What Do Biostatisticians Do in Biomedical Research?

1. What Do Biostatisticians Do inBiomedical Research? 生物統計學家在生物醫學研究中之角色 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

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

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

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

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

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

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

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

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

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

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

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

14. What Do Biostatisticians Do? At the End of the Study: Tips in Statistical analysis  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

15. What Do Biostatisticians Do? 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

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

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

18. KSBPS Kidney Stone - Blood Pressure Study Study Design: 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

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

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

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

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

24. KSBPS Kidney Stone - Blood Pressure Study In September, 1997, FDA issues: “Although an increase in blood pressuremay result after Lithotripsy for the treatmentof kidney stones, a 2 years prospective studysuggests that treatment with Lithotripsy willnot result in a difference in diastolic bloodpressure of  4 mmHg as compared to otherkidney stone therapies.”

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

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

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