Re-inventing drug development: A case study of the I-SPY 2 breast cancer clinical trials program

Background: In this case study, we profile the I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And molecular anaLysis 2), a unique breast cancer clinical trial led by researchers at 20 leading cancer centers across the US, and examine its potential to serve as a model of drug development for other disease areas. This multicenter collaboration launched in 2010 to reengineer the drug development process to be more efficient and patient-centered. Methods: We conduct several interviews with the I-SPY leadership as well as a literature review of relevant publications to assess the I-SPY 2 initiative. Results: To date, six drugs have graduated from I-SPY 2, identified as excellent candidates for phase 3 trials in their corresponding tumor subtype, and several others have been or are still being evaluated. These trials are also more efficient, typically involving fewer subjects and reaching conclusions more quickly, and candidates have more than twice the predicted likelihood of success in a smaller phase 3 setting compared to traditional trials. Conclusions: We observe that I-SPY 2 possesses several novel features that could be used as a template for more efficient and cost effective drug development, namely its adaptive trial design; precompetitive network of stakeholders; and flexible infrastructure to accommodate innovation.