When estimating the treatment effect after a group sequential test or a more complex adaptive design, the maximum likelihood estimate is liable to be biased. The ICH E20: Guideline on Adaptive Designs for Clinical Trials has “reliability of estimation” as a key topic. Methods have been developed to reduce the bias in estimators after group sequential and adaptive designs – or even eliminate...
Reliable estimation of treatment effects is essential for the benefit–risk assessment supporting the approval of new drugs and for the communication of trial results in the European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC). In adaptive designs, where trial adaptations such as sample size re-assessment, population enrichment, or treatment arm selection are...
In adaptive clinical trials, the conventional point estimators of the treatment effect are prone to bias. Similarly, the conventional confidence intervals are prone to incorrect coverage, as well as other undesirable statistical properties. Recent regulatory guidance, such as ICH E20, has highlighted the need to use adjusted estimators and confidence intervals for adaptive designs in order to...
Clinical trials have become more complex in recent decades. They have gradually become longer, involving more centers and more patients. With these tendencies, interim analyses of ongoing trials have become much more common and much research has been done on the design and analysis of data from adaptive trials. By now group-sequential trials are probably more frequent than single-stage...
