Indirect determination of biochemistry reference intervals using outpatient data

PLoS ONE, vol. 17, pp. e0268522

Abstract

The aim of this study was to determine reference intervals in an outpatient population from Vall d'Hebron laboratory using an indirect approach previously described in a Dutch population (NUMBER project). We used anonymized test results from individuals visiting general practitioners and analysed during 2018. Analytical quality was assured by EQA performance, daily average monitoring and by assessing longitudinal accuracy between 2018 and 2020 (using trueness verifiers from Dutch EQA). Per test, outliers by biochemically related tests were excluded, data were transformed to a normal distribution (if necessary) and means and standard deviations were calculated, stratified by age and sex. In addition, the reference limit estimator method was also used to calculate reference intervals using the same dataset. Finally, for standardized tests reference intervals obtained were compared with the published NUMBER results. Reference intervals were calculated using data from 509,408 clinical requests. For biochemical tests following a normal distribution, similar reference intervals were found between Vall d'Hebron and the Dutch study. For creatinine and urea, reference intervals increased with age in both populations. The upper limits of Gamma-glutamyl transferase were markedly higher in the Dutch study compared to Vall d'Hebron results. Creatine kinase and uric acid reference intervals were higher in both populations compared to conventional reference intervals. Medical test results following a normal distribution showed comparable and consistent reference intervals between studies. Therefore a simple indirect method is a feasible and cost-efficient approach for calculating reference intervals. Yet, for generating standardized calculated reference intervals that are traceable to higher order materials and methods, efforts should also focus on test standardization and bias assessment using commutable trueness verifiers.

Authors 11

1. Luisa María Martínez-Sánchez corresponding Aachen Department of Clinical Chemistry Laboratory Medicine

   Leiden University · Universitat Autònoma de Barcelona · Leiden University Medical Center · Vall d'Hebron Hospital Universitari

   Affiliation as printed

   Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

   Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain

   Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Leiden, The Netherlands

2. Christa M. Cobbaert Aachen Department of Clinical Chemistry Laboratory Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Leiden, The Netherlands

3. Raymond Noordam Aachen Department of Internal Medicine Section of Gerontology and Geriatrics

   Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

4. Nannette Brouwer
   Affiliation as printed

   Diagnost-IQ, Expert Centre for Clinical Chemistry, Purmerend, The Netherlands

5. Albert Blanco‐Grau

   Vall d'Hebron Hospital Universitari

   Affiliation as printed

   Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

6. Yolanda Villena-Ortiz

   Universitat Autònoma de Barcelona · Vall d'Hebron Hospital Universitari

   Affiliation as printed

   Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

   Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain

7. Marc Thelen

   Radboud University Medical Center · Amphia Ziekenhuis

   Affiliation as printed

   Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

   Laboratory for Clinical Chemistry and Hematology, Amphia, Breda, The Netherlands

   Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek, Nijmegen, The Netherlands

8. Roser Ferrer

   Vall d'Hebron Hospital Universitari

   Affiliation as printed

   Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

9. Ernesto Casís

   Vall d'Hebron Hospital Universitari

   Affiliation as printed

   Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

10. Francisco Rodríguez‐Frias

    Universitat Autònoma de Barcelona · Vall d'Hebron Hospital Universitari

    Affiliation as printed

    Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

    Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain

11. Wendy P. J. den Elzen Aachen Department of Clinical Chemistry Laboratory Medicine

    Leiden University · Leiden University Medical Center · Amsterdam Public Health · Vall d'Hebron Hospital Universitari · Amsterdam University Medical Centers

    Affiliation as printed

    Atalmedial Diagnostics Centre, Amsterdam, The Netherlands

    Clinical Laboratories, Biochemistry Department, Vall d'Hebron University Hospital, Barcelona, Spain

    Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Leiden, The Netherlands

    Department of Clinical Chemistry, Amsterdam Public Health research institute, Amsterdam UMC, Amsterdam, The Netherlands