BackgroundClinical practice guidelines are statements which are based on the best available evidence, and their goal is to improve the quality of patient care. Integrating clinical practice guidelines into computer systems can help physicians reduce medical errors and help them to have the best possible practice. Guideline-based clinical decision support systems play a significant role in supporting physicians in their decisions. Meantime, system errors are the most critical concerns in designing decision support systems that can affect their performance and efficacy. A well-developed ontology can be helpful in this matter. The proposed systematic review will specify the methods, components, language of rules, and evaluation methods of current ontology-driven guideline-based clinical decision support systems.MethodsThis review will identify literature through searching MEDLINE (via Ovid), PubMed, EMBASE, Cochrane Library, CINAHL, ScienceDirect, IEEEXplore, and ACM Digital Library. Gray literature, reference lists, and citing articles of the included studies will be searched. The quality of the included studies will be assessed by the mixed methods appraisal tool (MMAT-version 2018). At least two independent reviewers will perform the screening, quality assessment, and data extraction. A third reviewer will resolve any disagreements. Proper data analysis will be performed based on the type of system and ontology engineering evaluation data.DiscussionThe study will provide evidence regarding applying ontologies in guideline-based clinical decision support systems. The findings of this systematic review will be a guide for decision support system designers and developers, technologists, system providers, policymakers, and stakeholders. Ontology builders can use the information in this review to build well-structured ontologies for personalized medicine.Systematic review registrationPROSPERO CRD42018106501
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