公卫人

 找回密码
 立即注册

QQ登录

只需一步,快速开始

不劳无获:如何获取钢镚? 因为论坛,所以相逢。 捐赠百科答题至尊

公卫考研:一起风雨兼程 因为梦想,所以努力。 真题答案政治英语

职称考试:诸君逢考必过 因为热爱,所以执着。 模拟考场技能执医中级

查看: 1134|回复: 1

[分享] Clinical Trial Methodology (2010)

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

注册后推荐绑定QQ,之后方才可以使用下方的“用QQ帐号登录”。

您需要 登录 才可以下载或查看,没有帐号?立即注册

x
61yEAoXGxnL.jpg . p, C( g3 j9 O1 A' m
: ?% G( j4 B5 P3 Q. B, ^, D
Title: Clinical Trial Methodology
4 i  R% M9 T: K: _6 o) QAuthor(s): Karl E. Peace, Din Chen$ f5 q3 n, L. \$ @
Series: Biostatistics Series        ) V3 F; j+ f6 _; ~  O4 C/ w
Publisher: Chapman & Hall CRC
/ I3 T: @1 Z! o* v! K" t6 KYear: 2010       
: w- M  c+ g2 L* YEdition: 1+ Y" _' y9 ]' m4 m( y
Language: English
& c0 @/ }7 c, RPages: 420
. a" y* Y% H; I. \' Q& DISBN: 1584889179, 9781584889175, 1584889187, 9781584889182
" U$ P6 d4 n0 ]8 p1 h( n4 E, }Size: 3 MB (2647392 bytes)
- Q( b9 [7 n8 D& G% BExtension: pdf
4 |3 n) p0 Z( M
  ^% p, q- H6 j+ q

. M$ t. A7 u, M7 JFeatures; ^% O* c. L1 m. t' d  `; ]

( }+ c. `/ J' p# u/ P$ {7 w" G
  • 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
    9 }+ d, l, t  O( V

5 Q4 p- k% z7 q- m0 D% h7 n% Z3 {  Z: i5 d. @
5 O2 T; y, F$ n4 d: x& _+ q( P$ a
Summary
6 {! w# V8 T; P8 q' h& n0 D
( p6 ~5 |+ n# v# w) q$ ?  Q3 J9 NNow 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.
& T0 |0 B4 U8 `3 @1 I. U6 E% g* v1 A- E' _8 u( _
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.
6 k: \9 N3 D: [" A- ^
; A# @, U; k+ A0 z$ F  bAided 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.
* C! v' E" V4 Z  i5 B. X8 R% W6 H7 F  ]

8 ]6 ?" T% c5 E* s: Z8 T5 k& b. w" h- ~, e$ e4 w
Table of Contents
8 C. `, @1 [6 q* U$ x9 M8 Q+ m/ ^& o5 j* p% f0 ?: u9 j" Z
Overview of Clinical Trial Methodology 2 T2 N$ N- h. h! T
Clinical Trials ; f; ?4 B2 P, r- h  j' c6 k
Clinical Trial Methodology
+ Y: h4 `/ i3 a. fSummary of Clinical Trial Methodology
4 x7 g6 m( M, Z6 Z
. ~' ~& w2 i2 z# a2 l" K  D& g8 e0 dOverview of the Drug Development Process and Regulation of Clinical Trials ! l! e  Y+ P: ]& `7 Z% W
Introduction$ Z2 x# N& o, ]& C
The Drug Development Process5 c% ~' ^" W3 g6 W) V4 V
History of Drug Regulation
4 z* l- g8 v8 tPrinciples of Adequate and Controlled Investigations7 C8 N2 U- J2 U6 s& I: {/ W
Content and Format of the IND6 A( N/ z" D* R) i
Content and Format of the NDA$ g' ]8 o3 M5 Y
Organizational Structure of the FDA
/ a* l  f5 ]9 Y$ `) A, S. r" A8 yThe FDA Review Process
# J9 j4 d2 N6 v! iLabeling and the Package Insert
+ T: a2 K# N9 \) r$ _7 BPharmaceutical Company Organization and Role of the Biostatistician: y# q; Z4 I( L8 i
* ]( a& N" T: p' o
Ethical Considerations in the Design and Conduct of Clinical Trials
6 z9 j1 f/ _  g$ }8 ~; VIntroduction  |4 H. n; H1 d8 D) M: k$ |0 b
History and Evolution of Ethical Considerations in Clinical Trials: Key Milestones; v+ @1 X3 N% t5 Q7 d
Independent Review Boards( {# y/ ?4 @" l  v" W" D
Clinical Trial Ethics: Who Should Practice?, J! A9 A: c- j  E! `
Informed Consent, Sample Size, and Power( y- z; j/ C) V
Common Ethical Principles of Various Codes and Regulations( J, l* ^6 X/ {- H5 U; H
  X7 c2 N9 V" n% T5 M) J
Sample Size Considerations in Clinical Trials Pre-Market Approval
; U2 ^; J1 T: V; F4 ?% R8 AIntroduction
( K( E/ T4 {* {$ \0 G+ h' S7 BPhases of Clinical Trials and Objectives
+ _% B+ B6 U* u! j$ |3 q  WThe Clinical Development Plan: Pre-Market Approval
* W+ ]) u) }" T3 h; Y7 `Sample Size Requirements
% s7 J* J4 D% t9 Q  U8 v; c3 zExamples
4 X  D, G$ U8 tPhilosophical Issues
+ q# P5 V/ g# S- o. ~& B" }' K
0 D7 F6 E" h) j+ S" v# SSequential, Group Sequential, Stochastic Curtailment, and Adaptive Design Procedures in Clinical Trials
/ \* U. B, R9 q7 a( _; y+ Q" _Introduction' Y1 Z0 z5 H" R+ M6 b3 Q' m/ m# P
Sequential Procedures8 G  m- b1 r- Z! K# A
Group Sequential Procedures
/ q3 T: E$ P3 c2 C$ l+ AStochastic Curtailment( g5 ~& @& C3 l" |7 j; i  K
Adaptively Designed Clinical Trials+ p) {3 r3 f5 Z" ~; P

0 S. X2 |) Q* x: h  PBiostatistical Aspects of the Protocol 6 p. a! d# a! x* y/ L1 P& m
The Background or Rationale # H( S/ {- @/ R3 F
Objective
) ~. v2 P; v( T5 k6 U1 [6 t/ SPlan of Study
* e7 G/ y! |* gStatistical Analysis Section0 K/ O- \1 |9 m. `, N
Administration" ^# H- s- ^, l3 j1 B3 x
Protocol References Section
6 a: [1 s4 }- d2 W2 H" _7 i# Q3 S7 \5 h( i
The Statistical Analysis Plan ) R( n! ]1 ^- P# Z
Introduction
! [0 ~2 a( n, [3 w1 Z- zProtocol Objective% O' X) z' K0 D) k; B" m  @" ]
Efficacy Data Collected and Protocol Schema
1 o) v6 }+ I3 J: H7 S- Q* sPrimary and Secondary Efficacy Endpoints
6 Z! l6 u( Q  a6 J- z6 p  @; A/ J5 A5 s  ~Objectives, Translated as Statistical Hypotheses
% Y# R# T8 l4 U+ i* ]Protocol Design Features! m: n6 Q% d- p7 v
Statistical Analyses
/ I5 v( d' G; T, k( u) v4 ?" ]2 w. m# G& h0 O$ l, K! B
Pooling of Data from Multicenter Clinical Trials* p- b5 Y6 K& F0 j
Introduction+ K+ A4 I! N  ]$ h, j0 B
Multicenter Clinical Trial Experimental Setting * w, w. O- ^& u) f
Pre-Study Planning
1 K2 D- R1 Q$ k: C0 W5 M3 M7 `/ TMulticenter Clinical Trial Conduct ( s6 ^; U% _8 ]+ P/ e. ?3 F: |
Biostatistical Analysis4 |8 Q. n0 S6 v8 G3 N. T* j; G# P2 H
6 K7 r. `: i0 y" u
Validity of Statistical Inference2 P" W, |& {) o- y4 q& z& u1 i% u' d
Introduction/ ^4 R7 J# _$ l: \% `" A
Planning the Investigation
5 `9 T7 L- ^' b$ W& U1 p) q% bConducting the Investigation
, N, w+ B; v1 v  X/ L1 fStatistical Analyses, Interpretation, and Inference * \6 @( ^5 b& L4 e$ G) d7 j
Reporting Results of Investigations  t8 a8 R0 j2 T7 L( F- l

' G3 X* l# C  P0 w# o' TBioequivalence Clinical Trials 0 v' v1 W% e. x8 y
Introduction
7 d6 ]: C+ \3 E8 `0 n9 B3 _Absorption, Distribution, Metabolism, and Excretion (ADME)
+ a6 F" l% E: I& H! _) f$ mBioavailability
, z9 w9 L5 j6 J& C2 {Factors That Affect Bioavailability
- f# F8 a" ]! @/ vBlood Level Clinical Trials
( K( e- O0 x2 T" `9 E; }Bioequivalence% F6 D, w3 Q! G( W1 L& Q6 I
Design of Bioequivalence Trials$ M: C  U. O1 W' \, e
Analysis of Bioequivalence Trials   t7 B  R7 y( r. H9 N0 \6 Q) k0 x
Analysis of Ratios
- f" U1 t- |7 }% x/ n4 ZPharmacokinetic Models 0 w2 ^# `4 Q$ k7 j. }
Support of Bioequivalence Trials in the Pharmaceutical Industry . R6 U  u) L( O
Examples
/ _: O6 ?1 M1 u* Z. A9 `
* R" K# d. r% b; [# bDose and Frequency Determination from Phase II Clinical Trials in Stress Test-Induced Angina 5 {# k2 E/ i! U& s3 Z' {* J
Introduction
4 U: [  [0 r; Q" M& ~* G% Z4 `! fOverview of Response Surface Methodology& \1 [9 x0 ], D' a) m
Full Quadratic Response Surface Model
; V  c- m& J& \* \+ [$ g. u7 lPhase II Clinical Trial Program in Stress Test-Induced Angina
" k# F' w7 m8 v
; C+ U2 }, d: z. |' OConfirmation of Clinically Optimal Dosing in the Treatment of Duodenal Ulcers: A Phase III Dose Comparison Trial ( G0 n7 D0 Z( [% b6 a! [) A5 I
Introduction
: f- }% l& j- t4 Q) X; U! hBackground
3 S% P7 b# [& K- PObjective
6 X: M8 m3 Y8 E, GDesigning and Planning the Investigation
7 J+ Q% ~& H2 |- u: Y( M& PConducting the Investigation ) x' A* {' j" \" E( M
Statistical Analyses$ n. e4 p, \2 q# L9 e
Other Considerations% Z0 E5 W0 S3 h1 o
Innovative Aspects of the Clinical Trial Program' d5 z) d8 m: k2 w+ [

9 ]8 [. _( F: y& ]Pivotal Proof-of-Efficacy Clinical Trials in the Prevention of NANSAID-Induced Gastric Ulceration . ^* c; ~' S( y) U8 ~
Introduction5 B8 a" K: |. B, y
Rationale ; N; N" p( a- f
The Protocols; [* e- x7 h" |/ G$ z
Monitoring and Data Management3 C- h8 z% e( a: u; k4 @
FDA Meeting9 R. e. B( J6 {* E" Z' E

6 P3 P8 R4 S" q6 K; T% {# b7 T: FClinical Trials in the Treatment of Alzheimer’s Disease Based upon Enrichment Designs
/ B' I: w) j( X2 h) N. Z$ t8 TIntroduction
9 m# D  P+ Y; ?Enrichment Design Clinical Trials ( C# @: O, v! p8 g
Objective 0 _# M) @$ ~9 A' c" X  g
Primary Efficacy Endpoints # q/ L3 t( \! W9 U
Sample Size Determination# l# _! F" H6 M5 D
Statistical Methods
  O+ k2 B  _% v9 d. e; O( F  BResults+ p+ L- p9 \. X# c# Q
4 O1 E3 C2 s$ x+ A- `
A Clinical Trial to Establish Reduction of CHD Risk
5 M; S2 g6 B7 }' N" W% m% DIntroduction
9 V: w: {; {* H, X0 N8 DObjective ! c/ M, R. b/ N( m$ F
Designing and Planning the Investigation
! l% d1 Y  _5 H* @+ e% h/ Y! zConducting the Investigation
+ D2 u: Y$ K0 \2 E! hData Management
! O8 ~( B  l% ~2 y6 M5 FStatistical Analyses. i5 S, E& j- J# C
Results& e6 c4 Q( P; h
Summary% m( Z; A  m. ~* n9 J; l5 q- ?% s

7 b2 _1 z. H" O. o5 ^Pivotal Proof-of-Efficacy Clinical Trials in the Treatment of Panic Disorder ; S- [0 y7 n  l) t' v, y! [) q0 n
Introduction/ [/ t! C" x6 Z0 `
Design of Pivotal Proof-of-Efficacy Trials0 H0 {( i# C" a# L* i
Traditional Statistical Analysis Methods % S7 m8 K; G5 t" c3 B7 [
Overview of Efficacy Results of the Two Trials
" U0 H+ G5 V6 t5 A9 R; f( n) E  \Alternative Design and Analysis Strategies' G6 h6 v( P! K6 G4 s( ~, I/ r6 [* U

3 a/ K' S: A9 g3 E& r4 BCombination Clinical Trials ) b3 N: z5 N1 H6 T% |  h* Q8 T
Introduction
/ P/ _8 _6 j* P& l7 rTwo-by-Two Factorial Design
: y# J3 H3 o( ^* K. `2 Y" R% OEffectiveness of the Combination
7 G1 |3 J: m7 k% gContribution of Components to the Effectiveness of the Combination
$ ~+ i0 ?" V$ F2 @% M7 N0 t/ [Factorial Designs in Other Clinical Development Areas# Q+ d- R" a* }$ S' O  A" j' j% J
Example 1: Actifed in the Treatment of SAR Following DESI Review5 g* v  R6 e( u! e0 b
Example 2: Crossover Trial of Actifed in the Treatment of SAR& |7 W/ H5 F4 y( _' C
Example 3: Parallel Trial of Actifed in the Treatment of the Common Cold1 z- ^# J# Y6 }8 K5 \& q: ^/ b
3 T' N3 V6 m, U% M0 Y. \3 `' o+ X
Monitoring Clinical Trials for Adverse Events
3 Y, J; n" E% ^0 W$ b+ SIntroduction
; ~8 n1 ~! ^- w( i- A$ z# ~Designing for Safety: Antibiotic Rash Example: |% E$ A" R, z: W
Designing for Safety: Hypokalemia Example 9 O6 T2 i3 H4 g5 }+ C( T+ n1 L+ X
Designing for Safety: Hypertensive Rebound Example ( x" |! Q* Y# a, Y& O
Premarket Approval Trials: Designed for Efficacy ) z  `3 a, G4 s9 Q+ {! n' S
Premarket Approval Trials: Quality of Adverse Event Information
6 b5 h% X8 x, M# `8 p1 [Monitoring for Safety! [# {- S& G; O( Y; x" c; x
Statistical Methodology: Individual Trial4 m9 A% K3 ~* q
Example' O2 @) \1 F: p8 k6 |0 G
Statistical Methodology: Across Trials
+ `, ]( u/ O+ g; O& {. P5 u
% m! f8 @3 B4 z. z- D" [Index
3 p8 y! o& J3 d" W5 b
/ Y; y8 I7 R- u+ _7 NReferences appear at the end of each chapter.4 L) ]# T% ^) K! D
) P9 g3 K; p2 g2 r: P
9 j: S" Y. j( W1 k
, w1 p9 S8 Y$ T- F# q- }: V
Author(s) Bio% _, b/ _. e1 ]. e6 d4 g( R+ C

% f9 c- h/ {" r5 p( `& E6 MKarl 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.. m$ x; d' ~) R, ?
& [* f- G4 o  w2 j8 t
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.$ x! X4 d3 k$ u$ U6 z2 i
- d7 e6 _# c! o. l

3 h- s9 g6 o  w% S4 J4 k
; i3 k+ a- m: D( Y4 x Clinical Trial Methodology (2010).pdf (2.52 MB, 下载次数: 58)

本帖被以下淘专辑推荐:

tljuly 发表于 2017-12-23 23:08:15 | 显示全部楼层
好书!!多谢分享
回复

使用道具 举报

您需要登录后才可以回帖 登录 | 立即注册

本版积分规则

安卓版|我要捐赠|关于我们|接种问答|公卫人 ( 沪ICP备06060850号-3 )

GMT+8, 2018-1-21 02:33 , Processed in 0.314400 second(s), 45 queries , Gzip On, MemCache On.

Powered by Discuz! X3.3

© 2001-2017 Comsenz Inc.

快速回复 返回顶部 返回列表