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Multicenter Study
. 2014 Jul;30(5):424-34.
doi: 10.1002/dmrr.2510.

Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study

Hye-Seung Lee, Brant R Burkhardt, Wendy McLeod, Susan Smith, Chris Eberhard, Kristian Lynch, David Hadley, Marian Rewers, Olli Simell, Jin-Xiong She, Bill Hagopian, Ake Lernmark, Beena Akolkar, Anette G Ziegler, Jeffrey P Krischer; TEDDY study group
Collaborators
Multicenter Study

Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study

Hye-Seung Lee et al. Diabetes Metab Res Rev. 2014 Jul.

Erratum in

Abstract

Aims: The Environmental Determinants of Diabetes in the Young planned biomarker discovery studies on longitudinal samples for persistent confirmed islet cell autoantibodies and type 1 diabetes using dietary biomarkers, metabolomics, microbiome/viral metagenomics and gene expression.

Methods: This article describes the details of planning The Environmental Determinants of Diabetes in the Young biomarker discovery studies using a nested case-control design that was chosen as an alternative to the full cohort analysis. In the frame of a nested case-control design, it guides the choice of matching factors, selection of controls, preparation of external quality control samples and reduction of batch effects along with proper sample allocation.

Results and conclusion: Our design is to reduce potential bias and retain study power while reducing the costs by limiting the numbers of samples requiring laboratory analyses. It also covers two primary end points (the occurrence of diabetes-related autoantibodies and the diagnosis of type 1 diabetes). The resulting list of case-control matched samples for each laboratory was augmented with external quality control samples.

Keywords: TEDDY; batch effects; biomarker discovery; nested case-control design; type 1 diabetes.

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Figures

Figure 1
Figure 1
Average number of control samples collected
Figure 2
Figure 2
Control selection procedure
See this image and copyright information in PMC

References

    1. Barlow WE, Ichikawa L, Rosner D, Izumi S. Analysis of case-cohort designs. Journal of clinical epidemiology. 1999;52(12):1165–72. Epub 1999/12/02. - PubMed
    1. Langholz B, Thomas DC. Nested case-control and case-cohort methods of sampling from a cohort: a critical comparison. American journal of epidemiology. 1990;131(1):169–76. Epub 1990/01/01. - PubMed
    1. Wacholder S, Gail M, Pee D. Selecting an efficient design for assessing exposure-disease relationships in an assembled cohort. Biometrics. 1991;47(1):63–76. Epub 1991/03/01. - PubMed
    1. Rundle A, Ahsan H, Vineis P. Better cancer biomarker discovery through better study design. Eur J Clin Invest. 2012;42(12):1350–9. - PMC - PubMed
    1. Baker SG. Improving the biomarker pipeline to develop and evaluate cancer screening tests. Journal of the National Cancer Institute. 2009;101(16):1116–9. Epub 2009/07/04. - PMC - PubMed

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