Clin Chem Lab Med 2012;50(5):833–839 © 2012 by Walter de Gruyter • Berlin • Boston. DOI 10.1515/cclm-2011-0862 Opinion Paper A pragmatic proposal for permissible limits in external quality assessment schemes with a compromise between biological variation and the state of the art Rainer Haeckel 1, *, Werner Wosniok 2 , Josef Kratochvila 3 and Anna Carobene 4 1 Bremer Zentrum für Laboratoriumsmedizin, Bremen, Germany 2 Institut für Statistik, Universität Bremen, Bremen, Germany 3 SEKK Pardubice, Pardubice, Czech Republic 4 Diagnostica e Ricerca San Raffaele, Istituto Scientifico Universitario S.Raffaele, Milan, Italy Abstract Permissible limits for internal and external quality assurance are either based on biological variation or on the state of the art (technical feasibility). The former approach has a scien- tific basis, but, in some cases, leads to limits which are either not achievable under the present technology, or which are not stringent enough. If proficiency testing is mandatory, stringent limits which cannot be fulfilled by the majority of laboratories could lead to juristic consequences. Therefore, most national guidelines were based on the state of the art, however, with- out providing the underlying reasoning. A simple algorithm for permissible limits in external quality assessment schemes (EQAS) is proposed based on biological variation, technical feasibility and correlated to the rate of false positive results. The proposed limits are compared with some limits from sev- eral EQAS (RiliBÄK, SEKK, RCPA, CLIA, PROLARIT). The suggested limits are slightly more stringent than the German RiliBÄK, less stringent than the Australasian guide- lines and agreed best with the Czech SEKK and the Italian PROLARIT scheme. The graphical presentation of permis- sible limits strictly derived of biological variation with the proposed limits led to straight lines with different slopes and a cross-over at the limits for quantities with a medium biologi- cal variation (e.g., trijodthyronine). The greatest discordance between the various recommendations was observed for cal- cium, chloride, hemoglobin A 1c and sodium. Keywords: allowable quality specifications; biological varia- tion; external quality assessment; permissible limits. Introduction A well-accepted hierarchical model for establishing analyti- cal performance goals has been published by a consensus group (1) and has been reviewed several times (2, 3). A bet- ter term for “goals” may be permissible limits. Goals should be as good as possible stimulating laboratories to continu- ously improve their performance according to modern qual- ity management concepts, whereas permissible limits define the worst case which must not be surpassed. According to the hierarchical scheme, it is recommended to base permissible limits on scientific approaches which fulfill medical needs (2, 3). But what does this mean? A physician’ s needs cannot be used because they may change from region to region, and are difficult to obtain, depend on individual experience which dif- fers for specialists and the average (3). Unfortunately medi- cal needs are difficult to define and scientific approaches do not always fit to the state of the art (technical feasibility). The latter are sometimes either too stringent or too wide (4). Mandatory limits cannot be based on scientifically desirable values if they are not achievable with the present technology (state of the art). Otherwise, juristic consequences must be expected in the case of failures. Therefore, the state of the art somehow must be taken in consideration in mandatory qual- ity assurance. Fraser et al. (5) proposed to clarify different situations in which standards are set: for intra-laboratory use (with target specifications to facilitate the optimum delivery of health), for inter-laboratory use (with desirability quality standards) and acceptability quality standards (for EQAS that are set by legislation). However, Plebani and Lippi (6) argued against any dissociation between clinical and regula- tory specifications. Recently, a combined model has been proposed which con- siders a scientific approach (based on the rate of false positive results) and the state of the art for internal quality assurance (7). For external quality assessment schemes (EQAS), such a model has not been developed, yet. Most EQAS seem to adopt pragmatic positions, either z-scores (a posteriori) or consensus values established by a committee (a priori). The ISO 17043 standard proposed that a z-score of > 3 is unsatis- factory (8). Several consensus limits have been established *Corresponding author: Rainer Haeckel, Bremer Zentrum für Laboratoriumsmedizin, Klinikum Bremen Mitte, 28305 Bremen, Germany Phone: +49 412 273448, E-mail: rainer.haeckel@t-online.de Received October 5, 2011; accepted December 15, 2011; previously published online January 25, 2012 Brought to you by | Purdue University Libraries Authenticated Download Date | 5/27/15 1:48 PM