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A semiparametric method for comparing the discriminatory ability of biomarkers subject to limit of detection.

ABSTRACT: Receiver operating characteristic curves and the area under the curves (AUC) are often used to compare the discriminatory ability of potentially correlated biomarkers. Many biomarkers are subject to limit of detection due to the instrumental limitation in measurements and may not be normally distributed. Standard parametric methods assuming normality can lead to biased results when the normality assumption is violated. We propose new estimation and inference procedures for the AUCs of biomarkers subject to limit of detection by using the semiparametric transformation model allowing for heteroscedasticity. We obtain the nonparametric maximum likelihood estimators by maximizing the likelihood for the observed data with limit of detection. The proposed estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Additionally, we propose a Wald type test statistic to compare the AUCs of 2 potentially correlated biomarkers with limit of detection. Extensive simulation studies demonstrate that the proposed method is robust to nonnormality while performing as well as its parametric counterpart when the normality assumption is true. An application to an autism study is provided.

SUBMITTER: Yin L

PROVIDER: S-EPMC6219382 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A semiparametric method for comparing the discriminatory ability of biomarkers subject to limit of detection.

Yin Lixuan L Diao Guoqing G Liu Aiyi A

Statistics in medicine 20170725 26

Receiver operating characteristic curves and the area under the curves (AUC) are often used to compare the discriminatory ability of potentially correlated biomarkers. Many biomarkers are subject to limit of detection due to the instrumental limitation in measurements and may not be normally distributed. Standard parametric methods assuming normality can lead to biased results when the normality assumption is violated. We propose new estimation and inference procedures for the AUCs of biomarkers ...[more]

PMID: 28744876

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Project description:The concept of mentalizing has been widely studied, but almost exclusively through tasks with explicit instructions. Recent studies suggest that people also mentalize on a more implicit level. However, to our knowledge, no study to date has directly contrasted the effects of implicit and explicit mentalizing processes on an implicit dependent measure within-subjects. We implemented this by using two versions of an object detection task, differing only on secondary catch questions. We hypothesized that if explicit mentalizing relies on complementary processes beyond those underlying implicit mentalizing, this would be reflected in enhanced belief effects in the explicit version. Twenty-eight healthy adults watched movies in which, during the first phase, both they themselves and another agent formed a belief about the location of a ball, and although irrelevant, these beliefs could influence their ball detection reaction times in the second phase. After this response phase, there were occasional catch questions that were different for the explicit and implicit task version. Finally, self-report measures of autism spectrum disorder (ASD) symptomatology were included, as the literature suggests that ASD is related to a specific deficit in implicit mentalizing. Both in the explicit and implicit version, belief conditions had a significant effect on reaction times, with responses being slower when neither the participant nor the other agent expected the ball to be present compared to all other conditions. Importantly, after the implicit version, participants reported no explicit mentalizing awareness. In our neurotypical sample, ASD symptoms were not found to correlate with either explicit or implicit mentalizing. In conclusion, the reaction time patterns in the explicit and implicit version of the task show strikingly similar effects of mentalizing, indicating that participants processed beliefs to the same extent regardless of whether they mentalized explicitly or implicitly, with no additional effects for explicit processing.

Dataset Information

A semiparametric method for comparing the discriminatory ability of biomarkers subject to limit of detection.

Publications

A semiparametric method for comparing the discriminatory ability of biomarkers subject to limit of detection.

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