1
????????????????

• ??? ??
• ????????
• ????????

2

• ?????
• ??????????????????
• (??)
• ??.?????????
• 2002.5 ???. P85-P97.

3
??????????????,??????????????????,?????,????????,?
??????????????

• ?????
• (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
• HarmonisationDraft Guidelines on
  General Considerations for
• Clinical TrialsAvailbility.1997.5

4
????

• ???????????????????
• ????????????????????????????????????????????
  ?????

5
????
1.???? ???????????????????,??????????????
??
6
????
2.???????????? ???????????????,?????????????
??????????????????,????????????
7
????

• ????
• ???? (protocol)??????
• ?????(case report form, CRF)???
• ????(data management)?
• ??????????(statistical analysis plan)

8
????

• ?????????????
• ?????????????????
• ???????(principal investigator)???????????(clinica
  l study report)?

9
????
3.?????????? ????????????????????????????
???????????????????
10
??????????????

• 1.????
• ?????????????(effectiveness)????(safety)??????
• ????
• ????

11
??????????????

• (1)?????????
• ????(primary variable)??????(target
  variable)?????(primary endpoint)?
• ????(secondary variable)?

12
??????????????
(2)???? ??????????????????????????????,???
????????,?????????????????(composite
variable)??????????(rating scale)?????????
13
??????????????
(3)?????? ????????????????????????????????
?????????(global assessment variable),??????????(s
cale of ordered categorical ratings)?
14
??????????????
2.????? ??(bias)????,?????????????????????
?????????,???????????,???????????????
???(randomization)???(blinding)???????????
15
??????????????
(1)??? ???(randomization)
??????????????,?????,?????????????????????????????
??????????????? (stratified)???(block)??????
16
??????????????
(2)?? ??(blind method)????????????????????
??????????????????????????????(double-blind)???(si
ngle-blind)???(open-label)?
17
??????????????

• ??????????????????
• ???(placebo)??????????????????????,???????????
• ???(double dummy)????????????????????,????????????
  ??????????????

18
??????????????

• ??????????????????????????????????????????????????
  ??????,??,????????????

19
??????????????

1. ??????????????????????????????????????????????????
   ????????????????????????????????
   ??????????,?????????????????????????

20
??????????????
e) ????????? ????(emergency
envelope),??????????????????????
???????,???????????????????????,??????????,???????
????????????
21
??????????????

• f) ????
• ?????,????(treatment group)????(control
  group)??????,????????(unblinding)?????????????????
  ???

22
?????????????

• 1.???????
• ????? (parallel group design)
• ????(crossover design)
• ???? (factorial design)

23
?????(Parallel group design)
??????????????,??????????????????????????,????????
?????,?????????????,??????? ????(Crossover
design) ???????????(Sequence),?????(Period)?
???????????,??????????? ?????22?????
24
?????????????
2.?????(multicenter trial)??????????????????,?????
?????,??????????????????
25
?????????????

• ?????????????
• ?????????????,???????????(consistency test)?
• ??????????????????????????,????????,??????????????
  ????????????????????

26
?????????????

1. ?????????,???????????????,??CMH?????????(mixed
   effect model)?????????????????????????????????????
   ??,??,????????????,????????????

27
?????????????

1. ???????????,????????????????,????????????????????
   ??????,????????

28
?????????????

• 3. ?????
• ???(superiority)??
• ???(equivalence)??
• ????(non-inferiority)??

29
?????(Superiority)?? ???(Equivalence)?? ????(Non-i
nferiority)?? (1)???????????????????,???????,?????
??,????????? H0 ? Ha
????
30
(2)???????????????????????????????????,???????????
?????? (3)???????????????????????????????
???????????????,????????,????????????????,????????
???????????????????,????????????????????
31
???????????,???????????(?????)??????(??),?????
????????????????,?????????????????????????????????
??????????????,????????????
32
--????? --??????
?????????????? H0 ?
H0 Ha ???a0.05,ßlt0.20
33
?????????????
4.??????(group sequential design)?
???????????????,???????????????????I?????,????????
????????,?????I????????????(??a0.05)?????????a???
?(alpha spending function)??????
34
?????????????

• ???????????????
• ??????????????,???????????????
• ????????????????,?????????????????

35
?????????????

• 5. ????(sample size) ???????????????
• ?????
• ???????(?????????)
• ???????????
• ????????????????????

36
??1??SDA???????????????,???????????100?,????????
?200?(?????????),???????,??????240??
37
??2????????? ???????????????71.6,????49.1,?a
0.05,ßlt0.20,????????21??,H0P1P2
1-ß
ß
a
???n2
???n1
0.80134
0.19866
0.05
60
120
0.83464
0.16536
0.05
65
130
0.86201
0.13799
0.05
70
140
0.88608
0.11392
0.05
75
150
0.90630
0.09370
0.05
80
160
????n1160,n280,???a0.05,ß0.0937lt0.1? ???????,?
20?,?n1200,n2100?
38
?????

• ???????P10.60,????????P20.35,??????
• ????????

39
?????

• ???????0.7,???????0.7,D00.07(???p?10)
• ???? a0.05
• ß0.20 N1N2734
• ß0.10 N1N2927

40
??????

• ???????0.6,???????0.55
• ???? a0.05

41
?????????????
6. ????? (case report form)?
??????????????????,??????????????,????????????????
????,???????????? ???????????????????,????
?????????
42
?.???????????

• 1. ?????/??(Audit or inspection)???
• ???????????
• ????????????
• ????????
• ??????????

43
?.???????????
2. ????(interim analysis)????????????,??????????,?
??????????????????,????????????????,?????????????
???????????????a???????????????????????
44
?.???????????

• 3. ????????????????????????????????????
• ????????,???????????????????,????????????,???????
  ??????/?????

45
?.???????????

• ?????????????????????????,?????????????????????,??
  ?????,?????????
• ??????????????????

46
??????
?????????????,???????????
1.????????????????,?????????????????????????
47
??????
2.???????????????????(??????????/????????),???????
????????,???????,???????,????????????????????????,
????????????????
48
??????
3.??????????????,?????????????????????????????????
???????????????????,??????????,????????
49
??????
4.????????????????,????????,???????,??????????????
??????????????????(query list, query
form),?????????
50
??????
5.???????????????????????,??????????????????(datab
ase),????????????? 6.??????????????????????????,??
?????????????,??????????????,?????,?????
51
??????
7.????????????????????????????????,?????(range
check)?????(logic check)??????????????,???????????
?,???????????????????????????????????
52
??????
8.?????????,???????????(????????)????????????(visu
al check)????????????
53
??????
9.????(blind review)???????????????????,??????????
??????????,????????????????
54
??????

• ??????
• ???????????????
• ??????????(transformation)
• ????????(outlier)
• ????????(statistical model)??????????????

55
??????

• ????????(parametric statistics)?????????(non-
  parametric statistics)???????????????????
• ?????????????????????

56
??????
10.??????????????????,????????????????????????????
????????????????????????????
57
??????
1. ???????(statistical analysis
plan)???????????????????????????????????????????,?
????????????????(statistical tables)???
58
??????
?????????????????????????????????????,????????????
?????????????????????????????????,?????????
59
??????

• 2.???????(Analysis sets)??????????
• ???????
• ??I??????

60
??????

• ???????(intention-to-treat,??ITT)?????,??????????
  ???????
• ????(Full Analysis Set) ????????ITT???????????????
  ??????????????????????????????????????????????FAS?
  ?????

61
??????
????????? (per protocol,??PP),???????????
????????????????,??????????????
??????????????????????????,????????????
62
??????
????????????????,?????????????
??????????(safety set)???????????,????????????????
??????????????
63

• ????
• ???????(Safetey population)
• ??????????,??????????????????
• ?????(Full-Analysis-Set) (FAS)
• ??????????,??????? ????????????

64

• ??????(Per protocol) (PP)
• ???????????
• 1. ??????
• 2. ????,??????????????
• ??,??????
• 3. ?????(80120??)
• ?????????????
• 1.????????
• 2.????????
• 3.??????????

65
??????
3.???????(missing value)????????????????,???????(?
???????????)?????,????????????????????????????????
??????????????????,??????????,????,??????????
66

• LOCF??(Last observation carry forward)
• ?????????????????????????

67
??????
????????,?????????????????,???????????????????
??????????,???????????????,??????????,????????????
?????????,???????????????????????
68
??????
4.???? ?????,??????????,??????????????????????
????(transformation)??????????????????????????????

69
??????

• 5.??????
• ???????(descriptive statistical analysis)
• ????(hypothesis test)?????(parameter estimation)
• ?????????????
• ??????????

70
??????
6.????? (safety evaluation)???????????????????????
??????????????????????????,??????(survival
analysis)????????????
71
?. ??????

• ????????????????
• ?????????????????????
• ??????????/????
• ?????????????????????
• ????????????
• ???????????????

72
?. ??????

• ???????????????
• ?????????????????
• ???????????????????
• ???????????

73
?. ??????

• ?????????????
• ???????????????????
• ????????????????????????????????????

74
?. ??????

• ?????????,?????????,??
• ?????????????????
• ?????????????????
• ??????????????????

75
?. ??????
???????????????????,???????????????????(significan
t level)????(statistic)?????P????????????????,????
?????????????????