing Tests; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood*; D012372:ROC Curve
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen