
Contents
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13 Other Issues in Statistics I: Missing Data, Intention-to-Treat Analysis, and Covariate Adjustment
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Introduction Introduction
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Interim Analysis: Starting as a Large Trial and Finishing as a Small Trial Interim Analysis: Starting as a Large Trial and Finishing as a Small Trial
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The Alpha Spending Function The Alpha Spending Function
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The O’Brien Fleming Approach The O’Brien Fleming Approach
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The Haybittle-Peto Rule The Haybittle-Peto Rule
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The Pocock Approach The Pocock Approach
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Data Safety Monitoring Board Data Safety Monitoring Board
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When Are DSMBs Needed? When Are DSMBs Needed?
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How Do DSMBs Operate? How Do DSMBs Operate?
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Early Termination of a Trial Early Termination of a Trial
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Adaptive (Flexible) Design Adaptive (Flexible) Design
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Other Types of Designs: Design with Medical Devices Other Types of Designs: Design with Medical Devices
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Drugs versus Medical Devices Trials: Are They Different? Drugs versus Medical Devices Trials: Are They Different?
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Rationale for RCT Rationale for RCT
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Placebo Effect Placebo Effect
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Primary Endpoint Considerations Primary Endpoint Considerations
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Sample Size Considerations Sample Size Considerations
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Case Study: Interim Analysis: Trojan’s Horse in the Serenium Trial? Planning an Interim Analysis Case Study: Interim Analysis: Trojan’s Horse in the Serenium Trial? Planning an Interim Analysis
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An International Call An International Call
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The Successful Negotiation of Serenium Trial The Successful Negotiation of Serenium Trial
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Boarding to LA: Advantages and Disadvantages of Interim Analysis Boarding to LA: Advantages and Disadvantages of Interim Analysis
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The Sun Still Shines: Statistical Aspects of Interim Analysis The Sun Still Shines: Statistical Aspects of Interim Analysis
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Case Discussion Case Discussion
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Statistical Power and Interim Analysis Statistical Power and Interim Analysis
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Case Questions for Reflection Case Questions for Reflection
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Further Reading Further Reading
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References References
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Cite
Abstract
This chapter discusses the important aspect of changing trial aspects, including analyzing data, before formal completion of a trial. Interim analysis (or analyses before trial is finished) should be planned and described in the study protocol, before starting the trial, to ensure the potential penalties for doing such analyses do not invalidate trial results and/or satisfy ethical requirements. The chapter discusses reasons and methods to perform interim analysis. Based on the results from interim analysis, some adjustments in the trial should be required, including early termination. Although the main goal of adaptive design is to increase the success of clinical development, making the studies more efficient and more likely to demonstrate the effect of a treatment, the investigator needs to be careful when using these methods as they can also introduce other potential biases in the study.
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