Platform and Biomarker Stratified Trials

Chair: Anastasia Ivanova (UNC)
Vice Chair: Shibing Deng (Pfizer)

Speaker: Adrian Mander (GSK)
Title: Issues and challenges with designing and running a platform trial in type 1 diabetes
Abstract: A consortium was created in 2015, called INNODIA, with the idea of building a clinical network in Europe and subsequently running phase 2 clinical trials. A master protocol was created to allow heterogeneous sub-trials to be run with standardised data collection, lab analysis and trial operations. This talk will cover two of the sub-trials: the first one that changed from a blinded group-sequential design investigating Verapamil into a platform combination trial for early signal detection; and the second one that was a Bayesian dose-ranging trial of ATG in young adults and children. The Verapamil study was designed as a group-sequential design with a single futility stopping rule but was repurposed to allow additional unblinded arms for studying combinations of verapamil and other agents. New decision rules for initiation of the combination study did not alter the original study and maintained statistical operating characteristics. The Bayesian dose-ranging study used repeated measures longitudinal models to predict which doses to choose at several interim analyses whilst maintaining sufficient numbers on the highest dose and placebo.


Speaker: Andrea Jorgensen (University of Liverpool, UK)
Title: Planning biomarker-guided trials: points to consider
Abstract: Biomarker-guided trials, which allow targeted treatment strategies to be tested, are of increasing interest due to the expanding demand for stratified treatment approaches. A number of biomarker-guided trial designs have been proposed, including both biomarker-guided adaptive and non-adaptive trial designs, however navigating the literature to gain an understanding of the various designs and to identify the most appropriate for a given setting is challenging. As members of the MRC Trials Methodology Research Partnership (TMRP), we have developed an online tool, BiGTeD (www.bigted.org), to provide guidance on the design and analysis of the various designs, to aid those planning biomarker-guided trials in the future. Here, I will introduce the tool and demonstrate how it can be used to inform trial protocols and analysis plans. Further, prior to embarking on a biomarker-guided trial, evidence of the biomarker’s validity is essential, however we are unaware of any guidelines specifying the nature and extent of that evidence. We have undertaken a systematic review of biomarker-guided trials to explore the evidence of biomarker validity upon which they were designed. During my talk I will present the review’s findings together with some suggestions on how such evidence might be compiled in future.


Speaker: Lang Li (UNC)
Title: Design considerations for the PrecISE trial, a platform biomarker stratified trial
Abstract: PrecISE (Clinical Trials.gov NCT04129931) is an ongoing NHLBI sponsored clinical trial to screen five novel interventions that might work in severe asthma. Enrollment in each intervention is stratified by a biomarker-defined subgroup with potential enrichment after the interim analysis. We discuss biomarker-stratified trials with enrichment with PrecISE as an example.