Determination of reference limits: statistical concepts and tools for sample size calculation

2014 ◽  
Vol 52 (12) ◽  
Author(s):  
Stefan Wellek ◽  
Karl J. Lackner ◽  
Christine Jennen-Steinmetz ◽  
Iris Reinhard ◽  
Isabell Hoffmann ◽  
...  
Keyword(s):  
Sample Size ◽  
Diagnostic Marker ◽  
Parametric Method ◽  
Sample Size Calculation ◽  
Reference Intervals ◽  
Healthy Population ◽  
Reference Limits

AbstractReference limits are estimators for ‘extreme’ percentiles of the distribution of a quantitative diagnostic marker in the healthy population. In most cases, interest will be in the 90% or 95% reference intervals. The standard parametric method of determining reference limits consists of computing quantities of the form

Recommendation for the review of biological reference intervals in medical laboratories

2016 ◽  
Vol 54 (12) ◽  
Author(s):  
Joseph Henny ◽  
Anne Vassault ◽  
Guilaine Boursier ◽  
Ines Vukasovic ◽  
Pika Mesko Brguljan ◽  
...  
Keyword(s):  
Expert Panel ◽  
Clinical Chemistry ◽  
Simple Procedure ◽  
Reference Population ◽  
Reference Intervals ◽  
Medical Laboratories ◽  
Reference Limits ◽  
Original Procedure ◽  
Selection Of

AbstractThis document is based on the original recommendation of the Expert Panel on the Theory of Reference Values of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), updated guidelines were recently published under the auspices of the IFCC and the Clinical and Laboratory Standards Institute (CLSI). This document summarizes proposals for recommendations on: (i) The terminology, which is often confusing, noticeably concerning the terms of reference limits and decision limits. (ii) The method for the determination of reference limits according to the original procedure and the conditions, which should be used. (iii) A simple procedure allowing the medical laboratories to fulfill the requirements of the regulation and standards. The updated document proposes to verify that published reference limits are applicable to the laboratory involved. Finally, the strengths and limits of the revised recommendations (especially the selection of the reference population, the maintenance of the analytical quality, the choice of the statistical method used…) will be briefly discussed.

The Worthington "ultrafree" device evaluated for determination of ultrafiltrable calcium in serum.

1981 ◽  
Vol 27 (3) ◽  
pp. 466-468 ◽  
Author(s):  
J Toffaletti ◽  
D Tompkins ◽  
G Hoff
Keyword(s):  
Human Serum ◽  
Room Temperature ◽  
Reference Intervals ◽  
Effect Of Temperature ◽  
Healthy Population ◽  
Calcium Citrate ◽  
Coefficients Of Variation ◽  
Disposable Device

Abstract We evaluated a commercially-available disposable device ("Ultrafree," Worthington Diagnostics) for the anaerobic preparation of protein-free ultrafiltrates from serum for measurement of ultrafiltrable calcium. Sufficient filtrate for the analysis is obtained with 10 min from 0.2 to 0.4 mL of serum at room temperature. We assessed these ultrafilters with regard to permeability of calcium citrate, exclusion of proteins, frequency of leakage, and effect of temperature on results. Within-run and day-to-day coefficients of variation for human serum pools were 1.2 and 1.5%, respectively. Reference intervals (in mmol/L) for total (2.16-2.58), ultrafiltrable (1.44-1.67), dialyzable (1.25-1.41), and ionized (1.04-1.25) calcium have been determined for a healthy population of 69 women and 81 men, ages to 18 to 65 years. The device appears to be the most practicable yet available for use in making this measurement.

Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data

1994 ◽  
Vol 40 (12) ◽  
pp. 2209-2215 ◽  
Author(s):  
T Kouri ◽  
V Kairisto ◽  
A Virtanen ◽  
E Uusipaikka ◽  
A Rajamäki ◽  
...  
Keyword(s):  
Mean Corpuscular Volume ◽  
Age Groups ◽  
Hemoglobin Concentration ◽  
Reference Intervals ◽  
Hospitalized Patients ◽  
Healthy Individuals ◽  
Reference Limits ◽  
Health Related ◽  
Final Group

Abstract We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.

scholarly journals A simple transformation independent method for outlier definition

2018 ◽  
Vol 56 (9) ◽  
pp. 1524-1532 ◽  
Author(s):  
Martin Berg Johansen ◽  
Peter Astrup Christensen
Keyword(s):  
Detection Method ◽  
Reference Intervals ◽  
Independent Method ◽  
Medical Laboratories ◽  
Simple Transformation ◽  
Reference Limits ◽  
Definition Of ◽  
Box Cox Transformation ◽  
Better Than

AbstractBackground:Definition and elimination of outliers is a key element for medical laboratories establishing or verifying reference intervals (RIs). Especially as inclusion of just a few outlying observations may seriously affect the determination of the reference limits. Many methods have been developed for definition of outliers. Several of these methods are developed for the normal distribution and often data require transformation before outlier elimination.Methods:We have developed a non-parametric transformation independent outlier definition. The new method relies on drawing reproducible histograms. This is done by using defined bin sizes above and below the median. The method is compared to the method recommended by CLSI/IFCC, which uses Box-Cox transformation (BCT) and Tukey’s fences for outlier definition. The comparison is done on eight simulated distributions and an indirect clinical datasets.Results:The comparison on simulated distributions shows that without outliers added the recommended method in general defines fewer outliers. However, when outliers are added on one side the proposed method often produces better results. With outliers on both sides the methods are equally good. Furthermore, it is found that the presence of outliers affects the BCT, and subsequently affects the determined limits of current recommended methods. This is especially seen in skewed distributions. The proposed outlier definition reproduced current RI limits on clinical data containing outliers.Conclusions:We find our simple transformation independent outlier detection method as good as or better than the currently recommended methods.

Determination of reference intervals for serum magnesium

1990 ◽  
Vol 36 (5) ◽  
pp. 756-758 ◽  
Author(s):  
G O Duncanson ◽  
H G Worth
Keyword(s):  
Alkaline Phosphatase ◽  
Gaussian Distribution ◽  
Parametric Analysis ◽  
Serum Magnesium ◽  
Reference Interval ◽  
Reference Intervals ◽  
Age Related ◽  
Reference Limits ◽  
Males And Females

Abstract Using a discrete analyzer and a dye-binding method, we measured magnesium in 800 patients' samples received for routine analysis. By excluding data from samples for which the calcium and (or) alkaline phosphatase values were outside defined reference limits, we established a reference interval for magnesium. Because the data showed a gaussian distribution, we could use parametric analysis to establish age-related intervals for both males and females.

Simpler flame photometric determination of erythrocyte sodium and potassium: the reference range for apparently healthy adults.

1977 ◽  
Vol 23 (2) ◽  
pp. 275-278 ◽  
Author(s):  
K D Mayer ◽  
B J Starkey
Keyword(s):  
Elective Surgery ◽  
Photometric Determination ◽  
Sodium Concentration ◽  
Reference Intervals ◽  
Healthy Population ◽  
Electrolyte Disorders ◽  
Magnesium Chloride Solution ◽  
Sodium Potassium ◽  
Erythrocyte Sodium

Abstract Separated erythrocytes are washed repeatedly with iso-osmolar magnesium chloride solution, lysed by adding saponin, and sodium potassium measured in the diluted hemolysate by flame photometry. The coefficient of variation for the method was less than 4%. Reference intervals determined for a healthy population and hospitalized (elective surgery) patients without electrolyte disorders were 4.6-7.8 mmol/liter for erythrocyte sodium concentration and 94-110 mmol/liter for erythrocyte potassium concentration (2.5-97.5 percentiles).

scholarly journals Centile Charts II: Alternative Nonparametric Approach for Establishing Time-Specific Reference Centiles and Assessment of the Sample Size Required

2004 ◽  
Vol 50 (5) ◽  
pp. 907-914 ◽  
Author(s):  
Jenny K Griffiths ◽  
Terence C Iles ◽  
Martin Koduah ◽  
Arthur B J Nix
Keyword(s):  
Sample Size ◽  
Structural Characteristics ◽  
Sample Size Calculation ◽  
Reference Population ◽  
Reference Intervals ◽  
Sample Size Determination ◽  
Specific Reference ◽  
Nonparametric Method ◽  
Data Set ◽  
Nonparametric Approach

Abstract Background: Reference intervals, and more generally centile estimates, are used to characterize a reference population for the purposes of interpreting an individual patient’s clinical measurement. We describe methods of calculating reference intervals where these centiles vary with a covariate, usually age or time. Methods: The US Food and Drug Administration and the IFCC have made recommendations on two approaches: the parametric approach, which models the structural characteristics of the data set with a theoretical distribution, and the nonparametric approach, which makes no particular assumption about this structure. In this report we propose a nonparametric procedure that relies on the principles of regression and show how sample size determination can be assessed. We also show how the sample size calculation is influenced by the distribution of the times measured. Results: We illustrated our method on three data sets and compared the results for our proposed nonparametric method with parametric estimates. We showed that the bias is reduced and that the nonparametric method is less likely to produce fluctuating profiles. Conclusions: To achieve adequate precision the sample size needs to be larger than 120, as has often been recommended. If there is doubt about the parametric model, then threshold sample sizes may need to be as high as 500.

Biological factors affecting concentrations of serum LpAI lipoprotein particles in serum, and determination of reference limits

1990 ◽  
Vol 36 (4) ◽  
pp. 677-680 ◽  
Author(s):  
J Steinmetz ◽  
A Choukaife ◽  
S Visvikis ◽  
J Henny ◽  
G Siest
Keyword(s):  
Reference Population ◽  
Healthy Population ◽  
Apolipoprotein Ai ◽  
Morphometric Characteristics ◽  
Biological Factors ◽  
Factors Affecting ◽  
Lipoprotein Particles ◽  
Age Related ◽  
Reference Limits

Abstract We used an electroimmunoassay to measure LpAI lipoprotein particles (lipoproteins containing apolipoprotein AI but not apolipoprotein AII) in serum of a presumably healthy population of about 1000 subjects, noting sex- and age-related variations for the age interval four to 70 years. Results were higher for women than men. For males, the value for the 50th percentile of the distribution was highest in the 10- to 14-year subgroup, 0.69 g/L, decreasing to 0.60 g/L in adults. For females, the values increased regularly, from 0.59 g/L at ages four to 10 years to 0.79 g/L after age 55 years. The influence of puberty, menopause, oral contraceptives, alcohol consumption, and morphometric characteristics was studied. Only being overweight by more than 20% statistically influenced LpAI values in men and in women. We used these results to select a reference population and to establish reference limits of LpAI at ages 25 to 35 years: 0.40-0.95 g/L for men and 0.46-1.05 g/L for women.

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