On the assessment of the added value of new predictive biomarkers.

Background: The surge in biomarker development calls for research on statistical evaluation methodology to rigorously assess emerging biomarkers and classification models. Recently, several authors reported the puzzling observation that, in assessing the added value of new biomarkers to existing one...

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Publicado en:BMC Medical Research Methodology Vol. 13; no. 1; pp. 98 - 99
Autores principales: Chen, Weijie, Samuelson, Frank W, Gallas, Brandon D, Kang, Le, Sahiner, Berkman, Petrick, Nicholas
Formato: research Journal Article
Publicado: BioMed Central 2013
Acceso en línea:Ver este registro en EBSCOhost
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      pub: BioMed Central
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        10.1186/1471-2288-13-98
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        atl: On the assessment of the added value of new predictive biomarkers.
      aug:
        au:
          Chen, Weijie
          Samuelson, Frank W
          Gallas, Brandon D
          Kang, Le
          Sahiner, Berkman
          Petrick, Nicholas
        affil: Division of Imaging and Applied Mathematics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. weijie.chen@fda.hhs.gov.
      sug:
        subj:
          Biological Markers
          Models, Statistical
          Predictive Value of Tests
          Pharmacokinetics
          Human
          Probability
          Logistic Regression
      ab: Background: The surge in biomarker development calls for research on statistical evaluation methodology to rigorously assess emerging biomarkers and classification models. Recently, several authors reported the puzzling observation that, in assessing the added value of new biomarkers to existing ones in a logistic regression model, statistical significance of new predictor variables does not necessarily translate into a statistically significant increase in the area under the ROC curve (AUC). Vickers et al. concluded that this inconsistency is because AUC "has vastly inferior statistical properties," i.e., it is extremely conservative. This statement is based on simulations that misuse the DeLong et al. method. Our purpose is to provide a fair comparison of the likelihood ratio (LR) test and the Wald test versus diagnostic accuracy (AUC) tests.Discussion: We present a test to compare ideal AUCs of nested linear discriminant functions via an F test. We compare it with the LR test and the Wald test for the logistic regression model. The null hypotheses of these three tests are equivalent; however, the F test is an exact test whereas the LR test and the Wald test are asymptotic tests. Our simulation shows that the F test has the nominal type I error even with a small sample size. Our results also indicate that the LR test and the Wald test have inflated type I errors when the sample size is small, while the type I error converges to the nominal value asymptotically with increasing sample size as expected. We further show that the DeLong et al. method tests a different hypothesis and has the nominal type I error when it is used within its designed scope. Finally, we summarize the pros and cons of all four methods we consider in this paper.Summary: We show that there is nothing inherently less powerful or disagreeable about ROC analysis for showing the usefulness of new biomarkers or characterizing the performance of classification models. Each statistical method for assessing biomarkers and classification models has its own strengths and weaknesses. Investigators need to choose methods based on the assessment purpose, the biomarker development phase at which the assessment is being performed, the available patient data, and the validity of assumptions behind the methodologies.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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