Download - 新药临床试验的生物统计学 指导原则
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.2002.5 . P85-P97.
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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
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1
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2
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(protocol)(case report form, CRF)(data management)(statistical analysis plan)
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(principal investigator)(clinical study report)
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3
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1(effectiveness)(safety)
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(1)(primary variable)(target variable)primary endpoint(secondary variable)
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(2) (composite variable)(rating scale)
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(3) (global assessment variable)(scale of ordered categorical ratings)
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2 (bias) (randomization)(blinding)
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(1) (randomization) (stratified)(block)
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(2) (blind method)(double-blind)(single-blind)(open-label)
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(placebo)(double dummy)
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e) (emergency envelope)
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f (treatment group)(control group)(unblinding)
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1 (parallel group design)(crossover design) (factorial design)
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Parallel group design Crossover design Sequence,Period22
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2(multicenter trial)
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(consistency test)
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CMH(mixed effect model)
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3. (superiority)(equivalence)(non-inferiority)
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SuperiorityEquivalenceNon-inferiority1 H0 H
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23
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-- -- H0 H0
H
=0.05,
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4(group sequential design) II(=0.05)(alpha spending function)
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5. (sample size) ()
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1SDA100200240
- 0.906300.093700.05801600.886080.113920.05751500.862010.137990.05701400.834640.165360.05651300.801340.198660.05601201- n2 n1 2 71.6%,49.1%,=0.05,
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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
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0.70.7D0=0.07p10 =0.05=0.20 N1=N2=734=0.10 N1=N2=927
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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
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6. (case report form)
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1. /(Audit or inspection)
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2. (interim analysis)
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3. /
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1.
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2/
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3
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4query list, query form)
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5(database)6
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7(range check)(logic check)
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8()(visual check)
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9(blind review)
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(transformation)(outlier)(statistical model)
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(parametric statistics)(non- parametric statistics)
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10
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1. (statistical analysis plan)(statistical tables)
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2.Analysis setsI
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intention-to-treatITTFull Analysis Set ITTFAS
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(per protocolPP)
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safety set
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(Safetey population) (Full-Analysis-Set) (FAS)
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(Per protocol) (PP) 1. 2. , , 3. (80%120%)
1. 2. 3.
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3(missing value)
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LOCFLast observation carry forward
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4 (transformation)
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5(descriptive statistical analysis)(hypothesis test)(parameter estimation)
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. (safety evaluation)(survival analysis)
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/
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,
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(significant level)(statistic)