scholarly journals Recalibrating SARS-CoV-2 antigen rapid lateral flow test relative sensitivity from validation studies to absolute sensitivity for detecting individuals with live virus

2021 ◽  
Author(s):  
Irene Petersen ◽  
Alexander Crozier ◽  
Iain Buchan ◽  
Michael J Mina ◽  
Jonathan W Bartlett
Keyword(s):  
Validation Studies ◽  
Genetic Material ◽  
Relative Sensitivity ◽  
Lateral Flow ◽  
Relative Performance ◽  
Viral Kinetics ◽  
Live Virus ◽  
Predictive Values ◽  
Absolute Sensitivity ◽  
Performance Statistics

Testing for SARS-CoV-2 internationally has focused on COVID-19 diagnosis among symptomatic individuals using reverse transcriptase polymerase chain reaction (PCR) tests. Recently, however, SARS-CoV-2 antigen rapid lateral flow tests (LFT) have been rolled out in several countries for testing asymptomatic individuals in public health programmes. Validation studies for LFT have been largely cross-sectional, reporting sensitivity, specificity and predictive values of LFT relative to PCR. However, because PCR detects genetic material left behind for a long period when the individual is no longer infectious, these statistics can under-represent sensitivity of LFT for detecting infectious individuals, especially when sampling asymptomatic populations. LFTs (intended to detect individuals with live virus) validated against PCR (intended to diagnose infection) are not reporting against a gold standard of equivalent measurements. Instead, these validation studies have reported relative performance statistics that need recalibrating to the purpose for which LFT is being used. We present an approach to this recalibration. We derive a formula for recalibrating relative performance statistics from LFT vs PCR validation studies to give likely absolute sensitivity of LFT for detecting individuals with live virus. We show the differences between widely reported apparent sensitivities of LFT and its absolute sensitivity as a test of presence of live virus. After accounting for within-individual viral kinetics and epidemic dynamics within asymptomatic populations we show that a highly performant test of live virus should show a LFT-to-PCR relative sensitivity of less than 50% in conventional validation studies, which after re-calibration would be an absolute sensitivity of more than 80%. Further studies are needed to ascertain the absolute sensitivity of LFT as a test of infectiousness in COVID-19 responses. These studies should include sampling for viral cultures and longitudinal series of LFT and PCR, ideally in cohorts sampled from both contacts of cases and the general population.

Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT)

2011 ◽  
Vol 106 (12) ◽  
pp. 1197-1202 ◽  
Author(s):  
Jakob Hesberg ◽  
Sentot Santoso ◽  
Gregor Bein ◽  
Tamam Bakchoul ◽  
Ulrich Sachs
Keyword(s):  
Lateral Flow ◽  
Lateral Flow Immunoassay ◽  
Medical Patients ◽  
High Potency ◽  
Platelet Factor ◽  
Predictive Values ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Probability ◽  
Short Period ◽  
Test Probability

SummaryHeparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid singlesample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

scholarly journals Common misconceptions about validation studies

2020 ◽  
Vol 49 (4) ◽  
pp. 1392-1396
Author(s):  
Matthew P Fox ◽  
Timothy L Lash ◽  
Lisa M Bodnar
Keyword(s):  
Validation Studies ◽  
Gold Standard ◽  
Positive Impact ◽  
Standard Measure ◽  
Epidemiologic Research ◽  
Present Sample ◽  
Predictive Values ◽  
Study Results ◽  
Key Variables ◽  
Valid Information

Abstract Information bias is common in epidemiology and can substantially diminish the validity of study results. Validation studies, in which an investigator compares the accuracy of a measure with a gold standard measure, are an important way to understand and mitigate this bias. More attention is being paid to the importance of validation studies in recent years, yet they remain rare in epidemiologic research and, in our experience, they remain poorly understood. Many epidemiologists have not had any experience with validations studies, either in the classroom or in their work. We present an example of misclassification of a dichotomous exposure to elucidate some important misunderstandings about how to conduct validation studies to generate valid information. We demonstrate that careful attention to the design of validation studies is central to determining how the bias parameters (e.g. sensitivity and specificity or positive and negative predictive values) can be used in quantitative bias analyses to appropriately correct for misclassification. Whether sampling is done based on the true gold standard measure, the misclassified measure or at random will determine which parameters are valid and the precision of those estimates. Whether or not the validation is done stratified by other key variables (e.g. by the exposure) will also determine the validity of those estimates. We also present sample questions that can be used to teach these concepts. Increasing the presence of validation studies in the classroom could have a positive impact on their use and improve the validity of estimates of effect in epidemiologic research.

Evaluation of a New Nanoparticle-Based Lateral-Flow Immunoassay for the Exclusion of Heparin-Induced Thrombocytopenia (HIT),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3290-3290
Author(s):  
Ulrich J. Sachs ◽  
Jakob von Hesberg ◽  
Sentot Santoso ◽  
Gregor Bein ◽  
Tamam Bakchoul
Keyword(s):  
Conflicts Of Interest ◽  
Lateral Flow ◽  
Lateral Flow Immunoassay ◽  
Medical Patients ◽  
Platelet Factor ◽  
Predictive Values ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Probability ◽  
Short Period ◽  
Sample Test

Abstract Abstract 3290 Background: Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognize platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. Objectives: To evaluate a new lateral-flow immunoassay based on nanoparticle technology. Patients/methods: A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Results: Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT (median time, 11 min 30 sec) than to perform the other immunoassays. Conclusion: A newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT. Disclosures: No relevant conflicts of interest to declare.

Optimum Density in Emission Spectrography

1966 ◽  
Vol 20 (4) ◽  
pp. 219-222 ◽  
Author(s):  
Vratislav Svoboda
Keyword(s):  
Contrast Sensitivity ◽  
Characteristic Curve ◽  
Relative Sensitivity ◽  
Absolute Sensitivity ◽  
Optimum Density

The relation of optimum density of developed photographic plates to characteristic curve constants has been studied for two extreme cases: spectrographic estimation with high absolute sensitivity and with high relative sensitivity. While the values calculated for absolute sensitivities agree well with those obtained experimentally, the calculated values are slightly lower in the case of contrast sensitivity than experimental ones.

scholarly journals Spectral Sensitivities of Wolf Spider Eyes

1969 ◽  
Vol 54 (1) ◽  
pp. 1-32 ◽  
Author(s):  
Robert D. DeVoe ◽  
Ralph J. W. Small ◽  
Janis E. Zvargulis
Keyword(s):  
Energy Transfer ◽  
Visual Pigment ◽  
Scattered Light ◽  
Wolf Spider ◽  
Relative Sensitivity ◽  
Wolf Spiders ◽  
Absolute Sensitivity ◽  
Radiationless Energy Transfer ◽  
Accessory Pigment

ERG's to spectral lights were recorded from all eyes of intact wolf spiders. Secondary eyes have maximum relative sensitivities at 505–510 nm which are unchanged by chromatic adaptations. Principal eyes have ultraviolet sensitivities which are 10 to 100 times greater at 380 nm than at 505 nm. However, two animals' eyes initially had greater blue-green sensitivities, then in 7 to 10 wk dropped 4 to 6 log units in absolute sensitivity in the visible, less in the ultraviolet. Chromatic adaptations of both types of principal eyes hardly changed relative spectral sensitivities. Small decreases in relative sensitivity in the visible with orange adaptations were possibly retinomotor in origin. Second peaks in ERG waveforms were elicited from ultraviolet-adapted principal eyes by wavelengths 400 nm and longer, and from blue-, yellow-, and orange-adapted secondary eyes by wavelengths 580 nm and longer. The second peaks in waveforms were most likely responses of unilluminated eyes to scattered light. It is concluded that both principal and secondary eyes contain cells with a visual pigment absorbing maximally at 505–510 nm. The variable absolute and ultraviolet sensitivities of principal eyes may be due to a second pigment in the same cells or to an ultraviolet-absorbing accessory pigment which excites the 505 nm absorbing visual pigment by radiationless energy transfer.

Interpreting prevalence estimates of pathological gambling: Implications for policy

2005 ◽  
Author(s):  
Blas_ Gambino
Keyword(s):  
Positive Predictive Value ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Test Scores ◽  
Validation Studies ◽  
Empirical Measure ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Pathological Gamblers ◽  
Prevalence Estimates

Some guidelines for interpreting prevalence estimates for the purpose of establishing the number of pathological gamblers in the community are presented. The analysis is based on the concept of the likelihood ratio, a recommended procedure for validating criteria for defining cases based on test scores. It is shown that the likelihood ratio can be employed with available estimates of prevalence to translate cut-off scores into positive predictive value. Those cut-off scores associated with high positive predictive values provide an empirical measure of confidence that those gamblers who meet or exceed the cut-off criterion are pathological gamblers. A potential limitation of the analysis is the possible specificity of results to the validation studies employed to compute likelihood ratios and to the specific estimates of prevalence used to determine positive predictive value. A recommendation is presented for obtaining study- or community-specific validation evidence.

scholarly journals Analytical Method Performance Evaluation (AMPE)A Software Tool for Analytical Method Validation

2007 ◽  
Vol 90 (5) ◽  
pp. 1432-1438 ◽  
Author(s):  
Marco Acutis ◽  
Patrizia Trevisiol ◽  
Roberto Confalonieri ◽  
Gianni Bellocchi ◽  
Emanuele Grazioli ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Analytical Method ◽  
Validation Studies ◽  
Software Tool ◽  
Validation Data ◽  
Method Performance ◽  
Analytical Method Validation ◽  
Synthetic Indicators ◽  
Wide Range ◽  
Performance Statistics

Abstract A Windows-based software tool [Analytical Method Performance Evaluation (AMPE)] was developed to support the validation of analytical methods. The software implements standard statistical approaches commonly adopted in validation studies to estimate analytical method performance (limits of detection and quantitation, accuracy, specificity, working range, and linearity of responses) according to ISO 5725. In addition, AMPE proposes the application of innovative and unique approaches for the assessment of analytical method performance. Specifically, AMPE proposes the use of difference-based indexes to quantify the agreement between measurements and reference values, the use of pattern indexes to quantify methods bias with respect to specific external variables, and the application of fuzzy logic to aggregate into synthetic indicators the information collected independently via the different performance statistics traditionally estimated in validation studies. Aggregated measures are particularly useful for methods comparison, when more than one method is available for a specific analysis and itmay be of interest to identify the best performing one taking into account, simultaneously, the information available from different performance statistics. Illustrative examples of the type of outputs expected from AMPE-based validation sessions are given. The extensive data handling capabilities and the wide range of statistics supplied in the software package makes AMPE suitable for specific needs that may arise in different validation studies. The installation package, complete with a fully documented help file, is distributed free of charge to interested users along with input files exemplary of the type of entry data required to run validation data analyses.

Matching Bacteriological and Medico-Administrative Databases Is Efficient for a Computer-Enhanced Surveillance of Surgical Site Infections: Retrospective Analysis of 4,400 Surgical Procedures in a French University Hospital

2014 ◽  
Vol 35 (11) ◽  
pp. 1330-1335 ◽  
Author(s):  
Brice Leclère ◽  
Camille Lasserre ◽  
Céline Bourigault ◽  
Marie-Emmanuelle Juvin ◽  
Marie-Pierre Chaillet ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Reference Method ◽  
Surgical Site Infections ◽  
Data Sources ◽  
University Hospital ◽  
Administrative Databases ◽  
Predictive Values ◽  
Performance Statistics ◽  
Sensitivity Specificity ◽  
Combined Algorithm

Objective.Our goal was to estimate the performance statistics of an electronic surveillance system for surgical site infections (SSIs), generally applicable in French hospitalsMethods.Three detection algorithms using 2 different data sources were tested retrospectively on 9 types of surgical procedures performed between January 2010 and December 2011 in the University Hospital of Nantes. The first algorithm was based on administrative codes, the second was based on bacteriological data, and the third used both data sources. For each algorithm, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. The reference method was the hospital’s routine surveillance: a comprehensive review of the computerized medical charts of the patients who underwent one of the targeted procedures during the study period.Setting.A 3,000-bed teaching hospital in western France.Population.We analyzed 4,400 targeted surgical procedures.Results.Sensitivity results varied significantly between the three algorithms, from 25% (95% confidence interval, 17–33) when using only administrative codes to 87% (80%–93%) with the bacteriological data and 90% (85%–96%) with the combined algorithm. Fewer variations were observed for specificity (91%–98%), PPV (21%–25%), and NPV (98% to nearly 100%). Overall, performance statistics were higher for deep SSIs than for superficial infections.Conclusions.A reliable computer-enhanced SSI surveillance can easily be implemented in French hospitals using common data sources. This should allow infection control professionals to spend more time on prevention and education duties. However, a multicenter study should be conducted to assess the generalizability of this method.Infect Control Hosp Epidemiol 2014;35(11):1330–1335

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