An integrative paradigm to impart quality to correlative science.
Correlative studies are a primary mechanism through which insights can be obtained about the bioactivity and potential efficacy of candidate therapeutics evaluated in early-stage clinical trials. Accordingly, well designed and performed early-stage correlative studies have the potential to strongly influence further clinical development of candidate therapeutic agents, and correlative data obtained from early stage trials has the potential to provide important guidance on the design and ultimate successful evaluation of products in later stage trials, particularly in the context of emerging clinical trial paradigms such as adaptive trial design. Historically the majority of early stage trials have not generated meaningful correlative data sets that could guide further clinical development of the products under evaluation. In this review article we will discuss some of the potential limitations with the historical approach to performing correlative studies that might explain at least in part the to-date overall failure of such studies to adequately support clinical trial development, and present emerging thought and approaches related to comprehensiveness and quality that hold the promise to support the development of correlative plans which will provide meaningful correlative data that can effectively guide and support the clinical development path for candidate therapeutic agents.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Abramson Family Cancer Research Institute, Philadelphia, 19104-4283, USA. mkalos@exchange.upenn.edu
Michael
M
Kalos
D001681:Biological Assay / Q000379:methods / Q000592:standards; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011786:Quality Control; D015203:Reproducibility of Results; D012107:Research Design