||5R01CA207220-02 Interpret this number
||Sloan-Kettering Inst Can Research
||Inferential Methods to Assess the Incremental Value of New Biomarkers in Risk Classification Models
This proposal aims to develop statistical methods to evaluate improvement in risk classification measures due
to the inclusion of new biomarkers. Risk classification modeling has a direct impact on patient treatment and
health. These models are used to identify the need for diagnostic testing in the general population, or the type
of treatment to be administered in a specified patient population. The most common risk classification
improvement measures include the difference in the area under the receiver operating characteristic curve, the
net reclassification index, the integrated discrimination improvement, and the difference in sensitivity and
specificity. The new statistical methods will provide a metric to decide whether a change in patient risk,
stemming from the evaluation of new biomarkers, is random variation or a true improvement in the accuracy of
a risk classification model. The metric is defined through asymptotic distribution theory within a nested models
framework. Methods to assess improvement in the accuracy of risk models are not well-developed, with
current methods relying on classical hypothesis tests of association. These tests may lead to dissonance,
since the results of parametric association statistics may not align with the nonparametric risk improvement
statistics used in the models being evaluated. The objective of this grant proposal is to develop a coherent
statistical inferential strategy that directly measures the incremental value of new biomarkers in risk
classification models with binary and survival endpoints. The aims of the proposal are: 1) To develop
inferential methods for the difference in concordance probability measures from nested proportional hazards
models with a survival endpoint.2) To develop inferential methods for the incremental value of Net
Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) with binary and survival
regression models. 3) To develop inferential methods for the incremental value of sensitivity and specificity
with binary and survival regression models. Measures of risk classification improvement impact medical
decision making. The statistical evaluation of the incremental benefit of a new panel of markers, in relation to
clinical measures and laboratory tests that are acquired in the course of routine clinical practice, will play a role
in the level of confidence physicians and medical researchers have in updating their medical intervention
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