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新药临床试验的生物统计学 指导原则. 苏炳华 教授 上海第二医科大学 生物统计学教研室. 郑筱萸主编 《 化学药品和治疗用生物制品研究指导原则 》 (试行) 北京 . 中国医药科技出版社 2002.5 第一版 . P85-P97. 按照国家药品监督管理局的要求,本指导原则应引进先进的思想和现代方法,与国际接轨,又需结合我国实际,具有连续性、前瞻性和可操作性。. 依据的文件: ( 1 ) 《 中华人民共和国药品管理法 》 ( 2 ) 《 新药审批办法 》 ( 3 ) 《 药品临床试验管理规范 》 - PowerPoint PPT Presentation
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.2002.5 . P85-P97.
1 2 3 4 ICH-E9. Statistical Principles for Clinical Trials. 1998.2 5 FDA. Guideline for Format and content of Clinical and Statistical Sections of an Application. 1988.7 6 FDA-Docket No.97D-0188. International Conference on Harmonisation;Draft Guidelines on General Considerations for Clinical Trials;Availbility.1997.5
1
2
(protocol)(case report form, CRF)(data management)(statistical analysis plan)
(principal investigator)(clinical study report)
3
1(effectiveness)(safety)
(1)(primary variable)(target variable)primary endpoint(secondary variable)
(2) (composite variable)(rating scale)
(3) (global assessment variable)(scale of ordered categorical ratings)
2 (bias) (randomization)(blinding)
(1) (randomization) (stratified)(block)
(2) (blind method)(double-blind)(single-blind)(open-label)
(placebo)(double dummy)
e) (emergency envelope)
f (treatment group)(control group)(unblinding)
1 (parallel group design)(crossover design) (factorial design)
Parallel group design Crossover design Sequence,Period22
2(multicenter trial)
(consistency test)
CMH(mixed effect model)
3. (superiority)(equivalence)(non-inferiority)
SuperiorityEquivalenceNon-inferiority1 H0 H
23
-- -- H0 H0
H
=0.05,
4(group sequential design) II(=0.05)(alpha spending function)
5. (sample size) ()
1SDA100200240
P1=0.60,P2=0.35
Power
n1=n2
=0.05
0.20
0.80362
69
0.10
0.90088
88
=0.01
0.20
0.80137
99
0.10
0.90224
124
0.70.7D0=0.07p10 =0.05=0.20 N1=N2=734=0.10 N1=N2=927
0.60.55 =0.05
Power
Ne=Ns
D0=0.10
0.10
0.90015
185
0.20
0.80157
134
D0=0.05
0.10
0.90025
418
0.20
0.80059
302
6. (case report form)
1. /(Audit or inspection)
2. (interim analysis)
3. /
1.
2/
3
4query list, query form)
5(database)6
7(range check)(logic check)
8()(visual check)
9(blind review)
(transformation)(outlier)(statistical model)
(parametric statistics)(non- parametric statistics)
10
1. (statistical analysis plan)(statistical tables)
2.Analysis setsI
intention-to-treatITTFull Analysis Set ITTFAS
(per protocolPP)
safety set
(Safetey population) (Full-Analysis-Set) (FAS)
(Per protocol) (PP) 1. 2. , , 3. (80%120%)
1. 2. 3.
3(missing value)
LOCFLast observation carry forward
4 (transformation)
5(descriptive statistical analysis)(hypothesis test)(parameter estimation)
. (safety evaluation)(survival analysis)
/
,
(significant level)(statistic)