Abstract:
:The receiver operating characteristic curve is a commonly used tool for evaluating biomarker usefulness in clinical diagnosis of disease. Frequently, biomarkers being assessed have immeasurable or unreportable samples below some limit of detection. Ignoring observations below the limit of detection leads to negatively biased estimates of the area under the curve. Several correction methods are suggested in the areas of mean estimation and testing but nothing regarding the receiver operating characteristic curve or its summary measures. In this paper, the authors show that replacement values below the limit of detection, including those suggested, result in the same biased area under the curve when properly accounted for, but they also provide guidance on the usefulness of these values in limited situations. The authors demonstrate maximum likelihood techniques leading to asymptotically unbiased estimators of the area under the curve for both normally and gamma distributed biomarker levels. Confidence intervals are proposed, the coverage probability of which is scrutinized by simulation study. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods.
journal_name
Am J Epidemioljournal_title
American journal of epidemiologyauthors
Perkins NJ,Schisterman EF,Vexler Adoi
10.1093/aje/kwk011subject
Has Abstractpub_date
2007-02-01 00:00:00pages
325-33issue
3eissn
0002-9262issn
1476-6256pii
kwk011journal_volume
165pub_type
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