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J Proteome Res DOI:10.1021/pr400132j

Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

Publication TypeJournal Article
Year of Publication2013
AuthorsSkates, SJ, Gillette, MA, LaBaer, J, Carr, SA, Anderson, L, Liebler, DC, Ransohoff, D, Rifai, N, Kondratovich, M, Tezak, Z, Mansfield, E, Oberg, AL, Wright, I, Barnes, G, Gail, M, Mesri, M, Kinsinger, CR, Rodriguez, H, Boja, ES
JournalJ Proteome Res
Date Published2013 Dec 06
KeywordsAlgorithms, Biomarkers, Tumor, Blood Proteins, Cohort Studies, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Proteins, Neoplasms, Proteomics, Research Design, Sample Size, Sensitivity and Specificity, Specimen Handling

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.


Alternate JournalJ. Proteome Res.
PubMed ID24063748
PubMed Central IDPMC4039197
Grant ListU24 CA160034 / CA / NCI NIH HHS / United States
U01CA152990 / CA / NCI NIH HHS / United States
U24 CA159988 / CA / NCI NIH HHS / United States
U01 CA152990 / CA / NCI NIH HHS / United States
Z99 CA999999 / / Intramural NIH HHS / United States
P30 CA015083 / CA / NCI NIH HHS / United States
U24CA160034 / CA / NCI NIH HHS / United States
P50CA136393 / CA / NCI NIH HHS / United States
P50 CA136393 / CA / NCI NIH HHS / United States