Embed Size (px)
Citation preview
1
What Do Biostatisticians Do inBiomedical 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
What is Statistics?
A set of numbers or quantitative factssummarized in the form of charts, tables,and graphs
A field of study concerned with the methodsof obtaining, summarizing, and drawinginferences from data derived from groupsof individuals
Robert Woolson (1987)
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 StudiesPublic Health, Health Psychology, Behavior Science, Health Economics, Health Insurance, Bioethics, etc.
4
What is BioStatistics?
Science
Statistics Applied to Biomedical Data
Method
Technique
Strategy
5
What is BioStatistics?
MathematicsMedicine
Statistics
BiostatisticsBiostatistics
Collaborative ScienceCollaborative Science
BasicClinical
others
6
Physiology of Research
Truth in theUniverse
Truth in theStudy
Findingsin the Study
inferenceinference
InternalValidity
ExternalValidity
Investigator’s View:
Hulley & Cummings: Designing Clinical Research
7
Physiology of Research
Biostatistician’s + Investigator’s View:
InternalValidity
ExternalValidity
ResearchQuestion
StudyPlan
ActualStudydesign implement
8
Physiology of Research
Truth in theUniverse
Truth in theStudy
Findingsin the Study
inferenceinference
How Does it Work?
InternalValidity
ExternalValidity
ResearchQuestion
StudyPlan
ActualStudydesign implement
Hulley & Cummings: Designing Clinical Research
9
Collaborating Team Work
Principal InvestigatorBiostatisticianLab ScientistProject DirectorResearch NurseData Programmeretc.
10
Question from Biostatistician?
Feasible?
Reasonable?
Acceptable?
Doable?
Is the Study
??!!??!!
11
Before Designing the Study:
Pilot Study Primary Hypothesis Analysis Plan Choice of Variables Experimental Design
What Do Biostatisticians Do?
12
Sample Size CalculationSample Size Calculation Power AnalysisPower Analysis
Before Designing the Study:
N=2987?!
What Do Biostatisticians Do?
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
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
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
Example: KSBPSKKidney SStone - BBlood PPressure SStudy
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
KSBPSKKidney SStone - BBlood PPressure SStudy
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
KSBPSKKidney SStone - BBlood PPressure SStudy
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
KSBPSKKidney SStone - BBlood PPressure SStudy
Hypothesis :
DBP difference between controland ESWL groups is not greater2.5 mmHg at 24 month
20
KSBPSKKidney SStone - BBlood PPressure SStudy
Difficulties: Patients selection biasPatient’s follow-up visit interest is
LOWRenal function collection is costly and
unchangedDifferent device typeDifferent technology in device typeNew technology developed during the
study
21
KSBPSKKidney SStone - BBlood PPressure
SStudyStatistical solutions to some difficulties:
Patient’s follow-up visit interest is LOW:
reduce sample size, increase reduce sample size, increase effect sizeeffect size
Patients selection bias : statistical analysis controlling statistical analysis controlling covariatescovariates
22
Renal function collection is costlyand unchanged:
bioequivalence testbioequivalence test to revise protocol
Different device type and technologyin device type:
stratified data analysisstratified data analysis
KSBPSKKidney SStone - BBlood PPressure
SStudyStatistical solutions to some difficulties:
23
KSBPSKKidney SStone - BBlood PPressure
SStudyCan Statistics solve all the difficulties?
New technology developed duringthe study
Participants’ willingness
No !No !
24
KSBPSKKidney SStone - BBlood PPressure SStudy
In September, 1997, FDA issues:
““Although an increase in blood pressureAlthough an increase in blood pressuremay result after Lithotripsy for the treatmentmay result after Lithotripsy for the treatmentof kidney stones, a 2 years prospective studyof kidney stones, a 2 years prospective studysuggests that treatment with Lithotripsy willsuggests that treatment with Lithotripsy willnot result in a difference in diastolic bloodnot result in a difference in diastolic bloodpressure of pressure of 4 mmHg as compared to other 4 mmHg as compared to otherkidney stone therapies.”kidney stone therapies.”
25
Methodology developmentConsultantHealth- and bio- informaticsResearch protocols review Committee of Clinical Investigation (CCI) Internal Review Board (IRB)Regulatory review
What Do Biostatistician Do?then, now and future
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
