Understanding the impact of pre-analytic variation in haematological and clinical chemistry analytes on the power of association studies

Amadou Gaye, Tim Peakman, Martin D. Tobin, Paul R. Burton*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

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.

Original languageEnglish
Article numberdyu127
Pages (from-to)1633-1644
Number of pages12
JournalInternational Journal of Epidemiology
Volume43
Issue number5
DOIs
Publication statusPublished - 20 Aug 2014

Keywords

  • Biobank
  • Biosamples
  • Pre-analytical variation
  • Statistical power

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