Certain examples provide systems, methods, and apparatus for a content-based clinical information system. An example system includes a reference platform to define and provide core system capabilities and to interpret and execute content items while remaining application neutral. The example system includes a plurality of content items authored independent of the reference platform to define clinical functionality for one or more content-based clinical applications by leveraging the reference platform. In the example system, the plurality of content items is to be created and deployed independently of the creation and deployment of the one or more content-based clinical applications. The plurality of content items is to remain independent of the implementation of the reference platform to allow independent evolution of the platform and the one or more content-based clinical applications.