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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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+ v6 C9 l/ i0 T; \/ k"Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning."
6 Y( `; R7 c% k; V& S                                                                                                                                                     ——Albert Einstein
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Title: Design and Analysis of Clinical Trials: Concepts and Methodologies
: Y. \4 N6 \- U1 P# ]6 L; mAuthor(s): Shein-Chung Chow, Jen-Pei Liu$ s: K1 z* D0 ~* u" _* G  E4 \
Publisher: Wiley
6 }# ?& \2 e' f# Z# PYear: 2013        + S! C1 z# |9 `5 C, m- a
Edition: 3rd
( ~0 i# ~! W0 H( j4 {) M+ ?; {! uLanguage: English        . g+ Z& P7 ~- y% @
Pages: 892# S0 b! x# i! J- h' P
ISBN: 0470887656, 9780470887653       
" r; m4 B& x4 x+ E5 vID: 11684429 {6 v$ ]& `4 f  f& h
Size: 17 MB (17671149 bytes)        $ k/ a4 l7 T; N2 `4 j& j
Extension: pdf
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7 y0 L9 ?- V- ]# e; A3 ^8 zPraise for the Second Edition:6 |1 V: a. y2 V3 A& r
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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  ]! r' X  w& I
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The 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:
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0 u- p" b' I5 r+ H' V• 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# w/ D8 D+ X* [; e6 |( r- e5 s

& Q; F4 o. U0 N& C4 T( n; v• A balanced overview of current and emerging clinical issues as well as newly developed statistical methodologies" I+ L# ]7 a% B) R
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• Practical examples of clinical trials that demonstrate everyday applicability, with illustrations and examples to explain key concepts
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3 ?: ?  P$ e4 @) v5 V• New sections on bridging studies and global trials, QT studies, multinational trials, comparative effectiveness trials, and the analysis of QT/QTc prolongation, ]7 Z% l9 f/ o; `! u( j, v
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• A complete and balanced presentation of clinical and scientific issues, statistical concepts, and methodologies for bridging clinical and statistical disciplines( b) y' ^5 l" R: A& n
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• 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.. {/ I7 `9 _3 q, D
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( n. s8 L4 s2 J: s1 M  D- z% z- @Table of contents :
* v$ d' |- C5 v8 m3 \Design and Analysis of Clinical Trials......Page 3. `, ~; ~- `) o' e1 g8 ?
Contents......Page 7) y% o) a" i) h) D0 @, J4 ?
Preface......Page 13
2 M* Y; ]: p: l2 RPART I Preliminaries......Page 15! c* p7 R0 ~+ ]3 K9 n# I+ h
1.1 WHAT ARE CLINICAL TRIALS?......Page 17
% V) a4 a0 l8 e+ j0 K1.2 HISTORY OF CLINICAL TRIALS......Page 18
0 T$ I) p, a- P+ Y$ E! j1.3.1 The Food and Drug Administration......Page 24& ?5 G4 p. O5 j% g' u' p) i% Z
1.3.2 FDA Regulations for Clinical Trials......Page 27
+ n; o+ R2 S, A! T% C+ D1.3.3 Phases of Clinical Development......Page 29
4 e( n# Z; f' ~  Y. F+ u% I1.4 INVESTIGATIONAL NEW DRUG APPLICATION......Page 319 J# Y7 n/ C5 _9 h+ m
1.4.1 Clinical Trial Protocol......Page 33
' I' N" f$ ~0 y* |" m1.4.2 Institutional Review Board......Page 36
0 R& _* U  ~8 d% p- n0 ^6 _2 U% q1.4.5 Withdrawal and Termination of an IND......Page 378 J3 a# p& N' b$ i- ?) E
1.5 NEW DRUG APPLICATION......Page 38
3 O4 ?- s5 v/ [" w7 a/ u% Z1.5.1 Expanded Access......Page 406 K; i+ {/ v2 S! C4 r- N: ^
1.5.2 Abbreviated New Drug Application......Page 43
% [  w, f1 Z* |: o- ~1.5.3 Supplemental New Drug Application......Page 44
. K& X. R# u4 Z1 m' T1.6.1 Clinical Development Plan......Page 45- |- `  v7 J  \+ L  G" T2 P. A
1.6.2 Good Clinical Practice......Page 477 o7 A  g3 T$ z" n- z
1.7 AIMS AND STRUCTURE OF THE BOOK......Page 56; e8 V2 \) Z" @" {- k
2.1 INTRODUCTION......Page 59
5 F* A) p9 d! V# V7 i$ g$ l. Z6 A2.2.1 Uncertainty......Page 60
, a! e9 k  K; A, y, a% f" z2.2.2 Probability......Page 619 Y" z% i: e% e3 t  E9 Y
2.3.1 Bias......Page 63
/ M2 _1 G# B; S0 y5 h! y2 N9 p2.3.2 Variability......Page 68( R- J* K3 Y) J( F
2.4 CONFOUNDING AND INTERACTION......Page 71' f, {3 w" }1 n3 E
2.4.1 Confounding......Page 72
. K' k" A) w2 b0 ]5 P: @3 k/ A( A! M; ]2.4.2 Interaction......Page 75
0 e, k& p+ K, S. s$ Q2.5 DESCRIPTIVE AND INFERENTIAL STATISTICS......Page 80
* J4 i) N7 ~! H3 W9 Y. c2.6 HYPOTHESES TESTING AND p-VALUES......Page 82
9 F# r0 R8 O8 S; X, R4 u. |! a9 e2.6.1 p-Values......Page 84
. t$ |. y6 b( L+ ?$ |3 |2.6.2 One-Sided Versus Two-Sided Hypotheses......Page 86
" c7 S( W$ {# S. ]2 y2.7 CLINICAL SIGNIFICANCE AND CLINICAL EQUIVALENCE......Page 894 i; K" e+ t' j( [9 W
2.8 REPRODUCIBILITY AND GENERALIZABILITY......Page 93: ]1 s# b) i9 O* q6 y( F
2.8.1 Reproducibility......Page 94
+ x) H: B) I8 z2.8.2 Generalizability......Page 95  k5 q2 B1 i! ~5 O5 {" t3 A
3.1 INTRODUCTION......Page 99+ t$ f/ ~  S2 M
3.2 GOALS OF CLINICAL TRIALS......Page 100
9 w! Q: A4 E4 Y6 R; J2 S& @- d. ?3.3.1 Eligibility Criteria......Page 104
9 q2 w& Z; x0 o3.3.2 Patient Selection Process......Page 108
. R& K6 i$ i. N1 l! V3.3.3 Ethical Considerations......Page 1106 w  N0 @$ J8 C$ |$ y- r( d9 O
3.4 SELECTION OF CONTROLS......Page 111
; y' R7 J( s2 n" r" t! i3.4.1 Placebo Concurrent Control......Page 112
9 ~+ x( x2 H- J, r9 ?, l4 f3.4.2 Dose–Response Concurrent Control......Page 115  v, x# H: n: c+ o/ b) J" D
3.4.3 Active (Positive) Concurrent Control......Page 117# T+ I7 _( n( p: m1 B
3.4.4 No Treatment Concurrent Control......Page 118; u  T; V1 k  p! H& N/ M
3.5.1 Efficacy and Safety Assessment......Page 1193 M9 b% G0 i6 C9 E
3.5.2 Sample Size Estimation......Page 121
6 S% ~/ G( E; _# U3.5.3 Interim Analysis and Data Monitoring......Page 122, G1 l- {% l. V( S+ x
3.5.4 Statistical and Clinical Inference......Page 124- w; ?, W, r" A6 }% s
3.6 OTHER ISSUES......Page 126; V! _! _' T& `3 `, t' W( _+ N
3.6.3 Patient Compliance......Page 127
( i( c3 S. q7 B, p- c3.6.4 Missing Value and Dropout......Page 128
4 h! V$ C( U; @  M! A( A3.7 DISCUSSION......Page 129
. m0 k2 N6 n  `  ~7 J* e4.1 INTRODUCTION......Page 131
( E5 r$ X, g4 D- Z8 |4.2 RANDOMIZATION MODELS......Page 132/ m4 J: f# h" P+ j/ }
4.2.2 Invoked Population Model......Page 133
0 A1 ?5 r  R) s- V" Z: B5 W3 P4.2.3 Randomization Model......Page 134
, X5 i9 ~/ O6 @( B% i& {4.2.4 Stratification......Page 136! F$ Z/ a, G0 g. I8 V
4.3 RANDOMIZATION METHODS......Page 138
2 |. C! p7 z8 D# c2 @- |4.3.1 Complete Randomization......Page 1420 P/ y$ M  ?' }! H% z' U4 ]/ H# y
4.3.2 Permuted-Block Randomization......Page 147
0 Y9 n1 N( u; m+ ~% d4.3.3 Adaptive Randomization......Page 1518 }" e7 b8 {; q; }3 W0 b: p- R
4.4.1 Generation, Labeling, and Packaging......Page 1585 q3 P+ t, t0 J8 N5 I
4.4.2 Random Assignment......Page 160
+ `. J6 j, `( T# p5 n/ W% a9 t+ Y4.5 GENERALIZATION OF CONTROLLED RANDOMIZED TRIALS......Page 163
5 @) s! @, w; @& W6 M% u7 a4.6 BLINDING......Page 167( {; w0 ], C8 i' w0 }$ d4 e
4.7 DISCUSSION......Page 174
0 y4 b3 ~, `8 r) u" cPART II Designs and Their Classifications......Page 177
7 H; x9 R7 H# x/ R7 M- ]" \& H5.1 INTRODUCTION......Page 179$ }- N+ e% o' E# K$ Y+ g
5.2 PARALLEL GROUP DESIGNS......Page 181, ]; t! E% E$ c* Q1 }5 G4 g/ A
5.2.1 Run-in Periods......Page 183
+ j( t! \: D, Y8 j/ O- q5.2.2 Examples of Parallel Group Design in Clinical Trials......Page 1843 i# H2 Z" ?, ?4 l
5.3 CLUSTERED RANDOMIZED DESIGNS......Page 1868 I4 W  y4 ~: b7 P' f- Z, I! Y5 S$ l
5.4 CROSSOVER DESIGNS......Page 191- l' C/ |# x7 _
5.4.1 Higher-Order Crossover Designs......Page 1920 t/ W7 B) B  t8 G. a1 @* R
5.4.2 Williams Designs......Page 195) ~& Y' ~" J5 G+ d, }
5.4.4 Examples of Crossover Design in Clinical Trials......Page 196
9 u. G" `4 E+ c( }( V9 L5.5.1 Standard Titration Design......Page 199
3 V1 C9 C- I. ^' [3 O: [5.5.2 Forced Dose-Escalation Design......Page 203* X8 r8 i2 c) ?5 f! R% I
5.6 ENRICHMENT DESIGNS......Page 205
. c5 H; ?5 h& N2 T% Q$ |3 @5.7 GROUP SEQUENTIAL DESIGNS......Page 209
5 Y% a$ q8 g2 S5.8 PLACEBO-CHALLENGING DESIGNS......Page 211
/ v+ e2 u" t  V7 Q# n3 ~6 m& `5.8.1 Statistical Model and Inferences......Page 212
( K6 t' U' u6 X% S2 i8 Q3 g5.9 BLINDED READER DESIGNS......Page 2171 d; t/ ^$ E, m
5.10 DISCUSSION......Page 2212 O0 N) t% ?- S  C% e
6.1 INTRODUCTION......Page 225
# x+ \0 j  e: u& f4 e) F7 @6.2 GENERAL CONSIDERATIONS FOR PHASE ICANCER CLINICAL TRIALS......Page 227, j: q2 U& q! K/ g
6.3 SINGLE-STAGE UP-AND-DOWN PHASE I DESIGNS......Page 2282 j! L; @7 @# z
6.3.1 Design A—Standard Dose-Escalation Design......Page 229
8 G" U6 ~& v* {: `) F! P6.4 TWO-STAGE UP-AND-DOWN PHASE I DESIGNS......Page 231
- c( L+ {; }  E- k: R9 C6.4.2 Accelerated Titration Designs......Page 2323 h4 C7 s" O4 c' n- W- T
6.5 CONTINUAL REASSESSMENT METHOD PHASE I DESIGNS......Page 2333 f4 P, e9 i& w$ _# a  H
6.6.1 Single-Arm Trials......Page 236
" I: W" R& B+ v$ |6 }7 r6.6.2 Multiple-Arm Trials......Page 240. |  k1 t$ |( o8 L, \
6.7 RANDOMIZED PHASE II DESIGNS......Page 243
+ S- i  U* }3 S6.8 DISCUSSION......Page 246
# C1 W/ t& T% E6 a( Z: X7.1 INTRODUCTION......Page 251
" ?/ k, M8 t; X1 A8 ^2 N  w! P- w7.2 MULTICENTER TRIALS......Page 252
- n0 ]6 K" F/ ?! k/ A7.2.1 Treatment-by-Center Interaction......Page 253
, H6 I; w0 a& i( b8 J9 b. z9 H7.2.2 Practical Issues......Page 2554 f& _8 u7 H2 h
7.3 SUPERIORITY TRIALS......Page 259! K4 n+ s. k( X3 V6 F7 P: q
7.4.1 Primary Objectives......Page 2624 z) ]- ^: u+ [. D8 z7 E6 ?
7.4.2 Issues in Active Control Equivalence Trials......Page 263- B& B& N9 h- G2 R  ^
7.4.3 Interpretation of the Results of Active Control Trials......Page 267
$ p8 ?3 `4 ^3 n$ T2 o+ ^6 `5 l7.4.4 Equivalence/Noninferiority Limits......Page 2693 O/ W0 c( Q) E2 N* \0 P* f5 l
7.4.5 Statistical Methods......Page 272
/ B$ z  e5 D3 p# q$ x9 v7.5 DOSE–RESPONSE TRIALS......Page 2750 A2 `( Q/ W1 X) f2 d1 ]+ f6 k
7.5.1 Randomized Parallel Dose–Response Designs......Page 2764 U, t0 v3 B6 |8 {. Q8 b
7.5.3 Forced Titration (Dose-Escalation) Design......Page 278
- @4 R8 Z( C( N7.5.4 Optional Titration Design (Placebo-Controlled Titration to Endpoint)......Page 279
* I0 {" D5 ^* F0 I" e+ p0 p6 M7.6 COMBINATION TRIALS......Page 280
! d5 b  B, C% Y/ x7.6.1 Fixed-Combination Prescription Drugs......Page 2828 ]4 U$ _6 J4 ]# r$ b  X
7.6.2 Multilevel Factorial Design......Page 285
; Q1 A5 g& Z! V; \+ K& R7 }- h7.6.3 Global Superiority of Combination Drugs......Page 287
( ~, r( v( a5 J  Q$ T' o7.6.4 Method of Response Surface......Page 291
! [! ^' ?: C! X  I. J7.7.1 Introduction......Page 2921 u( P9 O) a9 n& T/ Z  ]6 W2 J
7.7.2 Ethnic Sensitivity and Necessity of Bridging Studies......Page 2934 p4 g5 m) O: o
7.7.4 Assessment of Similarity Based on Bridging Evidence......Page 296
' X0 \, O' ?) B7.8.1 Basic Design and Statistical Considerations......Page 299/ G0 r) w1 I7 B/ `" E
7.8.2 Types of Vaccine Immunogenicity Trials......Page 300
! `: g( i; x2 I! W  G" c/ g  F7.8.3 Statistical Methods......Page 302
8 r: ]) J: F8 A- i7.9 QT STUDIES......Page 305
4 `: k4 N& H/ d" J  V; z7.9.1 Study Designs and Models......Page 306
% [6 n; r. p. {, l  b2 z' R9 B5 ~" |7.9.2 Power and Sample Size Calculation......Page 307  `& T0 {& v* M6 P; W
7.9.3 Allocation Optimization......Page 311( i1 q0 C. i0 Y% o5 C
7.9.4 Remarks......Page 312
1 M& G3 C# L+ r% C, f6 x+ c7.10 DISCUSSION......Page 313
: j( s, H/ j* w) xPART III Analysis of Clinical Data......Page 317& W0 Y' X/ g$ w8 u4 l# Y) C
8.1 INTRODUCTION......Page 319
/ p; {( M8 L3 ?3 _0 e9 |- o8.2 ESTIMATION......Page 320
( V# @  M: @; ~/ p2 y+ B; v/ J7 D  [8.3 TEST STATISTICS......Page 324
9 K2 o4 R" n8 r8.3.1 Paired t Test......Page 326
# B8 D0 E$ A7 y' n. u! A& U1 j$ M6 m8.3.2 Two-Sample t Test......Page 327
! S1 p: v) b# _' x8.4.1 One-Way Classification......Page 3304 h+ x, `  w8 e$ q
8.4.2 Simultaneous Confidence Intervals......Page 332
4 G' B8 a  o: ?5 y  g/ c# O) v8.4.3 Two-Way Classification......Page 334: L2 E/ O3 }2 ^, M2 X: a
8.5 ANALYSIS OF COVARIANCE......Page 337# {0 P2 b' ~+ P  f( n$ l7 N7 ~
8.6 NONPARAMETRIC METHODS......Page 339
/ |5 t( U0 U( N% S% X! W0 P1 D8.6.1 Wilcoxon Signed Rank Test......Page 340* K4 i- p8 A! ~) E8 Y# L  o
8.6.2 Wilcoxon Rank Sum Test......Page 341" U1 A. F: S" |4 Z! {
8.6.3 Kruskal–Wallis Test......Page 3455 f& K5 ]1 x* i2 [2 ]( V
8.7.1 Assessment of Overall Average Effect Across Time......Page 346
$ w5 Q2 `4 }3 S7 y2 _( _1 p8.7.2 Detection of Time Effect......Page 348
& B3 d( a* U7 q! i' _( }8.7.3 Treatment-by-Time Interaction......Page 3494 T" |! y( j. j0 s4 |
8.7.4 Method of Generalized Estimating Equations (GEEs)......Page 351
  C3 a- W: I' C3 D$ M7 x* |- H2 g) \8.8 DISCUSSION......Page 355
. `; n* @/ o3 F9.1 INTRODUCTION......Page 357
3 v: R+ g! |/ f5 J: O8 d7 c9.2 STATISTICAL INFERENCE FOR ONE SAMPLE......Page 359# L. s; @  f# l5 `, ~$ ^! ?% t* }& S) P
9.3 INFERENCE OF INDEPENDENT SAMPLES......Page 372
+ y! g0 n+ ]2 I1 E( s9 Y; I9.4 ORDERED CATEGORICAL DATA......Page 378
4 A+ z  V5 V6 |1 B) T9.5 COMBINING CATEGORICAL DATA......Page 382
2 v- Z" S" ~, K9.6 MODEL-BASED METHODS......Page 388
- l  r* r0 X5 ~+ [3 x" ^* ]9.7 REPEATED CATEGORICAL DATA......Page 396
' ]' F7 _: l/ z) V) E+ O9.8 DISCUSSION......Page 401! l8 P0 e, W8 Q1 X+ {
10.1 INTRODUCTION......Page 403
, s8 j9 T$ s; ~8 ^0 v/ A9 Q10.2 ESTIMATION OF THE SURVIVAL FUNCTION......Page 405/ E  G0 i3 K  \, \
10.3 COMPARISON BETWEEN SURVIVAL FUNCTIONS......Page 413
1 G; {" s7 G. `$ @10.4 COX’S PROPORTIONAL HAZARD MODEL......Page 419
2 A: x$ W* X: p; N10.5 CALENDAR TIME AND INFORMATION TIME......Page 433
) G' K: D0 k" M8 D- h# @10.6 GROUP SEQUENTIAL METHODS......Page 438
7 ^) @6 H7 S! E8 D. Z9 X+ B' H: F10.7 DISCUSSION......Page 452
! i& c* Q9 a2 U11.1 INTRODUCTION......Page 4555 W7 g8 d* Y+ r
11.2.1 Study Objectives and Hypotheses......Page 456- F7 T1 [/ w' T9 \
11.2.2 Type I and Type II Errors......Page 458( t* P5 d. |$ y5 p$ ^& `, T' j
11.2.3 Precision Analysis......Page 4599 w6 l, e9 R5 I) [) R
11.2.4 Power Analysis......Page 460, j, K* F) D- B5 e) m3 f/ H
11.3.1 One-Sample Test for Mean......Page 461
4 h. _( M- E* A; n6 |5 l11.3.2 Two-Sample Test for Comparing Means......Page 462  l# ]3 P8 k: D+ J( p3 ^9 B
11.4.1 Sample Size Calculations for Analysis of Variance Models......Page 470
2 \' J& t9 ]3 o: b1 y2 Y11.4.2 Sample Size Calculations for Generalized Linear Models......Page 472. C2 W' a: S" U$ E
11.5 CENSORED DATA......Page 473
# \- C0 S! ?1 k, F11.6.1 Dose–Response Relationship......Page 478
. q/ C1 |; m0 P( D11.6.2 Minimum Effective Dose......Page 480
& S+ ^' r2 \6 L  B1 D# w. b7 B11.7.1 Point Hypotheses for Equality......Page 4850 |6 \' e$ G& x4 I. o! f& S
11.7.2 Interval Hypotheses for Equivalence......Page 487: F# m7 F# e- ]9 t! ]  R- c) {
11.7.3 Higher-Order Crossover Designs......Page 4925 \0 i+ i' P: h/ b  ^/ Y  m5 f+ c$ G
11.8 EQUIVALENCE AND NONINFERIORITY TRIALS......Page 495
4 N) s" Z4 m4 g, ?& Y8 ]2 \* A# B11.8.1 Independent Binary Endpoints......Page 496
6 D3 y  A, N' f" \% r( g5 R11.8.2 Paired Binary Endpoints......Page 498- j" D3 o$ B/ a) b8 y' ?
11.8.3 Independent Censored Endpoints......Page 500# n' F; a7 \9 l! L0 |
11.10 MULTINATIONAL TRIALS......Page 5045 B( i  e4 D$ r8 v3 ~1 |- Q4 n0 o
11.10.1 Selection of the Number of Sites......Page 505; K3 M7 Q) V# Q1 t5 }
11.10.2 Sample Size Calculation and Allocation......Page 5116 u0 D" Z3 Y- e
11.11 COMPARING VARIABILITIES......Page 514
' M' k$ @( s% i3 g11.11.1 Comparing Intrasubject Variabilities......Page 515) y, t& H* u9 L9 y! _
11.11.2 Comparing Intersubject Variabilities......Page 523
- A' D$ O6 v* r4 z7 T0 c/ B6 I- v11.12 DISCUSSION......Page 531) }; f* x2 d5 B# C$ P" i; p
PART IV Issues in Evaluation......Page 533% l' y( J# [8 J1 c4 z
12.1 INTRODUCTION......Page 535* `2 X% n4 D& H7 l/ n0 F$ r
12.2 BASELINE COMPARISON......Page 537
7 |" x' j% f" K5 s0 Y1 L& |12.3 INTENTION-TO-TREAT PRINCIPLE AND EFFICACY ANALYSIS......Page 542) j  @9 @  C$ g1 ~$ }( u
12.4 ADJUSTMENT FOR COVARIATES......Page 550
" g$ w9 r) L" G12.5 MULTICENTER TRIALS......Page 5551 x5 ]% d$ R" A+ M+ r$ M
12.6 MULTIPLICITY......Page 5625 `. f. H2 O, y" M' N0 x3 q
12.6.1 Multiple Comparisons......Page 5644 w2 c  q% B9 L$ A+ j7 E4 K1 f
12.6.2 Multiple Endpoints......Page 5669 q0 Q# r( w! a, U4 o3 b
12.6.3 Subgroup Analysis......Page 571) T7 C# P# w+ M7 Q6 y3 }" O. z
12.7.2 Regulatory Concerns......Page 5721 c8 e: A* \+ ^8 w
12.7.3 Early and Late Stages of Drug Development......Page 574
( V' q) v' C% O: A/ k( ~12.7.5 Data Monitoring Committee......Page 5750 J3 h8 w/ N7 ^
12.8 USE OF GENETIC INFORMATION FOR EVALUATION OF EFFICACY......Page 578) x; c5 W) n7 q" `* H' q9 a% y: R
12.9 SAMPLE SIZE REESTIMATION......Page 584
* Z" l* e4 t8 ~* f12.10 DISCUSSION......Page 586  x1 x) g7 F  j7 j2 t7 s* ~
13.1 INTRODUCTION......Page 587) F2 U- c& x9 a+ G" g% [% ~8 G
13.2 EXTENT OF EXPOSURE......Page 588
& U, D$ J6 Q, |- J2 I13.2.1 Risk of Exposure......Page 589, L' r) ?7 Y& G6 E( ^
13.2.2 Absorbing Events......Page 590
: n6 y" b9 N3 C4 l0 d7 j! j$ O- U13.2.3 Recurring Events with Negligible Duration......Page 591
$ S, T3 g0 t& \6 j13.2.4 Recurring Events with Nonnegligible Duration......Page 592
8 l* w' y. A  F' }4 p+ A13.2.5 Laboratory Data......Page 593
5 {; m7 d1 w# w+ g13.3.1 Definitions of Adverse Events......Page 596
0 W% L- S- ~, I) B% G; S$ Z13.3.2 COSTART......Page 6005 g( u2 h. _) S0 g/ g
13.3.3 MedDRA......Page 602+ E) _. G2 O. I0 ?' `
13.3.4 Common Toxicity Criteria......Page 6077 C! K# d, I$ l- L& y
13.4.1 Adverse Event Data Listing......Page 609
( K3 T$ {: i, y: b) B0 {  q13.4.2 Summary Tables of Adverse Events......Page 610! I$ {. w  i$ D2 T- O# ~. ^$ V
13.4.4 Analysis of Adverse Events......Page 611! c1 l* y+ ]" ~/ _$ f$ \8 v5 F4 G
13.5.2 Combinability of Laboratory Data......Page 6164 w  ~3 B! U# a# }3 ]5 A. L
13.5.3 Clinically Significant Changes......Page 618) Q5 t' C: J9 p% Q$ p( {
13.5.4 Shift Analysis......Page 619) z# C5 E7 D% C5 D* q6 z
13.6 ANALYSIS OF QT/QTc PROLONGATION......Page 624) t, B+ x. y: s
13.6.1 Test Under Parallel Group Design......Page 625& c8 x! M, P# y( w1 I3 @- f4 s
13.6.2 Test Under Crossover Design......Page 627
) L  Y+ E# U7 l# x1 f+ r13.6.4 Remarks......Page 628
9 U* j  |. K- C# j13.7 DISCUSSION......Page 629
9 p* N3 U5 n2 b; V' S$ u# }PART V Recent Development......Page 631
0 p( a$ N7 a* T, D14.1 INTRODUCTION......Page 633
7 K1 o/ H' M5 F& S& b% z$ L14.2 CONCEPTS AND STRATEGIES......Page 634; d- z+ @0 X! O/ s6 O6 j" \
14.3.1 Classifier, Prognostic, and Predictive Biomarkers......Page 637
# M# Y! m) A: W. J( v/ f14.3.2 Biomarker Development......Page 639
" j6 q; y: T7 W# T1 d. U14.3.3 Analytical Validation......Page 641
' d) {2 Z6 @. {14.3.4 Clinical Validation......Page 642
5 s, Z4 S$ C4 g/ X% V# I14.4.1 Considerations for Phase I Trials......Page 644
6 w' c& q1 b( O% W14.4.2 Considerations for Phase II Trials......Page 645% `/ A: e5 d3 W  n5 g
14.4.3 Considerations for Phase III Trials......Page 648  [# B5 P# h) Z" ?- L& K* E
14.5.1 Biomarker as a Covariate Versus a Stratification Factor......Page 654
6 ]; b5 l- i/ a8 c14.5.2 Treatment-by-Biomarker Interaction Versus Separate Analysis......Page 655
- c* U0 Q5 |* i- t% u# A14.5.3 Impact of the Measurement and Classification Error......Page 657
% }% R( N% |$ A, ?5 b14.6 DISCUSSION......Page 661: N1 X5 c) {' ?" q& L4 p
15.1 INTRODUCTION......Page 6636 x& N) x% J! G+ r
15.2 STUDY DESIGN......Page 665
; b# y) b/ m+ x9 T, s15.3 MEASURES OF DIAGNOSTIC ACCURACY......Page 670
, l/ s0 A4 e* h* O: G$ {0 h' p+ I15.4 REPORTING RESULTS......Page 677/ i' o! T0 r6 T/ l
15.5 SAMPLE SIZE ESTIMATION......Page 6863 p' M& L7 D  Q* M9 [
15.6 DISCUSSION......Page 689/ O& H4 t3 a/ x2 ]* V1 u+ q: U
16.1 INTRODUCTION......Page 691) K2 O( @! c  x$ X2 @7 i
16.2 BIOMARKER DEVELOPMENT......Page 692: S4 M, r' t4 s# b
16.2.1 Optimal Variable Screening......Page 6934 l/ U! t. V: g4 A; g) n
16.2.2 Model Selection and Validation......Page 694
* v, B. Q$ _( W- G4 I& q16.2.3 Remarks......Page 6953 p. M: `8 B/ x* V, V" {3 J
16.3.1 One-Way Translational Process......Page 696
# Y! `4 i8 x- F% }. l16.3.2 Two-Way Translational Process......Page 701
# }! n0 ~+ D- g16.4 ANIMAL MODEL VERSUS HUMAN MODEL......Page 703
  f4 Q+ L$ D0 g; U16.5.1 Power Analysis and Sample Size Calculation......Page 705
; U# y+ H4 w/ p) t8 \+ i2 I5 {5 p; I7 B16.5.2 Remarks......Page 709, r1 ^6 Z8 Q3 m& R7 l, K1 v" }% K
16.6 BRIDGING STUDIES......Page 710
- ~# y# ]. G4 x' B" G! B16.6.1 Test for Consistency......Page 711
5 l8 ^% n* N) I6 r* }16.6.3 Test for Similarity......Page 712
/ L: U. N+ P; e( o( m; Z16.7 DISCUSSION......Page 713
# C( d! A/ x. G16.8 APPENDIX......Page 7149 d( P' L- U1 e: k7 @$ B$ f
17.1 INTRODUCTION......Page 717
: c* q  O. d( ~; n: w. {. G17.2 WHAT IS ADAPTIVE DESIGN?......Page 718
: @- s% n9 m6 ]3 \! F/ q7 F) e17.2.2 Type of Adaptive Designs......Page 719
+ l, H* {8 l3 t" b* t( c! |17.3.1 Well-Understood Designs......Page 723+ M- o  o$ u8 R
17.3.2 LessWell-Understood Designs......Page 7248 s8 ~, W: d1 t8 Z' U4 d* t6 R
17.4.1 Clinical Operation Perspectives......Page 727; s2 @( g. q5 j; R7 V$ x6 k" H- d
17.4.3 Regulatory Perspectives......Page 729
& ^3 E1 K0 a; T3 J' N6 ]& l17.5.1 Moving Target Patient Population......Page 730
  \7 ?9 K8 C* @) x17.5.2 Statistical Inference with Covariate Adjustment......Page 731
: r8 ]6 L* X3 T! o! w6 U17.5.3 Bayesian Approach......Page 7333 l/ |/ u: `7 B" V
17.6.1 Adaptive Group Sequential Design......Page 735' ?( i) \8 f1 A0 B! Z, l, t
17.6.2 Adaptive Dose-Finding Design......Page 737
+ F+ l+ t+ T7 {- D17.6.3 Adaptive Seamless Designs......Page 739. v4 Y4 N9 p: ]! A' m' ^* |% T
17.6.4 Remarks......Page 740
$ Q4 C, N8 t- n17.7 OBSTACLES OF RETROSPECTIVE ADAPTATIONS......Page 7417 |  Q9 L# y5 I( b& z' R" B
17.8 DISCUSSION......Page 743; V' o5 C1 c; i# C
18.1 INTRODUCTION......Page 7477 r+ n7 U7 q; G# K& H0 d
18.2 FUNDAMENTAL DIFFERENCES......Page 748
/ \0 }1 `! h9 U( J7 m( S9 D5 q18.2.1 Medical Theory/Mechanism and Practice......Page 749" a8 Q( m5 I& M, S9 E
18.2.2 Techniques of Diagnosis......Page 7522 q% _. q6 t& v( m. i
18.2.3 Treatment......Page 753
' t0 p3 C" ?2 W$ x' t18.2.4 Remarks......Page 754
. ]0 ^9 A8 [& X. {3 F18.3.1 Study Design......Page 755; k- {. }: U. B0 m* p% O
18.3.2 Validation of Quantitative Instrument......Page 756
- {' [1 y. [! ^4 @18.3.4 Matching Placebo......Page 757$ V4 _# K. r3 e) O
18.4 OTHER ISSUES IN TCM RESEARCH AND DEVELOPMENT......Page 7585 L6 C; N  {. V8 ~- K
18.4.1 Test for Consistency......Page 759
! T- [) X, F0 H+ ^3 j% A. b9 M18.4.2 Stability Analysis......Page 761
" B, g! ]" c# V' j18.4.3 Animal Studies......Page 763
' F% \* R$ Q3 b% P$ b, t* g2 f" O3 `6 @18.4.5 Indication/Label......Page 7642 A6 v0 u* h2 e" s2 L& b
18.5 CONSORTIUM FOR GLOBALIZATION OF TRADITIONALCHINESE MEDICINE......Page 765
* H* s2 w/ e7 e9 a18.6 DISCUSSION......Page 766, f% n% L# Z; d' a
PART VI Conduct of Clinical Trials......Page 767( S. t- e9 K5 I  r# s
19.1 INTRODUCTION......Page 769
  w* r# o( ^  K, c" a19.2 STRUCTURE AND COMPONENTS OF A PROTOCOL......Page 770  s8 }" A2 u# M1 e- n  g6 B
19.3 POINTS TO BE CONSIDERED AND COMMON PITFALLS DURINGDEVELOPMENT AND PREPARATION OF A PROTOCOL......Page 776' i- b( e/ b( a: j1 ^! ^
19.4 COMMON DEPARTURES FOR IMPLEMENTATION OF A PROTOCOL......Page 779
( M( ^* W0 p3 O* w9 W19.5 MONITORING, AUDIT, AND INSPECTION......Page 785
! E- k. s2 v( L! }$ A" D19.6 QUALITY ASSESSMENT OF A CLINICAL TRIAL......Page 789) C! g  Z7 y% l6 |7 [
19.7 DISCUSSION......Page 791
, a6 n2 x5 w8 q5 L; V$ X# u20.1 INTRODUCTION......Page 7932 T6 |5 m5 V+ U% o9 `' ~' }
20.2.1 Part 11 Compliance......Page 795, e& ?+ ?  Z: c( Y
20.2.3 FDA Guidance on Bioresearch Monitoring—Compliance ProgramGuidance Manual......Page 796
. ?; m, z0 s6 t0 L20.3 DEVELOPMENT OF CASE REPORT FORMS......Page 797
3 O" V/ s  B' C# ^% J: b20.3.1 CRF Design......Page 7980 Z5 A$ C) w$ X3 k, N: L
20.3.2 CRF Flow and Tracking......Page 7991 u) @6 K/ `' L
20.4.2 Data Edit Check Specifications......Page 801
4 s. X; f6 l0 _9 b6 H! H) z20.5.1 Data Entry and Verification......Page 802( I7 w7 F5 s/ G0 y, W
20.5.2 Data Query......Page 8030 M; p/ u; H& a6 b& ^+ Z9 N0 ?! A
20.6 DATA VALIDATION AND QUALITY......Page 8058 r0 s4 f9 v  P) W: n8 X* V" \
20.7.2 Database Transfer......Page 806
2 z% `* k. R$ |  u  y20.8.2 Electronic Data Capture......Page 809$ V0 K- `. U3 h! k% P$ C3 f3 }9 I
20.8.4 Global Database and System......Page 810
( v; @) ~( `0 g' Q' V% @20.8.5 Role of the Statistician in the Data Management Process......Page 811
6 Y8 Y) g' Q0 D: D# ?References......Page 813
2 F0 }5 `" a% k6 `9 {9 @Appendix A......Page 859# Z7 I, O8 |& @7 \
Index......Page 865
3 y' a; b& D* ~( b1 h+ K- N! tWiley Series in Probability and Statistics......Page 885
/ N& ~* D" U9 O/ Y* m# Y* {  S
' y3 N! O" j# i" c( q$ E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)
5 `; N8 _0 E# ]2 P! D: T
& r2 k# `! e; j: x% i4 X# b说明:下面2个压缩包都要下载后解压!1 I3 Y* J4 l" v& _' }
Design and Analysis of Clinical Trials Concepts and Methodologies (3rd edition, .rar (7 MB, 下载次数: 335, 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% B' h$ d: K  w6 Y
牛啊!!!这种资源都能弄到!!

2 T0 p( D3 e9 p) |' y3 l4 d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+ C; Z* o+ A( ?) K6 D% I4 J
如果需要都是可以搞到的~~附件已挂出,需要请自行下载~~

' _  ]" G) n3 o+ D还好我钢镚多......
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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 11:358 Z4 p; i- o# e& x4 c
楼主是大骗子,两个都下了,解压的时候显示要第三部分

/ E9 R; _9 M5 x# N' y/ w& O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!
) t2 F" ~" \" T0 ]8 `0 @8 F8 J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!  O& x* H1 C! y3 z' J
1.jpg . o2 R- \5 D3 t  C0 e: q8 ]
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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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111111111
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mydream615 发表于 2014-11-29 22:02:06 | 显示全部楼层
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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nieli1990 发表于 2014-12-26 23:11:43 | 显示全部楼层
多谢楼主分享
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