Progress and problems in immunoassays for serum pituitary gonadotrophins: evidence from the UK external quality assessment schemes, (EQAS) 1980-1988.

Trends in the quality of assays for serum gonadotrophins performed by laboratories in the UK EQAS during the 1980s are reviewed, with particular reference to the effects of the recent introduction of immunometric assays (IMA) as an alternative to radioimmunoassay (RIA). IMA gave results which were on average 17% higher than RIA for FSH, and 33% lower for LH. These bias characteristics were not entirely accounted for by differences in assay standardisation, but appeared to reflect the different isoforms of the hormones detected by the monoclonal antibodies used in the IMA. Between-laboratory agreement remained, consequently, unsatisfactory overall (geometric coefficient of variation, GCV, 20-30%), although good within method groups (GCV 10%). IMA were less vulnerable to non-specific background interference than many RIA, and could avoid interference from HCG. Some IMA were, however, vulnerable to interference from heterophilic antibodies in patients' sera. The differences between RIA and the various IMA in numerical values reported, and in their vulnerability to interferences underline the need for care in interpreting assay results.

Quality of performance of assays for serum growth hormone in the United Kingdom (UK): evidence from the UK external quality assessment scheme, 1980-1987.

The performance of laboratories in the UK External Quality Assessment Scheme for growth hormone (GH) during the years 1980 to 1987 is reviewed. The number of participating laboratories has increased steadily and is at present 67; about one half use immunoradiometric assay (IRMA) kits and the use of such kits is increasing at the expense of 'in-house' radioimmunoassays (RIAs). The consensus mean, which is used as the target value for assessing performance, has remained accurate and reproducible against this changing background. The between-laboratory geometric coefficient of variation has remained at about 18% during the period reviewed, revealing unsatisfactory between-laboratory agreement. This is in part due to poor within-laboratory performance in a small proportion of laboratories but it is also due to the negative bias of some IRMA kits. Most IRMA kits do appear, however, to provide marginally better within-laboratory precision than RIA, and are less vulnerable to non-specific interference. The laboratory interpretation of results was assessed from time to time, and was generally satisfactorily performed. In an attempt to identify the causes of poor performance, a detailed survey of assay methods and laboratory practice has been carried out; the results are described in an associated report [1].

Quality of performance of assays for maternal serum alphafetoprotein in the United Kingdom: evidence from the UK external quality assessment scheme 1980-87.

Between-laboratory agreement in the UK EQAS for maternal serum alphafetoprotein has improved steadily since 1976 and the geometric coefficient of variation is now 8 to 9% at levels of 50 to 150 kU/L. The use of a common standard and commercial assay kits appear to have contributed to this trend. Within-laboratory performance is also generally good, about 50% of participants maintain a bias of less than 5%, together with a scatter of the bias of less than 10%. These data indicate that the quality of assay performance is adequate for the requirements of screening programmes for open neural tube effects. The improvement in laboratory performance is such that between-laboratory agreement is better expressed in kU/L than as multiples of the median. Errors in interpretation of clearly normal or abnormal results appear to be rare (0.4%), and contribute little to overall false positive and negative rates. However, they assume significance as most are due to avoidable errors.

Progress in immunoassays for serum prolactin: evidence from the UK External Quality Assessment Scheme (EQAS) 1980-1989.

The quality of serum prolactin assays routinely performed by UK laboratories has been monitored in an external quality assessment scheme (EQAS) over a 10-year period, during which participation in the EQAS increased three-fold, and considerable changes in methods and standardization were introduced. The all-laboratory mean was used as the sample target value, and proved to be stable and accurate. Overall between-laboratory agreement in the clinically important range improved from a geometric coefficient of variation (GCV) of 25% to 14%. This appears to reflect the increased use of kits in place of 'in-house' assays, the more widespread availability of international standards and the absence of any marked differences in bias between the commonly used methods. Published guidelines on the clinical interpretation of prolactin values should, therefore, be widely applicable. The EQAS data indicate that, in general, the quality of performance of prolactin assays is adequate for their clinical application.

Assays for prolactin: guidelines for the provision of a clinical biochemistry service.

This paper summarises the views of the authors on the provision of a prolactin assay service. We discuss the pathophysiology of prolactin secretion and the clinical indications that arise from that. We cover the rather complex issue of the definition of normal and elevated prolactin levels. From these considerations, certain guidelines on the analytical performance of prolactin assays and their provision in a clinical biochemistry service are given. The extent to which currently available methods and performance as revealed by the UK External Quality Assessment Scheme (EQAS) match these guidelines are described and certain conclusions are reached. Finally, probable future developments are briefly discussed. The main conclusions and recommendations are as follows: Reagents of appropriate quality are available to enable prolactin immunoassays to be provided in UK clinical biochemistry laboratories. These are provided either separately or in the form of kits from both commercial and NHS sources. There is no requirement for individual laboratories to undertake their own antiserum production or prolactin iodination. Acceptable performance (as defined using internal QC procedures and the UK EQAS) is achievable using these reagents/kits, although one commercial kit shows a consistent marked negative bias. Reference ranges, including 'normal ranges', show considerable between-centre variability. Many centres have not established their own ranges, even those using in-house methods. Reference ranges for use in clinical biochemistry laboratories are proposed in this report. Some general guidance on the provision of a prolactin service is given, although this does not differ in principle from that appropriate for other peptide hormone analytes. There is no evidence that centres with small workloads perform any worse than average, although it may be more cost-efficient for such centres to send the samples elsewhere. As with other peptide analytes, non-isotopic immunometric methodology is likely to replace current radioimmunoassay methods in the near future.

Improved performance of plasma gonadotrophin assays using common reagents and assay protocols: evidence from the UK External Quality Assessment Scheme.

Radioimmunoassay kits prepared in the Chelsea Hospital for Women for follicle stimulating hormone (FSH) and luteinising hormone (LH) have been used in 26 UK laboratories for over 2 years. Data from the UK External Quality Assessment Schemes for FSH and LH have been used to provide an independent assessment of the performance of these kits over a 12-month period. For both analytes, users of the kits were found to have: a low variability of the bias, implying good within-laboratory, between-assay precision; a lower between-laboratory, within-sample geometric coefficient of variation than users of 'own' methods, implying better between-laboratory agreement; method bias that did not differ significantly from laboratories using 'own' method protocols. This survey indicates that a non-commercial organisation can produce immunoassay kits that improve the quality of FSH and LH assays generally available.