Study Designs and Statistical Analyses for Biomarker Research 英文参考文献.docVIP

Sensors 2012, 12, 8966-8986; doi:10.3390/s120708966 OPEN ACCESS sensors ISSN 1424-8220 /journal/sensors Review Study Designs and Statistical Analyses for Biomarker Research Masahiko Gosho 1,*, Kengo Nagashima 1,2 and Yasunori Sato 3 1 Graduate School of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan 2 Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, Saitama 350-0295, Japan; E-Mail: nagasima@josai.ac.jp 3 Clinical Research Center, Chiba University of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan; E-Mail: yasu@faculty.chiba-u.jp * Author to whom correspondence should be addressed; E-Mail: robin_gosho@yahoo.co.jp; Tel.: +81-3-5228-8712. Received: 15 May 2012; in revised form: 21 June 2012 / Accepted: 21 June 2012 / Published: 29 June 2012 Abstract: Biomarkers are becoming increasingly important for streamlining drug discovery and development. In addition, biomarkers are widely expected to be used as a tool for disease diagnosis, personalized medication, and surrogate endpoints in clinical research. In this paper, we highlight several important aspects related to study design and statistical analysis for clinical research incorporating biomarkers. We describe the typical and current study designs for exploring, detecting, and utilizing biomarkers. Furthermore, we introduce statistical issues such as confounding and multiplicity for statistical tests in biomarker research. Keywords: biomarker adaptive design; confounding; multiplicity; predictive factor; statistical test 1. Introduction In recent years, biomarkers have played an increasingly important role in drug discovery, understanding the mechanism of action of a drug, investigating efficacy and toxicity signals at an early stage of pharmaceutical development, and in identifying patients likely to respond to treatment. In addition, severa