Study Protocol Representation

Abstract

Clinical research is an extremely complex process involving multiple stakeholders, regulatory frameworks, and environments. The core essence of a ­clinical study is the study protocol, an abstract concept that comprises a study’s investigational plan—including the actions, measurements, and analyses to be undertaken. The “planned study protocol” drives key scientific and biomedical activities during study execution and analysis. The “executed study protocol” ­represents the activities that actually took place in the study, often differing from the planned protocol, and is the proper context for interpreting final study results. To date, clinical research informatics (CRI) has primarily focused on facilitating ­electronic sharing of text-based study protocol documents. A much more powerful approach is to instantiate and share the abstract protocol information as a ­computable protocol model, or e-protocol, which will yield numerous potential benefits. At the design stage, the e-protocol would facilitate simulations to optimize study ­characteristics and could guide investigators to use standardized data elements and case report forms (CRFs). At the execution stage, the e-protocol could create ­human-readable text documents; facilitate patient recruitment processes; promote timely, complete, and accurate CRFs; and enhance decision support to minimize protocol deviations. During the analysis stage, the e-protocol could drive ­appropriate statistical techniques and results reporting, and support proper cross-study data ­synthesis and interpretation. With the average clinical trial costing millions of ­dollars, such increased efficiency in the design and execution of clinical research is critical. Our vision for achieving these major CRI advances through a computable study protocol is described in this chapter.