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Critical Review of Published Microarray Studies for Cancer Clinical 癌症临床发表的微阵列研究述评.ppt
Guidelines on Statistical Analysis and Reporting of DNA Microarray Studies of Clinical Outcome Richard Simon, D.Sc. Chief, Biometric Research Branch National Cancer Institute Bethesda Maryland USA BRB Website/brb Powerpoint presentations and audio files Reprints Technical Reports BRB-ArrayTools software BRB-ArrayTools Data Archive Sample Size Planning for Targeted Clinical Trials Publications Reviewed Searched Medline Hand screening of abstracts papers Original study on human cancer patients Published in English before December 31, 2004 Analyzed gene expression of more than 1000 probes Related gene expression to clinical outcome Types of Clinical Outcome Survival or disease-free survival Response to therapy 90 publications identified that met criteria Abstracted information for all 90 Performed detailed review of statistical analysis for the 42 papers published in 2004 Good Microarray Studies Have Clear Objectives Class Comparison (Gene Finding) Find genes whose expression differs among predetermined classes, e.g. tissue or experimental condition Class Prediction Prediction of predetermined class (e.g. treatment outcome) using information from gene expression profile Survival risk-group prediction Class Discovery Discover clusters of specimens having similar expression profiles Class Comparison and Class Prediction Not clustering problems Supervised methods Major Flaws Found in 40 Studies Published in 2004 Inadequate control of multiple comparisons in gene finding 9/23 studies had unclear or inadequate methods to deal with false positives 10,000 genes x .05 significance level = 500 false positives Misleading report of prediction accuracy 12/28 reports based on incomplete cross-validation Misleading use of cluster analysis 13/28 studies invalidly claimed that expression clusters based on differentially expressed genes could help distinguish clinical outcomes 50% of studies contained one or more major flaws Do’s Don’tsGeneral Do define and state the objecti
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