Analytical performance, reference values and decision limits. A need to differentiate between reference intervals and decision limits and to define analytical quality specifications.

With the increasing use of decision limits (action limits, cut-off points) specified for a number of analytical components in diagnosis and for action in critical situations, formulated in national or international recommendations, the traditional interpretation of reference intervals has been uncertain, and sometimes the two concepts are being mixed up by incorporating risk calculations in the reference intervals. There is, therefore, a need to clarify the two concepts and to keep them definitely separated. Reference intervals are the 95% limits for the descriptions of the distributions of the values of analytical components measured on reference samples from reference individuals. Decision limits are based on guidelines from national and international expert groups defining specific concentrations of certain components as limits for decision about diagnosis or well-defined specific actions. Analytical quality specifications for reference intervals have been defined for bias since the 1990s, but in the recommendations specified in the clinical guidelines analytical quality specifications are only scarcely defined. The demands for negligible biases are, however, even more essential for decision limits, as the choice is no longer left to the clinician, but emerge directly from the concentration. Even a small bias will change the number of diseased individuals, so the demands for negligible biases are obvious. A view over the analytical quality as published gives a variable picture of bias for many components, but with many examples of considerable bias which must be critical--yet no specifications have been stipulated until now.

Stability of heparin blood samples during transport based on defined pre-analytical quality goals.

BACKGROUND: In many countries and especially in Scandinavia, blood samples drawn in primary healthcare are sent to a hospital laboratory for analysis. The samples are exposed to various conditions regarding storage time, storage temperature and transport form. As these factors can have a severe impact on the quality of results, we wanted to study which combination of transport conditions could fulfil our pre-defined goals for maximum allowable error. METHODS: Samples from 406 patients from nine general practitioners (GPs) in two Danish counties were sent to two hospitals for analyses, during two periods (winter and summer). Transport conditions (mail, courier pick-up, or brought to hospital by public coach), storage time, storage temperature and centrifugation requirements were different in the two counties. Results were tested for deviation from a "0-sample", the blood sample taken, centrifuged and separated at the doctor's office within 45-60 min. This sample was considered as the best estimate of a comparison value. RESULTS: The pre-set quality goals were fulfilled for all the investigated components for samples transported to hospital by courier either as whole blood or as "on gel" after centrifugation, as long as the samples were stored at 20-25 degrees C and centrifuged/analysed within 5-6 h. A total of 4% of the samples sent by mail had mismatched identity, probably due to plasma being transferred to a new tube. CONCLUSIONS: Samples can be sent as unprocessed anticoagulated whole blood if the above mentioned conditions are met. There is no need for centrifugation in the primary sector. Neither mailing of samples with plasma "on gel" nor public transport by coach bus fulfil our analytical goals.

Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb).

BACKGROUND: The National Academy of Clinical Biochemistry (NACB) stresses that the reference intervals for thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) should be based on young men who lack certain risk factors and have serum TSH between 0.5 and 2.0 mIU/L. However, some young men without any of the risk factors have autoantibodies, and cannot be identified by the present tools. A model for reference intervals and cut-off values should not be influenced by the prevalence of risk factors. METHODS: We developed a model of "composite logarithmic Gaussian distributions" and tested it in 1441 well-characterised subjects without clinically overt thyroid disease. RESULTS: TPOAb and TgAb could be measured in all individuals. The 97.5% upper limits 1) on a traditional non-parametric scale, 2) according to the NACB criteria, and 3) for our model were 284, 24 and 9.8 kIU/L for TPOAb, and 84, 22 and 19 kIU/L for TgAb, respectively. The decision value (defined as the concentration corresponding to 0.1% false positives) was 15 kIU/L for TPOAb and 31 kIU/L for TgAb. Concentrations above our reference intervals affected the corresponding distribution of TSH values. For TRAb the upper reference limits were 1) 0.75 and 2) 0.75 IU/L, while our model was not applicable to TRAb because only 2-3% of the results were above the functional assay sensitivity. CONCLUSIONS: In contrast to the NACB guidelines, our model for TPOAb and TgAb is more robust, as it is independent of the characteristics of the reference population.