Selection Bias and Covariate Imbalances in Randomized Clinical Trials

Selection Bias and Covariate Imbalances in Randomized Clinical Trials......Page 3
Contents......Page 7
Preface......Page 11
Part I: Is There a Problem with Reliability in Medical Studies?......Page 15
1.1 Single-subject studies......Page 17
1.2 Case series and cohort studies......Page 18
1.3 Historical controls......Page 19
1.5 Matched studies......Page 20
1.6 Randomization......Page 23
1.7 Advance randomization......Page 25
1.8 Allocation concealment......Page 26
1.9 Residual selection bias......Page 28
2 Susceptibility of Randomized Trials to Subversion and Selection Bias......Page 31
2.1 Can randomized trials be subverted?......Page 32
2.2 If randomized trials are subverted, do they cease to be randomized trials?......Page 36
2.3 What is masking?......Page 39
2.4 What is allocation concealment?......Page 41
2.5 A double standard......Page 42
2.6 What if allocation concealment could be ensured?......Page 43
3 Evidence of Selection Bias in Randomized Trials......Page 51
3.1 The burden of proof regarding the existence of selection bias in randomized trials......Page 52
3.2 Indirect population-level evidence that selection bias exists in randomized trials......Page 55
3.3 Direct trial-level evidence that selection bias exists in randomized trials......Page 56
3.3.2 University Group Diabetes Program......Page 57
3.3.3 Talc and mustine for pleural effusions......Page 58
3.3.5 Oxytocin and amniotomy for induction of labor......Page 59
3.3.6 Western Washington Intracoronary Streptokinase Trial......Page 60
3.3.8 A trial to assess episiotomy......Page 61
3.3.9 Canadian National Breast Cancer Screening Study......Page 62
3.3.10 Surgical trial......Page 63
3.3.12 Coronary Artery Surgery Study......Page 64
3.3.13 Etanercept for children with juvenile rheumatoid arthritis......Page 65
3.3.14 Edinburgh Randomized Trial of Breast-Cancer Screening......Page 66
3.3.17 HIP Mammography Trial......Page 67
3.3.20 Effectiveness trial of a diagnostic test......Page 77
3.3.21 South African trial of high-dose chemotherapy for metastatic breast cancer......Page 78
3.3.23 Runaway Youth Study......Page 79
3.3.24 Cluster randomized trial of palliative care......Page 81
3.3.25 Randomized trial of methadone with or without heroin......Page 86
3.3.26 Randomized NINDS trial of tissue plasminogen activator for acute ischemic stroke......Page 88
3.3.27 Norwegian Timolol Trial......Page 89
3.3.28 Laparoscopic versus open appendectomy......Page 91
3.3.29 The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study......Page 92
3.3.30 The Heart Outcomes Prevention Evaluation (HOPE) Study......Page 93
3.4 In search of better evidence......Page 94
4.1 Quantifying the prediction of future allocations: balanced blocks......Page 99
4.2 Quantifying prediction of future allocations: unbalanced blocks......Page 104
4.3 Quantifying covariate imbalance resulting from selection bias......Page 108
4.4 Quantifying the bias resulting from covariate imbalance......Page 114
Part II: Actions to be Taken to Improve the Reliability of Medical Studies......Page 117
5 Preventing Selection Bias in Randomized Trials......Page 119
5.2 Biased Selection of Investigators......Page 120
5.3 Minimizing the prediction of future allocations......Page 121
5.3.1 The trade-off between selection bias and chronological bias......Page 123
5.3.2 Notation......Page 125
5.3.3 Varying the block sizes......Page 127
5.3.4 The maximal procedure......Page 129
5.3.5 Extensions......Page 135
6 Detecting Selection Bias in Randomized Trials......Page 137
6.1 Baseline Imbalances in Observed Covariates......Page 138
6.3 The selection covariate......Page 143
6.4 The role of the reverse propensity score in third-order residual selection bias......Page 144
6.5 Using the reverse propensity score To Test for selection bias: the Berger–Exner test and graph......Page 146
6.6 Using the screening log to test for selection bias......Page 156
6.7 The Ivanova-Barrier-Berger (IBB) Detection Method......Page 159
6.8 Interpreting negative tests of selection bias......Page 161
6.9 When should one test for selection bias?......Page 162
6.10 Who should test for selection bias?......Page 169
7 Adjusting for Selection Bias in Randomized Trials......Page 171
7.1 Methods proposed for addressing non-random baseline imbalances......Page 173
7.3 Selection bias arising from imperfect allocation concealment......Page 175
7.3.1 The RPS approach to adjusting for selection bias......Page 176
7.3.2 The Ivanova–Barrier–Berger (IBB) method for correcting selection bias......Page 179
8.1 Action points during the design phase of the trial......Page 185
8.2 Action points during the conduct of the trial......Page 188
8.3 Action points during the analysis of trial data......Page 192
8.4 Action points by party......Page 196
References......Page 201
Author Index......Page 213
Subject Index......Page 217
Statistics in Practice......Page 220