Using a thyroid disease-free population to define the reference interval for TSH and free T4 on the Abbott Architect analyser.

OBJECTIVE: Thyroid disease can be subtle in its presentation, and TSH reference intervals may be artefactually increased by including persons with subclinical thyroid disease. We have therefore used a thyroid disease-free population to determine TSH and fT4 reference intervals. DESIGN: Apparently healthy subjects were assessed by health questionnaire, drug history, clinical assessment and measurement of thyroid antibodies. PATIENTS: Healthy subjects in a community setting. MEASUREMENTS: TSH, free T4, antithyroglobulin and anti-TPO were measured on the Abbott Architect analyser. Subjects with clinical abnormalities, consumption of thyroid-active medications or with thyroid antibodies above the manufacturer-quoted reference intervals were excluded. TSH and fT4 data were log-transformed, and the central 95% was used to calculate reference intervals. We assessed whether these data were normally distributed. We compared samples spanning the reference intervals for both TSH and fT4 between different assays looking at biases. RESULTS: From a population of 1,606 subjects, 140 males (18%) and 284 females (34%) were excluded. The central population 95% for TSH was 0·43-3·28 mU/l and for fT4 10·8-16·8 pmol/l. There were no age- or sex-related differences. For both analytes, the distribution was not significantly different to a Gaussian distribution (P > 0·05). For 5 commonly used assays for TSH, the maximum difference in the upper limit of the TSH reference interval was 0·48 mU/l and for fT4 the maximum difference for the upper reference limit was 4·1 pmol/l. CONCLUSIONS: A substantial proportion of apparently healthy persons have subclinical thyroid disease. These subjects must be excluded for any thyroid hormone reference interval studies.

Implementation of the HbA1c IFCC unit --from the laboratory to the consumer: The New Zealand experience.

In 2007, an international consensus statement recommended that HbA1c results should be reported world-wide in IFCC units (mmol/mol) and also the more familiar derived percentage units using a master equation. In New Zealand, the HbA1c IFCC units have been successfully implemented and used exclusively since 3rd October 2011 (following a 2 year period of reporting both units) for both patient monitoring and the diagnosis of diabetes, with a diagnostic cut-off of ≥50 mmol/mol. The consultation process in New Zealand dates back to 2003, well before the international recommendations were made. It reflects the close cooperation between the clinical and laboratory communities in New Zealand, particularly through the agency of the New Zealand Society for the Study of Diabetes (NZSSD), a key organisation in New Zealand open to all those involved in the care of people with diabetes and the national advisory body on scientific and clinical diabetes care and standards. There was a phased process of consultation designed to increase familiarity and comfort with the new units and the final step was coupled with the adoption of HbA1c as a diagnostic test with some evidence-based pragmatism around using the rounded cut-off. Genuine clinical engagement is vital in such a process.

Bias Assessment of General Chemistry Analytes using Commutable Samples.

Harmonisation of reference intervals for routine general chemistry analytes has been a goal for many years. Analytical bias may prevent this harmonisation. To determine if analytical bias is present when comparing methods, the use of commutable samples, or samples that have the same properties as the clinical samples routinely analysed, should be used as reference samples to eliminate the possibility of matrix effect. The use of commutable samples has improved the identification of unacceptable analytical performance in the Netherlands and Spain. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has undertaken a pilot study using commutable samples in an attempt to determine not only country specific reference intervals but to make them comparable between countries. Australia and New Zealand, through the Australasian Association of Clinical Biochemists (AACB), have also undertaken an assessment of analytical bias using commutable samples and determined that of the 27 general chemistry analytes studied, 19 showed sufficiently small between method biases as to not prevent harmonisation of reference intervals. Application of evidence based approaches including the determination of analytical bias using commutable material is necessary when seeking to harmonise reference intervals.

Harmonising adult and paediatric reference intervals in australia and new zealand: an evidence-based approach for establishing a first panel of chemistry analytes.

Scientific evidence supports the use of common reference intervals (RIs) for many general chemistry analytes, in particular those with sound calibration and traceability in place. Already the Nordic countries and United Kingdom have largely achieved harmonised RIs. Following a series of workshops organised by the Australasian Association of Clinical Biochemists (AACB) between 2012 and 2014 at which an evidence-based approach for determination of common intervals was developed, pathology organisations in Australia and New Zealand have reached a scientific consensus on what adult and paediatric intervals we should use across Australasia. The aim of this report is to describe the processes that the AACB and the Royal College of Pathologists of Australasia have taken towards recommending the implementation of a first panel of common RIs for use in Australasia.

Evidence-based approach to harmonised reference intervals.

Although we are in the era of evidence-based medicine, there is still a substantial gap between theory and current practice with the application of reference intervals as decision making tools. Different laboratories may have different reference intervals for the same tests using the same analytical methods and platforms. These differences have the potential to confuse physicians making the assessment and monitoring of patients more difficult by providing discordant information. This paper attempts to demonstrate how to use evidence-based approach for harmonising reference intervals. In order to consider harmonisation we must first have an appreciation of the various factors that influence the determination of that reference interval such as the choice of individuals within the population studied, biological variability of the analyte studied, partitioning, sample collection, analytical aspects such as bias and statistical models. An a priori approach for determining reference intervals, whilst recommended, may be beyond the scope of most laboratories and consideration should be given to the use of a validated indirect a posteriori approach. Regardless of method used, the continuing application of an evidence-based approach in harmonised reference intervals to meet the quality expectations of physicians should be pursued.

Cross-reactivities of macroprolactin and big-prolactin in three commercial immunoassays for prolactin: a chromatographic analysis.

OBJECTIVES: To compare the recently released Elecsys Prolactin II with the Access and Centaur assays for reactivity with macroPRL, bigPRL and monomeric PRL in samples fractionated using gel filtration chromatography (GFC). METHODS: Prolactin (PRL) concentration was measured before (total PRL) and after GFC over Superdex 75 (n=16-18) using prolactin assays on the Access2 (Beckman Coulter Inc.) and Centaur (Siemens Medical Solutions Diagnostics) analyzers and the Prolactin II assay (Roche Diagnostics) on the Elecsys 2010 analyzer. The amounts of macroPRL, bigPRL and monomeric PRL were quantified from GFC peak areas. RESULTS: Total PRL concentrations in macroPRL-containing specimens were (means+/-SD, n=13), 842+/-496; 851+/-564 mIU/L (Access and Elecsys II, p>0.05) and 695+/-469 mIU/L (Centaur, p<0.05). Monomeric PRL (GFC peak area) was lower by the Centaur (p<0.05; Deming regression) than by the Access or Elecsys II assays. Method comparisons (Bland and Altman) therefore used PRL peak areas expressed as percent total PRL recovered after GFC. The mean differences for macroPRL and bigPRL, respectively, were (a) Elecsys PRL II-Access assay: -2.83% and -2.54% (both p<0.05); (b) Elecsys PRL II-Centaur: -1.56% (p>0.05) and -6.48% (p<0.05) and (c) Access-Centaur: 1.41% (p>0.05) and -3.95% (p<0.05). CONCLUSION: The new Elecsys Prolactin II assay has similar cross-reaction with macroPRL and bigPRL to the Access and Centaur Prolactin assays. The differences detected were small and unlikely to have clinical impact.