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Preface | |
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Randomization and the Clinical Trial | |
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Introduction | |
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Causation and association | |
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Randomized clinical trials | |
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Ethics of randomization | |
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Problems | |
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References | |
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Issues in the Design of Clinical Trials | |
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Introduction | |
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Study outcomes | |
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Sources of bias | |
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Standardization and masking | |
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Statistical analysis philosophy | |
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Losses to follow-up and noncompliance | |
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Covariates | |
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Experimental design | |
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Recruitment and follow-up | |
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Determining the number of randomized subjects | |
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Development of the main formula | |
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Example | |
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Survival trials | |
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Adjustment for noncompliance | |
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Additional considerations | |
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Problems | |
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References | |
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Randomization for Balancing Treatment Assignments | |
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Introduction | |
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The balancing properties of complete randomization | |
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Random allocation rule | |
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Truncated binomial design | |
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Permuted block designs | |
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Efron's biased coin design | |
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Wei's urn design | |
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Generalized biased coin designs | |
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Comparison of balancing properties | |
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K > 2 treatments | |
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Restricted randomization for unbalanced allocation | |
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Problems | |
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References | |
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Balancing on Known Covariates | |
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Introduction | |
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Stratified randomization | |
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Treatment imbalances in stratified trials | |
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Covariate-adaptive randomization | |
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Zelen's rule | |
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The Pocock-Simon procedure | |
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Wei's marginal urn design | |
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Optimal design based on a linear model | |
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Conclusions | |
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Problems | |
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References | |
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The Effects of Unobserved Covariates | |
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Introduction | |
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A bound on the probability of a covariate imbalance | |
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Accidental bias | |
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Maximum eigenvalue of [Sigma subscript T] | |
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Accidental bias for the biased coin designs | |
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Simulation results | |
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Conclusions | |
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Problems | |
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References | |
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Selection Bias | |
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Introduction | |
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The Blackwell-Hodges model | |
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Selection bias for the random allocation rule | |
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Selection bias for the truncated binomial design | |
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Selection bias in a permuted block design | |
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Permuted blocks using the random allocation rule | |
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Variable block design | |
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Permuted blocks with truncated binomial randomization | |
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Conclusions | |
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Selection bias for Efron's biased coin design | |
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Wei's urn design | |
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Generalized biased coin designs | |
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Controlling selection bias in practice | |
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Problems | |
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References | |
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Randomization as a Basis for Inference | |
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Introduction | |
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The population model | |
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The randomization model | |
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Permutation tests | |
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Linear rank tests | |
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Variance of the linear rank test | |
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Optimal rank scores | |
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Construction of exact permutation tests | |
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Large sample permutation tests | |
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Group sequential monitoring | |
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Problems | |
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References | |
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Appendix A: DCCT Data | |
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Appendix B: SAS Code for Conditional U D(0, 1) Linear Rank Test | |
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Inference for Stratified, Blocked, and Covariate-Adjusted Analyses | |
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Introduction | |
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Stratified analysis | |
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The Mantel-Haenszel procedure | |
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Linear rank test | |
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Small strata | |
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Stratified versus unstratified tests with stratified randomization | |
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Efficiency of stratified randomization in a stratified analysis | |
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Post-hoc stratified and subgroup analyses | |
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Complete randomization | |
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Random allocation rule | |
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Permuted block randomization with a random allocation rule | |
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Wei's urn design | |
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Pre- and post-stratified analyses | |
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Analyses with missing data | |
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Covariate-adjusted analyses | |
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Example 1: The Neonatal Inhaled Nitric Oxide Study | |
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A Blocked Randomization and Analysis | |
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A Post-Stratified Blocked Analysis | |
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Covariate-Adjusted Blocked Analysis | |
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Example 2: The Diabetes Control and Complications Trial | |
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A Stratified Urn Randomization and Analysis | |
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Urn Analysis with Missing Data | |
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Covariate-Adjusted Urn Analysis | |
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Conclusions | |
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Problems | |
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References | |
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Randomization in Practice | |
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Introduction | |
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Stratification | |
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Characteristics of randomization procedures | |
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Consideration of selection bias | |
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Implications for analysis | |
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Choice of randomization procedure | |
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Complete randomization | |
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Forced-balance designs | |
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Permuted block design | |
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Biased coin-type designs | |
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Generation and checking of sequences | |
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Implementation | |
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Packaging and labeling | |
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The actual randomization | |
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Special situations | |
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Some examples | |
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The Optic Neuritis Treatment Trial | |
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Vesnarinone in congestive heart failure | |
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The Diabetes Control and Complications Trial | |
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Captopril in diabetic nephropathy | |
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The Diabetes Prevention Program | |
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Adjuvant chemotherapy for locally invasive bladder cancer | |
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Problems | |
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References | |
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Response-Adaptive Randomization | |
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Introduction | |
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Historical notes | |
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Roots in bandit problems | |
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Roots in sequential stopping problems | |
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Roots in randomization | |
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Optimal allocation | |
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Response-adaptive randomization to target R* | |
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Sequential maximum likelihood procedure | |
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Doubly-adaptive biased coin design | |
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Urn models | |
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The generalized Friedman's urn model | |
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The randomized play-the-winner rule | |
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Ternary urn models | |
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Treatment effect mappings | |
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Problems | |
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References | |
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Inference for Response-Adaptive Randomization | |
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Introduction | |
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Population-based inference | |
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The likelihood | |
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Sufficiency | |
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Bias of the maximum likelihood estimators | |
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Confidence interval procedures | |
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Power | |
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Randomization-based inference | |
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Problems | |
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References | |
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Response-Adaptive Randomization in Practice | |
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Basic assumptions | |
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Bias, masking, and consent | |
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Logistical issues | |
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Selection of a procedure | |
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Benefits of response-adaptive randomization | |
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Some examples | |
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The Extracorporeal Membrane Oxygenation trial | |
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The fluoxetine trial | |
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Conclusions | |
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Problems | |
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References | |
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Some Useful Results in Large Sample Theory | |
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Some useful central limit theorems | |
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Martingales and sums of dependent random variables | |
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Martingales and triangular arrays | |
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Asymptotic normality of maximum likelihood estimators | |
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The likelihood | |
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Basic conditions for consistency and asymptotic normality | |
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Alternative conditions | |
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Conclusions | |
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Problems | |
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References | |
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Large Sample Inference for Complete and Restricted Randomization | |
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Introduction | |
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Complete randomization | |
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The unconditional test | |
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The conditional test | |
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Simulation results | |
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Random allocation rule | |
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Truncated binomial design | |
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Efron's biased coin design | |
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Wei's urn design | |
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Wei, Smythe, and Smith's general allocation rules | |
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The unconditional test for K > 2 treatments | |
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The conditional test for two treatments | |
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Conclusions | |
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Problems | |
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References | |
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Large Sample Inference for Response-Adaptive Randomization | |
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Introduction | |
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Maximum likelihood estimation | |
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Asymptotic normality of the maximum likelihood estimator: Urn models | |
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Delayed response | |
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Likelihood ratio test for K treatments | |
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Asymptotic properties of sequential maximum likelihood procedures | |
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Large sample linear rank tests | |
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Problems | |
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References | |
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Author Index | |
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Subject Index | |