Systematic review of the biological variation data for diabetes related analytes.

BACKGROUND: Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications. METHODS: Publications reporting data for glucose, HbA1c, adiponectin, C-peptide, fructosamine, insulin like growth factor 1 (IGF-1), insulin like growth factor binding protein 3 (IGFBP-3), insulin, lactate and pyruvate were identified using a systematic literature search. These publications were assessed using the BIVAC, receiving grades A, B, C or D, where A is of highest quality. A meta-analysis of the BVD from the assessed studies utilised weightings based upon BIVAC grades and the width of the data confidence intervals to generate global BVD estimates. RESULTS: BIVAC assessment of 47 publications delivered 1 A, 3 B, 39C and 4 D gradings. Publications relating to adiponectin, C-peptide, IGF-1, IGFBP-3, lactate and pyruvate were all assessed as grade C. Meta-analysis enabled global BV estimates for all analytes except pyruvate, lactate and fructosamine. CONCLUSIONS: This study delivers updated and evidence-based BV estimates for diabetes-related analytes. There remains a need for delivery of new high-quality BV studies for several clinically important analytes.

External quality assurance programs as a tool for verifying standardization of measurement procedures: Pilot collaboration in Europe.

INTRODUCTION: Current external quality assurance schemes have been classified into six categories, according to their ability to verify the degree of standardization of the participating measurement procedures. SKML (Netherlands) is a Category 1 EQA scheme (commutable EQA materials with values assigned by reference methods), whereas SEQC (Spain) is a Category 5 scheme (replicate analyses of non-commutable materials with no values assigned by reference methods). AIM: The results obtained by a group of Spanish laboratories participating in a pilot study organized by SKML are examined, with the aim of pointing out the improvements over our current scheme that a Category 1 program could provide. METHOD: Imprecision and bias are calculated for each analyte and laboratory, and compared with quality specifications derived from biological variation. RESULTS: Of the 26 analytes studied, 9 had results comparable with those from reference methods, and 10 analytes did not have comparable results. The remaining 7 analytes measured did not have available reference method values, and in these cases, comparison with the peer group showed comparable results. The reasons for disagreement in the second group can be summarized as: use of non-standard methods (IFCC without exogenous pyridoxal phosphate for AST and ALT, Jaffé kinetic at low-normal creatinine concentrations and with eGFR); non-commutability of the reference material used to assign values to the routine calibrator (calcium, magnesium and sodium); use of reference materials without established commutability instead of reference methods for AST and GGT, and lack of a systematic effort by manufacturers to harmonize results. CONCLUSIONS: Results obtained in this work demonstrate the important role of external quality assurance programs using commutable materials with values assigned by reference methods to correctly monitor the standardization of laboratory tests with consequent minimization of risk to patients.

The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation.

BACKGROUND: A proposal to calculate and use the reference change value (RCV) as an objective guide for interpreting the numerical results obtained in clinical laboratory serial testing is introduced in this study. METHODS: A database showing the results of a compilation of 191 publications on biological variation and including information on a number of analytes provided the standardized criterion based on biology for calculating the RCVs. RESULTS: For each of the 261 analytes included in the study, the RCV was determined using Harris's formula, replacing analytical imprecision with the desirable specification of analytical quality based on half the within-subject biological variation at 95% probability levels. The result is a guide for a common criterion to identify clinically significant changes in serial results. CONCLUSIONS: The RCV concept is an approach that can be offered by laboratories to assess changes in serial results. The RCV data in this study are presented as a point of departure for a widely applicable objective guide to interpret changes in serial results.

Commutability and traceability: their repercussions on analytical bias and inaccuracy.

The commutability of calibrators and accuracy control materials affects the traceable link between patient sample results and standards. We sought to identify the repercussions of commutability on various aspects of laboratory practice (calibration, control of bias and accuracy assessment) and to discover the solutions that can reduce the problems produced by non-commutability with presently available resources. Ten serum constituents, ten comparison procedures and 37 analytical procedures were studied. The information concerning accuracy and bias provided from materials found to be commutable in previous works was challenged with native serum results for each routine and reference method compared, using Passing-Bablok regression and decision limits derived from biological variation. We found that: (1) Use of commutable control materials did not assure reliable information on the bias (systematic component of analytical error) of analytical procedures, and (2) Results from native serum and commutable controls were very highly concordant, indicating that these materials provide a good indication of the inaccuracy (total analytical error) of results. We suggest that the performance of individual laboratories would be better evaluated by occasional use of native sera with values assigned by reference methods in EQAS schemes. Moreover, our findings support the idea that manufacturers should assign values to calibrators using reference methods and native sera to reduce matrix effects and promote traceability.

Current databases on biological variation: pros, cons and progress.

A database with reliable information to derive definitive analytical quality specifications for a large number of clinical laboratory tests was prepared in this work. This was achieved by comparing and correlating descriptive data and relevant observations with the biological variation information, an approach that had not been used in the previous efforts of this type. The material compiled in the database was obtained from published articles referenced in BIOS, CURRENT CONTENTS, EMBASE and MEDLINE using "biological variation & laboratory medicine" as key words, as well as books and doctoral theses provided by their authors. The database covers 316 quantities and reviews 191 articles, fewer than 10 of which had to be rejected. The within- and between-subject coefficients of variation and the subsequent desirable quality specifications for precision, bias and total error for all the quantities accepted are presented. Sex-related stratification of results was justified for only four quantities and, in these cases, quality specifications were derived from the group with lower within-subject variation. For certain quantities, biological variation in pathological states was higher than in the healthy state. In these cases, quality specifications were derived only from the healthy population (most stringent). Several quantities (particularly hormones) have been treated in very few articles and the results found are highly discrepant. Therefore, professionals in laboratory medicine should be strongly encouraged to study the quantities for which results are discrepant, the 90 quantities described in only one paper and the numerous quantities that have not been the subject of study.

Commutability between stabilized materials and fresh human serum to improve laboratory performance.

With the recent advances in laboratory technology, many quality-related problems have been improved. However, the issue of commutability, a factor that greatly affects daily decisions concerning patient status, still remains to be solved. This paper determines the commutability between 27 stabilized materials (controls and calibrators) and clinical specimens for five serum quantities, using carrier-bound reagent chemistry and conventional wet methods. Our aim was to pinpoint the specific problems related to non-commutable calibrators and controls in our setting, and minimize their effect in daily practice. We found major difficulties in selecting appropriate accuracy controls in carrier-bound reagent techniques, and in finding materials commutable for several analytes simultaneously. Several suggestions for reducing problems related to non-commutability, such as procedures for assigning values to multicalibrators, are proposed. We explain the apparent incongruencies observed in daily quality surveillance, when data from different control materials (internal quality control and external quality assessment) are evaluated. The conclusions emphasize the need for a combined effort (manufacturers, organizers of external quality assessment schemes and individual laboratories) to find the cause of, and eliminate, the negative repercussions on laboratory performance produced by non-commutability.

Procedure for studying commutability validated by biological variation.

In the field of laboratory medicine, the two quantitative approaches designed to identify the stabilized materials that produce results that are commutable with results from patients' samples were found to differ. In commutability evaluations, the responses of each material and each method studied are specific, thus, it is vital to standardise the procedure used for determining this characteristic. We incorporated statistical components from the two described methods that seemed to be consistent, and added a new element based on biological variation, to validate the criterion of acceptability that determines whether or not a material is commutable. The three methods for studying commutability (using the confidence interval [alpha = 0.05], the +/- 2s(yx) formula, and the limit based on biological variation as acceptability criteria) were applied to creatinine results from 31 stabilised materials and serum samples analysed with seven instruments, when compared against a reference method for creatinine analysis. Over the wide range of concentrations studied, the confidence interval limit and the biological variation limit coincided in the identification of commutable materials, whereas the +/- 2s(yx) was excessively permissive at normal and low concentration levels. We therefore recommend the use of Passing-Bablok regression with its confidence interval (alpha = 0.05) in studies concerning commutability. Using this method, commutability is simple to calculate with available software and, as validated by biological variation, results are reliable.

[Transferability of results in hematologic determinations]. / Transferibilidad de los resultados en determinaciones hematológicas.

PURPOSE: To evaluate inaccuracy of the results attained in several Servei Catalá de la Salut laboratories in order to assess if quality purposes are accomplished and results are transferable between them. MATERIAL AND METHODS: Two types of haematological analysers are used: those based upon volumetric measurements and those using light dispersion for particle counting. Inaccuracy was ascertained in accordance to the inter-laboratory quality control programme. The inter-series study was performed with commercial control material in each laboratory with their own data, the monthly coefficient of variation being found, and the mean of the CV of 12 months was then calculated. Intra-series inaccuracy with commercial control material was assessed in each laboratory three times a day for 10 days, and the inaccuracy with fresh patient blood was examined daily in triplicate. The analytical inaccuracy attained in patient samples was also compared with that attained with stabilized control materials. RESULTS: The inaccuracy quality limits were exceeded in the haematological constituents under study. Quality objectives were accomplished in the inter-series inaccuracy study for red cell count, white cell count, MCV, granulocytes and lymphocytes. Repeat fresh patient-blood assays can be used to assess intra-series inaccuracy for red and white cell counts, but not for platelet count. CONCLUSIONS: Inaccuracy of the blood constituents studied is not transferable. Inaccuracy for the commonest haematological values is transferable between laboratories. Intra-series inaccuracy for red and white cell counts can be assessed by repeated use of fresh patient-blood when control material is not available. Patient samples are not advisable as a control of the white cell differential count for intra-series inaccuracy studies in those systems using volumetric principles.

Biological variation in urine samples used for analyte measurements.

To determine the influence of biological variation on the reliability of data from different types of urine specimens, we measured nine analytes in first-morning, randomly collected, and 24-h samples of urine from 53 healthy individuals (14 men and 39 women). The urines were collected once a week for 10 weeks. The data obtained were used as a basis for specimen collection and to gain insight into the influence of urine quantities in the diagnosis, screening, and monitoring of patients. We found that 24-h urine expressed in output rather than concentration units is the most reliable specimen for diagnosis and monitoring for most of the analytes studied. On the basis of the ratio between estimated within- and between-subject variation, the tests with greatest medical usefulness for diagnosis and screening of specific pathologies are those measuring protein and sodium. Moreover, the results indicate that urine creatinine may be a poor test for diagnosis, monitoring, and screening.

Approaches for providing target values to improve usefulness of external quality assessment scheme. The Spanish experience.

The aim of this communication is to highlight the specific aspects of external quality assessment schemes that need to be discussed in a European context: target values, transferability of results and accredit of laboratories. The Spanish situation is presented here. The most reliable way to provide target values is to analyse the control samples by reference methods. However, it is not possible for the majority of national schemes and other approaches are presently used: the verification of consensus means is a practicable solution adopted in Spain. An initial network involving selected routine laboratories has been developed, to attain transferability of results. The traceability of routine calibrators from certified reference materials should be demonstrated. To accredit laboratories for licensing is a complex activity that should consider many aspects, results from the national quality assessment scheme bring one. A scoring system is being used in Spain for guidance, and the complete guidelines are under preparation.