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[分享] Clinical Trial Methodology (2010)

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sampson2010 发表于 2015-5-29 12:42:00 | 显示全部楼层 |阅读模式

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Title: Clinical Trial Methodology
" H4 _1 m) @% w( f. I/ cAuthor(s): Karl E. Peace, Din Chen
. j3 F# E7 A% w% l! f. l  N: t4 V! @Series: Biostatistics Series       
$ W; X" y  I$ VPublisher: Chapman & Hall CRC7 D+ }9 ^3 I4 ^% a( d
Year: 2010       
7 M) `8 t) G) Q! [2 M. V& |Edition: 1, t* H) D/ J- v% y' r3 u6 g
Language: English
* H% I2 \5 N4 e! NPages: 420- w. X. a6 T( U* ]& [
ISBN: 1584889179, 9781584889175, 1584889187, 9781584889182
. s+ ^! P/ ?' K" _Size: 3 MB (2647392 bytes)# }, j  l* J8 i
Extension: pdf
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  • Reviews legislation pertinent to the clinical development of drugs
  • Discusses the processes of drug research and development within the context of a typical pharmaceutical company
  • Presents general biostatistical principles of clinical trials, including protocol development and statistical analysis plan development
  • Provides case studies of clinical trials for the development of drugs to treat panic attacks, duodenal ulcers, and Alzheimer’s disease; to reduce coronary heart disease risk; and to prevent gastric ulcers and angina- Y/ y3 b* s4 q- \

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9 @& o8 ^5 z3 g5 F1 g# J2 BSummary3 E/ Z1 N2 P# d8 {7 J

# K7 |; x8 w+ c6 C' [8 ^Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide a valid inference about the objective of the trial. Drawing from the authors’ courses on the subject as well as the first author’s more than 30 years working in the pharmaceutical industry, Clinical Trial Methodology emphasizes the importance of statistical thinking in clinical research and presents the methodology as a key component of clinical research.
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From ethical issues and sample size considerations to adaptive design procedures and statistical analysis, the book first covers the methodology that spans every clinical trial regardless of the area of application. Crucial to the generic drug industry, bioequivalence clinical trials are then discussed. The authors describe a parallel bioequivalence clinical trial of six formulations incorporating group sequential procedures that permit sample size re-estimation. The final chapters incorporate real-world case studies of clinical trials from the authors’ own experiences. These examples include a landmark Phase III clinical trial involving the treatment of duodenal ulcers and Phase III clinical trials that contributed to the first drug approved for the treatment of Alzheimer’s disease.: D: B5 c0 S) l! L; S( _, F: @6 v8 d1 U( `
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Aided by the U.S. FDA, the U.S. National Institutes of Health, the pharmaceutical industry, and academia, the area of clinical trial methodology has evolved over the last six decades into a scientific discipline. This guide explores the processes essential for developing and conducting a quality clinical trial protocol and providing quality data collection, biostatistical analyses, and a clinical study report, all while maintaining the highest standards of ethics and excellence.: q) i$ o7 B1 B- i5 E
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Table of Contents
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Overview of Clinical Trial Methodology
1 X4 \: m. j" TClinical Trials   W2 N: E$ M( ?5 P: V4 P3 ]& k
Clinical Trial Methodology
7 ]& `- N6 i% Q( U9 lSummary of Clinical Trial Methodology" W. ^1 r3 Y: {

  z4 Y3 a) Q9 [0 K, p4 G& iOverview of the Drug Development Process and Regulation of Clinical Trials & Q, i& o1 O& H% D
Introduction% j! P9 t3 v1 S; @7 O$ ?4 [
The Drug Development Process% ?7 Q# h3 b* {) t0 \
History of Drug Regulation' H  H- M0 Q2 l* n: o3 Y; h4 k1 g
Principles of Adequate and Controlled Investigations6 b5 q+ n0 r8 f7 Q
Content and Format of the IND: r+ I; H! l/ [: R- I
Content and Format of the NDA
7 |3 r4 B. a& E5 J  s- FOrganizational Structure of the FDA
/ W& D9 o4 r/ Q7 x3 ^: IThe FDA Review Process
/ T( q4 @  z7 r( q1 w7 W" ZLabeling and the Package Insert + ^# @0 w. J2 V1 y% J
Pharmaceutical Company Organization and Role of the Biostatistician
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. V; A+ y5 B& y5 {, gEthical Considerations in the Design and Conduct of Clinical Trials
3 m9 U" ~" M8 b1 VIntroduction" V( G! y, Q# M" ~2 V
History and Evolution of Ethical Considerations in Clinical Trials: Key Milestones" n% D( P: V7 a
Independent Review Boards
" i+ Z# T: g6 a; iClinical Trial Ethics: Who Should Practice?' f) }* l! B7 J/ i
Informed Consent, Sample Size, and Power0 b' `* x* T* ~0 Y0 e* U4 J
Common Ethical Principles of Various Codes and Regulations/ H/ E% Z* F, `% A! I

8 a1 x4 y9 w1 }( D3 h  `* I9 fSample Size Considerations in Clinical Trials Pre-Market Approval
! M  m( p8 m  z  s3 lIntroduction4 m& f/ }' t+ `/ j; n
Phases of Clinical Trials and Objectives
  _3 C1 |6 Y& tThe Clinical Development Plan: Pre-Market Approval7 T$ ^( D8 D7 I+ E
Sample Size Requirements
0 Y/ x! ^/ E, Z# X! J1 xExamples0 V% b5 q- q* W; [" `6 }! H+ U
Philosophical Issues
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Sequential, Group Sequential, Stochastic Curtailment, and Adaptive Design Procedures in Clinical Trials
4 v! v# F& ~6 z  T4 @' I! SIntroduction
+ F) E- }3 V2 B7 I- _6 uSequential Procedures
$ j. ~9 R  [  Z+ J: q( B6 b% J0 PGroup Sequential Procedures' K6 T6 ?1 b( ]& _7 x/ `7 d
Stochastic Curtailment
" i6 Q- I4 S4 Z2 q7 j4 |Adaptively Designed Clinical Trials; T2 O, B1 c6 W  H

4 f: ?9 ]- t4 Q6 h& d: Y/ o* ]0 y5 h) UBiostatistical Aspects of the Protocol 3 e6 }) _5 t2 t$ G8 D5 B/ l
The Background or Rationale
' }3 m: C9 H$ Z, w0 z1 uObjective 2 t0 r4 i- u  Y. A8 l8 g3 M8 @0 U
Plan of Study
7 q5 z2 A" _2 f+ G" ~0 v$ k, d$ gStatistical Analysis Section
% [/ }) L: v: s) z' [; hAdministration' S6 k, \( t& @6 K8 y2 m$ \/ D- s1 ]/ e
Protocol References Section4 f& ^, o+ t" m- ]* W

  \; B9 E' N" ^0 `0 K* vThe Statistical Analysis Plan
$ _' ^* }, c) R: R& Q  M/ mIntroduction
/ i" s  a$ L/ f# l5 ?0 D% sProtocol Objective
9 @# X! c' C2 ?( MEfficacy Data Collected and Protocol Schema + Z1 c/ j( ^' e  C! J3 |
Primary and Secondary Efficacy Endpoints. a' N* K) B( D& o6 h" W
Objectives, Translated as Statistical Hypotheses- ]4 t, D" H! ]* {* z
Protocol Design Features
/ C. T, _" _6 M) f. ]. z& tStatistical Analyses
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Pooling of Data from Multicenter Clinical Trials1 {: n2 z/ b; O% w
Introduction: O* s' i: v  \3 M
Multicenter Clinical Trial Experimental Setting : a4 e9 v: K. ]
Pre-Study Planning
  P5 m* |3 N7 J- sMulticenter Clinical Trial Conduct 7 m& p, \0 s( w7 f# i; _9 v* e
Biostatistical Analysis
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Validity of Statistical Inference
, [0 Z- d  j! C% k* F: H6 V$ @6 k  iIntroduction* v( j5 g7 p* g. C4 F- K9 M
Planning the Investigation7 |/ \6 Q. g0 I2 O. }* K/ W/ u
Conducting the Investigation
9 J8 I7 R$ q" NStatistical Analyses, Interpretation, and Inference , f4 W) d7 n' e
Reporting Results of Investigations
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Bioequivalence Clinical Trials . p9 @- z5 H6 @
Introduction/ L! q0 ]2 m" P& f" @
Absorption, Distribution, Metabolism, and Excretion (ADME) 9 p9 e1 J( E6 }5 N1 P! t  v
Bioavailability 9 ^+ N/ ~$ A5 C0 D5 e7 q+ [
Factors That Affect Bioavailability
. M- H! d! V3 Y. ~9 RBlood Level Clinical Trials & B& K# n* b2 a' u1 W' L
Bioequivalence0 l' K$ F  Y. u7 I8 }. r: K% R
Design of Bioequivalence Trials6 U" v# n6 ]+ i5 }. M9 ~- }/ Y6 c
Analysis of Bioequivalence Trials & w0 D; [) h# O& U% g$ M1 k
Analysis of Ratios
' _8 x6 f/ T+ P1 x  C( IPharmacokinetic Models
3 t, D) k& o' f7 w, C6 l  {Support of Bioequivalence Trials in the Pharmaceutical Industry % k/ I; i5 C: P# [1 o
Examples& y: ?& i+ B5 q: m: A' H% P0 u2 b) e
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Dose and Frequency Determination from Phase II Clinical Trials in Stress Test-Induced Angina ) o/ j* T% a% M4 J" d/ [
Introduction
7 {1 c1 \5 W0 \% L9 HOverview of Response Surface Methodology; `2 z" j6 Q8 q; A$ u
Full Quadratic Response Surface Model
, |/ l4 a) P- M+ T* J4 |Phase II Clinical Trial Program in Stress Test-Induced Angina: s1 i* |6 M* E

# j! t* E1 s- {1 QConfirmation of Clinically Optimal Dosing in the Treatment of Duodenal Ulcers: A Phase III Dose Comparison Trial
% m1 k5 u; D9 C, kIntroduction4 `0 t. n' }0 H/ H, {/ K
Background ; \7 x, x6 B8 e. Y3 `3 K2 T: D
Objective ) D) M% k5 o& F. O: [' Y" X
Designing and Planning the Investigation. g+ r7 ]0 ~9 F" N4 `6 d; T
Conducting the Investigation , G% i/ ^7 r. B
Statistical Analyses7 T' R( x1 F( ^5 A6 T3 B
Other Considerations
1 A- i, }8 [. V5 h; BInnovative Aspects of the Clinical Trial Program
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7 g% c: E1 L' a; @5 E: z3 U9 TPivotal Proof-of-Efficacy Clinical Trials in the Prevention of NANSAID-Induced Gastric Ulceration   v& E) _9 Z4 \0 n8 X
Introduction5 T% |1 k0 i4 T1 z0 ?
Rationale
/ `$ y- `0 h9 p5 m) M9 KThe Protocols
' Q, i  [% H' r& c4 Q& \  [Monitoring and Data Management
/ t( g# s4 d: K, Q  z6 d1 GFDA Meeting
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2 \3 X( t( o: K2 s4 @  {2 NClinical Trials in the Treatment of Alzheimer’s Disease Based upon Enrichment Designs
0 ~( Z9 u7 ]1 A7 p# k) TIntroduction; A5 A% g% S7 w9 ?
Enrichment Design Clinical Trials
6 g5 K1 n9 ?0 s" q  G! vObjective
6 X) h) Y! g) _9 W, |3 UPrimary Efficacy Endpoints " ^; G: S" D- n8 O4 U, L5 g
Sample Size Determination( ?& l, w2 [% O4 O% O/ t% I
Statistical Methods
( v3 U1 w' A9 K4 [5 EResults
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" o9 f5 D. {3 O8 c9 t. l' {A Clinical Trial to Establish Reduction of CHD Risk
% D1 l* b, u% @7 i" J# U1 jIntroduction
/ ^/ o* q# k' v. Q/ |5 u) DObjective " J, `1 j6 |. b* ?) \
Designing and Planning the Investigation
; [4 B, E: O0 H7 d  A! _. bConducting the Investigation * D) S$ u6 P" N
Data Management ' q2 E; {+ J  U
Statistical Analyses
. N$ k0 W! g- B/ {1 S4 ?4 ~7 R8 xResults! y7 S& g6 C: A. w
Summary  u, U$ E- |( K5 d2 ^
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Pivotal Proof-of-Efficacy Clinical Trials in the Treatment of Panic Disorder " J4 N* y6 B* w  S6 R& S. |
Introduction( K1 E. B( J, c& w" i! z
Design of Pivotal Proof-of-Efficacy Trials; n  l' W) P" I  l& _1 k
Traditional Statistical Analysis Methods 1 [  a- w, I5 L5 G* P) T
Overview of Efficacy Results of the Two Trials
; j! ^& v7 u1 Y6 Y% z" pAlternative Design and Analysis Strategies
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Combination Clinical Trials : r! j7 Y8 I) e5 n2 l3 C, h5 c  ^
Introduction0 N% x3 S" D8 O) ~5 I3 ]
Two-by-Two Factorial Design 1 y2 b6 O# _; E5 g& f- U6 E
Effectiveness of the Combination  S' ]1 }, W/ x
Contribution of Components to the Effectiveness of the Combination ) y( G, g. \8 G( [* d4 V
Factorial Designs in Other Clinical Development Areas! J2 T) P+ h  _; c- O
Example 1: Actifed in the Treatment of SAR Following DESI Review
- n* W5 b+ t4 l5 N3 Q8 [; N0 pExample 2: Crossover Trial of Actifed in the Treatment of SAR1 U9 z# s! O7 W. \+ ?' G
Example 3: Parallel Trial of Actifed in the Treatment of the Common Cold
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- }: l( ?7 l& iMonitoring Clinical Trials for Adverse Events , s1 w! a2 d) F( Q8 u
Introduction8 }' ~0 R/ {* L7 t& ?, t
Designing for Safety: Antibiotic Rash Example
2 d  _" u, U! l+ v, Z& F1 S( aDesigning for Safety: Hypokalemia Example
, q+ j0 [" {; v& v. c2 UDesigning for Safety: Hypertensive Rebound Example
/ c2 s# g% g3 G$ r! GPremarket Approval Trials: Designed for Efficacy 3 h/ K% c( H2 d7 q* R; s  [" X2 \
Premarket Approval Trials: Quality of Adverse Event Information
# a; r- j* Q2 |Monitoring for Safety& B% i2 O2 _% O9 b# I
Statistical Methodology: Individual Trial
8 O2 @6 W: b: V  ^" n( _Example+ c" s+ w: g$ P9 L
Statistical Methodology: Across Trials
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# N: p+ R# {) o' J2 c# X8 R; ]( hIndex
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References appear at the end of each chapter.
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  y/ Z/ o0 b3 f- ^, V8 nAuthor(s) Bio8 S8 e4 f4 c. ^8 ]% O6 D5 n' U

( |) O- X! i! B. O2 XKarl E. Peace is the Georgia Cancer Coalition Distinguished Cancer Scholar, founding director of the Center for Biostatistics, and professor of biostatistics in the Jiann-Ping Hsu College of Public Health at Georgia Southern University.
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Din Chen is the Karl E. Peace Endowed Eminent Scholar Chair in Biostatistics and professor of biostatistics in the Jiann-Ping Hsu College of Public Health at Georgia Southern University.
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# F: L3 Y" u) @ Clinical Trial Methodology (2010).pdf (2.52 MB, 下载次数: 94)

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tljuly 发表于 2017-12-23 23:08:15 | 显示全部楼层
好书!!多谢分享
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芬2012 发表于 2018-4-23 14:29:53 | 显示全部楼层
已下载,感谢分享
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1582891835 发表于 2018-7-26 10:51:39 | 显示全部楼层
多谢楼主分享~
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