Carmen Ricos

Proposals for Setting Generally Applicable Quality Goals Solely Based on Biology

Callum G Fraser, Per Hyltoft Petersen, Jean-Claude Libeerand Carmen Ricosl From the Directorate of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DDI 9SY, UK, lClinical Chemistry Department, Odense University Hospital, Odense, Denmark, 2Clinical Biology Department, Institute of Hygiene and Epidemiology, Brussels, Belgium, and 3Clinical Biochemistry Department, University General Hospital, Vall dHebron, Barcelona, Spain

Combination of analytical quality specifications based on biological within- and between-subject variation

At a conference on ‘Strategies to Set Global Analytical Quality Specifications in Laboratory Medicine’ in Stockholm 1999, a hierarchy of models to set analytical quality specifications was decided. The consensus agreement from the conference defined the highest level as ‘evaluation of the effect of analytical performance on clinical outcomes in specific clinical settings’ and the second level as ‘data based on components of biological variation’. Here, the many proposals for analytical quality specifications based on biological variation are examined and the outcomes of the different models for maximum allowable combined analytical imprecision and bias are illustrated graphically. The following models were investigated. (1) The Cotlove et al. (1970) model defining analytical imprecision (%CVA) in relation to the within-subject biological variation (%CVw-s) as: %CVA≤ 0·5 × %CVW-S (where %CV is percentage coefficient of variation), (2) The Gowans et al. (1988) concept, which defines a functional relationship between analytical imprecision and bias for the maximum allowable combination of errors for the purpose of sharing common reference intervals. (3) The European Group for the Evaluation of Reagents and Analytical Systems in Laboratory Medicine (EGE Lab) Working Group concept, which combines the Cotlove model with the Gowans concept using the maximal acceptable bias. (4) The External Quality Assessment (EQA) Organizers Working Group concept, which is close to the EGE Lab Working Group concept, but follows the Gowans et al. concept of imprecision up to the limit defined by the model of Cotlove et al. (5) The ‘three-level’ concept classifying analytical quality into three levels: optimum, desirable and minimum. The figures created clearly demonstrated that the results obtained were determined by the basic assumptions made. When %CVW-S is small compared with the population-based coefficient of variation [%CVp = (%CV2 W-S +%CV2 B-S)1/2], the EGE Lab and EQA Organizers Working Group concepts become similar. Examples of analytical quality specifications based on biological variations are listed and an application on external quality control is illustrated for plasma creatinine.

Postanalytical external quality assessment of urine albumin in primary health care: an international survey.

BACKGROUNDnMicroalbuminuria (MA) is recognized as an important risk factor for cardiovascular and renal complications in diabetes. We sought to evaluate how screening for MA is conducted and how urine albumin (UA) results are interpreted in primary care internationally.nnnMETHODSnGeneral practitioners (GPs) received a case history-based questionnaire depicting a male type 2 diabetes patient in whom UA testing had not been performed. Questions were related to type of urine sample used for UA testing, need for a repeat test, whether UA testing was performed in the office laboratory, and what changes in UA results were considered clinically important [critical difference (CD)]. Participants received national benchmarking feedback reports.nnnRESULTSnWe included 2078 GPs from 9 European countries. Spot urine samples were used most commonly for first time office-based testing, whereas timed collections were used to a larger extent for hospital-based repeat tests. Repeat tests were requested by 45%-77% of GPs if the first test was positive. Four different measurement units were used by 70% of participants in estimating clinically important changes in albumin values. Stated CDs varied considerably among GPs, with similar variations in each country. A median CD of 33% was considered clinically important for both improvement and deterioration in MA, corresponding to an achievable analytical imprecision of 14%, when UA is reported as an albumin/creatinine ratio.nnnCONCLUSIONSnGuidelines on diagnosing MA are followed only partially, and should be made more practicable, addressing issues such as type of samples, measurement units, and repeat tests.

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

BACKGROUNDnConcern 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).nnnMETHODSnIn 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.nnnRESULTSnIn 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%.nnnCONCLUSIONSnApplication 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.

Analytical performance of 17 general chemistry analytes across countries and across manufacturers in the INPUtS project of EQA organizers in Italy, the Netherlands, Portugal, United Kingdom and Spain

Abstract Background: Optimum patient care in relation to laboratory medicine is achieved when results of laboratory tests are equivalent, irrespective of the analytical platform used or the country where the laboratory is located. Standardization and harmonization minimize differences and the success of efforts to achieve this can be monitored with international category 1 external quality assessment (EQA) programs. Methods: An EQA project with commutable samples, targeted with reference measurement procedures (RMPs) was organized by EQA institutes in Italy, the Netherlands, Portugal, UK, and Spain. Results of 17 general chemistry analytes were evaluated across countries and across manufacturers according to performance specifications derived from biological variation (BV). Results: For K, uric acid, glucose, cholesterol and high-density density (HDL) cholesterol, the minimum performance specification was met in all countries and by all manufacturers. For Na, Cl, and Ca, the minimum performance specifications were met by none of the countries and manufacturers. For enzymes, the situation was complicated, as standardization of results of enzymes toward RMPs was still not achieved in 20% of the laboratories and questionable in the remaining 80%. Conclusions: The overall performance of the measurement of 17 general chemistry analytes in European medical laboratories met the minimum performance specifications. In this general picture, there were no significant differences per country and no significant differences per manufacturer. There were major differences between the analytes. There were six analytes for which the minimum quality specifications were not met and manufacturers should improve their performance for these analytes. Standardization of results of enzymes requires ongoing efforts.

Diagnosing microalbuminuria and consequences for the drug treatment of patients with type 2 diabetes: A European survey in primary care

AIMSnTo assess general practitioners (GPs) knowledge of guideline recommendations on diagnosing microalbuminuria (MA) and to evaluate how this diagnosis influences drug treatment of diabetes patients.nnnMETHODSnA postal case-history based questionnaire describing a male patient (previously not tested for MA) with type 2 diabetes who had several risk markers for cardiovascular disease.nnnRESULTSn2078GPs from nine European countries were included, with response rates varying from 7% to 43%. Almost all GPs recommended annual testing for MA. Forty-five to 77% (depending on country) of GPs required more than one positive test to diagnose MA. The absolute increase in the percentages of GPs who would supplement the patients drug treatment if MA developed was: for anginotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) 23-50% (depending on country), for statins 0-19%, for acetylsalicylic acid 2-13%, and for hypoglycemic agents (tablets and insulin) 0-33%. The proportion of GPs recommending all four possible treatment modalities was low.nnnCONCLUSIONSnGuidelines for diagnosing MA were partly followed. ACEIs and ARBs were recommended when MA was present, but the recommended multifactorial treatment of cardiovascular risk markers was not implemented.

A Practical Approach to Minimizing Inaccuracy through Traceability, Using Limited Resources

~ Serum-based reference materials RM-391 projects.P it has been proposed that clinical laboratories should develop reference methods for assigning target values to fresh samples which may be used by manufacturers for calibrating their methods and by EQAS for routine methods assessment. 7 However, this combined approach will not become operative for some years and, in the interim, routine laboratories must produce satisfactory results. Without detracting from this effort, presently recognized to be the ideal solution, there are ways to improve laboratory results with existing resources. National external quality assessment schemes have control samples circulating among all the laboratories in a country. If this material were traceable back to reference standards, it would be an excellent means for demonstrating traceability in quantities and methods with minor matrix problems.t The purpose of this work is to provide a practical interim system to achieve traceability