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[分享] 经典临床试验教材:Design and Analysis of Clinical Trials (3rd edtion, 2013)

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本帖最后由 sampson2010 于 2014-12-11 11:28 编辑
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5 t, Q- M/ z: O* v4 \$ J* `; R% g9 h' K! m"Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning."/ D; T0 E$ |6 p* E& f. w
                                                                                                                                                     ——Albert Einstein0 O, R; d. Z  L
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Title: Design and Analysis of Clinical Trials: Concepts and Methodologies2 g# f9 F$ T4 W. G9 L
Author(s): Shein-Chung Chow, Jen-Pei Liu
  C) H, C, J) O. TPublisher: Wiley% }5 x" Z4 f" Y2 S- h
Year: 2013       
. I' G3 j* u% n" b4 e) aEdition: 3rd' s; \5 M- a. G. l* ]5 n
Language: English       
7 Z; @1 F/ ]6 S7 r. GPages: 8927 `7 ~8 K7 `" X
ISBN: 0470887656, 9780470887653       
% _5 z. x7 s; kID: 1168442
3 J8 e3 m" b+ m. q( I; V1 ~Size: 17 MB (17671149 bytes)       
; h* _  z0 y2 T' Z8 Z9 {6 n2 BExtension: pdf
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Praise for the Second Edition:5 Q* E) C7 @( m2 O0 A$ o, {
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“...a grand feast for biostatisticians. It stands ready to satisfy the appetite of any pharmaceutical scientist with a respectable statistical appetite.” —Journal of Clinical Research Best Practices
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$ L* X, |: A- S+ V  yThe Third Edition of Design and Analysis of Clinical Trials provides complete, comprehensive, and expanded coverage of recent health treatments and interventions. Featuring a unified presentation, the book provides a well-balanced summary of current regulatory requirements and recently developed statistical methods as well as an overview of the various designs and analyses that are utilized at different stages of clinical research and development. Additional features of this Third Edition include:) e% l, O+ E* r" X

+ k4 h8 q" a% b5 G7 g• New chapters on biomarker development and target clinical trials, adaptive design, trials for evaluating diagnostic devices, statistical methods for translational medicine, and traditional Chinese medicine: @$ |! ]+ L* p1 m

8 n0 w: j% j) j/ @  P• A balanced overview of current and emerging clinical issues as well as newly developed statistical methodologies9 c2 b. L; G) O/ F+ B
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• Practical examples of clinical trials that demonstrate everyday applicability, with illustrations and examples to explain key concepts7 z* m# P4 N  z. w/ c; Q8 v0 i, D2 @
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• New sections on bridging studies and global trials, QT studies, multinational trials, comparative effectiveness trials, and the analysis of QT/QTc prolongation
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" `3 [* t1 e/ t' ^6 n; X& F" q7 i+ ~• A complete and balanced presentation of clinical and scientific issues, statistical concepts, and methodologies for bridging clinical and statistical disciplines. i7 k- H2 @3 A$ o

' u/ v6 P/ p# O4 w" `• An update of each chapter that reflects changes in regulatory requirements for the drug review and approval process and recent developments in statistical design and methodology for clinical research and development
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Design and Analysis of Clinical Trials, Third Edition continues to be an ideal clinical research reference for academic, pharmaceutical, medical, and regulatory scientists/researchers, statisticians, and graduate-level students.
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Table of contents :
- q/ J% I* _% V& T9 [3 b" uDesign and Analysis of Clinical Trials......Page 3' V( [% F) ]  Z- E2 |8 i
Contents......Page 7* D' }7 q% c$ _
Preface......Page 13  _+ f; ~  I/ R  ?7 W/ G2 |* ~
PART I Preliminaries......Page 15
& C) W% l2 Z1 u9 }1.1 WHAT ARE CLINICAL TRIALS?......Page 17
0 n( [& k0 ~. O  _+ N8 d1.2 HISTORY OF CLINICAL TRIALS......Page 18
3 d. W  S( l* G+ G8 S7 l1 g4 z; g1.3.1 The Food and Drug Administration......Page 24
, B8 G3 E2 \6 S; t, D1.3.2 FDA Regulations for Clinical Trials......Page 27
, h  V" j2 }+ Y' c: p; H1.3.3 Phases of Clinical Development......Page 29" E3 c. w- x/ |4 a5 }( q
1.4 INVESTIGATIONAL NEW DRUG APPLICATION......Page 31- d5 J5 v' }* g2 W3 X
1.4.1 Clinical Trial Protocol......Page 33
- D( b- \& |% k1 z' Y; n1 s9 `4 s1.4.2 Institutional Review Board......Page 36
7 ]9 r/ m/ F# {* i1.4.5 Withdrawal and Termination of an IND......Page 37
2 c. n) L: N% t% c! C7 b: C# {1.5 NEW DRUG APPLICATION......Page 38
& ]8 l$ ^2 q, O0 i: \, R8 |1.5.1 Expanded Access......Page 40
( }1 j7 J( [/ I( ?( h: |1.5.2 Abbreviated New Drug Application......Page 43
3 q! V1 J, C7 n1.5.3 Supplemental New Drug Application......Page 44
1 @- C( }9 e' n1.6.1 Clinical Development Plan......Page 457 k. q8 L8 v! T% s3 u3 }4 W' o
1.6.2 Good Clinical Practice......Page 47
1 x3 F6 o6 J4 }7 `1.7 AIMS AND STRUCTURE OF THE BOOK......Page 56
" T! j! {. x7 P2.1 INTRODUCTION......Page 59- _+ d( }% v/ H* _+ m5 v# T
2.2.1 Uncertainty......Page 60. `4 t: {' G9 x+ \  }; n- b1 e
2.2.2 Probability......Page 61% \" s: q& Q, U# M* I$ s
2.3.1 Bias......Page 639 u" J$ H. Z/ [; K  q9 t
2.3.2 Variability......Page 68
1 Y2 I% |5 C1 n7 b7 p! Q2.4 CONFOUNDING AND INTERACTION......Page 71
) a: k0 _0 v! C5 }5 D( d; l2.4.1 Confounding......Page 72. ?3 A, l9 U9 e0 K
2.4.2 Interaction......Page 75, I  k  a8 Z1 b" T2 H# \! d. ~: i' K
2.5 DESCRIPTIVE AND INFERENTIAL STATISTICS......Page 80
$ \8 _" {. [1 p1 q1 j. [' Z. ]2.6 HYPOTHESES TESTING AND p-VALUES......Page 82
- Q/ D; K: G: T# y2.6.1 p-Values......Page 84
# N) I5 i0 y- K2 O. z& S9 W- U2.6.2 One-Sided Versus Two-Sided Hypotheses......Page 86) p2 s3 q$ b9 a3 o' H0 k# n# x
2.7 CLINICAL SIGNIFICANCE AND CLINICAL EQUIVALENCE......Page 89
- y8 O. j/ a0 S2 {- T* y( |; \2.8 REPRODUCIBILITY AND GENERALIZABILITY......Page 93* h. V' R2 a/ A, ?
2.8.1 Reproducibility......Page 94
& Q$ @5 H8 {- F! a2.8.2 Generalizability......Page 955 X+ n3 m- p8 H
3.1 INTRODUCTION......Page 99
  L# x/ T# g* H. m' U0 S, [8 [3.2 GOALS OF CLINICAL TRIALS......Page 1004 {. v* _- ]+ o2 q
3.3.1 Eligibility Criteria......Page 104
( e' Q2 n5 v& w3.3.2 Patient Selection Process......Page 108' _' e2 x4 l$ k7 A+ h
3.3.3 Ethical Considerations......Page 110
: ]! H- g6 y' f& K  S9 m3.4 SELECTION OF CONTROLS......Page 111
9 M  z& L3 p. S; w6 e  K5 o3.4.1 Placebo Concurrent Control......Page 112
) P# L3 D! a  W( n8 W  o3.4.2 Dose–Response Concurrent Control......Page 115
" u; U* L: F* U- u. y3.4.3 Active (Positive) Concurrent Control......Page 117
! V- B9 {  K4 g7 A4 G; x* }5 k3.4.4 No Treatment Concurrent Control......Page 118
6 K7 W8 D  h( ?) K3.5.1 Efficacy and Safety Assessment......Page 119& E2 M1 R$ M! [
3.5.2 Sample Size Estimation......Page 121
2 |/ i0 o& v- m8 Z1 Z3.5.3 Interim Analysis and Data Monitoring......Page 1221 p- \+ l6 k  |3 l2 S* \
3.5.4 Statistical and Clinical Inference......Page 124
4 M* f7 s1 A* b3 W0 U3.6 OTHER ISSUES......Page 126
/ A* U- ~- ]0 u# N  S+ g3.6.3 Patient Compliance......Page 127' D1 g+ t2 j/ O, H. r& `
3.6.4 Missing Value and Dropout......Page 128
* I+ V- y7 W, @5 r+ e! o3.7 DISCUSSION......Page 129
* _) M& O) l/ ^6 f+ ^4.1 INTRODUCTION......Page 131
0 h! e- D5 R% L6 _4.2 RANDOMIZATION MODELS......Page 132
8 q  y. l* ?2 r( I4.2.2 Invoked Population Model......Page 133
# f  F! M( K0 G4.2.3 Randomization Model......Page 134
( {& I- j: F5 m5 A! j% @4.2.4 Stratification......Page 136
" |' X4 g9 a, X* V$ E. `4.3 RANDOMIZATION METHODS......Page 138# g' T7 O0 H! w5 K
4.3.1 Complete Randomization......Page 142' T/ S' N0 T5 q4 G; ^% I6 E' [2 K
4.3.2 Permuted-Block Randomization......Page 1475 U, o, B1 H8 \* z
4.3.3 Adaptive Randomization......Page 1513 b* ~' |" }% `/ Q# ~, y& O
4.4.1 Generation, Labeling, and Packaging......Page 1588 J) \3 k  X6 Y
4.4.2 Random Assignment......Page 160
# {3 Q1 I; Y% b1 g8 ?# O6 Y8 x4.5 GENERALIZATION OF CONTROLLED RANDOMIZED TRIALS......Page 163
3 R: y, ?0 I" F- M+ `# D4.6 BLINDING......Page 167
. G/ D: g* o8 A$ N$ ]( b$ I7 `4.7 DISCUSSION......Page 174- T; P/ E6 b1 l7 Q+ [& _
PART II Designs and Their Classifications......Page 177
, a. A8 k: X8 e: C5.1 INTRODUCTION......Page 179
# b% ?0 ~1 v9 d& H6 n" d1 d7 E  {5.2 PARALLEL GROUP DESIGNS......Page 181* W5 q: y, I3 {) X% E6 f6 W- f- @
5.2.1 Run-in Periods......Page 1831 t- X! i4 h; ?/ i: v
5.2.2 Examples of Parallel Group Design in Clinical Trials......Page 184
2 j  n6 b5 i. [5.3 CLUSTERED RANDOMIZED DESIGNS......Page 186
' Q! b3 a+ C1 l( S" R5.4 CROSSOVER DESIGNS......Page 191. d9 \+ Q  X9 l0 T8 t8 _& a, `1 J
5.4.1 Higher-Order Crossover Designs......Page 192
' J5 R  c) H+ @0 g* I# `5.4.2 Williams Designs......Page 195, R/ N  E& e3 O+ H
5.4.4 Examples of Crossover Design in Clinical Trials......Page 196  W' ~$ r% Y) D0 Z! R3 o. S
5.5.1 Standard Titration Design......Page 199
- c- F1 }; P4 h) b# I5.5.2 Forced Dose-Escalation Design......Page 203
% x  b! H2 g, |5.6 ENRICHMENT DESIGNS......Page 205
* k, `  c1 u  y  f: y5 G9 v5.7 GROUP SEQUENTIAL DESIGNS......Page 209. E2 H5 q! S5 w, k
5.8 PLACEBO-CHALLENGING DESIGNS......Page 211
8 x: a  o. _% n2 [) {$ T5.8.1 Statistical Model and Inferences......Page 212" ]" T: m# e4 B2 z
5.9 BLINDED READER DESIGNS......Page 217
* C. {- p7 B& z& T* a5.10 DISCUSSION......Page 2219 G7 B5 s* M, B
6.1 INTRODUCTION......Page 225  }* e% r6 ~* _+ ]5 [/ G) P0 q
6.2 GENERAL CONSIDERATIONS FOR PHASE ICANCER CLINICAL TRIALS......Page 227
* g, \) U  r5 O/ m% V6.3 SINGLE-STAGE UP-AND-DOWN PHASE I DESIGNS......Page 228
& |$ ]0 X" b, I, r6.3.1 Design A—Standard Dose-Escalation Design......Page 2299 {) K- I3 O7 h6 P% Q* c
6.4 TWO-STAGE UP-AND-DOWN PHASE I DESIGNS......Page 2318 K! b$ V8 v. Z9 H- _: D6 U% L
6.4.2 Accelerated Titration Designs......Page 232
: r$ u0 k! ]* @) n6.5 CONTINUAL REASSESSMENT METHOD PHASE I DESIGNS......Page 233
5 L5 }+ B6 ~9 ~) E, N+ E$ ~6.6.1 Single-Arm Trials......Page 236
& k' S; |+ n- n' ~( h6.6.2 Multiple-Arm Trials......Page 2402 M0 Q* p$ D  ?% n: v$ J
6.7 RANDOMIZED PHASE II DESIGNS......Page 243% [2 m# @* e$ ?
6.8 DISCUSSION......Page 246
1 M4 ^7 B3 v6 k8 P  H. p7.1 INTRODUCTION......Page 251
+ D: S% c8 N  f- ]7.2 MULTICENTER TRIALS......Page 252
" a, T0 s3 s8 t6 p7.2.1 Treatment-by-Center Interaction......Page 253- a, C" W5 q8 T& I
7.2.2 Practical Issues......Page 255* q7 V: ]1 z1 k1 g& A. Y
7.3 SUPERIORITY TRIALS......Page 2592 V. R3 H9 t- ]( k
7.4.1 Primary Objectives......Page 262
1 }" [; Y' ~4 I  ]5 ~1 q1 P7.4.2 Issues in Active Control Equivalence Trials......Page 263
+ G  O" N; A0 @* r2 ]7.4.3 Interpretation of the Results of Active Control Trials......Page 267" }2 ?- {2 u6 |3 k
7.4.4 Equivalence/Noninferiority Limits......Page 269; {( p2 E! A+ V  \' l
7.4.5 Statistical Methods......Page 272
* N: o+ K5 [- I8 T7.5 DOSE–RESPONSE TRIALS......Page 2757 r+ Y. [; U$ @7 f0 _
7.5.1 Randomized Parallel Dose–Response Designs......Page 276! ~- V2 ^$ ~9 \5 q1 f8 T
7.5.3 Forced Titration (Dose-Escalation) Design......Page 278
$ j- `5 z8 d! q7.5.4 Optional Titration Design (Placebo-Controlled Titration to Endpoint)......Page 279
! `  ^- M2 c8 B( N5 V. Y6 Y" f% P7.6 COMBINATION TRIALS......Page 280$ P9 w$ A& ?' ~7 U3 z) X+ v5 h
7.6.1 Fixed-Combination Prescription Drugs......Page 282
: A, u. S6 @9 E( |, J7.6.2 Multilevel Factorial Design......Page 285
/ Y5 f* J( R: f* v# S7.6.3 Global Superiority of Combination Drugs......Page 287
: b% C5 w- F1 Z& J+ o1 M7.6.4 Method of Response Surface......Page 291
0 b. d: {8 [! }7 z7.7.1 Introduction......Page 292
* r; o  d' s* s9 |/ e7.7.2 Ethnic Sensitivity and Necessity of Bridging Studies......Page 293
) a& W: [* z* R+ l# Q7.7.4 Assessment of Similarity Based on Bridging Evidence......Page 296
: V& k7 [: S$ n, H! F2 p7.8.1 Basic Design and Statistical Considerations......Page 299
% e' O# j7 U- f- [7 I9 y7.8.2 Types of Vaccine Immunogenicity Trials......Page 300
  A( ]! X7 W. u7 o7.8.3 Statistical Methods......Page 302
2 @) J$ y* o! \: c+ X7.9 QT STUDIES......Page 305
5 ~( H% @. I6 d9 [% y7.9.1 Study Designs and Models......Page 306
0 {; N0 g6 _/ b, k" ^, ~1 k7.9.2 Power and Sample Size Calculation......Page 307
: i- _3 D9 f8 n& |) W! l7.9.3 Allocation Optimization......Page 311
& Q( p& i9 j1 P9 _7.9.4 Remarks......Page 312' E4 P0 M6 \+ ]% E$ U5 p/ M' }
7.10 DISCUSSION......Page 313
4 p; {3 A- t% b8 ^; m% `# s  H6 xPART III Analysis of Clinical Data......Page 317
. ?% a6 J* W& Z) t8.1 INTRODUCTION......Page 319
9 M7 L  r7 D7 v. W* [) Y" X& t8.2 ESTIMATION......Page 320  x7 m& D3 F2 m4 |: X
8.3 TEST STATISTICS......Page 324
, {5 X9 A7 X# h8.3.1 Paired t Test......Page 3268 Y6 ?& K* g1 {; Y0 _
8.3.2 Two-Sample t Test......Page 327. L- Y# R  Y) ~
8.4.1 One-Way Classification......Page 330+ E# _9 C" ?% W4 W( S
8.4.2 Simultaneous Confidence Intervals......Page 332
2 t& i/ x! F0 w- n# c1 I# M  B$ \8.4.3 Two-Way Classification......Page 334
  Z$ R3 T4 i+ y1 I' \9 H- P8.5 ANALYSIS OF COVARIANCE......Page 337& n* ]1 A: S: D2 L$ d  s
8.6 NONPARAMETRIC METHODS......Page 339
* e1 p+ c; B4 [0 z8.6.1 Wilcoxon Signed Rank Test......Page 340
- a8 t7 l6 Q/ I8.6.2 Wilcoxon Rank Sum Test......Page 341
' h- D1 i. p% ^: `5 W/ L' _) b8.6.3 Kruskal–Wallis Test......Page 345' C$ h. D  T! _1 N* m
8.7.1 Assessment of Overall Average Effect Across Time......Page 3462 z. E! ]) P: a, N) F8 c/ ?6 n+ L4 ~
8.7.2 Detection of Time Effect......Page 348
% e9 e& r: t' N0 f8.7.3 Treatment-by-Time Interaction......Page 349. U$ `4 U: D/ _% D4 A' U2 s
8.7.4 Method of Generalized Estimating Equations (GEEs)......Page 351* B6 O/ t- b# A  o
8.8 DISCUSSION......Page 3559 M' ^7 }( E! m; d
9.1 INTRODUCTION......Page 357
- R9 k% y5 a3 C3 Y8 Q+ d' N9.2 STATISTICAL INFERENCE FOR ONE SAMPLE......Page 359
$ m3 h2 b9 ~4 Q7 p4 ]- b; }/ [9.3 INFERENCE OF INDEPENDENT SAMPLES......Page 3727 {" w0 C0 a5 {/ }3 \
9.4 ORDERED CATEGORICAL DATA......Page 378$ T2 K" G" J2 S8 O( U9 q6 ]3 M
9.5 COMBINING CATEGORICAL DATA......Page 382/ R6 P3 x, e- W' w5 u
9.6 MODEL-BASED METHODS......Page 388
& {. r+ t% f3 R- z$ j  X8 X9.7 REPEATED CATEGORICAL DATA......Page 396
8 F3 f1 j2 u+ N+ f8 B6 N" w9.8 DISCUSSION......Page 4013 o8 U3 [" J/ a2 W9 _! @+ J
10.1 INTRODUCTION......Page 403; X/ h* Z) Y/ t' f7 K
10.2 ESTIMATION OF THE SURVIVAL FUNCTION......Page 405
+ y. J# ?2 |8 Z2 t10.3 COMPARISON BETWEEN SURVIVAL FUNCTIONS......Page 4139 I( G% U( M  ^) \& U, H
10.4 COX’S PROPORTIONAL HAZARD MODEL......Page 419# {6 h) g& ^' @  g6 ~* F
10.5 CALENDAR TIME AND INFORMATION TIME......Page 433
" i6 l2 l* f% s, j( o( `% }: B7 E10.6 GROUP SEQUENTIAL METHODS......Page 438
. |" L0 n! `7 P10.7 DISCUSSION......Page 452
; h5 h' U) d2 T) c11.1 INTRODUCTION......Page 4551 c1 d+ W: c& y; I* A# }' l+ O$ S7 B
11.2.1 Study Objectives and Hypotheses......Page 456) L$ l+ \' {9 I" h: J( b  L
11.2.2 Type I and Type II Errors......Page 4581 N) p1 S( K/ j# [; t) z% p* }# J
11.2.3 Precision Analysis......Page 459
0 J) H) e3 v! F  V% \5 b* @5 }7 ~0 H" S4 ?11.2.4 Power Analysis......Page 460* y' o+ g* m9 ^. z: ~$ L7 g) e
11.3.1 One-Sample Test for Mean......Page 461
* ~, S7 N* }* M0 i2 i11.3.2 Two-Sample Test for Comparing Means......Page 462" s, I2 k& T7 C$ W+ r1 w6 h, i
11.4.1 Sample Size Calculations for Analysis of Variance Models......Page 470
+ ?! i+ F5 u% b11.4.2 Sample Size Calculations for Generalized Linear Models......Page 472+ S  z% j; ?+ r+ S# s. u
11.5 CENSORED DATA......Page 473
6 J+ o" q4 @7 w0 P11.6.1 Dose–Response Relationship......Page 478
4 J' Y' K& A) z; K; p' r/ w11.6.2 Minimum Effective Dose......Page 480
  h$ w4 _0 i) k) i! R11.7.1 Point Hypotheses for Equality......Page 4850 k# Z2 p! t$ F' P5 K  N. ^
11.7.2 Interval Hypotheses for Equivalence......Page 4878 P& R! Y3 d4 J9 Z. q+ m3 [! X
11.7.3 Higher-Order Crossover Designs......Page 492, e' S! Y' C/ O5 Z; _
11.8 EQUIVALENCE AND NONINFERIORITY TRIALS......Page 4959 C7 A" ~: [' `( N* X
11.8.1 Independent Binary Endpoints......Page 496
' t5 v# w+ U7 ^/ B11.8.2 Paired Binary Endpoints......Page 498! R7 d! N9 ^- k% V
11.8.3 Independent Censored Endpoints......Page 5009 S$ X& p5 f$ \# C
11.10 MULTINATIONAL TRIALS......Page 504! n' C; R: K. m/ A6 D+ _
11.10.1 Selection of the Number of Sites......Page 505
* [8 S3 v! O% z' U% C- U11.10.2 Sample Size Calculation and Allocation......Page 5113 C  X& N& s' n
11.11 COMPARING VARIABILITIES......Page 514, B  c; ~1 i1 M, o! n4 P) d. k3 s$ s
11.11.1 Comparing Intrasubject Variabilities......Page 515
- J/ R  h9 c( Z/ a2 [11.11.2 Comparing Intersubject Variabilities......Page 5236 C0 R, S" ]8 J* H8 k0 U
11.12 DISCUSSION......Page 531) x( G+ D$ p3 `+ Z  U  V
PART IV Issues in Evaluation......Page 533
! Y6 l6 Q6 z3 Q2 F12.1 INTRODUCTION......Page 535+ i% f, m4 D& T6 i
12.2 BASELINE COMPARISON......Page 537; N; l+ w4 l% V; {5 E& |3 c8 ?$ }: C4 d
12.3 INTENTION-TO-TREAT PRINCIPLE AND EFFICACY ANALYSIS......Page 542
0 X* T3 A) f) h  g  a: f0 U12.4 ADJUSTMENT FOR COVARIATES......Page 550
4 u2 Q) k$ ?- D& h! `( g12.5 MULTICENTER TRIALS......Page 555
: y2 T8 O. t* d) o+ f12.6 MULTIPLICITY......Page 562
) K( i! z- K9 G: t12.6.1 Multiple Comparisons......Page 564
8 A$ k- {# j* i0 D5 ~2 b12.6.2 Multiple Endpoints......Page 566) g% u: [+ P8 S3 Z
12.6.3 Subgroup Analysis......Page 571: K, o) ]/ h! l3 k! t
12.7.2 Regulatory Concerns......Page 572* B. c. c# R' Y" A- I
12.7.3 Early and Late Stages of Drug Development......Page 574
0 q- \7 h( G- C0 h$ D. @12.7.5 Data Monitoring Committee......Page 575! ]1 m% F  ~$ x9 S
12.8 USE OF GENETIC INFORMATION FOR EVALUATION OF EFFICACY......Page 578
9 u0 M6 V. q% z, H12.9 SAMPLE SIZE REESTIMATION......Page 5847 a- S% \& S2 `7 p5 N
12.10 DISCUSSION......Page 586
# a% J  A2 X5 H5 X/ p13.1 INTRODUCTION......Page 5872 Q+ y/ R# M+ \1 f; O+ o! c
13.2 EXTENT OF EXPOSURE......Page 588- f# D& I. C# F  ^2 l# Q
13.2.1 Risk of Exposure......Page 589" o+ a2 m6 C4 t. j
13.2.2 Absorbing Events......Page 590
5 T( d. }- g4 F$ m- r) ?13.2.3 Recurring Events with Negligible Duration......Page 5913 m: v: ]) r$ x
13.2.4 Recurring Events with Nonnegligible Duration......Page 5920 ]# c( t2 a! D6 s
13.2.5 Laboratory Data......Page 5931 s0 \- g& ]: n" x& m7 M
13.3.1 Definitions of Adverse Events......Page 596
# r: v1 ~' A" o# j: `  V* a# H" s13.3.2 COSTART......Page 600
1 I* ^* `! ]' m+ y7 V. P' T+ q( M13.3.3 MedDRA......Page 602
% A0 w+ v+ h- @! O- R13.3.4 Common Toxicity Criteria......Page 607
/ b  m1 ?. L* X! O/ T# a13.4.1 Adverse Event Data Listing......Page 609  h/ X/ o% }: f$ Y2 D
13.4.2 Summary Tables of Adverse Events......Page 610
. B$ _" Z+ X3 [13.4.4 Analysis of Adverse Events......Page 611& t! v1 ~. p6 C: |
13.5.2 Combinability of Laboratory Data......Page 616$ s: |/ \0 x' g8 ^" W, W
13.5.3 Clinically Significant Changes......Page 618, M: M% K7 q% m1 R
13.5.4 Shift Analysis......Page 619
) F3 _2 a( [0 Q8 |13.6 ANALYSIS OF QT/QTc PROLONGATION......Page 624) s- H" N8 H1 p* v. u8 ]. {
13.6.1 Test Under Parallel Group Design......Page 6257 F# X' j( q4 W4 n
13.6.2 Test Under Crossover Design......Page 627
# s8 B6 Q' j  G$ N/ Q7 \) j13.6.4 Remarks......Page 628; R# j  a( C! Y* W
13.7 DISCUSSION......Page 629
& M% z5 \5 U* T: V; oPART V Recent Development......Page 631; E* j: P2 @4 j$ x, l
14.1 INTRODUCTION......Page 6334 k. u: A$ \& y7 d
14.2 CONCEPTS AND STRATEGIES......Page 6343 n' j, @: e; V& \2 s
14.3.1 Classifier, Prognostic, and Predictive Biomarkers......Page 637
  q' T/ E. F# W3 K( O4 z" j: C9 L14.3.2 Biomarker Development......Page 639& |( v3 r8 W0 E8 c( L
14.3.3 Analytical Validation......Page 641
! b/ [/ ~' c9 r7 j1 s14.3.4 Clinical Validation......Page 642
( P- v  `' D8 a0 k/ q7 n14.4.1 Considerations for Phase I Trials......Page 644: e9 Q3 ]" K2 u
14.4.2 Considerations for Phase II Trials......Page 645  r: Q9 }, O9 c# v! v; i6 V
14.4.3 Considerations for Phase III Trials......Page 648$ b+ }& F8 g1 |* N8 v9 c2 E' z, T* }7 R
14.5.1 Biomarker as a Covariate Versus a Stratification Factor......Page 654$ q% l4 K/ Y$ }, k( I3 m) v. |
14.5.2 Treatment-by-Biomarker Interaction Versus Separate Analysis......Page 655
  L! R, w& D1 ?# |14.5.3 Impact of the Measurement and Classification Error......Page 657
( K; y2 ?3 C% s3 V14.6 DISCUSSION......Page 661
2 f9 ~% l& H0 _1 r8 J+ G15.1 INTRODUCTION......Page 663
, T: l. R: X' s+ w, v15.2 STUDY DESIGN......Page 665: Q  V1 X9 ]+ f! c/ F2 s
15.3 MEASURES OF DIAGNOSTIC ACCURACY......Page 670
5 Z& M% O2 v, R* K9 k. V15.4 REPORTING RESULTS......Page 677
! E4 `" `" l% U15.5 SAMPLE SIZE ESTIMATION......Page 686
$ k9 ?' Q0 I& ^9 R3 P7 S0 b' Z15.6 DISCUSSION......Page 689
% v7 D7 Q, @1 N" ?! ~16.1 INTRODUCTION......Page 691
7 v" _! O# F7 S/ g! r16.2 BIOMARKER DEVELOPMENT......Page 6925 x9 l6 n5 u: _9 o: P
16.2.1 Optimal Variable Screening......Page 693
2 s9 A. n* d0 p16.2.2 Model Selection and Validation......Page 694
7 d3 \. F! i1 ]' n16.2.3 Remarks......Page 695
9 Q( K* H! Q& Q2 I& X( n16.3.1 One-Way Translational Process......Page 696
5 q; }: y5 G. [2 b, Z( U16.3.2 Two-Way Translational Process......Page 701
9 Z4 u! y4 R1 l16.4 ANIMAL MODEL VERSUS HUMAN MODEL......Page 703  `* k9 o2 O% K( I* E$ I
16.5.1 Power Analysis and Sample Size Calculation......Page 705
. U7 {4 u! ]0 l+ p+ o2 l16.5.2 Remarks......Page 7091 h; l5 P) l0 Y: A5 _/ ?% K/ x
16.6 BRIDGING STUDIES......Page 710
! |+ S9 \6 w5 ?16.6.1 Test for Consistency......Page 711: u  x3 A. L- C! c, G$ |
16.6.3 Test for Similarity......Page 712- {  z2 Y* B* H' |/ {4 S) W) T
16.7 DISCUSSION......Page 713
' u* b, J) W7 W& t+ n' V16.8 APPENDIX......Page 714
; |* U5 S; |  k17.1 INTRODUCTION......Page 717) F  [* z# a6 p+ A$ y: i* K
17.2 WHAT IS ADAPTIVE DESIGN?......Page 718
2 Y8 L/ S  t/ H  D% l17.2.2 Type of Adaptive Designs......Page 719
: e# O- V* r+ F. b0 n8 O  X/ b17.3.1 Well-Understood Designs......Page 723
, E! f6 {' K4 v17.3.2 LessWell-Understood Designs......Page 724) S/ K% z, U, m5 }* E
17.4.1 Clinical Operation Perspectives......Page 727' u% [/ T* E5 X
17.4.3 Regulatory Perspectives......Page 729
7 B, e) C. q# n% a9 F17.5.1 Moving Target Patient Population......Page 730
3 J' z9 M/ |, e) Q17.5.2 Statistical Inference with Covariate Adjustment......Page 731+ Y# ^5 h- }# M6 V' B/ F" m
17.5.3 Bayesian Approach......Page 733
) a0 Q/ b( j3 ?2 j/ y  R9 m17.6.1 Adaptive Group Sequential Design......Page 735
% o! s, x% K- x; V17.6.2 Adaptive Dose-Finding Design......Page 737
  G7 T/ l/ V4 ?4 b' \1 w17.6.3 Adaptive Seamless Designs......Page 739. U' ~! U4 F, s
17.6.4 Remarks......Page 740' x, o, C+ C0 e) w# C6 w* T
17.7 OBSTACLES OF RETROSPECTIVE ADAPTATIONS......Page 741
+ R# P, r& {: U' d17.8 DISCUSSION......Page 7435 i- S. w8 C7 _) B6 i7 s( m5 J
18.1 INTRODUCTION......Page 7473 A* y2 }& `5 c+ ]% k. m7 o, E8 q
18.2 FUNDAMENTAL DIFFERENCES......Page 7483 v2 n" J5 d+ `; f7 q
18.2.1 Medical Theory/Mechanism and Practice......Page 749' `( p& [1 N/ O- t4 e' ]
18.2.2 Techniques of Diagnosis......Page 752
1 X7 C& I  J- x8 z9 o18.2.3 Treatment......Page 753, \! Y: ~8 r1 @6 h) Y+ N
18.2.4 Remarks......Page 7549 q; {& ^2 t, ?8 C! [
18.3.1 Study Design......Page 7556 d. a$ b: Q# v7 g4 R
18.3.2 Validation of Quantitative Instrument......Page 7563 q, ]! ]! J* h8 P* r6 Y
18.3.4 Matching Placebo......Page 757
) I) [4 D4 w( N$ X( a0 M  X18.4 OTHER ISSUES IN TCM RESEARCH AND DEVELOPMENT......Page 758
9 O2 \8 a5 k  {4 E% R9 r8 G18.4.1 Test for Consistency......Page 7592 N6 k& `4 }" Y7 G" e" x) m  Z9 \
18.4.2 Stability Analysis......Page 761
" k3 K2 e. Y- c0 C8 d! Q18.4.3 Animal Studies......Page 763( n. A9 B2 T& z6 y" R) L- q
18.4.5 Indication/Label......Page 764
2 ~+ n6 v5 |. l0 g' [* h& m6 x18.5 CONSORTIUM FOR GLOBALIZATION OF TRADITIONALCHINESE MEDICINE......Page 7659 x; Y0 \" G( q3 ~- ~
18.6 DISCUSSION......Page 766
0 R" O6 R) ?+ g8 `, XPART VI Conduct of Clinical Trials......Page 767
- V! t8 e& t# b8 s19.1 INTRODUCTION......Page 769
3 t% }3 M! e; D0 o4 K5 A* R6 g19.2 STRUCTURE AND COMPONENTS OF A PROTOCOL......Page 7706 f0 z. q4 x" d$ X
19.3 POINTS TO BE CONSIDERED AND COMMON PITFALLS DURINGDEVELOPMENT AND PREPARATION OF A PROTOCOL......Page 776; [" i8 |  E2 M* H2 f7 l3 }8 |
19.4 COMMON DEPARTURES FOR IMPLEMENTATION OF A PROTOCOL......Page 779
5 R/ Y1 O. h( R4 p19.5 MONITORING, AUDIT, AND INSPECTION......Page 785
8 R. T# P! Y0 y0 a" {7 ?0 Y7 l19.6 QUALITY ASSESSMENT OF A CLINICAL TRIAL......Page 7898 v* ~4 ^* I  B/ f6 C$ F
19.7 DISCUSSION......Page 791
$ G  P' }( p4 c7 o9 Z20.1 INTRODUCTION......Page 793
  F- @+ K& z/ I0 Z20.2.1 Part 11 Compliance......Page 795
/ w+ f6 [5 V& m# W- [( Y20.2.3 FDA Guidance on Bioresearch Monitoring—Compliance ProgramGuidance Manual......Page 796. Q; R1 t2 k5 C2 W4 q$ q$ Q
20.3 DEVELOPMENT OF CASE REPORT FORMS......Page 797( X# K* D* |* H7 I
20.3.1 CRF Design......Page 798) ?% [! s; m& d
20.3.2 CRF Flow and Tracking......Page 799, @% ?7 O3 `1 o1 x: A! l
20.4.2 Data Edit Check Specifications......Page 801
6 d4 E/ F5 D) ~0 @$ g7 s20.5.1 Data Entry and Verification......Page 802" H1 Y5 @+ v/ A8 Y. G1 B
20.5.2 Data Query......Page 8037 L/ r# V4 i1 Y" C* [
20.6 DATA VALIDATION AND QUALITY......Page 8059 ]+ z, W) p% K( ~* b3 M5 o/ g
20.7.2 Database Transfer......Page 806% Z! p3 A# P. m
20.8.2 Electronic Data Capture......Page 809
7 b0 r, d# ?1 W0 U. |4 k! x20.8.4 Global Database and System......Page 8109 ?! i, |; z1 F% s8 H4 R
20.8.5 Role of the Statistician in the Data Management Process......Page 8114 z8 ~0 {2 k. P
References......Page 813
5 X+ C  Y/ n5 o( W; w  N0 |+ J- KAppendix A......Page 859
+ j# ^3 ]6 S  D6 H/ {Index......Page 865# Q) l" {0 f2 b' X/ u7 R) Z3 N( ?
Wiley Series in Probability and Statistics......Page 885
7 l3 N' T- [( ^, B$ Y6 p# K7 p; }  e) q+ S
需要本书第2版的请点击:临床试验的设计与分析(英文原版,第2版)  C8 d: \6 A$ Y$ q8 S% a- C/ P1 o

* M) x. \# P0 B说明:下面2个压缩包都要下载后解压!, a: Z# \# F, X' M; h: U
Design and Analysis of Clinical Trials Concepts and Methodologies (3rd edition, .rar (7 MB, 下载次数: 396, 售价: 5 分钢镚)
, @$ v  {9 f) @( f1 m$ k$ j; g5 { Design and Analysis of Clinical Trials Concepts and Methodologies (3rd edition, .rar (4.04 MB, 下载次数: 339, 售价: 5 分钢镚)
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jiangl0 发表于 2014-8-24 20:19:45 | 显示全部楼层
牛啊!!!这种资源都能弄到!!
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 楼主| sampson2010 发表于 2014-8-24 21:30:38 | 显示全部楼层
jiangl0 发表于 2014-8-24 20:19
4 p% X6 ]9 A! F牛啊!!!这种资源都能弄到!!
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如果需要都是可以搞到的~~附件已挂出,需要请自行下载~~
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jiangl0 发表于 2014-8-25 19:24:52 | 显示全部楼层
sampson2010 发表于 2014-8-24 21:30, k" h7 \2 b2 N+ T# E. q
如果需要都是可以搞到的~~附件已挂出,需要请自行下载~~
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xinhenan 发表于 2014-11-27 11:35:58 | 显示全部楼层
楼主是大骗子,两个都下了,解压的时候显示要第三部分
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 楼主| sampson2010 发表于 2014-11-27 12:26:01 | 显示全部楼层
xinhenan 发表于 2014-11-27 11:35
# p, A5 c0 x8 }楼主是大骗子,两个都下了,解压的时候显示要第三部分

. X: i3 U2 K8 h狗血喷人之前,先动动脑子弄明白是不是自己解压或者下载的时候有问题,导致附件有损,无法正常解压缩!% j* U; B) z3 B/ d+ T9 V
本人再次解压缩查看上传的附件的个数和大小发现没有问题!
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不喜勿下
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xinhenan 发表于 2014-11-27 14:09:03 | 显示全部楼层
本帖最后由 xinhenan 于 2014-11-27 14:13 编辑
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谢谢啦,成功下载,成功解压。
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李庆奎 发表于 2014-12-7 12:08:37 | 显示全部楼层
为啥解压有问题
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多谢楼主分享
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