Dataset Information

Estimating the optimal threshold for a diagnostic biomarker in case of complex biomarker distributions.

ABSTRACT:

Background

Estimating the optimal threshold (and especially the confidence interval) of a quantitative biomarker to be used as a diagnostic test is essential for medical decision-making. This is often done with simple methods that are not always reliable. More advanced methods work well but only for biomarkers with very simple distributions. In fact, biomarker distributions are often complex because of a natural heterogeneity in marker expression and other heterogeneities due to various disease stages, laboratory equipments, etc. Methods are required to estimate a biomarker optimal threshold in case of heterogeneity and complex distributions.

Methods

A previously described Bayesian method developed for normally distributed biomarkers is applied to two flexible distributions; namely, a Student-t and a mixture of Dirichlet processes. Here, numerical studies assess the adequacy of the previous method with both distributions. Two applications are presented: the diagnosis of treatment failure after prostate cancer treated by ultrasound and the early diagnosis of cancers of the upper aerodigestive tract.

Results

Bayesian inference provided reliable credible intervals in terms of bias and coverage probability. The two distributions analysed gave meaningful clinical interpretations in both applications.

Conclusions

Reliable methods can be used to estimate a biomarker optimal threshold, even in case of complex distributions.

SUBMITTER: Subtil F

PROVIDER: S-EPMC4062774 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Estimating the optimal threshold for a diagnostic biomarker in case of complex biomarker distributions.

Subtil Fabien F Rabilloud Muriel M

BMC medical informatics and decision making 20140614

<h4>Background</h4>Estimating the optimal threshold (and especially the confidence interval) of a quantitative biomarker to be used as a diagnostic test is essential for medical decision-making. This is often done with simple methods that are not always reliable. More advanced methods work well but only for biomarkers with very simple distributions. In fact, biomarker distributions are often complex because of a natural heterogeneity in marker expression and other heterogeneities due to various ...[more]

PMID: 24927622

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Project description:BackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.MethodsWe performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.FindingsTwo hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73-0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79-0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0-69·0%) than CRP (28·1%, 95% CI: 20·2-41·8%) (p = 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2-98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3-99·9%) was higher.InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

Dataset Information

Estimating the optimal threshold for a diagnostic biomarker in case of complex biomarker distributions.

Background

Methods

Results

Conclusions

Publications

Estimating the optimal threshold for a diagnostic biomarker in case of complex biomarker distributions.

Similar Datasets

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