Objective To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM)

Background In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (FbhCG), total human chorionic gonadotrophin (ThCG), a-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies.

There is significant temporal variation in mean log10MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.

The distribution of blood spot TSH data from neonates in Wales has revealed no evidence to support the hypothesis that the population is iodine deficient. However, given that mild iodine deficiency has been reported in a cohort that will be childbearing in the next decade, we recommend that the distribution of neonatal blood spot TSH concentrations is monitored by the UK newborn screening programmes to identify any emerging trends in iodine status. Further studies to correlate maternal urinary iodine and newborn blood spot TSH are required to clarify the TSH cut-off points associated with mild iodine deficiency relevant to the time of blood spot sampling in the UK.

A modified cumulative sum technique has been applied to radioimmunoassay quality control data. The method is approximately 50% more efficient in detecting systematic changes in the mean and variance of quality control values for plasma samples than more widely used conventional methods. The salient features of the technique have been restricted to changes in the mean quality control value of a plasma pool, but potential applications to changes in variance and as a diagnostic aid to problems in radioimmunoassay have been evaluated. The method is independent of computing facilities and statistical expertise since all computations have been presented in the form of a nomogram and thus can be used by technicians at the bench.

Background: Reference intervals, and more generally centile estimates, are used to characterize a reference population for the purposes of interpreting an individual patient's clinical measurement. We describe methods of calculating reference intervals where these centiles vary with a covariate, usually age or time. Methods: The US Food and Drug Administration and the IFCC have made recommendations on two approaches: the parametric approach, which models the structural characteristics of the data set with a theoretical distribution, and the nonparametric approach, which makes no particular assumption about this structure. In this report we propose a nonparametric procedure that relies on the principles of regression and show how sample size determination can be assessed. We also show how the sample size calculation is influenced by the distribution of the times measured. Results: We illustrated our method on three data sets and compared the results for our proposed nonparametric method with parametric estimates. We showed that the bias is reduced and that the nonparametric method is less likely to produce fluctuating profiles. Conclusions: To achieve adequate precision the sample size needs to be larger than 120, as has often been recommended. If there is doubt about the parametric model, then threshold sample sizes may need to be as high as 500.

This survey introduces the subject of internal quality assessment from a historical point of view, presents a unified approach to notation, concepts and definitions, and describes briefly those quality control procedures that are used most commonly in clinical chemistry. It is not the aim of this report to comment on all the individual contributions made in this field, but rather to concentrate on the principles. Particular emphasis is centered around assessment criteria to compare the efficiencies of selected control procedures for monitoring analyte concentrations in biological fluids. The question of whether to compare control schemes by means of average run lengths, run length distribution functions or average cost functions is considered. A rationalized approach based on the comparison of optimal procedures, using average run length, is adopted.

A cumulative sum technique has been specially designed to monitor the error between replicate determinations made on quality control plasma for consecutive batches of assays. This procedure has played a vital role in assessing assay performance. Special consideration has been given to small sample sizes (n = 2 or 3) which is generally the rule rather than the exception in many situations. This technique has been applied to numerous steroid radioimmunoassays and has ensured that both the mean value and the standard error of hormone levels of a quality control pool were under control. Data from routine assays of oestriol and testosterone in plasma from women are presented. Since this technique provides a sensitive measure of monitoring error, it assists the endocrinologist in elucidating statistical inferences which are a manifestation of assay performance.