Implementation Of Immunohistochemistry Assays For Clinical Trial Sample Analyses

Immunohistochemistry (IHC) is an essential tool for visualization and assessment of protein expression in sections of tissue in the context of sample morphology. IHC is utilized in preclinical applications to determine target engagement and pharmacodynamics, as well as proof of concept studies. However, transitioning an assay from the preclinical stage to implementation for human clinical trial sample analyses can be challenging for a number of reasons. For example, correlation of preclinical results on surrogate tissues may not be indicative of the final results in humans and assay conditions and reagents may need to be changed for optimal use on human formalin-fixed paraffin-embedded (FFPE) tissue. In clinical trials, IHC can be deployed to address different types of biomarker needs, such as for prospective patient enrollment where the assay validated to stringent clinical laboratory standards, or as a research assay used solely to generate observational data. Using a chromogen-based oncology IHC biomarker analyses as an example, this chapter will cover a range of considerations for implementation of IHC assays in clinical trials, from sample collection considerations through assay validation and implementation.