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A note on statistical repeatability and study design for high‐throughput assays

Characterizing the technical precision of measurements is a necessary stage in the planning of experiments and in the formal sample size calculation for optimal design. Instruments that measure multiple analytes simultaneously, such as in high‐throughput assays arising in biomedical research, pose p...

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Detalles Bibliográficos
Autores principales: Nicholson, George, Holmes, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299465/
https://www.ncbi.nlm.nih.gov/pubmed/27882571
http://dx.doi.org/10.1002/sim.7175
Descripción
Sumario:Characterizing the technical precision of measurements is a necessary stage in the planning of experiments and in the formal sample size calculation for optimal design. Instruments that measure multiple analytes simultaneously, such as in high‐throughput assays arising in biomedical research, pose particular challenges from a statistical perspective. The current most popular method for assessing precision of high‐throughput assays is by scatterplotting data from technical replicates. Here, we question the statistical rationale of this approach from both an empirical and theoretical perspective, illustrating our discussion using four example data sets from different genomic platforms. We demonstrate that such scatterplots convey little statistical information of relevance and are potentially highly misleading. We present an alternative framework for assessing the precision of high‐throughput assays and planning biomedical experiments. Our methods are based on repeatability—a long‐established statistical quantity also known as the intraclass correlation coefficient. We provide guidance and software for estimation and visualization of repeatability of high‐throughput assays, and for its incorporation into study design. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.