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Full Description
This newly updated edition of the benchmark guide to computer-assisted clinical trials provides a comprehensive primer for prospective managers. It covers every critical issue of the design and conduct of clinical trials, including study design, organization, regulatory agency liaison, data collection and analysis, as well as recruitment, software, monitoring, and reporting.
Keeping the same user-friendly format as the original, this Second Edition features new examples and the latest developments in regulatory guidelines, such as e-submission procedures and computerized direct data acquisition. The new edition also reflects the increasing globalization of clinical trial activities, and includes new information about international standards and procedures, including the Common Technical Document and CDISC standards.
This step-by-step guide is supported by handy checklists and extracts from submitted protocols. Experienced author and consultant Phillip Good incorporateshumorous yet instructive anecdotes to illustrate common pitfalls. Based on the proven industrial formula of planning, implementing, and finally performing essential checks, the book's three sections-"Plan," "Do," and "Check"-includethe following material:
* Should the trials be conducted?
* Put it in the computer and keep it there
* Staffing for success
* Designing trials and determining sample size
* Budgeting
* Recruiting and retaining patients and physicians
* Data management
* Monitoring the trials
* Data analysis
* After action review
* Exception handling
Executive and managerial professionals involved in the design and analysis of clinical experiments, along with clinical research associates, biostatisticians, and students in public health will find A Manager's Guide an indispensable resource.
Praise for the First Edition:
". . . readable, informative and at times witty . . . never stops being concise and well written . . . a book worth a read . . ."
-Statistics in Medicine
"The book is very prescriptive and full of lists and tables with which to guide managers in making effective decisions in using computer-assisted clinical trials in pharmaceutical studies." -Technometrics
"This book is must-have reading for anyone in the business . . ."
-Clinical Chemistry
Contents
1 Cut Costs and Increase Profits 1
No Excuse for the Wastage 1
Front-Loaded Solution 2
Downsizing 3
Think Transnational 3
A Final Word 4
2 Guidelines 7
Start with Your Reports 7
The Wrong Way 9
Keep it in the Computer 9
Don't Push the River 10
KISS 11
Plug the Holes as They Arise 12
Pay for Results, Not Intentions 13
Plan, Do, Then Check 13
Part I Plan 15
3 Prescription for Success 17
Plan 17
A. Predesign Phase 17
B. Design the Trials 17
Do 19
C. Obtain Regulatory Agency Approval for the Trials 19
D. Form the Implementation Team 19
E. Line Up Your Panel of Physicians 19
F. Develop the Data Entry Software 19
G. Test the Software 20
H. Train 20
I. Recruit Patients 20
J. Set Up External Review Committees 20
K. Conduct the Trials 20
L. Develop Suite of Programs for Use in Data Analysis 20
M. Analyze and Interpret the Data 21
Check 21
N. Complete the Submission 21
4 Staffing for Success 23
The People You Need 23
Design Team 23
Obtain Regulatory Approval for the Trials 25
Track Progress 25
Implementation Team 26
Develop Data Entry Software 26
Test the Software 27
Line Up Your Panel of Physicians 28
External Laboratories 28
Site Coordinators 28
External Review Committees 29
Recruit and Enroll Patients 29
Transnational Trials 30
Conduct the Trials 30
Programs for Data Analysis 30
Analyze and Interpret the Data 31
The People You Don't Need 31
For Further Information 33
5 Design Decisions 35
Should the Study Be Performed? 36
Should the Trials Be Transnational? 37
Study Objectives 37
End Points 38
Secondary End Points 39
Should We Proceed with a Full-Scale Trial? 41
Tertiary End Points 41
Baseline Data 41
Who Will Collect the Data? 41
Quality Control 42
Study Population 44
Timing 45
Closure 46
Planned Closure 46
Unplanned Closure 46
Be Defensive. Review, Rewrite, Review Again 49
Checklist for Design 50
Budgets and Expenditures 50
For Further Information 51
6 Trial Design 55
Baseline Measurements 56
Controlled Randomized Clinical Trials 57
Randomized Trials 58
Blocked Randomization 59
Stratified Randomization 60
Single- vs. Double-Blind Studies 60
Allocation Concealment 62
Exceptions to the Rule 62
Sample Size 63
Which Formula? 64
Precision of Estimates 64
Bounding Type I and Type II Errors 66
Equivalence 68
Software 68
Subsamples 69
Loss Adjustment 69
Number of Treatment Sites 70
Alternate Designs 70
Taking Cost into Consideration 72
For Further Information 73
7 Exception Handling 75
Patient Related 75
Missed Doses 75
Missed Appointments 75
Noncompliance 76
Adverse Reactions 76
Reporting Adverse Events 76
When Do You Crack the Code? 77
Investigator Related 77
Lagging Recruitment 77
Protocol Deviations 78
Site-Specific Problems 78
Closure 79
Intent to Treat 80
Is Your Planning Complete? 80
Part II Do 81
8 Documentation 83
Guidelines 84
Common Technical Document 84
Reporting Adverse Events 86
Initial Submission to the Regulatory Agency 87
Sponsor Data 88
Justifying the Study 88
Objectives 89
Patient Selection 89
Treatment Plan 90
Outcome Measures and Evaluation 90
Procedures 90
Clinical Follow-Up 90
Adverse Events 91
Data Management, Monitoring, Quality Control 91
Statistical Analysis 91
Investigator Responsibilities 92
Ethical and Regulatory Considerations 93
Study Committees 93
Appendixes 94
Sample Informed Consent Form 94
Procedures Manuals 95
Physician's Procedures Manual 96
Laboratory Guidelines 97
Interim Reports 97
Enrollment Report 98
Data in Hand 98
Adverse Event Report 99
Annotated Abstract 99
Final Reports(s) 102
Regulatory Agency Submissions 102
e-Subs 104
Journal Articles 104
For Further Information 105
9 Recruiting and Retaining Patients and Physicians 107
Selecting Your Clinical Sites 107
Recruiting Physicians 108
Teaching Hospitals 109
Clinical Resource Centers 109
Look to Motivations 110
Physician Retention 111
Get the Trials in Motion 111
Patient Recruitment 112
Factors in Recruitment 112
Importance of Planning 113
Ethical Considerations 114
Mass Recruiting 114
Patient Retention 115
Ongoing Efforts 116
Run-In Period 117
Budgets and Expenditures 118
For Further Information 118
10 Computer-Assisted Data Entry 123
Pre-Data Screen Development Checklist 124
Develop the Data Entry Software 124
Avoid Predefined Groupings in Responses 126
Screen Development 126
Radio Button 128
Pull-Down Menus 129
Type and Verify 129
When the Entries are Completed 130
Audit Trail 132
Electronic Data Capture 132
Data Storage: CDISC Guidelines 133
Testing 136
Formal Testing 137
Stress Testing 138
Training 139
Reminder 139
Support 140
Budgets and Expenditures 141
For Further Information 141
11 Data Management 143
Options 143
Flat Files 143
Hierarchical Databases 145
Network Database Model 146
Relational Database Model 146
Which Database Model? 149
Object-Oriented Databases 150
Clients and Servers 150
One Size Does Not Fit All 151
Combining Multiple Databases 151
A Recipe for Disaster 152
Transferring Data 154
Quality Assurance and Security 155
Maintaining Patient Confidentiality 155
Access to Files 155
Maintaining an Audit Trail 157
Security 157
For Further Information 158
12 Are You Ready? 161
Pharmaceuticals/Devices 161
Software 162
Hardware 162
Documentation 162
Investigators 162
External Laboratories 163
Review Committees 163
Patients 163
Regulatory Agency 163
Test Phase 163
13 Monitoring the Trials 165
Roles of the Monitors 165
Before the Trials Begin 167
Kick-Off Meetings 168
Duties During Trial 169
Site Visits 169
Between Visits 170
Other Duties 173
Maintaining Physician Interest in Lengthy Trials 173
14 Managing the Trials 175
Recruitment 176
Supplies 176
Late and Incomplete Forms 176
Dropouts and Withdrawals 178
Protocol Violations 178
Adverse Events 179
Quality Control 179
Visualize the Data 180
Roles of the Committees 183
Termination and Extension 184
Extending the Trials 186
Budgets and Expenditures 186
For Further Information 187
15 Data Analysis 189
Report Coverage 189
Understanding Data 190
Categories 190
Metric Data 192
Statistical Analysis 194
Categorical Data 196
Ordinal Data 197
Metric Data 198
An Example 199
Time-to-Event Data 200
Step By Step 203
The Study Population 203
Reporting Primary End Points 204
Exceptions 204
Adverse Events 207
Analytical Alternatives 207
When Statisticians Can't Agree 208
Testing for Equivalence 209
Simpson's Paradox 210
Estimating Precision 211
Bad Statistics 213
Using the Wrong Method 213
Deming Regression 213
Choosing the Most Favorable Statistic 214
Making Repeated Tests on the Same Data 214
Ad Hoc, Post Hoc Hypotheses 215
Interpretation 217
Documentation 218
For Further Information 219
A Practical Guide to Statistical Terminology 222
Part III Check 225
16 Check 227
Closure 227
Patient Care 227
Data 228
Spreading the News 228
Postmarket Surveillance 228
Budget 228
Controlling Expenditures 229
Process Review Committee 229
Trial Review Committee 230
Investigatory Drug or Device 230
Interactions 232
Adverse Events 232
Collateral Studies 233
Future Studies 234
For Further Information 234
Appendix Software 237
Choices 237
All in One 237
Almost All in One 238
Project Management 238
Data Entry 239
Handheld Devices 239
Touch Screen 239
Speech Recognition 239
e-CRFs 240
Do it Yourself 240
Data Collection Via the Web 240
Preparing the Common Technical Document 241
Data Management 241
Data Entry and Data Management 242
Small-Scale Clinical Studies 242
Clinical Database Managers 242
Data Analysis 243
Utilities 244
Sample Size Determination 244
Screen Capture 245
Data Conversion 245
Author Index 247
Subject Index 251
