Critical comments to a recent EFLM recommendation for the review of reference intervals

2017 ◽  
Vol 55 (3) ◽  
Author(s):  
Rainer Haeckel ◽  
Werner Wosniok ◽  
Farhad Arzideh ◽  
Jakob Zierk ◽  
Eberhard Gurr ◽  
...  
Keyword(s):  
Gold Standard ◽  
Reference Intervals ◽  
Direct Approach ◽  
Confidence Limits ◽  
Common Reference ◽  
Reference Limits ◽  
Age Range

AbstractIn a recent EFLM recommendation on reference intervals by Henny et al., the direct approach for determining reference intervals was proposed as the only presently accepted “gold” standard. Some essential drawbacks of the direct approach were not sufficiently emphasized, such as unacceptably wide confidence limits due to the limited number of observations claimed and the practical usability for only a limited age range. Indirect procedures avoid these disadvantages of the direct approach. Furthermore, indirect approaches are well suited for reference limits with large variations during lifetime and for common reference limits.

Partitioning biochemical reference data intosubgroups: comparison of existing methods

2004 ◽  
Vol 42 (7) ◽  
Author(s):  
Ari Lahti
Keyword(s):  
Reference Data ◽  
Reference Interval ◽  
Reference Intervals ◽  
New Method ◽  
Poor Correlation ◽  
Specific Reference ◽  
Common Reference ◽  
Reference Limits ◽  
The Common ◽  
The Ideal

AbstractFour existing methods for partitioning biochemical reference data into subgroups are compared. Two of these, the method of Sinton et al. and that of Ichihara and Kawai, are based on a quotient of a difference between the subgroups and the reference interval for the combined distribution. The criterion of Sinton et al. appears rather stringent and could lead to recommendations to apply a common reference interval in many cases where establishment of group-specific reference intervals would be more useful. The method of Ichihara and Kawai is similar to that of Sinton et al., but their criterion, based on a quantity derived from between-group and within-group variances, seems to lead to inconsistent results when applied to some model cases. These two methods have the common weakness of using gross differences between subgroup distributions as an indicator of differences between their reference limits, while distributions with different means can actually have equal reference limits and those with equal means can have different reference limits. The idea of Harris and Boyd to require that the proportions of the subgroup distributions outside the common reference limits be kept reasonably close to the ideal value of 2.5% as a prerequisite for using common reference limits seems to have been a major improvement. The other two methods considered, that of Harris and Boyd and the “new method” follow this idea. The partitioning criteria of Harris and Boyd have previously been shown to provide a poor correlation to those proportions, however, and the weaknesses of their method are summarized in a list of five drawbacks. Different versions of the new method offer improvements to these drawbacks.

scholarly journals Impact of Subgroup Prevalences on Partitioning of Gaussian-distributed Reference Values

2002 ◽  
Vol 48 (11) ◽  
pp. 1987-1999 ◽  
Author(s):  
Ari Lahti ◽  
Per Hyltoft Petersen ◽  
James C Boyd
Keyword(s):  
Reference Interval ◽  
Reference Population ◽  
Reference Intervals ◽  
Source Population ◽  
Distributed Data ◽  
New Model ◽  
Common Reference ◽  
Reference Limits ◽  
Partitioning Problem ◽  
Analytical Expressions

Abstract Background: The aims of this report were to examine how unequal subgroup prevalences in the source population may affect reference interval partitioning decisions and to develop generally applicable guidelines for partitioning gaussian-distributed data. Methods: We recently proposed a new model for partitioning reference intervals when the underlying data distribution is gaussian. This model is based on controlling the proportions of the subgroup distributions that fall outside each of the common reference limits, using the distances between the reference limits of the subgroup distributions as functions to these proportions. We examine the significance of the unequal prevalence effect for the partitioning problem and quantify it for distance partitioning criteria by deriving analytical expressions to express these criteria as a function of the ratio of prevalences. An application example, illustrating various aspects of the importance of the prevalence effect, is also presented. Results: Dramatic shrinkage of the critical distances between reference limits of the subgroups needed for partitioning was observed as the ratio of prevalences, the larger one divided by the smaller one, was increased from unity. Because of this shrinkage, the same critical distances are not valid for all ratios of prevalences, but specific critical distances should be used for each particular value of this ratio. Although proportion criteria used in determining the need for reference interval partitioning are not dependent on the prevalence effect, this effect should be accounted for when these criteria are being applied by adjusting the sample sizes of the subgroups to make them correspond to the ratio of prevalences. Conclusions: The prevalences of subgroups in the reference population should be known and observed in the calculations for every reference interval study, irrespective of whether distance or proportion criteria are being used to determine the need for reference interval partitioning. We present detailed methods to account for the prevalences when applying each of these types of criteria. Analytical expressions for the distance criteria, to be used when high precision is needed, and approximate distances, to be used in practical work, are derived. General guidelines for partitioning gaussian distributed data are presented. Following these guidelines and using the new model, we suggest that partitioning can be performed more reliably than with any of the earlier models because the new model not only offers an improved correspondence between the critical distances and the critical proportions, but also accounts for the prevalence effect.

scholarly journals Objective Criteria for Partitioning Gaussian-distributed Reference Values into Subgroups

2002 ◽  
Vol 48 (2) ◽  
pp. 338-352 ◽  
Author(s):  
Ari Lahti ◽  
Per Hyltoft Petersen ◽  
James C Boyd ◽  
Callum G Fraser ◽  
Nils Jørgensen
Keyword(s):  
Reference Values ◽  
Geographic Area ◽  
Reference Intervals ◽  
Critical Values ◽  
Final Decision ◽  
Gaussian Distributions ◽  
New Model ◽  
Reference Limit ◽  
Common Reference ◽  
Reference Limits

Abstract Background: The aim of this study was to develop new and useful criteria for partitioning reference values into subgroups applicable to gaussian distributions and to distributions that can be transformed to gaussian distributions. Methods: The proposed criteria relate to percentages of the subgroups outside each of the reference limits of the combined distribution. Critical values suggested as partitioning criteria for these percentages were derived from analytical bias quality specifications for using common reference intervals throughout a geographic area. As alternative partitioning criteria to the actual percentages, these were transformed mathematically to critical distances between the reference limits of the subgroup distributions, to be applied to each pair of reference limits, the upper and the lower, at a time. The new criteria were tested using data on various plasma proteins collected from ∼500 reference individuals, and the outcomes were compared with those given by the currently widely applied and recommended partitioning model of Harris and Boyd, the “Harris-Boyd model”. Results: We suggest 4.1% as the critical minimum percentage outside that would justify partitioning into subgroups, and 3.2% as the critical maximum percentage outside that would justify combining them. Percentages between these two values should be classified as marginal, implying that nonstatistical considerations are required to make the final decision on partitioning. The correlation between the critical percentages and the critical distances was mathematically precise in the new model, whereas this correlation is rather approximate in the Harris-Boyd model because focus on the difference between means in this model makes high precision hard to achieve. The application examples suggested that the new model is more radical than the Harris-Boyd model. Conclusions: New percentage and distance criteria, to be used for partitioning gaussian-distributed data, have been developed. The distance criteria, applied separately to both reference limit pairs of the subgroup distributions, seemed more reliable and correlated more accurately with the critical percentages than the distance criteria of the Harris-Boyd model. As opposed to the Harris-Boyd model, the new model is easily adjustable to new critical values of the percentages, should they need to be changed in the future.

scholarly journals Diurnal variation of leukocyte counts affects the indirect estimation of reference intervals

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Antje Torge ◽  
Rainer Haeckel ◽  
Mustafa Özcürümez ◽  
Alexander Krebs ◽  
Ralf Junker
Keyword(s):  
Diurnal Variation ◽  
Indirect Method ◽  
Venous Blood ◽  
Direct Methods ◽  
Reference Intervals ◽  
Indirect Methods ◽  
Indirect Estimation ◽  
Late Afternoon ◽  
Reference Limits ◽  
Leukocyte Counts

Abstract It has been observed that the estimation of reference intervals of leukocytes in whole venous blood leads to higher upper reference limits (uRLs) with indirect methods than has been reported in the literature determined by direct approaches. This phenomenon was reinvestigated with a newer, more advanced indirect method, and could be confirmed. Furthermore, a diurnal variation was observed with lower values during the morning and higher values in the late afternoon and at night. This observation can explain why indirect approaches using samples collected during 24 h lead to higher uRLs than direct methods applied on samples collected presumably in the morning.

Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Hallvard Lilleng ◽  
Stein Harald Johnsen ◽  
Tom Wilsgaard ◽  
Svein Ivar Bekkelund
Keyword(s):  
Creatine Kinase ◽  
General Population ◽  
Reference Interval ◽  
Reference Intervals ◽  
Control Analysis ◽  
Age Group ◽  
Background Population ◽  
Norwegian Population ◽  
Reference Limits ◽  
Laboratory Reference

AbstractLaboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses.New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromsø Study. URL was defined as the 97.5 percentile.New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men ≥50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04).URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Comparison of Validity of Mapping between Drug Indications and ICD-10

2014 ◽  
Vol 53 (03) ◽  
pp. 195-201 ◽  
Author(s):  
Y. Choi ◽  
C. Jung ◽  
Y. Chae ◽  
M. Kang ◽  
J. Kim ◽  
...  
Keyword(s):  
Gold Standard ◽  
Kappa Statistic ◽  
Direct Approach ◽  
Free Text ◽  
Good Opportunity ◽  
Mapping Approach ◽  
Icd 10 ◽  
Standard Terminology ◽  
The Mean ◽  
Experienced Nurse

SummaryBackground: Mapping of drug indications to ICD-10 was undertaken in Korea by a public and a private institution for their own purposes. A different mapping approach was used by each institution, which presented a good opportunity to compare the validity of the two approaches.Objectives: This study was undertaken to compare the validity of a direct mapping approach and an indirect terminology based mapping approach of drug indications against the gold standard drawn from the results of the two mapping processes.Methods: Three hundred and seventy-five cardiovascular reference drugs were selected from all listed cardiovascular drugs for the study. In the direct approach, two experienced nurse coders mapped the free text indications directly to ICD-10. In the indirect terminology based approach, the indications were extracted and coded in the Korean Standard Terminology of Medicine. These terminology coded indications were then manually mapped to ICD-10. The results of the two approaches were compared to the gold standard. A kappa statistic was calculated to see the compatibility of both mapping approaches. Recall, precision and F1 score of each mapping approach were calculated and analyzed using a paired t-test.Results: The mean number of indications for the study drugs was 5.42. The mean number of ICD-10 codes that matched in direct approach was 46.32 and that of indirect terminology based approach was 56.94. The agreement of the mapping results between the two approaches were poor (kappa = 0.19). The indirect terminology based approach showed higher recall (86.78%) than direct approach (p < 0.001). However, there was no difference in precision and F1 score between the two approaches.Conclusions: Considering no differences in the F1 scores, both approaches may be used in practice for mapping drug indications to ICD-10. However, in terms of consistency, time and manpower, better results are expected from the indirect terminology based approach.

scholarly journals Impact of age, body weight and metabolic risk factors on steroid reference intervals in men

2020 ◽  
Vol 182 (5) ◽  
pp. 459-471
Author(s):  
Marco Mezzullo ◽  
Guido Di Dalmazi ◽  
Alessia Fazzini ◽  
Margherita Baccini ◽  
Andrea Repaci ◽  
...  
Keyword(s):  
Risk Factors ◽  
Reference Intervals ◽  
Metabolic Risk Factors ◽  
Specific Reference ◽  
Metabolic Risk ◽  
Cross Sectional ◽  
Cholesterol Ratio ◽  
Age Related ◽  
Reference Limits ◽  
17 Hydroxyprogesterone

Objective To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design Cross-sectional study. Methods Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (−0.34 nmol/L, P = 0.045), cortisol (−87 nmol/L, P = 0.045–0.002) and corticosterone (−10.1 nmol/L, P = 0.048–0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.

Reference Intervals for Serum Alpha-Fetoprotein and Carcinoembryonic Antigen in Chinese Han Ethnic Males from the Fangchenggang Area Male Health and Examination Survey

2011 ◽  
Vol 26 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Xue Qin ◽  
Liwen Lin ◽  
Zengnan Mo ◽  
Hui Lv ◽  
Yong Gao ◽  
...  
Keyword(s):  
Carcinoembryonic Antigen ◽  
Reference Intervals ◽  
Alpha Fetoprotein ◽  
Male Health ◽  
Significant Difference ◽  
Reference Limits ◽  
Age Dependent ◽  
Serum Alpha Fetoprotein ◽  
Serum Cea ◽  
Normally Distributed

Objectives We calculated upper 95% reference limits for serum alpha-fetoprotein (AFP)and carcinoembryonic antigen (CEA) according to the CLSI/NCCLS C28-A3 guideline. Material and methods Serum samples from 1400 healthy male subjects were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum AFP and CEA values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. Results Serum AFP and CEA values were not normally distributed but log normally distributed. The upper 95% reference limits of the reference intervals were ≤4.76 IU/mL (nonparametric) or ≤4.56 IU/mL (parametric) for AFP and ≤5.57 ng/mL (nonparametric) or ≤5.82 ng/mL (parametric) for CEA. The distribution of AFP levels was found to be consistent between the non-smoking and smoking (p=0.740) and non-drinking and drinking groups (p=0.698). The distribution of serum CEA levels was significantly higher in the smoking than the non-smoking group (p<105), whereas there was no significant difference in this respect between the non-drinking and drinking groups (p=0.147). A significant increase with age was found both for serum AFP and CEA levels, and the age-dependent reference intervals were calculated. Conclusions The reference intervals for serum AFP and CEA show a slight deviation compared to previously reported reference levels. Distinct reference intervals of serum CEA must be established for smoking and non-smoking populations. In addition, age-dependent reference intervals should be implemented in clinical laboratories.

Diagnostic Accuracy of Rapid Diagnostic Kits Test for Diagnosis of Malaria

2021 ◽  
Vol 15 (10) ◽  
pp. 2826-2828
Author(s):  
Muhammad Ahsan Zafar ◽  
Sidra Khalid ◽  
Talha Munir
Keyword(s):  
Diagnostic Accuracy ◽  
Gold Standard ◽  
Female Ratio ◽  
Diagnostic Kits ◽  
Negative Results ◽  
Malaria Antigen ◽  
The Mean ◽  
Sensitivity Specificity ◽  
Age Range ◽  
Male To Female

Objective: To assess the diagnostic accuracy of rapid diagnostic kits test for diagnosis of malaria taking microscopy as gold standard Methodology: A total of 375 cases with age range 18-65 years of either gender as suspected for malaria were included in the study. We excluded all those cases already taking anti-malarial drugs. The study was conducted at Chughtais Lahore Lab, Lahore. Required blood sample were obtained following aseptic measures. Malaria RDT SD Bioline Malaria Antigen Pf/Pan (Catalogue No. 05FK60, Standard Diagnostics Inc, Hagal-Dong, Korea, from now on referred as “SD RDT”) was used. Patients were labeled as positive or negative on the basis of reports from hematology department assessed by microscopy and patients were labeled as positive or negative Results: The mean age of the patients was 41.84±13.44 years, male to female ratio of the patients was 1.01:1. The sensitivity, specificity, and diagnostic accuracy of the RDT for diagnosing malaria was 96.79%, 96.28% and 96.53% respectively taking microscopy as gold standard Conclusion: Rapid diagnostic kits is very useful reliable test with high diagnostic accuracy for diagnosis of malaria taking microscopy as gold standard Keywords: Microscopy, Rapid Diagnostic kits, Malaria,

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