01 Introduction
1.1 (collection) (organization) (analysis) (interpretation) (presentation) 1.1 1.2 (Biostatistics) Biometry Biometrics (Public Health) (Medicine) (Biology) 1.2 2
01 1.3 20 (Biometricians)Walter Weldon(1860-1906) Karl Pearson(1857-1936) (Mendelians)Charles Davenport(1866-1944) William Bateson(1861-1926) Wilhelm Johannsen(1857-1927) 1930 (Neo-Darwinian modern evolutionary synthesis) 1. Sir Ronald A. Fisher(1890-1962) (The Genetical Theory of Natural Selection) 2. Sewall G. Wright(1889-1988) (Population genetics) 3. J. B. S Haldane(1892-1964) The Causes of Evolution (natural selection) (Mendelian genetics) D'Arcy Thompson(1860-1948) On Growth and Form (biostatistician) (statistician) (Epidemiology) 3
1.3 1.4 1. (Public health) (Epidemiology) 2. 3. (Ecology) 4. (Genomics) (Proteomics) 5. (Systems biology) 1.4 4
01 6. (Population genetics) (statistical genetics) (genotype) (phenotype) 7. 1.5 " any form of planned experiment which involves patients and is designed to elucidate the most appropriate treatment of future patients with a given medical condition." Pocock, from Clinical Trials: A Practical Approach (1984). 1747 "Salisbury" James F. Lind 12 6 2 6 1.5 C (scurvy) James F. Lind 1.5 Salisbury James F. Lind www. jameslindlibrary.org 5
1.6 1920 R.A. Fisher 1947 1948 (randomized controlled clinical trial, RCT) (streptomycin) (tuberculosis) Sir Austin Bradford Hill 1.6 R.A. Fisher (British Medical Research British Medical Journal Council) 1948 www. jameslindlibrary.org British Medical Journal 1.6 1.7 1. 2. 3. 1. (pre-clinical trial) (in vitro) (in vivo) 2. (Investigational New Drug Application, IND) 3. (Phase I) 15~20 (pharmacokinetics, PK) (safety) (Maximum Tolerated Dose, MTD) 6
01 4. (Phase II) 50~200 (multiple doses) (Exploratory Phase) 5. (Phase III) (FDA) 2 p<0.05 p<0.01 p<0.001 (Confirmatory Phase) 6. (NDA)New Drug Application(NDA)/Product License Application (PLA) 7. Phase IV-Post Marketing 1.7 7
1.8 1. Blinding (Doubleblind experiment) (placebo) (Single-blind experiment) (Open-label experiment) 2. Clinical Trial (randomized controlled clinical trial, RCT) 3. Cohort Study (exposure) (observational study) 4. Case-Control Study (risk factors) (rare diseases) 5. Cross-Sectional Study Horizontal survey 6. Case Report or Case Series (descriptive study) 7. Randomized Controlled Study 8. Systematic Error (true value) 9. Sampling Bias 10. Longitudinal study Cohort Study Case-Control Study 8
01 11. Variable (characteristics) (data) 1.9 (Retrospective study) (Prospective study) Case-Control Study Randomized Control Study 1.8 1.9 1.1 (selection bias) (observer bias) 9
1. (Biostatistics) 2. 3. 20 20 4. 5. 6. 7. 8. 9. 10. 11. 12. (Double-blind experiment) (Single-blind experiment) (Open-label) 10
01 13. (Phase III) 14. (Investigational New Drug Application, IND) (New Drug Application, NDA) 15. 16. 17. 18. 19. 11
1. James E. De Muth. Am J Health-Syst Pharm-Vol 66 Jan 1, 2009, 70-81. 2. (http://www1.cde.org.tw/ct_taiwan/notes.html) 3. (Center for Drug Evaluation) (http://www2.cde.org.tw/pages/default.aspx) 4. Grimes DA, Schultz KF: An overview of clinical research: the lay of the land. Lancet 359:57-61, 2002. 5. Gordis L: Epidemiology, 3rd Edition, Philadelphia, Elsevier Saunders, 2004. 6. Rosner B: Fundamentals of Biostatistics, 4th Edition, Daxbury Press, 1995. 7. Grimes DA, Schultz KF: Bias and causal associations in observational research. Lancet 359:248-252, 2002. 8. Grimes DA, Schultz KF: Cohort studies: marching towards outcomes. Lancet 359: 341-345, 2002. 9. Schultz KF, Grimes DA: Case-control studies: research in reverse. Lancet 359:431-434, 2002. 10. Streiner DL, Norman GR: Health Measurement Scales: A Practical Guide to their Development and Use, 2nd Edition, New York, Oxford University Press, 2000. 11. Jaeschke R, Guyatt GH, Sackett DL: Users guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. Jama 271:703-707, 1994. 12. Guyatt G, Jaeshke R, Heddle N, et al. Basic statistics for clinicians: 2. Interpreting study results: confidence intervals. CMAJ 152:169-173, 1995. 13. Katz MH: Multivariable analysis: a primer for readers of medical research. Ann Intern Med 138:644-650, 2003. 12
01 14. Campbell MJ: Statistics at Square Two, 4th Edition, London, BMJ Publishing Group, 2004. 15. Joseph Massaro. Clinical Trials: Understanding Biostatistics. Powerpoints presented on March 21, 2008. 16. Schumacher M, Schulgen G, 2007: Methodik klinischer Studien. 2. Aufl. Springer. 17. Friedman LM, Furberg CD, demets DL, 1998: Fundamentals of Clinical Trials. Third edition. Springer. 18. Senn S, 2007: Statistical Issues in Drug Development. Second edition. Wiley. 13
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02 Population and Sample Microsoft Excel
2.1 (population) object (parameter) (sample) (statistic) 2.1 2.2 2.2 2.1 (parameter) (statistic) μ σ s σ 2 s 2 N n ρ r 16
02 2.3 (Sampling methods) 2.3 1. (simple random sampling) 2.4 17
2. (systematic sampling) 2.5 3. (stratified sampling) 2.6 18
02 4. (cluster sampling) 2.7 5. (convenience sampling) 6. (probability-proportional-to-size sampling) 7. (quota sampling) 8. (panel sampling) (1) (nonsampling error) (survey) (2) (sampling error) 19
2.4 Microsoft Excel Microsoft Excel 2013 1. Microsoft Excel Microsoft Office Microsoft Office 2013 Excel 2013 Excel 2.8 Excel 2013 2. 2.9 20