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Published in: BMC Medical Research Methodology 1/2014

Open Access 01-12-2014 | Research article

A modified Wald interval for the area under the ROC curve (AUC) in diagnostic case-control studies

Authors: Martina Kottas, Oliver Kuss, Antonia Zapf

Published in: BMC Medical Research Methodology | Issue 1/2014

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Abstract

Background

The area under the receiver operating characteristic (ROC) curve, referred to as the AUC, is an appropriate measure for describing the overall accuracy of a diagnostic test or a biomarker in early phase trials without having to choose a threshold. There are many approaches for estimating the confidence interval for the AUC. However, all are relatively complicated to implement. Furthermore, many approaches perform poorly for large AUC values or small sample sizes.

Methods

The AUC is actually a probability. So we propose a modified Wald interval for a single proportion, which can be calculated on a pocket calculator. We performed a simulation study to compare this modified Wald interval (without and with continuity correction) with other intervals regarding coverage probability and statistical power.

Results

The main result is that the proposed modified Wald intervals maintain and exploit the type I error much better than the intervals of Agresti-Coull, Wilson, and Clopper-Pearson. The interval suggested by Bamber, the Mann-Whitney interval without transformation and also the interval of the binormal AUC are very liberal. For small sample sizes the Wald interval with continuity has a comparable coverage probability as the LT interval and higher power. For large sample sizes the results of the LT interval and of the Wald interval without continuity correction are comparable.

Conclusions

If individual patient data is not available, but only the estimated AUC and the total sample size, the modified Wald intervals can be recommended as confidence intervals for the AUC. For small sample sizes the continuity correction should be used.
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Literature
1.
go back to reference EMA: Guideline on clinical evaluation of diagnostic agents. Doc. Ref. CPMP/EWP/1119/98/Rev. 1. 2010 EMA: Guideline on clinical evaluation of diagnostic agents. Doc. Ref. CPMP/EWP/1119/98/Rev. 1. 2010
2.
go back to reference Cochrane C, Ebmeier K: Diffusion tensor imaging in parkinsonian syndromes. systematic review and meta-analysis. Neurology. 2013, 80 (9): 857-864. 10.1212/WNL.0b013e318284070c.CrossRefPubMedPubMedCentral Cochrane C, Ebmeier K: Diffusion tensor imaging in parkinsonian syndromes. systematic review and meta-analysis. Neurology. 2013, 80 (9): 857-864. 10.1212/WNL.0b013e318284070c.CrossRefPubMedPubMedCentral
3.
go back to reference Wang L, Fahim M, Hayen A, Mitchell R, Baines L, Lord S, Craig J, Webster A: Cardiac testing for coronary artery disease in potential kidney transplant recipients. Cochrane Database Syst Rev. 2011, 12: 1-105.CrossRef Wang L, Fahim M, Hayen A, Mitchell R, Baines L, Lord S, Craig J, Webster A: Cardiac testing for coronary artery disease in potential kidney transplant recipients. Cochrane Database Syst Rev. 2011, 12: 1-105.CrossRef
4.
go back to reference Ziegler A, König I, Schulz-Knappe M: Challenges in planning and conducting diagnostic studies with molecular biomarkers. Dtsch Med Wochenschr. 2013, 138: 2-13.CrossRef Ziegler A, König I, Schulz-Knappe M: Challenges in planning and conducting diagnostic studies with molecular biomarkers. Dtsch Med Wochenschr. 2013, 138: 2-13.CrossRef
5.
go back to reference Ostroff R, Mehan M, Stewart A, Ayers D, Brody E, Williams S, Levin S, Black B, Harbut M, Carbone M, Gobaraju C, Pass H: Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a non-invasive proteomics-based surveillance tool. PLoS One. 2012, 7 (10): 46091-101371. 10.1371/journal.pone.0046091.CrossRef Ostroff R, Mehan M, Stewart A, Ayers D, Brody E, Williams S, Levin S, Black B, Harbut M, Carbone M, Gobaraju C, Pass H: Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a non-invasive proteomics-based surveillance tool. PLoS One. 2012, 7 (10): 46091-101371. 10.1371/journal.pone.0046091.CrossRef
6.
go back to reference Lim R, Lappas M, Riley C, Borregaard N, Moller H, Ahmed N, Rice G: Investigation of human cationic antimicrobial protein-18 (hcap-18), lactoferrin and cd163 as potential biomarkers for ovarian cancer. J Ovarian Res. 2013, 6 (1): 5-10.1186/1757-2215-6-5.CrossRefPubMedPubMedCentral Lim R, Lappas M, Riley C, Borregaard N, Moller H, Ahmed N, Rice G: Investigation of human cationic antimicrobial protein-18 (hcap-18), lactoferrin and cd163 as potential biomarkers for ovarian cancer. J Ovarian Res. 2013, 6 (1): 5-10.1186/1757-2215-6-5.CrossRefPubMedPubMedCentral
7.
go back to reference Dellon E, Chen X, Miller C, Woosley J, Shaheen N: Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. Am J Gastroenterol. 2012, 107: 1503-1511. 10.1038/ajg.2012.202.CrossRefPubMedPubMedCentral Dellon E, Chen X, Miller C, Woosley J, Shaheen N: Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. Am J Gastroenterol. 2012, 107: 1503-1511. 10.1038/ajg.2012.202.CrossRefPubMedPubMedCentral
8.
go back to reference Bamber D: The area above the ordinal dominance graph and the area below receiver operating characteristic graph. J Math Psychol. 12: 387-415. Bamber D: The area above the ordinal dominance graph and the area below receiver operating characteristic graph. J Math Psychol. 12: 387-415.
9.
go back to reference Qin G, Hotilovac L: Comparison of non-parametric confidence intervals for the area under the roc curve of a continuous-scale diagnostic test. Stat Methods Med Res. 2008, 17: 207-221. Qin G, Hotilovac L: Comparison of non-parametric confidence intervals for the area under the roc curve of a continuous-scale diagnostic test. Stat Methods Med Res. 2008, 17: 207-221.
10.
go back to reference Pepe M: The Statistical Evaluation of Medical Tests for Classification and Prediction. 2003, Oxford: Oxford University Press Pepe M: The Statistical Evaluation of Medical Tests for Classification and Prediction. 2003, Oxford: Oxford University Press
11.
go back to reference Brunner E, Puri M: Nonparametric methods in factorial designs. Stat Papers. 2001, 42: 1-52. 10.1007/s003620000039.CrossRef Brunner E, Puri M: Nonparametric methods in factorial designs. Stat Papers. 2001, 42: 1-52. 10.1007/s003620000039.CrossRef
12.
go back to reference Newcombe R: Confidence Intervals for Proportions and Related Measures of Effect Size. 2013, London: Chapman & Hall/CRC Biostatistics Series Newcombe R: Confidence Intervals for Proportions and Related Measures of Effect Size. 2013, London: Chapman & Hall/CRC Biostatistics Series
13.
go back to reference Newcombe R: Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998, 17: 857-872. 10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E.CrossRefPubMed Newcombe R: Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998, 17: 857-872. 10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E.CrossRefPubMed
14.
go back to reference He X, Wu S: Confidence intervals for the binomial proportion with zero frequency. Pharma SUG. 2009, 10-2009. He X, Wu S: Confidence intervals for the binomial proportion with zero frequency. Pharma SUG. 2009, 10-2009.
15.
go back to reference Agresti A, Coull B: Approximate is better than "exact" for interval estimations of binomial proportions. Am Stat. 1998, 52 (2): 119-126. Agresti A, Coull B: Approximate is better than "exact" for interval estimations of binomial proportions. Am Stat. 1998, 52 (2): 119-126.
16.
go back to reference Burton A, Altman D, Royston P, Holder R: The design of simulation studies in medical statistics. Stat Med. 2006, 25: 4279-4292. 10.1002/sim.2673.CrossRefPubMed Burton A, Altman D, Royston P, Holder R: The design of simulation studies in medical statistics. Stat Med. 2006, 25: 4279-4292. 10.1002/sim.2673.CrossRefPubMed
17.
go back to reference Ruymgaart F: A unified approach to the asymptotic distribution theory of certain midrank statistics. Lecture Notes on Mathematics, Statistique Non Parametrique Asymptotique, No 821. 1980, Berlin: Springer, 1-18.CrossRef Ruymgaart F: A unified approach to the asymptotic distribution theory of certain midrank statistics. Lecture Notes on Mathematics, Statistique Non Parametrique Asymptotique, No 821. 1980, Berlin: Springer, 1-18.CrossRef
18.
go back to reference Brunner E, Munzel U, Puri M: The multivariate nonparametric behrens-fisher problem. J Stat Plan Inference. 2002, 108: 37-53. 10.1016/S0378-3758(02)00269-0.CrossRef Brunner E, Munzel U, Puri M: The multivariate nonparametric behrens-fisher problem. J Stat Plan Inference. 2002, 108: 37-53. 10.1016/S0378-3758(02)00269-0.CrossRef
19.
go back to reference Inc SI: SAS/STAT®;9.3 User’s Guide. 2011, Cary, North Carolina: SAS Institute Inc. Inc SI: SAS/STAT®;9.3 User’s Guide. 2011, Cary, North Carolina: SAS Institute Inc.
20.
go back to reference Wilson E: Probable inference, the law of succession, and statistical inference. J Am Stat Assoc. 1927, 22: 209-212. 10.1080/01621459.1927.10502953.CrossRef Wilson E: Probable inference, the law of succession, and statistical inference. J Am Stat Assoc. 1927, 22: 209-212. 10.1080/01621459.1927.10502953.CrossRef
21.
go back to reference Clopper C, Pearson E: The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934, 26 (4): 404-413. 10.1093/biomet/26.4.404.CrossRef Clopper C, Pearson E: The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934, 26 (4): 404-413. 10.1093/biomet/26.4.404.CrossRef
22.
go back to reference Birnbaum Z, Klose O: Bounds for the variance of the mann-whitney statistic. Ann Math Stat. 1957, 38: 933-945.CrossRef Birnbaum Z, Klose O: Bounds for the variance of the mann-whitney statistic. Ann Math Stat. 1957, 38: 933-945.CrossRef
23.
go back to reference Wieand S, Gail M, James B, James K: A family of non-parametric statistics for comparing diagnostic markers with paired and unpaired data. Biometrika. 1989, 76: 585-592. 10.1093/biomet/76.3.585.CrossRef Wieand S, Gail M, James B, James K: A family of non-parametric statistics for comparing diagnostic markers with paired and unpaired data. Biometrika. 1989, 76: 585-592. 10.1093/biomet/76.3.585.CrossRef
Metadata
Title
A modified Wald interval for the area under the ROC curve (AUC) in diagnostic case-control studies
Authors
Martina Kottas
Oliver Kuss
Antonia Zapf
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2014
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/1471-2288-14-26

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