Jump to ContentJump to Main Navigation
Show Summary Details

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

IMPACT FACTOR increased in 2015: 3.017
Rank 5 out of 30 in category Medical Laboratory Technology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

SCImago Journal Rank (SJR) 2015: 0.873
Source Normalized Impact per Paper (SNIP) 2015: 0.982
Impact per Publication (IPP) 2015: 2.238

249,00 € / $374.00 / £187.00*

See all formats and pricing


Select Volume and Issue


30,00 € / $42.00 / £23.00

Get Access to Full Text

The evolution of the reference value concept

Ralph Gräsbeck

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 42, Issue 7, Pages 692–697, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2004.118, June 2005

Publication History

Published Online:


This manuscript reviews the introduction of the concept of reference values, the corresponding philosophy, and subsequent recommendations reflecting the different subtopics of the field. The generally unrecognised phenomenon that laboratory results of the population tended to be lognormal instead of Gaussian attracted the attention of the author, who became sceptical of the concept of normal values because of its ambiguity. Together with N.-E. Saris a new concept of reference values was launched at a congress in 1969. Briefly, clinical measurements should be interpreted against values from proper control subjects. Subsequently international, regional and national societies established expert panels which produced recommendations covering the general principles and terminology of reference values, the concept of health, standardised specimen collection and preanalytical factors, statistical treatment of collected values, stratification of data, relating observed (patient) values to reference values, etc. The importance of using correct terminology, taking into consideration the aim of ordering the laboratory test and some neglected procedures (e.g., survival values) are emphasised. New developments such as reference changes are mentioned. The field has evolved largely as the result of constructive international teamwork.

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Marnee J. McKay, Jennifer N. Baldwin, Paulo Ferreira, Milena Simic, Natalie Vanicek, Claire E. Hiller, Elizabeth J. Nightingale, Niamh A. Moloney, Kate G. Quinlan, Fereshteh Pourkazemi, Amy D. Sman, Leslie L. Nicholson, Seyed J. Mousavi, Kristy Rose, Jacqueline Raymond, Martin G. Mackey, Angus Chard, Markus Hübscher, Caleb Wegener, Alycia Fong Yan, Kathryn M. Refshauge, and Joshua Burns
Physiotherapy, 2015
Maria Edvardsson, Märtha Sund Levander, Jan Ernerudh, Elvar Theodorsson, and Ewa Grodzinsky
Journal of Evaluation in Clinical Practice, 2015, Volume 21, Number 2, Page 229
S. Milani, J. M. H. Buckler, C. J. H. Kelnar, L. Benso, G. Gilli, I. Nicoletti, G. Faglia, G. Radetti, G. Bona, Y. Schonbeck, S. Van Buuren, M. Hermanussen, G. Grugni, N. Marazzi, P. B. Júlíusson, M. Roelants, K. Hoppenbrouwers, R. Hauspie, R. Bjerknes, H. Lejarraga, and A. Sartorio
Journal of Endocrinological Investigation, 2012, Volume 35, Number 2, Page 224
Richard Y. Wang, Kathleen L. Caldwell, and Robert L. Jones
Journal of Medical Toxicology, 2014, Volume 10, Number 2, Page 232
Ralph Gräsbeck
Biochimie, 2013, Volume 95, Number 5, Page 970
Miljenko Šimpraga, Tomislav Šmuc, Krešimir Matanović, Lada Radin, Ana Shek-Vugrovečki, Iva Ljubičić, and Aleksandar Vojta
Small Ruminant Research, 2013, Volume 112, Number 1-3, Page 1
Raquel M. Walton
Veterinary Clinical Pathology, 2012, Volume 41, Number 2, Page 175
Davide Giavarina, Romolo M. Dorizzi, and Antonio Fortunato
Clinical Biochemistry, 2007, Volume 40, Number 15, Page 1143
Samuel Lurie, Einam Rahamim, Irena Piper, Abraham Golan, and Oscar Sadan
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2008, Volume 136, Number 1, Page 16
Gurdeep Singh Dhatt, Glenn Griffin, and Mukesh M. Agarwal
Clinica Chimica Acta, 2006, Volume 364, Number 1-2, Page 226
Craig A. Downs, Cheryl M. Woodley, Robert H. Richmond, Lynda L. Lanning, and Richard Owen
Marine Pollution Bulletin, 2005, Volume 51, Number 5-7, Page 486
V. Brusasco, R. Crapo, and G. Viegi
Revue des Maladies Respiratoires, 2007, Volume 24, Number 3, Page 11
Anders Kallner
Scandinavian Journal of Clinical & Laboratory Investigation, 2010, Volume 70, Number s242, Page 34
Farhad Arzideh, Gunnar Brandhorst, Eberhard Gurr, Wilhelm Hinsch, Torsten Hoff, Lennart Roggenbuck, Gregor Rothe, Gerhard Schumann, Bernd Wolters, Werner Wosniok, and Rainer Haeckel
LaboratoriumsMedizin, 2009, Volume 33, Number 2, Page 52
Mario Plebani, Ferruccio Ceriotti, Gianni Messeri, Cosimo Ottomano, Nicola Pansini, and Pierangelo Bonini
LaboratoriumsMedizin, 2006, Volume 30, Number 3, Page 118
Mario Plebani
Clinical Chemical Laboratory Medicine, 2006, Volume 44, Number 6
Olaf Boehm, Berndt Zur, Alexander Koch, Nguyen Tran, Rainer Freyenhagen, Matthias Hartmann, and Kai Zacharowski
Biological Chemistry, 2007, Volume 388, Number 5
Rebecca S. Nicolich, Monica C. Padilha, and Francisco R. de Aquino Neto
Drug Testing and Analysis, 2010, Volume 2, Number 11-12, Page 599
Mark M. Kushnir, Alan L. Rockwood, and Jonas Bergquist
Mass Spectrometry Reviews, 2010, Volume 29, Number 3, Page 480
Jürgen Durner
Angewandte Chemie International Edition, 2009, Volume 49, Number 6, Page 1026
Hyung Hoi Kim, Hae Sook Hong, Shine Young Kim, Tung Tran, Ji Min Lee, Hwa Sun Kim, and Hune Cho
Healthcare Informatics Research, 2010, Volume 16, Number 1, Page 15
International Journal of Laboratory Hematology, 2007, Volume 29, Number 3, Page 195
Clinical and Laboratory Haematology, 2006, Volume 0, Number 0, Page 061206090712002
Llorenç Quintó, John J. Aponte, Jahit Sacarlal, Mateu Espasa, Pedro Aide, Inacio Mandomando, Caterina Guinovart, Eusebio Macete, Margarita M. Navia, Ricardo Thompson, Clara Menéndez, and Pedro L. Alonso
Tropical Medicine and International Health, 2006, Volume 11, Number 11, Page 1741

Comments (0)

Please log in or register to comment.