A new robust statistical model for interpretation of differences in serial test results from an individual

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Federica Braga ◽  
Simona Ferraro ◽  
Francesca Ieva ◽  
Anna Paganoni ◽  
Mauro Panteghini
Keyword(s):  
Statistical Model ◽  
Frequency Distribution ◽  
Population Based ◽  
Reference Intervals ◽  
Test Results ◽  
Protein Distribution ◽  
Reactive Protein ◽  
Serial Test ◽  
Reference Change Value ◽  
Serial Measurements

AbstractPopulation-based reference intervals have very limited value for the interpretation of laboratory results when analytes display high biological individuality. In these cases, the longitudinal evaluation of individual results using the reference change value (RCV) is the recommended approach. However, the traditional model for RCV calculation requires a Gaussian frequency distribution of data and risks to overestimate the parameter if a correlation between within-subject serial measurements is present.We propose and validate an alternative non-parametric statistical model for interpretation of differences in serial results from an individual, overcoming data distribution and correlation issues.After describing the traditional and newly proposed statistical models, we compared them with each other using a simulation on three specific analytes displaying different concentration distributions in biological setting. We demonstrated that when analyte concentrations followed a Gaussian frequency distribution, as in the case of glycated hemoglobin, both methods can be used equally. On the contrary, if analyte concentrations present a bimodal (e.g., chromogranin A) or skewed (e.g., C-reactive protein) distribution, the information obtained by two statistical methods is different.The proposed statistical approach may be more appropriate in assessing difference between serial measurements when individual data are not normally distributed.

Annual biological variation and personalized reference intervals of clinical chemistry and hematology analytes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shuo Wang ◽  
Min Zhao ◽  
Zihan Su ◽  
Runqing Mu
Keyword(s):  
Clinical Chemistry ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Annual Data ◽  
Healthy Individuals ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Personalized Diagnosis

Abstract Objectives A large number of people undergo annual health checkup but accurate laboratory criterion for evaluating their health status is limited. The present study determined annual biological variation (BV) and derived parameters of common laboratory analytes in order to accurately evaluate the test results of the annual healthcare population. Methods A total of 43 healthy individuals who had regular healthcare once a year for six consecutive years, were enrolled using physical, electrocardiogram, ultrasonography and laboratory. The annual BV data and derived parameters, such as reference change value (RCV) and index of individuality (II) were calculated and compared with weekly data. We used annual BV and homeostatic set point to calculate personalized reference intervals (RIper) which were compared with population-based reference intervals (RIpop). Results We have established the annual within-subject BV (CVI), RCV, II, RIper of 24 commonly used clinical chemistry and hematology analytes for healthy individuals. Among the 18 comparable measurands, CVI estimates of annual data for 11 measurands were significantly higher than the weekly data. Approximately 50% measurands of II were <0.6, the utility of their RIpop were limited. The distribution range of RIper for most measurands only copied small part of RIpop with reference range index for 8 measurands <0.5. Conclusions Compared with weekly BV, for annual healthcare individuals, annual BV and related parameters can provide more accurate evaluation of laboratory results. RIper based on long-term BV data is very valuable for “personalized” diagnosis on annual health assessments.

Analytical quality specifications for common reference intervals

2004 ◽  
Vol 42 (7) ◽  
Author(s):  
Carmen Ricós ◽  
Maria Vicenta Doménech ◽  
Carmen Perich
Keyword(s):  
Real Life ◽  
Reference Interval ◽  
Population Based ◽  
Reference Intervals ◽  
Healthy Population ◽  
Analytical Quality ◽  
Related Factors ◽  
Cross Sectional ◽  
Reference Change Value ◽  
Quality Specifications

AbstractInterpretation oflaboratory test results requires comparison to some type of reference value or reference interval. These comparisons can be cross-sectional (population-based reference interval and cut-off values) or longitudinal (reference change value). Quality specifications for cross-sectional comparison have been established by determining the influence of analytical bias and imprecision on the percentage ofthe healthy population falling outside the reference limits, when sharing population-based reference intervals in a Gaussian distribution ofresults. Quality specifications for longitudinal comparisons are equally important and are often overlooked, since less work has been done in this area. Some criteria suggest that a difference between consecutive results designates a true change in a patient health status when the difference is higher than the within-subject biological variation plus the within-laboratory analytical variation. In this chapter we discuss the clinical considerations and laboratory-related factors that must be considered when quality specifications are applied to sharing reference comparisons. Real life experience shows that different analytical methods can produce comparable results when common quality goals are established, and quality can be achieved through a willingness to work together. Within the existing organization, the current specifications for analytical quality and a dedication to quality health care makes it possible to achieve transferability between laboratories within a geographic area.

Evaluation of biological variations in glucose and glycated hemoglobin levels in healthy individuals

2017 ◽  
Vol 43 (5) ◽  
pp. 495-501
Author(s):  
Cihan Coskun ◽  
Berrin Bercik Inal ◽  
Humeyra Ozturk Emre ◽  
Sehide Baz ◽  
Alper Gumus ◽  
...  
Keyword(s):  
International Organizations ◽  
Glycated Hemoglobin ◽  
Reference Interval ◽  
Reference Intervals ◽  
Study Group ◽  
Test Results ◽  
Healthy Individuals ◽  
Reference Change Value ◽  
Performance Specifications ◽  
Index Of Individuality

Abstract Objective: In this study, we firstly aimed to determine components of biological variations (BVCs) in levels of glucose and glycated hemoglobin (HbA1c) in detail based on guidance from relevant organizations and experts. We also investigated whether reference intervals for both analytes were useful for evaluations, particularly consecutive test results. Methods: The study group consisted of 36 healthy volunteers. Samples were collected from each individual 4 times every 2 weeks for 45 days. All samples were assayed in duplicate within a single run. Finally, we estimated BVCs and the analytical performance specifications of both analytes. Results: Our results were fairly compatible with current biological variations (BVs) in both analytes reported in a database. It was calculated as within biological variation (CVI)=4.2% and between-subject variation (CVG)=5.3% for glucose while calculating as CVI=1.7% and CVG=4.5% for HbA1c. According to these results, the index of individuality (II) of glucose was higher than 0.6 while HbA1c’s II was lower than this value. Conclusion: We thought that guidelines from relevant international organizations should be followed to standardize the study design and to appropriately calculate BVCs for any analyte in BV studies. Finally, reference change value should be used to evaluate meaningful differences in HbA1c levels instead of reference interval.

Personalized reference intervals – statistical approaches and considerations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdurrahman Coskun ◽  
Sverre Sandberg ◽  
Ibrahim Unsal ◽  
Fulya G. Yavuz ◽  
Coskun Cavusoglu ◽  
...  
Keyword(s):  
Laboratory Test ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Test Results ◽  
Data Quality Assessment ◽  
Laboratory Test Results ◽  
Variation Database ◽  
Statistical Approaches

Abstract For many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on ‘prediction intervals’ can be applied. The first model utilizes estimates of ‘within-person biological variation’ which are based on an individual’s own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of ‘within-subject biological variation’, which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals’ test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.

scholarly journals Determining biological variation of serum parathyroid hormone in healthy adults

2019 ◽  
Vol 29 (3) ◽  
pp. 506-512 ◽  
Author(s):  
Müjgan Ercan ◽  
Esin Avcı ◽  
Muhittin Serdar ◽  
Turan Turhan ◽  
Esra Fırat Oğuz ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Reference Change Value ◽  
Performance Specifications ◽  
Calcium Metabolism Disorders ◽  
Serum Pth

Introduction: Measurement of parathyroid hormone (PTH) is essential in the investigation and management of calcium metabolism disorders. To assess the significance of any assay result when clinical decision making biological variation (BV) of the measurand must be taken into consideration. The aim of the present study is determining the BV parameters for serum PTH. Materials and methods: Blood samples were taken at weekly intervals from 20 healthy subjects for ten weeks in this prospective BV study. Serum “intact PTH” concentrations were measured with electrochemiluminescence method. Biological variation parameters were estimated using the approach proposed by Fraser. Results: The values of within-subject biological variation (CVI), between-subject biological variation (CVG), analytical variation (CVA), reference change value (RCV) and individuality index (II) for serum PTH were 21.1%, 24.9%, 3.8%, 59.4% and 0.8%, respectively. Within-subject biological variation and CVG were also determined according to gender separately; 18.5% and 24.0%; 26.2% and 18.6% for male and female, respectively. Calculated desirable precision and bias goals were < 10.6% and < 6.3%, respectively. Conclusion: This study may contribute to BV data on serum PTH as it includes a sufficient number of volunteers from both genders over an acceptable period of time. We do not recommend the usage of population-based reference intervals for serum PTH concentrations. Reference change value may be helpful for the evaluation of serial serum PTH results. Nonetheless, evaluation of data according to gender is necessary when setting analytical performance specifications.

No relation between biomarkers at age 47–49 and aortic diameter after 14–19 years of follow-up – a population-based study

VASA ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 291-295 ◽  
Author(s):  
Soumia Taimour ◽  
Moncef Zarrouk ◽  
Jan Holst ◽  
Olle Melander ◽  
Gunar Engström ◽  
...  
Keyword(s):  
Population Based ◽  
Aortic Diameter ◽  
Aortic Dilatation ◽  
Population Based Study ◽  
Reactive Protein ◽  
Abdominal Aortic ◽  
Long Term Follow Up ◽  
Old Men

Abstract. Background: Biomarkers reflecting diverse pathophysiological pathways may play an important role in the pathogenesis of abdominal aortic aneurysm (aortic diameter ≥30 mm, AAA), levels of many biomarkers are elevated and correlated to aortic diameter among 65-year-old men undergoing ultrasound (US) screening for AAA. Probands and methods: To evaluate potential relationships between biomarkers and aortic dilatation after long-term follow-up, levels of C-reactive protein (CRP), proneurotensin (PNT), copeptin (CPT), lipoprotein-associated phospholipase 2 (Lp-PLA2), cystatin C (Cyst C), midregional proatrial natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM) were measured in 117 subjects (114 [97 %] men) aged 47–49 in a prospective population-based cohort study, and related to aortic diameter at US examination of the aorta after 14–19 years of follow-up. Results: Biomarker levels at baseline did not correlate with aortic diameter after 14–19 years of follow up (CRP [r = 0.153], PNT [r = 0.070], CPT [r = –.156], Lp-PLA2 [r = .024], Cyst C [r = –.015], MR-proANP [r = 0.014], MR-proADM [r = –.117]). Adjusting for age and smoking at baseline in a linear regression model did not reveal any significant correlations. Conclusions: Tested biomarker levels at age 47–49 were not associated with aortic diameter at ultrasound examination after 14–19 years of follow-up. If there are relationships between these biomarkers and aortic dilatation, they are not relevant until closer to AAA diagnosis.

scholarly journals Serum C-Reactive Protein Is Negatively Associated With Olfactory Identification Ability in Older Adults

i-Perception ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 204166952110099
Author(s):  
Ingrid Ekström ◽  
Davide Liborio Vetrano ◽  
Goran Papenberg ◽  
Erika J. Laukka
Keyword(s):  
Statistical Significance ◽  
Population Based ◽  
Rate Of Change ◽  
Odor Identification ◽  
Sensitivity Analyses ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Olfactory Identification ◽  
Olfactory Ability ◽  
Serum Crp

Importance Olfactory deficits are common in aging and associated with several conditions linked to inflammation. A few studies suggest that increased concentration of pro-inflammatory biomarkers may be related to olfactory deficits, but these associations are understudied in population-based samples. Objective To investigate the association between serum concentrations of C-reactive protein (CRP) and olfactory identification level as well as rate of change in aging. Methods We included 1,721 participants (mean age 70.5 years; 61.9% female) with at least two olfactory assessments across the 12-year follow-up. Baseline level and change in odor identification were estimated with linear mixed models as a function of CRP levels, derived from blood plasma at baseline. Results Results indicated a negative dose–response association between CRP level and odor identification scores at baseline, after adjustment for demographic, cognitive, health, and lifestyle factors. CRP levels ranging between 11 and 20 mg/L were significantly related to lower olfactory ability (β = −0.811, 95% confidence interval [CI] [−1.503 to −0.118]; p = .022). Likewise, CRP values above 20 mg/L were related to lower olfactory scores, an association that approached statistical significance (β = −0.996, 95% CI [−2.045 to 0.054]; p = .063). We found no associations between CRP and olfactory change ( ps > .368). Sensitivity analyses showed that associations between CRP and olfaction were confined to younger participants (age ≤72 years) and men ( ps < .034). Conclusions Our findings suggest a negative association between serum CRP levels and olfactory identification ability in aging that may be dependent on age and sex.

scholarly journals Effect of 1 mg/kg oral prednisolone on biochemical analytes in ten dogs: a cross-over study

2021 ◽  
Author(s):  
Helena Pettersson ◽  
Carl Ekstrand ◽  
Anna Hillström ◽  
Inger Lilliehöök
Keyword(s):  
Clinical Relevance ◽  
Control Period ◽  
Iron Concentration ◽  
Oral Prednisolone ◽  
Reference Intervals ◽  
Specific Reference ◽  
Test Results ◽  
Prednisolone Treatment ◽  
Anti Inflammatory ◽  
And Control

AbstractPrednisolone is used for treatment of inflammatory, allergic, neoplastic, and immune-mediated diseases in dogs. As a glucocorticoid, prednisolone has biochemical effects, which may interfere with the interpretation of biochemistry test results. The aim of this study is to investigate the effects of prednisolone treatment in an anti-inflammatory dose on common biochemical analytes in dogs and to evaluate the clinical relevance of the changes. Ten beagle dogs, enrolled in a cross-over study, were treated with oral prednisolone (1 mg/kg 24 h) for 10 days. Blood samples were collected at day 0, 1, 3, 6, 9, 10, 12, 16, and 20. Data was analyzed using a general linear model with time and treatment as fixed factors. Pairwise comparisons were done between prednisolone and control period for each dog and sampling. Significant results were further evaluated for clinical relevance using laboratory-specific reference intervals and reference change values (RCVs), when available. Statistically significant changes were observed for ALP activity and iron concentration, which increased to levels exceeding the RCV, and several results were outside reference intervals. Phosphate and bile acids increased significantly, while amylase, lipase, and cholesterol decreased significantly, but with mean/median results remaining within reference intervals. Anti-inflammatory prednisolone treatment did not induce significant changes in ALT, GLDH, GGT, cPLI, glucose, or calcium. Treatment with an anti-inflammatory dose of prednisolone induced changes in several analytes. Only the increases in ALP and iron were of such magnitude that they are expected to affect the clinical interpretation of test results.

scholarly journals Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Norie Saito ◽  
Masato Furuhashi ◽  
Masayuki Koyama ◽  
Yukimura Higashiura ◽  
Hiroshi Akasaka ◽  
...  
Keyword(s):  
General Population ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Population Based ◽  
Causal Link ◽  
Fatty Acid Binding ◽  
Reactive Protein ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
The Relationship

AbstractFatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1–T3), Kaplan–Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20–22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.

scholarly journals Biological variation and reference change value data for serum copper, zinc and selenium in Turkish adult population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ceylan Bal ◽  
Serpil Erdogan ◽  
Gamze Gök ◽  
Cemil Nural ◽  
Betül Özbek ◽  
...  
Keyword(s):  
Adult Population ◽  
Reference Intervals ◽  
Serum Copper ◽  
Biological Variation ◽  
Serum Samples ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Copper Zinc ◽  
Clinically Significant ◽  
Analytical Variation

Abstract Objectives Calculation of biological variation (BV) components is very important in evaluating whether a test result is clinically significant. The aim of this study is to analyze BV components for copper, zinc and selenium in a cohort of healthy Turkish participants. Methods A total of 10 serum samples were collected from each of the 15 healthy individuals (nine female, six male), once a week, during 10 weeks. Copper, zinc and selenium levels were analyzed by atomic absorption spectrometer. BV parameters were calculated with the approach suggested by Fraser. Results Analytical variation (CVA), within-subject BV (CVI), between-subject BV (CVG) values were 8.4, 7.1 and 4.3 for copper; 4.2, 9.1 and 13.7 for zinc; 7.6, 2.5 and 6.9 for selenium, respectively. Reference change values (RCV) were 30.46, 27.56 and 22.16% for copper, zinc and selenium, respectively. The index of individuality (II) values were 1.65, 0.66 and 0.36 for copper, zinc and selenium, respectively. Conclusions According to the results of this study, traditional reference intervals can be used for copper but we do not recommend using it for zinc and selenium. We think that it would be more accurate to use RCV value for zinc and selenium in terms of following significant changes in recurrent results of a patient.

Sign in / Sign up

Export Citation Format

Share Document