Cut point computation in immunogenicity assays: a tutorial

2016 ◽  
pp. 84-108
Author(s):  
Proveen D Dass ◽  
Masood U Khan
Keyword(s):  
Cut Point ◽  
Immunogenicity Assays

scholarly journals Confirmatory cut point has limited ability to make accurate classifications in immunogenicity assays

Bioanalysis ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 245-256
Author(s):  
Robert J Kubiak ◽  
Rosalinda HGP Arends ◽  
Nancy Lee ◽  
Meina Liang ◽  
Jianchun Zhang ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Cut Points ◽  
Limited Ability ◽  
Cut Point ◽  
Confirmatory Assay ◽  
Drug Naïve ◽  
Point Determination ◽  
Antidrug Antibodies ◽  
Immunogenicity Assays

Aim: Competitive inhibition with excess unlabeled drug is used to confirm the presence of antidrug antibodies (ADA) in study samples. We evaluated specific and nonspecific responses from both drug-naive and drug-treated subjects to identify conditions required by the confirmatory assay to make accurate ADA classifications. Results: Nonspecific signal measured in drug-naive samples used to determine assay cut points was uniformly low and close to the screening cut point. Confirmatory assays performed on incurred study samples with nonspecific responses significantly above the level observed during cut point determination resulted in incorrect ADA classifications. Conclusion: Intensity of confirmatory response should be proportional to the screening response and therefore, to ensure accurate ADA classifications, the confirmatory responses cannot be considered as independent but need to be evaluated in relation to the screening responses.

Statistical methods and tool for cut point analysis in immunogenicity assays

2013 ◽  
Vol 389 (1-2) ◽  
pp. 79-87 ◽  
Author(s):  
Lanju Zhang ◽  
Jianchun Jason Zhang ◽  
Robert J. Kubiak ◽  
Harry Yang
Keyword(s):  
Statistical Methods ◽  
Cut Point ◽  
Point Analysis ◽  
Immunogenicity Assays

Comparison of GA-Shift Neighbourhood Mutation and GA-Pairs Exchange Mutation with Multi Cut Point Crossover in Solving RICH-VRP

2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Ismail Ismail ◽  
Sanusi Sanusi ◽  
Pratiwi Hendro Wahyudiono ◽  
Nurdiana Daeng Pawawo
Keyword(s):  
Cut Point ◽  
Rich Vrp

scholarly journals Post-traumatic stress impact on health outcomes in Gulf War Illness

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Mary Jeffrey ◽  
Fanny Collado ◽  
Jeffrey Kibler ◽  
Christian DeLucia ◽  
Steven Messer ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Short Form ◽  
Gulf War ◽  
Ptsd Symptoms ◽  
Symptom Presentation ◽  
Trauma Symptoms ◽  
Post Traumatic Stress ◽  
Gulf War Illness ◽  
Cut Point ◽  
Wide Range

Abstract Background Gulf War Illness (GWI) is a chronic, multi-symptomatic disorder affecting an estimated 25–32% of the returning military veterans of the 1990–1991 Persian Gulf War. GWI presents with a wide range of symptoms including fatigue, muscle pain, cognitive problems, insomnia, rashes and gastrointestinal issues and continues to be a poorly understood illness. This heterogeneity of GWI symptom presentation complicates diagnosis as well as the identification of effective treatments. Defining subgroups of the illness may help alleviate these complications. Our aim is to determine if GWI can be divided into distinct subgroups based on PTSD symptom presentation. Methods Veterans diagnosed with GWI (n = 47) and healthy sedentary veteran controls (n = 52) were recruited through the Miami Affairs (VA) Medical Health Center. Symptoms were assessed via the RAND short form health survey (36), the multidimensional fatigue inventory, and the Davidson trauma scale. Hierarchal regression modeling was performed on measures of health and fatigue with PTSD symptoms as a covariate. This was followed by univariate analyses conducted with two separate GWI groups based on a cut-point of 70 for their total Davidson Trauma Scale value and performing heteroscedastic t-tests across all measures. Results Overall analyses returned two symptom-based subgroups differing significantly across all health and trauma symptoms. These subgroups supported PTSD symptomatology as a means to subgroup veterans. Hierarchical models showed that GWI and levels of PTSD symptoms both impact measures of physical, social, and emotional consequences of poor health (ΔR2 = 0.055–0.316). However, GWI appeared to contribute more to fatigue measures. Cut-point analysis retained worse health outcomes across all measures for GWI with PTSD symptoms compared to those without PTSD symptoms, and healthy controls. Significant differences were observed in mental and emotional measures. Conclusions Therefore, this research supports the idea that comorbid GWI and PTSD symptoms lead to worse health outcomes, while demonstrating how GWI and PTSD symptoms may uniquely contribute to clinical presentation.

scholarly journals High neutrophil to lymphocytes ratio is associated with nutritional risk in hospitalised, unselected cancer patients: a cross-sectional study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jéssika M Siqueira ◽  
Jéssika D P Soares ◽  
Thaís C Borges ◽  
Tatyanne L N Gomes ◽  
Gustavo D Pimentel
Keyword(s):  
Logistic Regression ◽  
Cancer Patients ◽  
Systemic Inflammation ◽  
Roc Curve ◽  
Cross Sectional Study ◽  
Nutritional Risk ◽  
Sectional Study ◽  
Cross Sectional ◽  
Cut Point ◽  
Nrs 2002

AbstractCancer patients possess metabolic and pathophysiological changes and an inflammatory environment that leads to malnutrition. This study aimed to (i) determine whether there is an association between neutrophil-to-lymphocyte ratio (NLR) and nutritional risk, and (ii) identify the cut-off value of NLR that best predicts malnutrition by screening for nutritional risk (NRS 2002). This cross-sectional study included 119 patients with unselected cancer undergoing chemotherapy and/or surgery. The NRS 2002 was applied within 24 h of hospitalisation to determine the nutritional risk. Systemic inflammation was assessed by blood collection, and data on C-reactive protein (CRP), neutrophils, and lymphocytes were collected for later calculation of NLR. A receiver operating characteristic (ROC) curve was used to identify the best cut-point for NLR value that predicted nutritional risk. Differences between the groups were tested using the Student’s t-, Mann–Whitney U and Chi-Square tests. Logistic regression analyses were performed to assess the association between NLR and nutritional risk. The ROC curve showed the best cut-point for predicting nutritional risk was NLR > 5.0 (sensitivity, 60.9%; specificity, 76.4%). The NLR ≥ 5.0 group had a higher prevalence of nutritional risk than the NLR < 5.0 group (NLR ≥ 5.0: 73.6% vs. NLR < 5.0: 37.9%, p = 0.001). The NLR group ≥ 5.0 showed higher values of CRP and NLR than the NLR < 5.0 group. In addition, patients with NLR ≥ 5.0 also had higher NRS 2002 values when compared to the NLR < 5.0 group (NLR ≥ 5.0: 3.0 ± 1.1 vs. NLR < 5.0: 2.3 ± 1.2, p = 0.0004). Logistic regression revealed an association between NRS and NLR values. In hospitalised unselected cancer patients, systemic inflammation measured by NLR was associated with nutritional risk. Therefore, we highlight the importance of measuring the NLR in clinical practice, with the aim to detect nutritional risk.

An immunoinhibition approach to overcome the impact of pre-existing antibodies on cut point establishment for immunogenicity assessment of moxetumomab pasudotox

2016 ◽  
Vol 435 ◽  
pp. 68-76 ◽  
Author(s):  
Amy K. Schneider ◽  
Inna Vainshtein ◽  
Lorin K. Roskos ◽  
Carlos Chavez ◽  
Bo Sun ◽  
...  
Keyword(s):  
Cut Point ◽  
Immunogenicity Assessment ◽  
The Impact

The Rowland Universal Dementia Assessment Scale (RUDAS): a multicultural cognitive assessment scale

2004 ◽  
Vol 16 (1) ◽  
pp. 13-31 ◽  
Author(s):  
Joella E. Storey ◽  
Jeffrey T. J. Rowland ◽  
David A. Conforti ◽  
Hugh G. Dickson
Keyword(s):  
Roc Curve ◽  
Predictive Accuracy ◽  
Geriatric Medicine ◽  
Community Dwelling ◽  
Assessment Scale ◽  
Elderly Persons ◽  
Roc Curve Analysis ◽  
Simple Method ◽  
Cognitive Domains ◽  
Cut Point

Objective: To develop and validate a simple method for detecting dementia that is valid across cultures, portable and easily administered by primary health care clinicians.Design: Culture and Health Advisory Groups were used in Stage 1 to develop culturally fair cognitive items. In Stage 2, clinical testing of 42 items was conducted in a multicultural sample of consecutive new referrals to the geriatric medicine outpatient clinic at Liverpool Hospital, Sydney, Australia (n=166). In Stage 3, the predictive accuracy of items was assessed in a random sample of community-dwelling elderly persons stratified by language background and cognitive diagnosis and matched for sex and age (n=90).Measurements: A research psychologist administered all cognitive items, using interpreters when needed. Each patient was comprehensively assessed by one of three geriatricians, who ordered relevant investigations, and implemented a standardized assessment of cognitive domains. The geriatricians also collected demographic information, and administered other functional and cognitive measures. DSM-IV criteria were used to assign cognitive diagnoses. Item validity and weights were assessed using frequency and logistic regression analyses. Receiver-operating characteristic (ROC) curve analysis was used to determine overall predictive accuracy of the RUDAS and the best cut-point for detecting cognitive impairment.Results: The 6-item RUDAS assesses multiple cognitive domains including memory, praxis, language, judgement, drawing and body orientation. It appears not to be affected by gender, years of education, differential performance factors and preferred language. The area under the ROC curve for the RUDAS was 0.94 (95% CI 0.87–0.98). At a cut-point of 23 (maximum score of 30), sensitivity and specificity were 89% and 98%, respectively. Inter-rater (0.99) and test-retest (0.98) reliabilities were very high.Conclusions: The 6-item RUDAS is portable and tests multiple cognitive domains. It is easily interpreted to other languages, and appears to be culturally fair. However, further validation is needed in other settings, and in longitudinal studies to determine its sensitivity to change in cognitive function over time.

scholarly journals Relation of Airway Responsiveness to Methacholine to Parent and Child Reporting of Symptoms Suggecting Asthma

1996 ◽  
Vol 3 (2) ◽  
pp. 115-123 ◽  
Author(s):  
JM FitzGerald ◽  
DE Fester ◽  
MM Morris ◽  
M Schulzer ◽  
FE Hargreave ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Roc Curve ◽  
Airway Hyperresponsiveness ◽  
Respiratory Symptoms ◽  
Respiratory Illness ◽  
Airway Responsiveness ◽  
Methacholine Challenge ◽  
Cut Point ◽  
The Past ◽  
History Of

BACKGROUND:The lack of a relationship between airway responsiveness and respiratory symptoms in epidemiological studies of children may, in part, reflect inaccuracies in symptom reporting or inadequate knowledge by the parent of the child's symptoms.OBJECTIVE:To relate airway responsiveness to methacholine in children with symptoms of respiratory illness in the child as reported by the parent and as reported by the child.POPULATION:Eight- to 10-year-old (n=290) randomly sampled schoolchildren.SETTING:Seven randomly selected schools in Ontario.METHODS:Parents completed a mailed questionnaire regarding the child's respiratory health. Children completed a similar interview-administered questionnaire at school and underwent methacholine challenge testing by the tidal breathing method.RESULTS:The cumulative prevalence of a history of physician-diagnosed asthma was 9.0%, and of any wheezing it was 25.5%. A further 9% of children reported wheezing not documented by their parent. Of 229 children consenting to methacholine challenge, 78 (34.1%) showed airway responsiveness in the range generally associated with asthma in adults (provocation concentration of methacholine causing a 20% fall [PC20] in forced expired volume in 1 s [FEV1] 8 mg/mL or less); half of these children had no history of respiratory symptoms reported by the parent. The sensitivity of airway hyperresponsiveness defined by a cut-point for PC208 mg/mL or less in relation to any history of recurrent wheezing reported by the parent was 48% and did not improve if only symptoms within the past year were considered (sensitivity 44%); the specificity of the test for parent-reported symptoms ever was 71%, and 68% in those with symptoms in the past year. None of these sensitivities or specificities was increased by using symptoms reported by the child or by combining parent and child reported symptoms. Receiver operating characteristic (ROC) curves for sensitivity and specificity of the methacholine test were constructed for parent and child reports of symptoms. For all symptom strata, the cut-point of PC20producing optimal balance of sensitivity and specificity was between 4 and 8 mg/mL. A parental questionnaire positive for physician-diagnosed asthma was strongly related to methacholine response, producing an ROC curve with an area significantly different from 0.5 (P=0.006), as did all parent-reported wheezing (P=0.009). If the child reported asthma, there was an equally strong relationship, with a positive ROC curve (P=0.001), as there was for all child-reported wheezing (P=0.048).CONCLUSIONS:Airway hyperresponsiveness to methacholine in children relates closely with asthma and wheezing reported by either the parent or the child. In addition, the results confirm that respiratory symptoms and airway hyperresponsiveness are common in Canadian children, and that airway hyperresponsiveness may be found in children with no history of respiratory illness either at present or in the past.

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