Pragmatic Trials and New Informatics Methods to Supplement or Replace Phase IV Trials

Given the importance of clinical trials (CT) for the approval of new drugs, and the many current obstacles to CT execution, there is an urgent need for CT improvement. This chapter discusses pragmatic trials and other informatics-enabled enhancements to Phase IV CT that completely change the original definitions of CT and may be seen as full replacements to Phase IVs. These developments are important for reducing costs and time-lines for the CT process, reducing risk of withdrawal from the market, and they are also useful for drug repurposing. Importantly, the future of Phase IV CTs is one that relies heavily on data collected via the EHR enabling a continuous and individualized Phase IV trial model. The EHR thus is a foundation to a continuous pragmatic Phase IV registry and a key tool in support of precision medicine.