Digitalization of the decision-making process in healthcare has been promoted to improve clinical performance and patient outcomes. The implementation of Clinical Practice Guidelines (CPGs) using Clinical Decision Support Systems (CDSSs) is widely developed in order to achieve this purpose within clinical information systems. Nevertheless, due to several factors such as (i) incompleteness of CPG clinical knowledge, (ii) out-of-date contents, or (iii) knowledge gaps for specific clinical situations, guideline-based CDSSs may not completely satisfy clinical needs. The proposed architecture aims to cope with guideline knowledge gaps and pitfalls by harmonizing different modalities of decision support (i.e. guideline-based CDSSs, experience-based CDSSs, and data mining-based CDSSs) and information sources (i.e. CPGs and patient data) to provide the most complete, personalized, and up-to-date propositions to manage patients. We have developed a decisional event structure to retrieve all the information related to the decision-making process. This structure allows the tracking, computation, and evaluation of all the decisions made over time based on patient clinical outcomes. Finally, different user-friendly and easy-to-use authoring tools have been implemented within the proposed architecture to integrate the role of clinicians in the whole process of knowledge generation and validation. A use case based on Breast Cancer management is presented to illustrate the performance of the implemented architecture.