scholarly journals A statistical model of COVID-19 testing in populations: effects of sampling bias andtesting errors

Author(s):  
Lucas Böttcher ◽  
Maria R. D'Orsogna ◽  
Tom Chou

We develop a statistical model for the testing of disease prevalence in a population. The model assumes a binary test result, positive or negative, but allows for biases in sample selection and both type I (false positive) and type II (false negative) testing errors. Our model also incorporates multiple test types and is able to distinguish between retesting and exclusion after testing. Our quantitative framework allows us to directly interpret testing results as a function of errors and biases. By applying our testing model to COVID-19 testing data and actual case data from specific jurisdictions, we are able to estimate and provide uncertainty quantification of indices that are crucial in a pandemic, such as disease prevalence and fatality ratios. This article is part of the theme issue ‘Data science approach to infectious disease surveillance’.

2021 ◽  
Author(s):  
Lucas Böttcher ◽  
Tom Chou ◽  
Maria R. D'Orsogna

We develop a statistical model for the testing of disease prevalence in a population. The model assumes a binary test result, positive or negative, but allows for biases in sample selection and both type I (false positive) and type II (false negative) testing errors. Our model also incorporates multiple test types and is able to distinguish between retesting and exclusion after testing. Our quantitative framework allows us to directly interpret testing results as a function of errors and biases. By applying our testing model to COVID-19 testing data and actual case data from specific jurisdictions, we are able to estimate and provide uncertainty quantification of indices that are crucial in a pandemic, such as disease prevalence and fatality ratios.


2021 ◽  
Author(s):  
Ravi Jandhyala

Abstract Background: Previous research assessed the accuracy of disease-severity measurement in clinical studies as a mathematical relationship between the set of endpoints selected and the disease-severity scale (DSS), a surrogate for the theoretical Neutral list of indicators representing the disease phenotype. New DSSs are continually developed, so clinical studies’ operationalisation of the Neutral list and resulting relative neutrality may vary over time. We assessed variation in the neutrality of clinical studies over time and the probability of false positive and false negative classifications at different disease prevalence rates.Methods: We used search strings extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021 per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Overall, 483 studies and 12 rare diseases met inclusion criteria. We extracted all indicators from clinical studies and calculated neutrality and its components, sensitivity and specificity, as well as the probability of misclassifications at 20%, 50% and 80% disease prevalence rates at two time points, the times of publication of the first and last DSS. Surrogate Neutral lists were the first DSS and a composite of all later DSSs.Results: Over time, the neutrality of clinical studies increased for six diseases and decreased for five diseases, driven by sensitivity for all but Friedreich ataxia. The neutrality of clinical studies in encephalitis decreased, but sensitivity remained constant at zero. At both timepoints, the likely false negative rate increased and the likely false positive rate decreased with increasing disease prevalence. The probability that the least neutral clinical study for most diseases would yield a false positive result was equal to one at all disease prevalence rates. Conclusions: The potential for accurate clinical trial disease-severity measurement increases over time. Neutral theory showed that endpoint selection and DSSs may need improvement in Charcot Marie Tooth disease, Gaucher disease Type I, Huntington’s disease, Sjogren’s syndrome and Tourette syndrome. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical trials may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.


JIMD Reports ◽  
2021 ◽  
Author(s):  
Adam J. Guenzel ◽  
Patricia L. Hall ◽  
Anna I. Scott ◽  
Christina Lam ◽  
Irene J. Chang ◽  
...  

2014 ◽  
Vol 59 (02) ◽  
pp. 1450017 ◽  
Author(s):  
YONG KANG CHEAH ◽  
ANDREW K. G. TAN

This paper examines how socio-demographic and health-lifestyle factors determine participation and duration of leisure-time physical activity in Malaysia. Based on the Malaysia Non-Communicable Disease Surveillance-1 data, Heckman's sample selection model is employed to estimate the probability to participate and duration on physical activity. Results indicate that gender, age, years of education and family illness history are significant in explaining participation probability in leisure-time physical activity. Gender, income level, smoking-status and years of education are significant in explaining the weekly duration conditional on participation, whereas smoking-status and years of education are significant in determining the unconditional level of leisure-time physical activity.


2021 ◽  
Vol 2020 (1) ◽  
pp. 145
Author(s):  
Bradford Lee ◽  
Justin Bailey

English is not a single entity, but rather composed of infinite varieties known collectively as World Englishes. Published research in the Japanese context has overwhelmingly reported students’ preference for the Standard American variety, with Japanese English being typically subject to scorn. However, the current study argues that this established narrative has been subject to sampling bias due to homogeneous study locales (mostly in-and-around the Tokyo area) and sample selection (mostly English or Communication majors). Our precursor research on non-English majors residing in rural Japan found no statistical difference between the number of students preferring native English teachers vs. Japanese ones (Lee & Bailey, 2020). Following this line of research, the current study reports on a qualitative investigation into the sentiments of this underrepresented population. The factors of effective communication, interest in language-learning strategies, and peace-of-mind were found to be behind the students’ positive sentiments towards Japanese Teachers of English. 英語は単一ではなく無限の種類があり、それらは総称して「世界英語(複数形)」と呼ばれている。 これまでに発表された日本に関する研究では、学生が標準的なアメリカン・イングリッシュを好むという報告が圧倒的に多く、ジャパニーズ・イングリッシュは軽蔑の対象とされてきた。しかし本論はこのような結果は研究場所(主に東京周辺)とサンプルの選択方法(主に英語またはコミュニケーション専攻の学生)が均一的であるため、サンプリングバイアスの影響を受けていることを指摘した。日本の地方在住の非英語専攻の学生を対象とした筆者たちによる先行研究では、ネイティブの英語教師を好む学生と日本人教師を好む学生の間に統計的な違いは見つからなかった (Lee & Bailey, 2020)。この一連の調査を受けて、本論では過小評価された集団の感情に関する定性的調査の結果を報告した。 日本人の英語教師に対する学生の好意的な感情の背後には、効果的なコミュニケーション、語学学習戦略への関心、そして安心感という要因があることがわかった。


2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Atle Mysterud ◽  
Hildegunn Viljugrein ◽  
Christer M. Rolandsen ◽  
Aniruddha V. Belsare

The intensive harvesting of hosts is often the only practicable strategy for controlling emerging wildlife diseases. Several harvesting approaches have been explored theoretically with the objective of lowering transmission rates, decreasing the transmission period or specifically targeting spatial disease clusters or high-risk demographic groups. Here, we present a novel model-based approach to evaluate alternative harvest regimes, in terms of demographic composition and rates, intended to increase the probability to remove all infected individuals in the population during the early phase of an outbreak. We tested the utility of the method for the elimination of chronic wasting disease based on empirical data for reindeer ( Rangifer tarandus ) in Norway, in populations with (Nordfjella) and without (Hardangervidda) knowledge about exact disease prevalence and population abundance. Low and medium harvest intensities were unsuccessful in eliminating the disease, even at low prevalence. High-intensity harvesting had a high likelihood of eliminating the disease, but probability was strongly influenced by the disease prevalence. We suggest that the uncertainty about disease prevalence can be mitigated by using an adaptive management approach: forecast from models after each harvest season with updated data, derive prevalence estimates and forecast further harvesting. We identified the problems arising from disease surveillance with large fluctuations in harvesting pressure and hence sample sizes. The elimination method may be suitable for pathogens that cause long-lasting infections and with slow epidemic growth, but the method should only be attempted if there is a low risk of reinfection, either by a new disease introduction event (e.g. dispersing hosts) or due to environmental reservoirs. Our simulations highlighted the short time window when such a strategy is likely to be successful before approaching near complete eradication of the population.


2009 ◽  
Vol 55 (12) ◽  
pp. 2207-2213 ◽  
Author(s):  
Barbara W Adam ◽  
Timothy H Lim ◽  
Elizabeth M Hall ◽  
W Harry Hannon

Abstract Background: Succinylacetone (SUAC) is the primary metabolite accumulated in tyrosinemia type I—an inborn error of metabolism that, if untreated, can cause death from liver failure during the first months of life. Newborn screening laboratories measure SUAC in dried blood spot (DBS) samples to detect asymptomatic tyrosinemia type I. We used panels of SUAC-enriched DBSs to compare and evaluate the performance of these screening tests. Methods: We prepared sets of DBS materials enriched with predetermined SUAC concentrations and distributed samples of these materials, along with a screening practices questionnaire, to laboratories that perform SUAC tests. We compared their reported SUAC concentrations and questionnaire responses to identify screening practices that affect SUAC test outcomes. Results: Data from 2 pilot surveys showed large differences among laboratories in SUAC recoveries, reproducible within-laboratory recoveries, and stable performance of the DBS materials. Results from 257 proficiency test analyses contained a total of 6 false-negative misclassifications. Reported recoveries of added SUAC ranged from 0 to >200%. Low-biased SUAC recoveries were associated with 1 method used by 5 laboratories. All laboratories that reported SUAC recoveries ≥100% used DBS matrix calibrators. Conclusions: The wide ranges of SUAC concentrations reported for pilot and proficiency testing specimens demonstrate a need to harmonize quantitative results among laboratories. Although DBS matrix calibrators are important for optimizing SUAC recoveries, the preparation of these calibrators is not standardized among laboratories. Certified DBS-based SUAC calibrators are needed for accuracy and harmonization.


2019 ◽  
Vol 8 (5) ◽  
pp. 932-964 ◽  
Author(s):  
Roderick J A Little ◽  
Brady T West ◽  
Philip S Boonstra ◽  
Jingwei Hu

Abstract With the current focus of survey researchers on “big data” that are not selected by probability sampling, measures of the degree of potential sampling bias arising from this nonrandom selection are sorely needed. Existing indices of this degree of departure from probability sampling, like the R-indicator, are based on functions of the propensity of inclusion in the sample, estimated by modeling the inclusion probability as a function of auxiliary variables. These methods are agnostic about the relationship between the inclusion probability and survey outcomes, which is a crucial feature of the problem. We propose a simple index of degree of departure from ignorable sample selection that corrects this deficiency, which we call the standardized measure of unadjusted bias (SMUB). The index is based on normal pattern-mixture models for nonresponse applied to this sample selection problem and is grounded in the model-based framework of nonignorable selection first proposed in the context of nonresponse by Don Rubin in 1976. The index depends on an inestimable parameter that measures the deviation from selection at random, which ranges between the values zero and one. We propose the use of a central value of this parameter, 0.5, for computing a point index, and computing the values of SMUB at zero and one to provide a range of the index in a sensitivity analysis. We also provide a fully Bayesian approach for computing credible intervals for the SMUB, reflecting uncertainty in the values of all of the input parameters. The proposed methods have been implemented in R and are illustrated using real data from the National Survey of Family Growth.


2020 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Dawn S. Peck ◽  
Jean M. Lacey ◽  
Amy L. White ◽  
Gisele Pino ◽  
April L. Studinski ◽  
...  

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.


2010 ◽  
Vol 22 (1) ◽  
pp. 181 ◽  
Author(s):  
I. Cassar-Malek ◽  
Y. Heyman ◽  
B. Picard ◽  
C. Richard ◽  
P. Chavatte-Palmer ◽  
...  

Information on clone offspring F1 is limited, especially in species with a long inter-generation interval such as cattle. As cloned cattle exhibit a slight delay in muscle maturation until puberty (Jurie et al. 2009 Animal 3, 244-250), the present study aimed to investigate the contractile and metabolic muscle characteristics of F1 at 8, 12, and 18 months of age. Repeated biopsies of the semitendinosus muscle were collected on 10 F1 heifers born after AI of cloned cows at the experimental farm of INRA. Muscle characteristics of these offspring were compared with those of 9 female clones and 8 AI control heifers previously biopsied at the same ages. All animals (clones, F1, and controls) were female Holstein, born and raised under the same conditions in the same farm. Biopsy samples were stored frozen at -80°C until analysis for contractile and metabolic characteristics. The type of contractile fibers was determined from the proportion of the different myosin heavy chain (MyHC) isoforms separated by electrophoresis. Oxidative metabolism was assessed by isocitrate dehydrogenase (ICDH) and cytochrome-c oxidase (COX) activities (μmol min-1 per gram of muscle). Data were analyzed separately for each time of biopsy using the GLM procedure of SAS (SAS Institute, Cary, NC, USA). The statistical model contained the group as fixed effect. When a significant effect was detected, differences between least squares means were further separated by the PDIFF option of SAS. Comparison of contractile characteristics from the 3 groups of animals is presented in Table 1. The proportion of MyHC I (slow oxidative isoform) and MyHC IIx (fast glycolytic isoform) in the muscles of F1 was not significantly different from those of controls at 8 and 12 months of age. F1 had different muscle contractile properties compared with clones at 12 months of age. At 8 months of age, F1 had greater ICDH activity than controls (1.39 ± 0.22 v. 0.54 ± 0.007; P ≤ 0.002) and greater COX activities (11.4 ± 1.6 v. 4.2 ± 0.9; P ≤ 0.003), but this was not observed later on. Altogether, these data indicate that the muscles of F1 were more oxidative than those of controls. This was not related to a higher percentage of type I fibers but rather to a higher percentage of type IIA fibers. A delay in muscle maturation was only partially found in F1. Table 1.Contractile characteristics (mean ± SE) of the semitendinosus muscle from controls (n = 8), clones (n = 9) and clone offspring (F1, n = 10) heifers


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