1. 1 What Do Biostatisticians Do in Biomedical Research? 張啟仁教授 C. J. Chang, Ph.D. 台大醫學院臨床醫學研究所 台大醫院醫學研究部 11/13/2000 生物統計學家在生物醫學研究中之角色

2. 2 What is Statistics? A set of numbers or quantitative facts summarized in the form of charts, tables, and graphs A field of study concerned with the methods of obtaining, summarizing, and drawing inferences from data derived from groups of individuals Robert Woolson (1987)

3. 3 Biomedical Research  Basic Science Research 基礎醫學研究 Lab Studies, Animal Studies, Bench Work  Clinical Medicine Research 臨床醫學研究 Disease Studies, Experimental Studies, Interventional Studies, Clinical Epidemiology  Clinical Trials Studies 臨床試驗研究 Drug Studies, Pre-Clinical, Phase I, II, III, IV  Other Related Studies Public Health, Health Psychology, Behavior Science, Health Economics, Health Insurance, Bioethics, etc.

4. 4 What is BioStatistics?  Science Statistics Applied to Biomedical Data  Method  Technique  Strategy

5. 5 What is BioStatistics? Mathematics Medicine Statistics Biostatistics Collaborative Science Basic Clinical others

6. 6 Physiology of Research Truth in the Universe Truth in the Study Findings in the Study inference Internal Validity External Validity Investigator’s View: Hulley & Cummings: Designing Clinical Research

7. 7 Physiology of Research Biostatistician’s + Investigator’s View: Internal Validity External Validity Research Question Study Plan Actual Study designimplement

8. 8 Physiology of Research Truth in the Universe Truth in the Study Findings in the Study inference How Does it Work? Internal Validity External Validity Research Question Study Plan Actual Study designimplement Hulley & Cummings: Designing Clinical Research

9. 9 Collaborating Team Work Principal Investigator Biostatistician Lab Scientist Project Director Research Nurse Data Programmer etc.

10. 10 Question from Biostatistician? Feasible? Reasonable? Acceptable? Doable? Is the Study ??!!

11. 11 Before Designing the Study:  Pilot Study  Primary Hypothesis  Analysis Plan  Choice of Variables  Experimental Design What Do Biostatisticians Do?

12. 12 Sample Size Calculation  Sample Size Calculation Power Analysis  Power Analysis Before Designing the Study: N=2987 ?! What Do Biostatisticians Do?

13. 13 During the Study:  TEAM work  Questionnaire Design  Data Base Management  Quality Assurance/Quality Control  Monthly, Semi Annual, Annual Reports  Interim Data Analysis  etc... What Do Biostatisticians Do?

14. 14 At the End of the Study:  Always start with descriptive statistics  Scatter plot  Use of appropriate variable  Use simple, efficient, and practical methods  Time independent vs. time dependent covariates  Not necessary advanced methods  Use most popular, acceptable statistical packages  Use universal recognizable data format Tips in Statistical analysis What Do Biostatisticians Do?

15. 15 Making Conclusions and Interpretation  How to control type-I, II errors  One answer for one hypothesis  Statistical vs. clinical significance  Over powered vs. under powered  Multiple comparisons  Over stretch statistical method What Do Biostatisticians Do?

16. 16 Example: KSBPS KSBPS Kidney Stone - Blood Pressure Study A study of the effects of Extracoporeal Shock Wave Lithotripsy (ESWL) on Hypertension Funded by National Electronic Manufacture Association (NEMA) and approved by FDA in 1990 PI : Michael Alderman, M.D. Co-PI : Chee Jen Chang, Ph.D. Co-PI : Jonathan Tobin, Ph.D. Albert Einstein College of Medicine 腎結石病人使用電動碎石機後 與高血壓相關性之研究

17. 17 KSBPS KSBPS Kidney Stone - Blood Pressure Study Experimental study : ESWL vs. open surgery Non randomized and non musked design study Post marketing surveillance study Phase IV study Prospective two year follow up study for 4 years Multi centers study Original Protocol:

18. 18 KSBPS KSBPS Kidney Stone - Blood Pressure Study Sample size : 900 control, 900 ESWL patients Primary variables : SBP/DBP at baseline, 6, 12, and 24 months Secondary variables: Renal functions at 0, 6, 12, and 24 months Covariates: Demographic variables, stone burden Study Design:

19. 19 KSBPS KSBPS Kidney Stone - Blood Pressure Study Hypothesis : DBP difference between control and ESWL groups is not greater 2.5 mmHg at 24 month

20. 20 KSBPS KSBPS Kidney Stone - Blood Pressure Study Difficulties: Patients selection bias Patient’s follow-up visit interest is LOW Renal function collection is costly and unchanged Different device type Different technology in device type New technology developed during the study

21. 21 KSBPS KSBPS Kidney Stone - Blood Pressure Study Statistical solutions to some difficulties: Patient’s follow-up visit interest is LOW: reduce sample size, increase effect size Patients selection bias : statistical analysis controlling covariates

22. 22 Renal function collection is costly and unchanged: bioequivalence test to revise protocol Different device type and technology in device type: stratified data analysis KSBPS KSBPS Kidney Stone - Blood Pressure Study Statistical solutions to some difficulties:

23. 23 KSBPS KSBPS Kidney Stone - Blood Pressure Study Can Statistics solve all the difficulties? New technology developed during the study Participants’ willingness No !

24. 24 KSBPS KSBPS Kidney Stone - Blood Pressure Study In September, 1997, FDA issues: “Although an increase in blood pressure may result after Lithotripsy for the treatment of kidney stones, a 2 years prospective study suggests that treatment with Lithotripsy will not result in a difference in diastolic blood pressure of  4 mmHg as compared to other kidney stone therapies.”

25. 25  Methodology development  Consultant  Health- and bio- informatics  Research protocols review Committee of Clinical Investigation (CCI) Internal Review Board (IRB)  Regulatory review What Do Biostatistician Do? then, now and future

26. 26  Teaching (university, medical school)  Research (institute, foundation)  Government Agency (NIH, CDC)  Regulatory Agency (FDA)  Industry (Pharmaceutical, Biotech.)  Consulting (CRO) What Do Biostatistician Do? then, now and future

27. 27 Thank You! Email:cjchang@ha.mc.ntu.edu.tw Phone: 02-2312-3456 ext 6588 Fax:02-2371-0262