scholarly journals Estimating the false positive rate of highly automated SARS-CoV-2 nucleic acid amplification testing

2021 ◽  
Author(s):  
Christopher M. Chandler ◽  
Lori Bourassa ◽  
Patrick C. Mathias ◽  
Alexander L. Greninger
Keyword(s):  
Nucleic Acid ◽  
High Throughput ◽  
False Positive ◽  
False Positive Rate ◽  
Epidemiological Data ◽  
Pcr Primers ◽  
Nucleic Acid Amplification ◽  
Molecular Testing ◽  
Nucleic Acid Amplification Testing ◽  
Positive Rate

AbstractMolecular testing for infectious diseases is generally both very sensitive and specific. Well-designed PCR primers rarely cross-react with other analytes, and specificities seen during test validation are often 100%. However, analytical specificities measured during validation may not reflect real-world performance across the entire testing process. Here, we use the unique environment of SARS-CoV-2 screening among otherwise well individuals to examine the false positivity rate of high throughput so-called “sample-to-answer” nucleic acid amplification testing (NAAT) on three commercial assays: the Hologic Panther Fusion®, Hologic Aptima® transcription mediated amplification (TMA), and Roche cobas® 6800. We used repetitive sampling of the same person as the gold standard to determine test specificity rather than retesting of the same sample. We examined 451 people repetitively sampled over 7 months via nasal swab, comprising 7,242 results. During the study period there were twelve positive tests (0.17%) from 9 people. Eight positive tests (0.11%, five individuals) were considered bona fide true positives based on repeat positives or outside testing and epidemiological data. One positive test had no follow-up testing or metadata and could not be adjudicated. Three positive tests (three individuals) did not repeat as positive on a subsequent collection, nor did the original positive specimen test positive on an orthogonal platform. We consider these three tests false positives and estimate the overall false positive rate of high-throughput automated, sample-to-answer NAAT testing to be approximately 0.041% (3/7242). These data help laboratorians, epidemiologists, and regulators understand specificity and positive predictive value associated with high-throughput NAAT testing.

scholarly journals Estimating the false positive rate of highly automated SARS-CoV-2 nucleic acid amplification testing

2021 ◽  
Author(s):  
Christopher M. Chandler ◽  
Lori Bourassa ◽  
Patrick C. Mathias ◽  
Alexander L. Greninger
Keyword(s):  
Nucleic Acid ◽  
High Throughput ◽  
Real World ◽  
Validation Studies ◽  
False Positive Rate ◽  
Pcr Primers ◽  
Test Validation ◽  
Nucleic Acid Amplification ◽  
Molecular Testing ◽  
Positive Rate

Molecular testing for infectious diseases is generally both very sensitive and specific (1). Well-designed PCR primers rarely cross-react with other analytes, and specificities seen during test validation are often 100% (2). However, analytical specificities measured during limited validation studies may not reflect real-world performance across the entire testing process. Surprisingly, there is exceedingly little literature on the specificity of high-throughput, sample-to-answer PCR testing, which critically informs debates on future SARS-CoV-2 screening algorithms.

scholarly journals False-positive HIV nucleic acid amplification testing during CAR T-cell therapy

2017 ◽  
Vol 88 (4) ◽  
pp. 305-307 ◽  
Author(s):  
Ella J. Ariza-Heredia ◽  
Bruno P. Granwehr ◽  
George M. Viola ◽  
Micah Bhatti ◽  
James M. Kelley ◽  
...  
Keyword(s):  
T Cell ◽  
Nucleic Acid ◽  
Cell Therapy ◽  
False Positive ◽  
Nucleic Acid Amplification ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Nucleic Acid Amplification Testing ◽  
Car T Cell Therapy ◽  
Car T

Improving diagnosis of acute appendicitis with atypical findings by Tc-99m HMPAO leukocyte scan

2002 ◽  
Vol 41 (01) ◽  
pp. 37-41 ◽  
Author(s):  
S. Shung-Shung ◽  
S. Yu-Chien ◽  
Y. Mei-Due ◽  
W. Hwei-Chung ◽  
A. Kao
Keyword(s):  
Acute Appendicitis ◽  
False Positive ◽  
False Positive Rate ◽  
Accurate Method ◽  
Clinical Findings ◽  
Pathological Findings ◽  
Lower Quadrant ◽  
Predictive Values ◽  
Positive Rate

Summary Aim: Even with careful observation, the overall false-positive rate of laparotomy remains 10-15% when acute appendicitis was suspected. Therefore, the clinical efficacy of Tc-99m HMPAO labeled leukocyte (TC-WBC) scan for the diagnosis of acute appendicitis in patients presenting with atypical clinical findings is assessed. Patients and Methods: Eighty patients presenting with acute abdominal pain and possible acute appendicitis but atypical findings were included in this study. After intravenous injection of TC-WBC, serial anterior abdominal/pelvic images at 30, 60, 120 and 240 min with 800k counts were obtained with a gamma camera. Any abnormal localization of radioactivity in the right lower quadrant of the abdomen, equal to or greater than bone marrow activity, was considered as a positive scan. Results: 36 out of 49 patients showing positive TC-WBC scans received appendectomy. They all proved to have positive pathological findings. Five positive TC-WBC were not related to acute appendicitis, because of other pathological lesions. Eight patients were not operated and clinical follow-up after one month revealed no acute abdominal condition. Three of 31 patients with negative TC-WBC scans received appendectomy. They also presented positive pathological findings. The remaining 28 patients did not receive operations and revealed no evidence of appendicitis after at least one month of follow-up. The overall sensitivity, specificity, accuracy, positive and negative predictive values for TC-WBC scan to diagnose acute appendicitis were 92, 78, 86, 82, and 90%, respectively. Conclusion: TC-WBC scan provides a rapid and highly accurate method for the diagnosis of acute appendicitis in patients with equivocal clinical examination. It proved useful in reducing the false-positive rate of laparotomy and shortens the time necessary for clinical observation.

Predicting Fetal Chromosome Anomalies in the First Trimester Using Pregnancy Associated Plasma Protein-A: A Comparison of Statistical Methods

1993 ◽  
Vol 32 (02) ◽  
pp. 175-179 ◽  
Author(s):  
B. Brambati ◽  
T. Chard ◽  
J. G. Grudzinskas ◽  
M. C. M. Macintosh
Keyword(s):  
Logistic Regression ◽  
General Population ◽  
Likelihood Ratio ◽  
False Positive ◽  
False Positive Rate ◽  
Ratio Method ◽  
Detection Rates ◽  
Gaussian Distributions ◽  
Positive Rate ◽  
Likelihood Ratio Method

Abstract:The analysis of the clinical efficiency of a biochemical parameter in the prediction of chromosome anomalies is described, using a database of 475 cases including 30 abnormalities. A comparison was made of two different approaches to the statistical analysis: the use of Gaussian frequency distributions and likelihood ratios, and logistic regression. Both methods computed that for a 5% false-positive rate approximately 60% of anomalies are detected on the basis of maternal age and serum PAPP-A. The logistic regression analysis is appropriate where the outcome variable (chromosome anomaly) is binary and the detection rates refer to the original data only. The likelihood ratio method is used to predict the outcome in the general population. The latter method depends on the data or some transformation of the data fitting a known frequency distribution (Gaussian in this case). The precision of the predicted detection rates is limited by the small sample of abnormals (30 cases). Varying the means and standard deviations (to the limits of their 95% confidence intervals) of the fitted log Gaussian distributions resulted in a detection rate varying between 42% and 79% for a 5% false-positive rate. Thus, although the likelihood ratio method is potentially the better method in determining the usefulness of a test in the general population, larger numbers of abnormal cases are required to stabilise the means and standard deviations of the fitted log Gaussian distributions.

Identification of and Correction for Publication Bias: Comment

2019 ◽  
Author(s):  
Amanda Kvarven ◽  
Eirik Strømland ◽  
Magnus Johannesson
Keyword(s):  
Publication Bias ◽  
False Positive ◽  
Large Scale ◽  
Meta Analysis ◽  
False Positive Rate ◽  
Effect Sizes ◽  
Replication Studies ◽  
Moderate Reduction ◽  
Positive Rate ◽  
Meta Analyses

Andrews & Kasy (2019) propose an approach for adjusting effect sizes in meta-analysis for publication bias. We use the Andrews-Kasy estimator to adjust the result of 15 meta-analyses and compare the adjusted results to 15 large-scale multiple labs replication studies estimating the same effects. The pre-registered replications provide precisely estimated effect sizes, which do not suffer from publication bias. The Andrews-Kasy approach leads to a moderate reduction of the inflated effect sizes in the meta-analyses. However, the approach still overestimates effect sizes by a factor of about two or more and has an estimated false positive rate of between 57% and 100%.

scholarly journals PRATD: A Phased Remote Access Trojan Detection Method with Double-Sided Features

Electronics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1894
Author(s):  
Chun Guo ◽  
Zihua Song ◽  
Yuan Ping ◽  
Guowei Shen ◽  
Yuhei Cui ◽  
...  
Keyword(s):  
False Positive ◽  
Detection Method ◽  
False Positive Rate ◽  
True Positive Rate ◽  
Remote Access ◽  
Detection Methods ◽  
Security Threats ◽  
True Positive ◽  
Trojan Detection ◽  
Positive Rate

Remote Access Trojan (RAT) is one of the most terrible security threats that organizations face today. At present, two major RAT detection methods are host-based and network-based detection methods. To complement one another’s strengths, this article proposes a phased RATs detection method by combining double-side features (PRATD). In PRATD, both host-side and network-side features are combined to build detection models, which is conducive to distinguishing the RATs from benign programs because that the RATs not only generate traffic on the network but also leave traces on the host at run time. Besides, PRATD trains two different detection models for the two runtime states of RATs for improving the True Positive Rate (TPR). The experiments on the network and host records collected from five kinds of benign programs and 20 famous RATs show that PRATD can effectively detect RATs, it can achieve a TPR as high as 93.609% with a False Positive Rate (FPR) as low as 0.407% for the known RATs, a TPR 81.928% and FPR 0.185% for the unknown RATs, which suggests it is a competitive candidate for RAT detection.

Evidence for Age-Adjusted D-Dimer to Rule out Pulmonary Embolism: An Institutional Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S5-S5
Author(s):  
Ridin Balakrishnan ◽  
Daniel Casa ◽  
Morayma Reyes Gil
Keyword(s):  
Pulmonary Embolism ◽  
False Positive ◽  
False Positive Rate ◽  
Moderate Risk ◽  
Older Population ◽  
Statistical Measures ◽  
Positive Rate ◽  
Risk Patients ◽  
D Dimer ◽  
Rule Out

Abstract The diagnostic approach for ruling out suspected acute pulmonary embolism (PE) in the ED setting includes several tests: ultrasound, plasma d-dimer assays, ventilation-perfusion scans and computed tomography pulmonary angiography (CTPA). Importantly, a pretest probability scoring algorithm is highly recommended to triage high risk cases while also preventing unnecessary testing and harm to low/moderate risk patients. The d-dimer assay (both ELISA and immunoturbidometric) has been shown to be extremely sensitive to rule out PE in conjunction with clinical probability. In particularly, d-dimer testing is recommended for low/moderate risk patients, in whom a negative d-dimer essentially rules out PE sparing these patients from CTPA radiation exposure, longer hospital stay and anticoagulation. However, an unspecific increase in fibrin-degradation related products has been seen with increase in age, resulting in higher false positive rate in the older population. This study analyzed patient visits to the ED of a large academic institution for five years and looked at the relationship between d-dimer values, age and CTPA results to better understand the value of age-adjusted d-dimer cut-offs in ruling out PE in the older population. A total of 7660 ED visits had a CTPA done to rule out PE; out of which 1875 cases had a d-dimer done in conjunction with the CT and 5875 had only CTPA done. Out of the 1875 cases, 1591 had positive d-dimer results (>0.50 µg/ml (FEU)), of which 910 (57%) were from patients older than or equal to fifty years of age. In these older patients, 779 (86%) had a negative CT result. The following were the statistical measures of the d-dimer test before adjusting for age: sensitivity (98%), specificity (12%); negative predictive value (98%) and false positive rate (88%). After adjusting for age in people older than 50 years (d-dimer cut off = age/100), 138 patients eventually turned out to be d-dimer negative and every case but four had a CT result that was also negative for a PE. The four cases included two non-diagnostic results and two with subacute/chronic/subsegmental PE on imaging. None of these four patients were prescribed anticoagulation. The statistical measures of the d-dimer test after adjusting for age showed: sensitivity (96%), specificity (20%); negative predictive value (98%) and a decrease in the false positive rate (80%). Therefore, imaging could have been potentially avoided in 138/779 (18%) of the patients who were part of this older population and had eventual negative or not clinically significant findings on CTPA if age-adjusted d-dimers were used. This data very strongly advocates for the clinical usefulness of an age-adjusted cut-off of d-dimer to rule out PE.

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