ABSTRACT
It is often the case in drug development, particularly in oncology, that a randomized trial is launched with considerable uncertainty about the final sample size required to demonstrate a clinically meaningful and statistically significant improvement in results over the control treatment. Group-sequential designs have an established role in randomized trials and allow for safety monitoring as well as early decisions regarding efficacy and futility of the new treatment. In some trials, it may be interesting to foresee the possibility of adapting the final sample size if results at an interim analysis suggest the possibility of a positive trial, albeit with a less pronounced treatment effect than initially anticipated. Such adaptive designs that allow for sample-size reassessment have gained traction in recent years. However, they pose several issues that require consideration and advanced statistical input. In this webinar, we will play the part of a sponsor consulting a statistician with the goal of designing a randomized trial with sample-size reassessment. We will discuss the concept of conditional power and the promising-zone method, and we will present a pragmatic view of some issues, including when to plan the sample-size reassessment in the course of the accrual, how to select the amount of sample-size increase, and how to operate such trials in practice. We will also discuss the pros- and cons- of using this type of design in relation to the clinical setting in which the trial is designed and endpoints it uses. Moreover, we will discuss the regulators’ views and illustrate our discussion with practical examples.
SPEAKER
PROF JOHN SIMES AO
Founding Director of the NHMRC Clinical Trials Centre, University of Sydney: john.simes@ctc.usyd.edu.au
He is Founding Director of the NHMRC Clinical Trials Centre involved in over 120 clinical trials and 80,000 patients in cancer, caridiovascular disease and neonatal medicine. He is also Founding Director of Sydney Catalyst (which helps facilitate translational cancer research with 30 member institutions in Sydney and regional NSW); a practicing medical oncologist in neuro-oncology at Royal Prince Alfred Hospital and Chris O’Brien Lifehouse; and Professor of Clinical Epidemiology at the Faculty of Medicine, University of Sydney. He is also a senior principal research fellow of NHMRC.
He has served on many national and international clinical trials’ research committees including cancer, cardiovascular studies and neonatal trials. He has a major interest in growing clinical trial evidence relevant to clinical practice in all its aspects, from better trial design through to more effective translation
