Clinical Trials Handbook Design and Conduct

by Meinert, Curtis L.

• ISBN13: 9781118218464
• ISBN10: 1118218469
• Edition: 1st
• Format: Hardcover
• Copyright: 2012-11-13
• Publisher: Wiley

Summary

Written by an eminent epidemiologist and clinician, this comprehensive book outlines and categorizes the required methodological steps employed in the clinical trial evaluation process. The author appropriately mixes the scientific, logistical, ethical, psychological, behavioral, and administrative issues inherent in the field, while also emphasizing conduct, performance, and protocol. With questions posed to pique reader interest; concepts readily available through an organizational hierarchy; and PowerPoint slide suggestions showcased throughout, this is a must-have book for all practicing clinicians and teachers of clinical trials courses.

Author Biography

CURTIS L. MEINERT, PhD, is Professor in the Departments of Epidemiology and Biostatistics at the Johns Hopkins Bloomberg School of Public Health, where he served as founder of the Johns Hopkins Center for Clinical Trials. He is a Fellow of the American College of Epidemiology, the American Association for the Advancement of Science, the American Heart Association, and the Society for Clinical Trials. Dr. Meinert has focused his research on the methodological issues in clinical trials, including their design, conduct, policy, and practice. He is the author of Clinical Trials Dictionary: Terminology and Usage Recommendations, Second Edition (Wiley).

Table of Contents

Preface xi

On planning xiii

Explanatory notes, focus, and conventions xv

I. General 3

1. Terminology 4

2. Definitions 6

3. Measurement units 8

4. Trial type 9

5. Design and flow schematics 12

6. Design and operating principles 13

7. Counting and analysis rules 14

8. Multi-study umbrella name 16

9. Study name 18

II. Design specifications 21

10. Objective 22

11. Specific aims 24

12. Experimental variable 25

13. Treatment unit 26

14. Primary outcome 28

15. Outcome measures 31

16. Design synopsis 33

III. Funding 37

17. Type of funding initiative 38

18. Funding: Specifications 40

19. Funding: Terminology 42

20. Funding: Type 50

21. Funding: Initiative 51

22. Funding: Period 53

23. Funding: Budget 54

24. Funding: Mode 56

IV. Treatment groups/treatment administration 59

25. Study groups 60

26. Comparison group 62

27. Study treatments 64

28. Test treatments 66

29. Control/comparison treatment 68

30. Placebo treatment 75

31. Sham treatment 80

32. Treatment modality 82

33. Treatment schedule 83

34. Treatment compliance measures 85

35. Protocol overrides 88

36. Protocol bailouts 90

V. Masking 93

37. Mask/masking: Definitions 94

38. Masking principles 97

39. Masking, censoring, and shielding specifications 99

40. Drug masking procedure 101

41. Drug packaging and labeling 103

42. Drug supply 106

43. Masking safeguards 108

44. Unmasking treatment assignment 109

45. Results blackouts 110

VI. Bias and variance control 113

46. Bias control procedures 114

47. Stratification 117

48. Variance control procedures 120

49. Separations 122

VII. Treatment assignment/randomization 123

50. Assignment methods: Fixed vs adaptive 124

51. Treatment assignment: Random vs nonrandom 126

52. Randomization: Complete vs restricted 129

53. Randomization unit 132

54. Randomization: Procedures 134

VIII. IRBs and consents 135

55. IRBs 136

56. IRBs: Models and procedures 138

57. Consent 143

58. Consent: Checklist 150

59. Consent: Disclaimers and notifications 153

60. Consent: Principles and purpose 155

61. Consent: Process 157

62. Consent: Types 160

63. Consent: Questions and answers 162

IX. Enrollment and followup 167

64. Notation 168

65. Timing conventions 171

66. Required approvals, permissions, accesses, and supplies 173

67. Start-up design 175

68. Start-up checklist 179

69. Recruitment design 180

70. Enrollment goals 182

71. Enrollment quotas 184

72. Followup: Terminology 189

73. Followup: Method 193

74. Followup: Length 195

75. Closeout design 196

76. Missed visit 199

77. Dropout 200

78. Loss to followup 204

79. Study timetable 207

80. Critical event path analysis 209

81. Eligibility criteria 212

82. Exclusions from enrollment 215

83. Eligibility and exclusions by reason 219

X. Sample size 221

84. Sample size: Design 222

85. Sample size: Specifications 226

86. Sample size: Calculation 229

87. Fixed versus sequential sample size designs 231

88. Fixed versus adaptive designs 233

89. Designed subgroup comparisons 235

XI. Data collection and processing 239

90. Contact schedule 240

91. Examinations/visits 241

92. Examination/clinic visit schedule 245

93. Data collection 249

94. Data collection: Schedules and procedures 252

95. Data flow 255

96. Data processing procedures 257

97. Laboratory tests 260

98. Readings 262

99. Tissue repositories 266

100. Form design: Principles and procedures 268

101. Time window specifications 272

102. Data entry design 274

103. Data sharing: Internal 280

104. Data sharing: External 283

XII. Study centers 287

105. Center types 288

106. Centers 291

107. Center requirements 293

XIII. Investigators/study staff 297

108. Investigator requirements 298

109. Clinic staffing requirements 300

110. Research group/Investigators 302

XIV. Committees 305

111. Key committees 306

112. Standing and working committees 307

113. Committee rules and procedures 308

114. Study officers 312

115. Study chair/vice-chair 313

116. Executive committee 317

117. Executive committee members 319

118. Steering committee 320

119. Steering committee members 322

120. Steering committee: Questions, answers, and observations 324

121. Steering committee representation models 327

XV. Treatment effects monitoring 331

122. Treatment effects monitoring 332

123. Treatment effects monitoring: Purpose 334

124. Treatment effects monitoring: Approach 336

125. Treatment effects monitoring: Masking 338

126. Stopping rules and guidelines 340

127. Treatment effects monitoring: Questions and answers 342

128. Treatment effects monitoring committee 345

129. Treatment effects monitoring committee: Questions and answers 347

XVI. Quality control and assurance 351

130. Quality control and assurance procedures 352

131. Performance monitoring 356

132. Training procedures 358

133. Assurances and certifications 359

134. Site visiting procedures 361

135. Audit procedures 364

XVII. Data analysis 367

136. Analysis datasets 368

137. Analysis questions regarding study results publications 370

138. Frequentist vs Bayesian analysis 372

139. Final analysis 374

140. Subgroup analysis 376

XVIII. Publication/presentation 379

141. Publication 380

142. Publication policy 382

143. Authorship 384

144. Credits 389

145. Presentation policy 393

XIX. Policies 395

146. Policies 396

147. Publicity policy 397

148. Policy on access to study documents 398

149. Policy on access to study data and results 400

150. Policy on advertising for patients 403

151. Policy on incentive payments 404

152. Policy on payment of patient related travel expenses 406

153. Ancillary study policy 407

154. Policy on patient care related payments 409

155. Policy on conflicts of interest 410

156. Substudy policy 413

XX. Adverse events 415

157. Adverse events 416

158. Adverse event reporting procedures 420

XXI. Miscellaneous 423

159. Key study documents 424

160. Design synopsis 425

161. Slide sets 426

162. Study CV 427

163. Study website 428

164. Study history log 429

165. Landmark events and dates 431

166. Registration 433

Appendices 435

Appendix 1. Design summaries 437

Appendix 2. Sample design slide sets 457

Appendix 3. Template worksheets and slides 489

References 505

Index 516