Using a combination of reference tests to assess the accuracy of a new diagnostic test

Alonzo, Todd A.; Pepe, Margaret S.

doi:10.1002/(sici)1097-0258(19991130)18:22<2987::aid-sim205>3.0.co;2-b

Cited by 209 publications

(89 citation statements)

References 48 publications

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“…We compared estimates of sensitivity and specificity for each test using the following standards to classify patients as infected: (i) three different single cervical test reference standards (patients were classified as infected if the cervical culture, cervical LCR, or cervical PCR test result was positive) and (ii) three different two-test reference standards (patients were classified as infected if either the cervical or urethral culture, cervical or urine LCR, or cervical or urine PCR test result was positive). A two-test refer-ence standard in which subjects are classified as infected if either reference test is positive has been advocated to improve reference standard sensitivity and, thereby, reduce underestimation of evaluated test specificity due to false-negative reference standard results (1).…”

Section: Patient Populationmentioning

confidence: 99%

Head-to-Head Multicenter Comparison of DNA Probe and Nucleic Acid Amplification Tests for Chlamydia trachomatis Infection in Women Performed with an Improved Reference Standard

et al. 2002

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Few evaluations of tests for Chlamydia trachomatis have compared nucleic acid amplification tests (NAATs)with diagnostic tests other than those by culture. In a five-city study of 3,551 women, we compared the results of commercial ligase chain reaction (LCR) and PCR tests performed on cervical swabs and urine with the results of PACE 2 tests performed on cervical swabs, using independent reference standards that included both cervical swabs and urethral swab-urine specimens. Using cervical culture as a standard, the sensitivities of PACE 2, LCR, and PCR tests with cervical specimens were 78.1, 96.9, and 89.9%, respectively, and the specificities were 99.3, 97.5, and 98.2%, respectively. Using either cervical swab or urine LCR-positive tests as the standard decreased sensitivities to 60.8% for PACE 2 and to 75.8 and 74.9% for PCR with cervical swabs and urine, respectively. Specificities increased to 99.7% for PACE 2 and to 99.7 and 99.4% for PCR with cervical swabs and urine, respectively. Sensitivities with a cervical swab-urine PCR standard were 61.9% for PACE 2 and 85.5 and 80.8% for LCR with cervical swabs and urine, respectively. Specificities were 99.6% for PACE 2 and 99.0 and 98.9% for LCR with cervical swabs and urine, respectively. Cervical swab versus urine differences were significant only for PCR specificities (P ‫؍‬ 0.034). Overall, LCR sensitivity exceeded that of PCR, and sensitivities obtained with cervical swabs exceeded those obtained with urine specimens by small amounts. These data have substantiated, using a large multicenter sample and a patient standard, that LCR and PCR tests performed on endocervical swabs and urine are superior to PACE 2 tests for screening C. trachomatis infections in women. In our study, NAATs improved the detection of infected women by 17 to 38% compared to PACE 2.Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection in the United States (6). Untreated infections can have devastating consequences for the female reproductive tract by causing pelvic inflammatory disease with serious sequelae such as infertility, ectopic pregnancy, and chronic pelvic pain. Because the majority of infections, particularly in women, are unrecognized clinically, screening with laboratory tests followed by antibiotic treatment is the most important means of intervention and control. The diagnostics industry has responded to this large public health need with steady improvements in test technologies. Concomitantly, methodology used for evaluation of these newly developed tests has evolved in a parallel fashion.Historically, isolation of C. trachomatis in culture was used as the reference standard for classifying patients as infected or uninfected in new test evaluations (3). Culture was chosen for this purpose because it has nearly 100% specificity, resulting from the highly distinctive morphology of specifically stained chlamydial inclusion bodies grown in host cells, and because it was the most sensitive method available at the time. Thus, virtually all of th...

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Section: Patient Populationmentioning

confidence: 99%

Head-to-Head Multicenter Comparison of DNA Probe and Nucleic Acid Amplification Tests for Chlamydia trachomatis Infection in Women Performed with an Improved Reference Standard

et al. 2002

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“…The high BST specificity observed in this study implies a similarly high positive predictive value for this assay [23]. In these circumstances, it is highly likely that the 51(78 less 27 in agreement between CRS and BST) animals positive to the BST, but negative to the CRS, is a reflection of what our gold standard missed, and hence represented truly infected individuals [1]. This observation may be explained by a gold standard which was biased towards animals that had mounted a strong humoral, but not necessarily a strong CMI response to infection.…”

Section: Evaluating the Brucellin Skin Test As An Additional Test To mentioning

confidence: 72%

“…In an ideal situation a new diagnostic test should be evaluated against a perfect gold standard test which assigns infection status with certainty [1]. In field studies involving bovine brucellosis a perfect gold standard is not available and a less than perfect standard must be employed [18,20].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore the dilemma of the reference standard influences the legitimacy of comparison. In situations where the index test is sensitive enough to correctly identify positive cases beyond the identification spectrum of the reference standard, the new assay is erroneously judged as showing a high false positive reactor rate when they are indeed true positives [1]. With a CRS composed of the RBT, CFT and iELISA, our study set out to investigate the diagnostic performance of the BST in South African herds and its potential to contribute to the improvement of the diagnostic sensitivity of the currently used brucellosis serological methods.…”

Section: Evaluating the Brucellin Skin Test As An Additional Test To mentioning

confidence: 99%

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Evaluating the Brucellin Skin Test as an Additional Test to Control Bovine Brucellosis

Nyanhongo¹

2017

SOJMID

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Brucellosis is a bacterial disease of high veterinary importance, besides being a significant zoonosis worldwide. It is characterised by variable, and at times long and latent, incubation periods, which makes its control and eradication a challenging effort. No single test is able to identify all stages of the disease with high sensitivity. The brucellin skin test, which has been proved to identify some acute and chronic latent stages of brucellosis, has not been validated in South Africa. The objective of this study was to evaluate the brucellin skin test in brucellosis free, as well as confirmed infected cattle herds, under South African commercial farming conditions. The results indicate that the brucellin skin test has a high specificity (99.2% (95% confidence interval (CI): 98.1% -99.7%)), and that despite a relatively low sensitivity (42.9 % (95% CI: 30.5% -56.0%)), it was able to identify all the infected herds and detect more infected heifers in infected herds when compared to the routinely used Rose Bengal Test and Complement Fixation Test. It was concluded that the brucellin skin test could be used in parallel with serological tests to improve the sensitivity of the current diagnostic strategy in chronically infected herds where eradication of the disease has proven problematic. Removal of more infected heifers would decrease infection pressure and streamline vaccination towards heifers not exposed to Brucella abortus.

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“…Sensitivity, specificity, PPV, NPV, accuracy were calculated to test the diagnostic yield and kappa agreement was done to test validity of microscopy and ICT in relation to PCR results considering it a nominated gold standard. According to composite reference standard (CRS) of Alonzo and Pepe (1999) that suppose the present gold standard test (microscopy) is highly specific but not very sensitive was used to define true positive cases. The present study considered tpi nested-PCR (nPCR) as a reference standard and 18S cPCR as a resolver.…”

Section: Discussionmentioning

confidence: 99%

Molecular detection of giardiasis among children at Cairo University Pediatrics Hospitals

et al. 2015

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Giardiasis is a prevailing intestinal disease in children. This study aimed to determine molecular prevalence of Giardia intestinalis in children attending Cairo University Pediatrics Hospitals, using copro-PCR assays, conventional methods and to evaluate diagnostic effectiveness of used tests. 229 fecal samples were collected from children suffering from gastrointestinal symptoms and examined for Giardia by microscopy, Immuno-chromatographic test (ICT), copro-DNA using two PCR assays targeting tpi [nested-PCR (nPCR)] and 18S [conventional-PCR (cPCR)] genes. Out of 229 samples assessed, Giardia was diagnosed in 13.9, 17, 17.9, 4.8 % of cases using microscopy, ICT, nPCR (tpi) and cPCR (18S), respectively. Nominating both PCR assays as composite reference standard, microscopy and ICT were of reliable specificity (100 and 96.9 %) and accuracy (95.6 and 93.6 %) but of limited sensitivity (78.6 and 76.2 %). Kappa agreement showed, there was substantial agreement of ICT (0.776) and almost perfect agreement of microscopy (0.839) with PCR assays. Giardia showed a molecular prevalence of 18.3 % (42/229). ICT assay for Giardia surpassed microscopy but both couldn't be used as a consistent single detection method due to their lowered sensitivities. nPCR targeting tpi is a reliable diagnostic test aiding to determine true prevalence of Giardia.

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Using a combination of reference tests to assess the accuracy of a new diagnostic test

Cited by 209 publications

References 48 publications

Head-to-Head Multicenter Comparison of DNA Probe and Nucleic Acid Amplification Tests for Chlamydia trachomatis Infection in Women Performed with an Improved Reference Standard

Head-to-Head Multicenter Comparison of DNA Probe and Nucleic Acid Amplification Tests for Chlamydia trachomatis Infection in Women Performed with an Improved Reference Standard

Evaluating the Brucellin Skin Test as an Additional Test to Control Bovine Brucellosis

Molecular detection of giardiasis among children at Cairo University Pediatrics Hospitals

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