The ability to evaluate predictive and pharmacodynamic biomarkers in a global, multicenter clinical trial is often constrained by factors related to sample collection and processing.

Our Precision Medicine team in collaboration with our Translational Research Consortium is focused on developing and validating innovative methodologies to remove barriers and enhance the capabilities of implementing standardized Precision Medicine approaches in multicenter clinical trials.  With the development of targeted therapies to treat chronic inflammatory diseases it’s becoming more important than ever to monitor immune functions systemically or at the site of action.  Standardized sample procurement and single cell technologies will be essential to identify biomarkers and characterize the drug’s mechanism of action to enable tailored drug therapies.

Flow cytometry is a powerful tool to evaluate the immune response to drug therapy, however its application to clinical trials was historically limited by interlaboratory variability. To address this limitation, our team conducted a prospective, multicenter study to evaluate the interlaboratory variability in flow cytometric analysis and determined that a central gating strategy can be implemented to standardize data analysis and reduce interlaboratory variability (Westera et al., 2017).

With the emergence of GI-targeted compounds in development the potential of using flow cytometry to monitor immune cell changes at the site of action holds promise to accelerate drug development.  However, the evaluation of biopsy specimens by flow cytometry was limited due to the rapid loss of viable cells making the collection, storage and shipping of samples from site to laboratory for central analysis challenging.  To address these constraints, we evaluated the effect of different storage conditions and mediums to develop and validate a cryopreservation method for mucosal tissue biopsies that requires minimal manipulation by the sites and allows for centralized flow cytometric analysis of marker-positive cells in multicenter clinical trials (Wildenberg et al., 2018).  We further evaluated longer-term stability of mucosal tissue biopsies which allows batched analysis of cryopreserved biopsy specimens (Vande Casteele and Wildenberg, 2019).