Critical appraisal and meta-analysis of biological variation estimates for kidney related analytes.

OBJECTIVES: Kidney markers are some of the most frequently used laboratory tests in patient care, and correct clinical decision making depends upon knowledge and correct application of biological variation (BV) data. The aim of this study was to review available BV data and to provide updated BV estimates for the following kidney markers in serum and plasma; albumin, creatinine, cystatin C, chloride, potassium, sodium and urea. CONTENT: Relevant studies were identified from a historical BV database as well as by systematic literature searches. Retrieved publications were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC compliant studies with similar design were performed to deliver global estimates of within-subject (CVI) and between-subject (CVG) BV estimates. Out of the 61 identified papers, three received a BIVAC grade A, four grade B, 48 grade C, five grade D grade and one was not appraised as it did not report numerical BV estimates. Most studies were identified for creatinine (n=48). BV estimates derived from the meta-analysis were in general lower than previously reported estimates for all analytes except urea. For some measurands, BV estimates may be influenced by age or states of health, but further data are required. SUMMARY: This review provides updated global BV estimates for kidney related measurands. For all measurands except for urea, these estimates were lower than previously reported. OUTLOOK: For the measurands analyzed in this review, there are sufficient well-designed studies available to publish a trustworthy estimate of BV. However, for a number of newly appearing kidney markers no suitable data is available and additional studies are required.

Standardization in laboratory medicine: Two years' experience from category 1 EQA programs in Spain.

INTRODUCTION: Standardization is the ability to obtain interchangeable results leading to same medical interpretation. External quality assessment (EQA) is the main support of the on-going harmonization initiatives. Aim of study was to evaluate results obtained from two years category 1 EQA program experience in Spain and determine the impact of applying this type of EQA program on the analytical standardization. MATERIALS AND METHODS: According to the analytical method, traceability and instrument different groups were established which results were evaluated by calculating mean, coefficient of variation and percent of deviation to the reference value. Analytical performance specifications used to the results' evaluation were derived from biological variation for bias and from the inter-laboratory coefficients of variation found in a previous pilot study. RESULTS: Only creatinine measured by enzymatic methods gave excellent results, although few laboratories used this method. Creatine kinase and GGT gave good precision and bias in all, but one instrument studied. For the remaining analytes (ALT, ALP, AST, bilirubin, calcium, chloride, glucose, magnesium, potassium, sodium, total protein and urate) some improvement is still necessary to achieve satisfactory standardization in our setting. CONCLUSIONS: The two years of category 1 EQA program experience in Spain have manifested a lack of standardization of 17 most frequent biochemistry tests used in our laboratories. The impact of the information obtained on the lack of standardization is to recommend abandoning methods such as ALT, AST without exogenous pyridoxal phosphate, Jaffe method for creatinine, and do not use non-commutable calibrators, such as aqueous solutions for calcium and sodium.

Laboratory sample stability. Is it possible to define a consensus stability function? An example of five blood magnitudes.

BACKGROUND: The stability limit of an analyte in a biological sample can be defined as the time required until a measured property acquires a bias higher than a defined specification. Many studies assessing stability and presenting recommendations of stability limits are available, but differences among them are frequent. The aim of this study was to classify and to grade a set of bibliographic studies on the stability of five common blood measurands and subsequently generate a consensus stability function. METHODS: First, a bibliographic search was made for stability studies for five analytes in blood: alanine aminotransferase (ALT), glucose, phosphorus, potassium and prostate specific antigen (PSA). The quality of every study was evaluated using an in-house grading tool. Second, the different conditions of stability were uniformly defined and the percent deviation (PD%) over time for each analyte and condition were scattered while unifying studies with similar conditions. RESULTS: From the 37 articles considered as valid, up to 130 experiments were evaluated and 629 PD% data were included (106 for ALT, 180 for glucose, 113 for phosphorus, 145 for potassium and 85 for PSA). Consensus stability equations were established for glucose, potassium, phosphorus and PSA, but not for ALT. CONCLUSIONS: Time is the main variable affecting stability in medical laboratory samples. Bibliographic studies differ in recommedations of stability limits mainly because of different specifications for maximum allowable error. Definition of a consensus stability function in specific conditions can help laboratories define stability limits using their own quality specifications.

The Biological Variation Data Critical Appraisal Checklist: A Standard for Evaluating Studies on Biological Variation.

BACKGROUND: Concern has been raised about the quality of available biological variation (BV) estimates and the effect of their application in clinical practice. A European Federation of Clinical Chemistry and Laboratory Medicine Task and Finish Group has addressed this issue. The aim of this report is to (a) describe the Biological Variation Data Critical Appraisal Checklist (BIVAC), which verifies whether publications have included all essential elements that may impact the veracity of associated BV estimates, (b) use the BIVAC to critically appraise existing BV publications on enzymes, lipids, kidney, and diabetes-related measurands, and (c) apply metaanalysis to deliver a global within-subject BV (CVI) estimate for alanine aminotransferase (ALT). METHODS: In the BIVAC, publications were rated as A, B, C, or D, indicating descending compliance for 14 BIVAC quality items, focusing on study design, methodology, and statistical handling. A D grade indicated that associated BV estimates should not be applied in clinical practice. Systematic searches were applied to identify BV studies for 28 different measurands. RESULTS: In total, 128 publications were identified, providing 935 different BV estimates. Nine percent achieved D scores. Outlier analysis and variance homogeneity testing were scored as C in >60% of 847 cases. Metaanalysis delivered a CVI estimate for ALT of 15.4%. CONCLUSIONS: Application of BIVAC to BV publications identified deficiencies in required study detail and delivery, especially for statistical analysis. Those deficiencies impact the veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to deliver robust global estimates for safe clinical application.

Category 1 external quality assessment program for serum creatinine.

BACKGROUND: The Commission of Analytical Quality and the Committee of External Quality Programs of Spanish Society of Laboratory Medicine (SEQC) in collaboration with the Dutch Foundation for the Quality organized the first national category 1 External Quality Assessment Programs (EQAP) pilot study. The aim is to evaluate the standardization of serum creatinine measurements in the Spanish laboratories through a category 1 external quality assurance program with commutable material and reference method assigned values. METHODS: A total of 87 Spanish laboratories were involved in this program in 2015. Each day a sample control was measured by duplicate during 6 consecutive days. Percentage deviations and coefficients of variation obtained were compared with quality specifications derived from biological variation. RESULTS: A total of 1044 creatinine results were obtained. Laboratories were coded in 11 different method-traceability combinations. Only enzymatic methods get all results within the acceptability limits. DISCUSSION: To participate in a category 1 EQAP is a valuable tool to assess the standardization degree in our country; a big effort should be made to promote laboratories to change their procedures and to use enzymatic creatinine methods, in order to achieve a satisfactory standardization degree for this important analyte.

Biologic Variation Approach to Daily Laboratory.

Biological variation gives valuable information about how the living organism regulates its constituents within and between subjects; this information on the behavior of body components allows us to derive consequences concerning reference populations and intervals. With a more pragmatic approach biological variation has three uses: setting the appropriate analytical performance specification for each analyte to limit the amount of error that laboratory could introduce in its measurements, to help distinguish health from disease, and to implement internal quality control with the automatic verification of results.

Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience.

BACKGROUND: Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. METHODS: A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. RESULTS: A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). CONCLUSIONS: For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase.

Evaluación multicéntrica de materiales para el control de calidad de los índices séricos / Multicenter evaluation of materials for the quality control of the serum indexes

Introducción. La hemólisis, la turbidez y la presencia de concentraciones elevadas de bilirrubina son las fuentes de interferencia más frecuentes en el laboratorio clínico. Muchos analizadores incorporan sistemas de detección de estos interferentes denominados «índices séricos» de hemólisis, ictericia y lipidemia. El grado de veracidad de los índices no suele ser verificado por la dificultad en conseguir materiales de referencia adecuados. En este trabajo se presentan los resultados de un estudio interlaboratorios de los índices hemólisis, ictericia y lipidemia empleando materiales de referencia con concentraciones conocidas de los interferentes. Material y métodos. En el estudio han participado los laboratorios clínicos de 10 centros con 7 analizadores distintos. Los materiales de referencia de índices séricos contenían concentraciones conocidas de bilirrubina, hemoglobina (hemolisado) y triglicéridos (Intralipid). Resultados. Todos los instrumentos proporcionaron resultados aceptables para el índice de ictericia y de hemólisis. Entre los analizadores que dan valores cuantitativos se encontraron resultados bajos en uno de los analizadores para los materiales que contenían Intralipid. Los analizadores que expresan el resultado en forma de un intervalo proporcionaron resultados correctos para los materiales con turbidez menor y bajos para el material con turbidez mayor. Conclusiones. Los materiales de referencia utilizados han demostrado su utilidad para verificar los índices séricos de ictericia, hemólisis y lipidemia en los analizadores. Generalmente los índices proporcionados por los instrumentos concuerdan entre sí y con los valores asignados. Las diferencias más importantes entre analizadores se encuentran en el índice de lipidemia (AU)

Introduction. Hemolysis, turbidity and the presence of high concentrations of bilirubin are the most frequent sources of interference in the clinical laboratory. Many analyzers incorporate detection systems for these interferents called “serum indexes” of hemolysis, icterus and lipidemia. The accuracy of such indexes is usually not verified by the difficulty in obtaining appropriate reference materials. In this work we show the results of an interlaboratory study of hemolysis, icterus and lipidemia indexes using reference materials containing known concentrations of these interfering substances. Material and methods. Ten clinical laboratories from different centres have participated in the study using 7 different analyzers. The reference materials for the serum indexes contained known concentrations of bilirubin, hemoglobin (hemolysate) and triglycerides (Intralipid). Results. All instruments provided acceptable results for the icterus and hemolysis index. Among the analyzers providing quantitative values, low results were found in one of the analyzers for materials containing Intralipid. The analyzers expressing the result as an interval provided correct results for materials with low turbidity but a low result for the material with the highest turbidity. Conclusions. The reference materials used have proved to be useful to verify the serum indexes for hemolysis, icterus and lipidemia in analyzers. The results obtained in different instruments generally agree among them and with the assigned values. The most important differences between analyzers were found in the lipidemia index (AU)

Rationale for using data on biological variation.

The aims of this study are: 1) to use the data included in the biological variation (BV) database to address the usability of BV estimates; and 2) to use different examples from the authors' laboratories to illustrate the use and the usefulness of BV data in laboratory medicine. The BV database is an essential tool for laboratory management. Examples of application of data derived from BV are given in this paper, such as analytical performance specifications that have been included in various quality control software designed to optimize operative rules; also they have been incorporated as acceptability limits in external quality assurance reports. BV data from pathological status are of utmost interest for monitoring patients and differences between the intra-individual coefficients of variation (CVI) estimated from healthy and patients are shown. However, for a number of analytes there are limited data available and for many there are no data, consequently new studies should be encouraged at an international level. In addition, developing international criteria to evaluate publications dealing with the estimation of BV components would be of the utmost interest. We are ready and willing to collaborate with such worthy initiatives. The first EFLM strategic conference on analytical performance specifications is an excellent opportunity for debating these ideas.

Biological variation database: structure and criteria used for generation and update.

BACKGROUND: Numerical data on the components of biological variation (BV) have many uses in laboratory medicine, including in the setting of analytical quality specifications, generation of reference change values and assessment of the utility of conventional reference values. METHODS: Generation of a series of up-to-date comprehensive database of components of BV was initiated in 1997, integrating the more relevant information found in publications concerning BV. A scoring system was designed to evaluate the robustness of the data included. The database has been updated every 2 years, made available on the Internet and derived analytical quality specifications for imprecision, bias and total allowable error included in the tabulation of data. RESULTS AND CONCLUSIONS: Our aim here is to document, in detail, the methodology we used to evaluate the reliability of the included data compiled from the published literature. To date, our approach has not been explicitly documented, although the principles have been presented at many symposia, courses and conferences.

Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience.

BACKGROUND: Hemolysis is the main cause of non-quality samples in clinical laboratories, producing the highest percentage of rejections in the external assurance programs of preanalytical quality. The objective was to: 1) study the agreement between the detection methods and quantification of hemolysis; 2) establish comparable hemolysis interference limits for a series of tests and analytical methods; and 3) study the preanalytical variables which most influence hemolysis production. METHODS: Different hemoglobin concentration standards were prepared using the reference method. Agreement was studied between automated methods [hemolytic indexes (HI)] and reference method, as well as the interference according to hemolysis degree in various biochemical tests was measured. Preanalytical variables which could influence hemolysis production were studied: type of extraction, type of tubes, transport time, temperature and centrifugation conditions. RESULTS: Good agreement was obtained between hemoglobin concentrations measured using the reference method and HI, for the most of studied analyzers, particularly those giving quantitative HI. The hemolysis interference cut-off points obtained for the majority of tests studied (except LDH, K) are dependent on the method/analyzer utilized. Furthermore, discrepancies have been observed between interference limits recommended by the manufacturer. The preanalytical variables which produce a lower percentage of hemolysis rejections were: centrifugation at the extraction site, the use of lower volume tubes and a transport time under 15 min at room temperature. CONCLUSIONS: The setting of interference limits (cut-off) for each used test/method, and the study of preanalytical variability will assist to the results harmonization for this quality indicator.

Current status of verification practices in clinical biochemistry in Spain.

BACKGROUND: Verification uses logical algorithms to detect potential errors before laboratory results are released to the clinician. Even though verification is one of the main processes in all laboratories, there is a lack of standardization mainly in the algorithms used and the criteria and verification limits applied. A survey in clinical laboratories in Spain was conducted in order to assess the verification process, particularly the use of autoverification. METHODS: Questionnaires were sent to the laboratories involved in the External Quality Assurance Program organized by the Spanish Society of Clinical Biochemistry and Molecular Pathology. Seven common biochemical parameters were included (glucose, cholesterol, triglycerides, creatinine, potassium, calcium, and alanine aminotransferase). RESULTS: Completed questionnaires were received from 85 laboratories. Nearly all the laboratories reported using the following seven verification criteria: internal quality control, instrument warnings, sample deterioration, reference limits, clinical data, concordance between parameters, and verification of results. The use of all verification criteria varied according to the type of verification (automatic, technical, or medical). Verification limits for these parameters are similar to biological reference ranges. Delta Check was used in 24% of laboratories. Most laboratories (64%) reported using autoverification systems. Autoverification use was related to laboratory size, ownership, and type of laboratory information system, but amount of use (percentage of test autoverified) was not related to laboratory size. CONCLUSIONS: A total of 36% of Spanish laboratories do not use autoverification, despite the general implementation of laboratory information systems, most of them, with autoverification ability. Criteria and rules for seven routine biochemical tests were obtained.

Quality indicators and specifications for key analytical-extranalytical processes in the clinical laboratory. Five years' experience using the Six Sigma concept.

BACKGROUND: The results of 5 years of experience (2004-2008) with process-based quality management using quality indicators for key laboratory processes (analytic and extra-analytic) in a group of clinical laboratories affiliated with the Catalan Health Institute are presented. Our purpose was to analyze the evolution of the indicators, identify processes that require corrective measures, and obtain specifications that are more robust than the preliminary ones proposed in a previous study by the same group. METHODS: The yearly average was recorded for each indicator in each laboratory, the yearly interlaboratory median was calculated, and the changes occurring were studied to determine their continuity in the 5-year period. For each indicator, the average of the yearly medians was calculated and the results transformed to the Six Sigma scale to estimate the degree of control over the related process. It was suggested to establish the yearly interlaboratory median as the desirable specification for each indicator. RESULTS: The medians for most indicators were stable during the period studied. Thus, the specifications proposed in the first study were considered robust in these cases. The Six Sigma statistic provided added value in this study because it enabled detection of processes that should be improved, in which case the specifications proposed were considered provisional despite their stability. After identifying processes that have the greatest impact on patient safety, the group set a specification of 0%, regardless of the actual specification obtained, although the members are conscious of the difficulty in attaining this level of quality. Certain processes that are in a period of change obtained specifications that are considered in a phase of consolidation. CONCLUSIONS: The results for indicators related with sample collection indicate that the process is stable and well controlled. However, based on the results for Hemolyzed serum sample, the group saw the need for installing centrifuges in all phlebotomy centers and established a recommendation to unify the system for measuring hemolysis. The indicator External control exceeds acceptance limit clearly highlighted the need to rigorously monitor the analytic phase of the clinical laboratory. The values obtained for the indicator Reports from referred tests exceed delivery time show that there is considerable deviation regarding the expected report delivery time, whereas for in-house laboratory reports, delivery time is satisfactory.

Variación biológica. Revisión desde una perspectiva práctica / Biological variation. A review from a practical perspective

Los autores realizan una revisión exhaustiva sobre la variación biológica, con el objeto de resaltar su aplicación práctica en la rutina diaria del laboratorio clínico. Se describe brevemente el método de estimación de los componentes de la variación biológica y se detalla la base de datos actualizada bianualmente y disponible para los profesionales del sector. Se pormenoriza el uso práctico en el control interno del proceso analítico, en la evaluación de los datos del control interno y externo, así como en la detección de errores analíticos y extraanalíticos. Finalmente, se explica con claridad cómo notificar la posibilidad de un cambio significativo en el estado de salud del paciente en el informe analítico (AU)

This is an exhaustive review on biological variation, which aims to highlight its practical application in daily routine of clinical laboratories. The methodology to estimate the components of biological variation is summarised and a database, which is updated every two years and available to professionals of the area, is explained in detail. Daily application of data derived from biological variation in daily practice in internal and external quality control, as well as, in the detection of analytical and non-analytical errors is clearly explained. Last, but not least, examples are given on how to notify to clinicians on possible changes in patients health status (AU)

Indicators and quality specifications for strategic and support processes related to the clinical laboratory: four years' experience.

BACKGROUND: Quality specifications for indicators of the key analytic processes have been defined by international consensus. However, only preliminary specifications for laboratory-related strategic and support processes have been developed. The present study attempts to increase the robustness of the preliminary proposed specifications. METHODS: Recovering records and incidences occurred over a 4-year follow-up period, for 12 indicators, used in all laboratories from this group regarding strategic and support processes. RESULTS AND CONCLUSIONS: The results obtained indicate that it is better to establish an interval rather than a fixed value for the majority of indicators. Longer studies are needed to properly assess some quality specifications, and data recording system must be standardized in others. Additional, multicenter studies are needed to establish more robust specifications and determine the state of the art of laboratories in other settings.

Aplicación del modelo Seis-Sigma en la mejora de la calidad analítica del laboratorio clínico / Application of the Six-Sigma model to improve analytical quality in the clinical laboratory

Introducción. El modelo Seis Sigma es una herramienta de gestión de la calidad que se basa en la medida de la variabilidad de un proceso, en términos de desviación típica o de fallos por millón. Implica haber definido previamente una especificación de la calidad para el proceso que se investiga. Material y método. Este trabajo estudia los datos obtenidos en los programas de garantía externa de la calidad de la Sociedad Española de Bioquímica Clínica y Patología Molecular (SEQC), con el propósito de deducir consecuencias prácticas que aseguren el diagnóstico y el seguimiento correctos del paciente, mediante el informe aportado por el laboratorio. Se incluyen magnitudes biológicas con especificaciones de la calidad definidas para situaciones clínicas concretas (colesterol, glucosa, glucohemoglobina y antígeno prostático específico total) y con valores de variación biológica bajos (ión sodio, albúmina), intermedios (colesterol, creatinina, glucosa) y altos (hierro, triglicéridos). El valor sigma se calcula mediante el cociente entre el límite de tolerancia establecido y la variabilidad del proceso. Resultados. Los valores sigma obtenidos son adecuados (>=3) si se toman especificaciones muy permisivas, mientras que no lo son cuando se desea cumplir la especificación derivada de la variación biológica. Ello indica que los instrumentos y métodos analíticos disponibles en nuestro mercado requieren un procedimiento de control de la calidad muy cuidadoso (procesamiento de varias muestras control, necesidad de realizar repeticiones, etc.). Conclusiones. En ningún caso se debe confundir el objetivo de alcanzar la calidad necesaria para el adecuado uso clínico del informe analítico con el de conseguir un laboratorio industrialmente productivo; ambos forman parte del concepto de calidad total(AU)

Introduction. The Six Sigma model is a management tool based on measuring process variability, in terms of standard deviation or defects per million. It involves defining the specifications of the quality desired for the process investigated. Material and method. This work uses data obtained by the laboratories participating in the external surveys organized by the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC), with the aim of promoting practical recommendations for assuring satisfactory patient diagnosis or monitoring through the laboratory report. The analytes included have quality specifications defined for specific clinical situations (cholesterol, glucose, HbA1C, total PSA) and have narrow (albumin, sodium), medium (cholesterol, creatinine, glucose) and wide (iron, triglyceride) biological variations. Results from control materials with the relevant concentrations to make clinical decisions have been used in this study. Sigma matrix is calculated from the ratio between quality specification and process coefficient of variation. Results. Results obtained show that sigma values are good (>=3) when using permissive quality specifications, whereas they are poor if quality specifications are derived from biological variation. This finding indicates that instruments and methods available in our field require a strict quality control procedure (several control samples per run, repeated tests, etc.). Conclusions. The objective of obtaining the quality required for adequate clinical use, must not be confused with that of achieving an economically productive laboratory; both are part of the concept of total quality management(AU)

Preanalytical quality control program - an overview of results (2001-2005 summary).

BACKGROUND: Preanalytical variables, such as sample collection, handling, transport, and storage, may affect patient results. The number of errors in the preanalytical phase may decrease by following standardized procedures. METHODS: A retrospective analysis (2001-2005) of results obtained through the Spanish Society of Clinical Chemistry and Molecular Pathology Quality Assessment Program for the Preanalytical Phase has been carried out to summarize data regarding the main factors affecting the preanalytical phase quality. In such a program, participants are asked to register rejections and causes for rejection of routine or stat samples usually and locally collected at their laboratories. RESULTS: Results discussed refer to 105 laboratories. Of the 4,715,132 tubes expected to be received during the data collection period among participating laboratories and according to determinations included by clinicians in the request form, 32,977 (0.699%) offered a cause for rejection. Whole blood-EDTA samples and serum samples accounted for 75.6% of all samples collected among laboratories, although they only corresponded to 55.8% of all registered rejections. In total, 81% of rejections arose as a result of the following reasons: "specimen not received" (37.5%), "hemolysis" (29.3%), and "clotted sample" (14.4%). Moreover, plasma-citrate-erythrocyte sedimentation rate exhibited the highest percentage of rejection (1.473%), whereas the lowest rate corresponded to whole blood-EDTA (0.381%). CONCLUSIONS: Overall percentage of rejection is similar to previously published data. As some of the included variables have turned out to be irrelevant, the program has been simplified from the year 2006 onwards.

Quality indicators and specifications for strategic and support processes in laboratory medicine.

BACKGROUND: This work is the second part of a study regarding indicators and quality specifications for the non-analytical processes in laboratory medicine. Five primary care and five hospital laboratories agreed on the indicators for two strategic processes (quality planning and project development) and various support processes (client relationships, instrument and infrastructure maintenance, safety and risk prevention, purchases and storage, personnel training). METHODS: In the majority of cases, the median values recorded over 1 year is considered to be the state-of-the-art in our setting and proposed as the quality specification for the indicators stated. Values have been stratified according to primary care and hospital laboratory for referred tests and group of personnel for training. In some cases, the specifications have been set equal to zero events, such as serious incidents in the infrastructure maintenance process and number of work accidents in the safety and risk prevention process. RESULTS AND CONCLUSIONS: In light of this study, an effort is needed to optimize decisions regarding corrective actions and to move from a subjective individual criterion to systematic and comparative management. This preliminary study provides a comprehensive vision of a subject that could motivate further research and advances in the quality of laboratory services.

Within-subject biological variation in disease: collated data and clinical consequences.

Quantitative data on the components of biological variation (BV) are used for several purposes, including calculating the reference change value (RCV) required for the assessment of the significance of changes in serial results in an individual. Pathology may modify the set point in diseased patients and, more importantly, the variation around that set-point. Our aim was to collate all published BV data in situations other than health. We report the within-subject coefficient of variation (CV(I)) for 66 quantities in 34 disease states. We compared the results with the CV(I) determined in healthy individuals and examined whether the data derived in specific diseases could be useful for clinical applications. For the majority of quantities studied, CV(I) values are of the same order in disease and health: thus the use of RCV derived from healthy subjects for monitoring patients would be reasonable. However, for a small number of quantities considered to be disease specific markers, the CV(I) differed from those in health. This could mean that RCV derived from healthy CV(I) may be inappropriate for monitoring patients in certain diseases. Hence, disease-specific RCVs may be clinically useful.

Integration of data derived from biological variation into the quality management system.

BACKGROUND: [corrected] Data on within- and between-subject biological variation are available for around 250 analytes commonly used in medical laboratories. METHODS: Integration of this data into the quality system occurs at all three levels of laboratory activity: (a) Preanalytic process: biological variation provides the basis for selecting the most appropriate specimen for analysis, for defining sample stability and for deciding suitable timing between samplings; (b) analytic process: biological variation-derived goals are fundamental for designing internal quality control procedures, and for evaluating laboratory performance; and (c) postanalytic process: delta checks based on within-subject biological variation values are used for validating results and for interpreting serial results from a patient. CONCLUSION: The biological variation is a pillar for managing quality in laboratory medicine.