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Title: Understanding the impact of pre-analytic variation in haematological and clinical chemistry analytes on the power of association studies
Authors: Gaye, A.
Peakman, T.
Tobin, Martin D.
Burton, P. R.
First Published: 1-Aug-2014
Publisher: Oxford University Press (OUP)
Citation: International Journal of Epidemiology, 2014, 43 (5), pp. 1633-1644
Abstract: BACKGROUND: Errors, introduced through poor assessment of physical measurement or because of inconsistent or inappropriate standard operating procedures for collecting, processing, storing or analysing haematological and biochemistry analytes, have a negative impact on the power of association studies using the collected data. A dataset from UK Biobank was used to evaluate the impact of pre-analytical variability on the power of association studies. METHODS: First, we estimated the proportion of the variance in analyte concentration that may be attributed to delay in processing using variance component analysis. Then, we captured the proportion of heterogeneity between subjects that is due to variability in the rate of degradation of analytes, by fitting a mixed model. Finally, we evaluated the impact of delay in processing on the power of a nested case-control study using a power calculator that we developed and which takes into account uncertainty in outcome and explanatory variables measurements. RESULTS: The results showed that (i) the majority of the analytes investigated in our analysis, were stable over a period of 36 h and (ii) some analytes were unstable and the resulting pre-analytical variation substantially decreased the power of the study, under the settings we investigated. CONCLUSIONS: It is important to specify a limited delay in processing for analytes that are very sensitive to delayed assay. If the rate of degradation of an analyte varies between individuals, any delay introduces a bias which increases with increasing delay. If pre-analytical variation occurring due to delays in sample processing is ignored, it affects adversely the power of the studies that use the data.
DOI Link: 10.1093/ije/dyu127
ISSN: 0300-5771
eISSN: 1464-3685
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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