Home Tutorials Video Courses Case Studies Software Research Presentations Technical Reports Short Course Design, Monitoring, and Analysis of Clinical Trials Scott S. Emerson, M.D., Ph.D. |
Abstract
Increasingly, clinical trials are conducted using group sequential methods in order to address the ethical and efficiency
issues that arise when performing experiments with human volunteers. The design, conduct, and analysis of a sequential
clinical trial is necessarily more involved than that for a clinical trial in which the data would only be analyzed at
the end of the study. However, the basic tenets of careful consideration of the scientific question and clinical setting
remains the same. In this short course we present an overview of the issues that must be considered when
conducting a group sequential trial.
Presentation Materials | Format | Size (KB) |
Presentation Handouts Day 1 | 362 | |
Presentation Handouts Day 2 | 466 | |
Case Studies, Part 1 Handouts | 238 | |
Case Studies, Part 2 Handouts | 174 | |
Example Protocol Handouts | 30 |
Day One: Scientific Setting | Day Two: Statistical Design | |||
Slides | Audio-Video (min:sec) | Slides | Audio-Video (min:sec) | |
1-29 | Introduction and Overview: (24:28) | 1-41 | Sample Size: (73:45) | |
Scientific and clinical setting | Standard formula; Application to common probability models; Adjustment for baseline; Crossover; Clustering | |||
30-57 | Phases of Clinical Trials: (39:37) | 42-58 | Sequential Sampling: (29:05) | |
Definition of an "indication"; Phase I, II, III, IV trials; Efficacy vs effectiveness | Control of type I error; Error spending | |||
58-72 | Primary Endpoints: (36:47) | 59-71 | Sampling Distribution: (07:47) | |
Multiple comparison problem; Criteria for primary clinical endpoint; Composite / co-primary endpoints | Effect on distribution of estimate, Z, P | |||
73-101 | Surrogate Endpoints: (22:24) | 72-101 | Inferential Methods: (20:33) | |
Historical examples; Potential mechanisms of treatment effect on clinical and surrogate endpoints; Validation of surrogate endpoints | Adjusted estimates, p values | |||
102-114 | Refining Scientific Hypotheses: (13:36) | 102-108 | Nonbinding Futility Boundaries: (11:45) |
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Causation versus association; Allowing for variation in response | Effect on power, inference | |||
115-123 | Controls: (06:35) | 109-123 | Boundary Scales: (13:01) | |
Historical controls; Concurrent controls | Correspondence with error spending, Bayesian, conditional power | |||
124-134 | Randomization: (40:13) | 124-136 | Dangers of Statistical Scales: (13:18) | |
Establishing cause and effect; Ensuring comparability of treatment arms; Analytic models | Potential for unethical stopping rules | |||
135-142 | Blinding: (16:33) | 137-147 | Relative Advantages of Scales: (27:08) | |
Advantages; Logistics; Blinding of DSMB | Use of estimates, Z scores, error spending scales | |||
143-177 | Summarizing Treatment Effect: (34:02) | 148-169 | Stochastic Curtailment: (25:36) | |
Statistical primary endpoint: Summary measures; Criteria for selection of summary measure; Use of the mean; Censored data | Issues with conditional power; predictive power | |||
178-202 | Scientific Burden of Evidence: (15:51) | 170-185 | Evaluation of Designs: (15:50) | |
Superiority, noninferiority, approximate equivalence; Clinical trials with active controls | Criteria for choosing among candidate designs | |||
203-230 | Ethical Issues re Treatment and Eligibility: (22:41) | 186-203 | Adaptive Designs: (15:57) | |
Definition of treatments: Planning for noncompliance; Definition of target population: Inclusion and exclusion criteria | Adaptive re-powering of study | |||
231-254 | Statistical Criteria for Evidence: (15:30 ) | 204-208 | Documentation of Design: (08:03) | |
Frequentist and Bayesian frameworks; Parametric, semiparametric, and nonparametric probability models | Parameters to specify in protocol | |||
255-297 | Criteria for Sample Size: (23:45) | 37-72 | Sepsis Case Study: (29:39) | |
Reporting results; Precision of results | ||||
298-300 | Scientific Review of Clinical Trial Design: (04:05) | 73-126 | Hodgkin's Case Study: (40:09) | |
Scientific issues; Scientific review of statistical issues |
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