The role of ontologies and decision frameworks in computer-interpretable guideline execution

Computer-Interpretable Guidelines (CIGs) are machine readable representations of Clinical Practice Guidelines (CPGs) that serve as the knowledge base in many knowledge-based systems oriented towards clinical decision support. Herein we disclose a comprehensive CIG representation model based on Web Ontology Language (OWL) along with its main components. Additionally, we present results revealing the expressiveness of the model regarding a selected set of CPGs. The CIG model then serves as the basis of an architecture for an execution system that is able to manage incomplete information regarding the state of a patient through Speculative Computation. The architecture allows for the generation of clinical scenarios when there is missing information for clinical parameters.FCT - Fundação para a Ciência e a Tecnologia (SFRH/BD/85291/ 2012)info:eu-repo/semantics/publishedVersio

Computerization of workflows, guidelines and care pathways: a review of implementation challenges for process-oriented health information systems

There is a need to integrate the various theoretical frameworks and formalisms for modeling clinical guidelines, workflows, and pathways, in order to move beyond providing support for individual clinical decisions and toward the provision of process-oriented, patient-centered, health information systems (HIS). In this review, we analyze the challenges in developing process-oriented HIS that formally model guidelines, workflows, and care pathways. A qualitative meta-synthesis was performed on studies published in English between 1995 and 2010 that addressed the modeling process and reported the exposition of a new methodology, model, system implementation, or system architecture. Thematic analysis, principal component analysis (PCA) and data visualisation techniques were used to identify and cluster the underlying implementation ‘challenge’ themes. One hundred and eight relevant studies were selected for review. Twenty-five underlying ‘challenge’ themes were identified. These were clustered into 10 distinct groups, from which a conceptual model of the implementation process was developed. We found that the development of systems supporting individual clinical decisions is evolving toward the implementation of adaptable care pathways on the semantic web, incorporating formal, clinical, and organizational ontologies, and the use of workflow management systems. These architectures now need to be implemented and evaluated on a wider scale within clinical settings

Moving towards a new paradigm of creation, dissemination, and application of computer-interpretable medical knowledge

Computer-Interpretable Guidelines (CIGs) exploit the scientific strength of evidence-based medicine to make recommendations available in Clinical Decision Support Systems. However, systems that deploy them have not been widely successful, in part due to the limitations of CIG frameworks in the adoption of inclusive and open technologies and the use of Artificial Intelligence techniques as tools to make their systems stronger and more adaptable. In this work we propose a web-based CIG framework to tackle some of these challenges and facilitate the integration of CIG-based advice not only in the everyday activities of health care professionals but also in the lives of whoever may need it.This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope UID/CEC/00319/2013. The work of Tiago Oliveira is supported by a FCT grant with the reference SFRH/BD/8- 5291/ 2012.info:eu-repo/semantics/publishedVersio

A Scalable Architecture for Incremental Specification and Maintenance of Procedural and Declarative Clinical Decision-Support Knowledge

Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians’ assessment was significantly lower than the assessment of the knowledge engineers

Design of a goal ontology for medical decision-support

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2005.Includes bibliographical references (leaves 34-36).Objectives: There are several ongoing efforts aimed at developing formal models of medical knowledge and reasoning to design decision-support systems. Until now, these efforts have focused primarily on representing content of clinical guidelines and their logical structure. The present study aims to develop a computable representation of health-care providers' intentions to be used as part of a framework for implementing clinical decision-support systems. Our goal is to create an ontology that supports retrieval of plans based on the intentions or goals of the clinician. Methods: We developed an ontological representation of medical goals, plans, clinical scenarios and other relevant entities in medical decision-making. We used the resulting ontology along with an external ontology inference engine to simulate selection of clinical recommendations based on goals. The ontology instances used in the simulation were modeled from two clinical guidelines. Testing the design: Thirty-two clinical recommendations were encoded in the experimental model. Nine test cases were created to verify the ability of the model to retrieve the plans. For all nine cases, plans were successfully retrieved. Conclusion: The ontological design we developed supported effective reasoning over a medical knowledge base.(cont.) The immediate extension of this approach to be fully developed in medical applications may be partially limited by the lack of available editing tools. Many efforts in this area are currently aiming to the development of needed technologies.by Davide Zacacagnini [i.e. Zaccagnini].S.M

Decentralised Clinical Guidelines Modelling with Lightweight Coordination Calculus

Background: Clinical protocols and guidelines have been considered as a major means to ensure that cost-effective services are provided at the point of care. Recently, the computerisation of clinical guidelines has attracted extensive research interest. Many languages and frameworks have been developed. Thus far, however,an enactment mechanism to facilitate decentralised guideline execution has been a largely neglected line of research. It is our contention that decentralisation is essential to maintain a high-performance system in pervasive health care scenarios. In this paper, we propose the use of Lightweight Coordination Calculus (LCC) as a feasible solution. LCC is a light-weight and executable process calculus that has been used successfully in multi-agent systems, peer-to-peer (p2p) computer networks, etc. In light of an envisaged pervasive health care scenario, LCC, which represents clinical protocols and guidelines as message-based interaction models, allows information exchange among software agents distributed across different departments and/or hospitals. Results: We outlined the syntax and semantics of LCC; proposed a list of refined criteria against which the appropriateness of candidate clinical guideline modelling languages are evaluated; and presented two LCC interaction models of real life clinical guidelines. Conclusions: We demonstrated that LCC is particularly useful in modelling clinical guidelines. It specifies the exact partition of a workflow of events or tasks that should be observed by multiple "players" as well as the interactions among these "players". LCC presents the strength of both process calculi and Horn clauses pair of which can provide a close resemblance of logic programming and the flexibility of practical implementation

MuCIGREF: multiple computer-interpretable guideline representation and execution framework for managing multimobidity care

Clinical Practice Guidelines (CPGs) supply evidence-based recommendations to healthcare professionals (HCPs) for the care of patients. Their use in clinical practice has many benefits for patients, HCPs and treating medical centres, such as enhancing the quality of care, and reducing unwanted care variations. However, there are many challenges limiting their implementations. Initially, CPGs predominantly consider a specific disease, and only few of them refer to multimorbidity (i.e. the presence of two or more health conditions in an individual) and they are not able to adapt to dynamic changes in patient health conditions. The manual management of guideline recommendations are also challenging since recommendations may adversely interact with each other due to their competing targets and/or they can be duplicated when multiple of them are concurrently applied to a multimorbid patient. These may result in undesired outcomes such as severe disability, increased hospitalisation costs and many others. Formalisation of CPGs into a Computer Interpretable Guideline (CIG) format, allows the guidelines to be interpreted and processed by computer applications, such as Clinical Decision Support Systems (CDSS). This enables provision of automated support to manage the limitations of guidelines. This thesis introduces a new approach for the problem of combining multiple concurrently implemented CIGs and their interrelations to manage multimorbidity care. MuCIGREF (Multiple Computer-Interpretable Guideline Representation and Execution Framework), is proposed whose specific objectives are to present (1) a novel multiple CIG representation language, MuCRL, where a generic ontology is developed to represent knowledge elements of CPGs and their interrelations, and to create the multimorbidity related associations between them. A systematic literature review is conducted to discover CPG representation requirements and gaps in multimorbidity care management. The ontology is built based on the synthesis of well-known ontology building lifecycle methodologies. Afterwards, the ontology is transformed to a metamodel to support the CIG execution phase; and (2) a novel real-time multiple CIG execution engine, MuCEE, where CIG models are dynamically combined to generate consistent and personalised care plans for multimorbid patients. MuCEE involves three modules as (i) CIG acquisition module, transfers CIGs to the personal care plan based on the patient’s health conditions and to supply CIG version control; (ii) parallel CIG execution module, combines concurrently implemented multiple CIGs by performing concurrency management, time-based synchronisation (e.g., multi-activity merging), modification, and timebased optimisation of clinical activities; and (iii) CIG verification module, checks missing information, and inconsistencies to support CIG execution phases. Rulebased execution algorithms are presented for each module. Afterwards, a set of verification and validation analyses are performed involving real-world multimorbidity cases studies and comparative analyses with existing works. The results show that the proposed framework can combine multiple CIGs and dynamically merge, optimise and modify multiple clinical activities of them involving patient data. This framework can be used to support HCPs in a CDSS setting to generate unified and personalised care recommendations for multimorbid patients while merging multiple guideline actions and eliminating care duplications to maintain their safety and supplying optimised health resource management, which may improve operational and cost efficiency in real world-cases, as well

Guideline-based decision support in medicine : modeling guidelines for the development and application of clinical decision support systems

Guideline-based Decision Support in Medicine Modeling Guidelines for the Development and Application of Clinical Decision Support Systems The number and use of decision support systems that incorporate guidelines with the goal of improving care is rapidly increasing. Although developing systems that are both effective in supporting clinicians and accepted by them has proven to be a difficult task, of the systems that were evaluated by a controlled trial, the majority showed impact. The work, described in this thesis, aims at developing a methodology and framework that facilitates all stages in the guideline development process, ranging from the definition of models that represent guidelines to the implementation of run-time systems that provide decision support, based on the guidelines that were developed during the previous stages. The framework consists of 1) a guideline representation formalism that uses the concepts of primitives, Problem-Solving Methods (PSMs) and ontologies to represent guidelines of various complexity and granularity and different application domains, 2) a guideline authoring environment that enables guideline authors to define guidelines, based on the newly developed guideline representation formalism, and 3) a guideline execution environment that translates defined guidelines into a more efficient symbol-level representation, which can be read in and processed by an execution-time engine. The described methodology and framework were used to develop and validate a number of guidelines and decision support systems in various clinical domains such as Intensive Care, Family Practice, Psychiatry and the areas of Diabetes and Hypertension control

What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

[EN] In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?Gatta, R.; Vallati, M.; Fernández Llatas, C.; Martinez-Millana, A.; Orini, S.; Sacchi, L.; Lenkowicz, J.... (2020). What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper. International Journal of Environmental research and Public Health (Online). 17(18):1-19. https://doi.org/10.3390/ijerph17186616S1191718Guyatt, G. (1992). Evidence-Based Medicine. JAMA, 268(17), 2420. doi:10.1001/jama.1992.03490170092032Hripcsak, G., Ludemann, P., Pryor, T. A., Wigertz, O. B., & Clayton, P. D. (1994). Rationale for the Arden Syntax. Computers and Biomedical Research, 27(4), 291-324. doi:10.1006/cbmr.1994.1023Peleg, M. (2013). Computer-interpretable clinical guidelines: A methodological review. Journal of Biomedical Informatics, 46(4), 744-763. doi:10.1016/j.jbi.2013.06.009Van de Velde, S., Heselmans, A., Delvaux, N., Brandt, L., Marco-Ruiz, L., Spitaels, D., … Flottorp, S. (2018). A systematic review of trials evaluating success factors of interventions with computerised clinical decision support. Implementation Science, 13(1). doi:10.1186/s13012-018-0790-1Rawson, T. M., Moore, L. S. P., Hernandez, B., Charani, E., Castro-Sanchez, E., Herrero, P., … Holmes, A. H. (2017). A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately? Clinical Microbiology and Infection, 23(8), 524-532. doi:10.1016/j.cmi.2017.02.028Greenes, R. A., Bates, D. W., Kawamoto, K., Middleton, B., Osheroff, J., & Shahar, Y. (2018). Clinical decision support models and frameworks: Seeking to address research issues underlying implementation successes and failures. Journal of Biomedical Informatics, 78, 134-143. doi:10.1016/j.jbi.2017.12.005Garcia, C. dos S., Meincheim, A., Faria Junior, E. R., Dallagassa, M. R., Sato, D. M. V., Carvalho, D. R., … Scalabrin, E. E. (2019). Process mining techniques and applications – A systematic mapping study. Expert Systems with Applications, 133, 260-295. doi:10.1016/j.eswa.2019.05.003Bhargava, A., Kim, T., Quine, D. B., & Hauser, R. G. (2019). A 20-Year Evaluation of LOINC in the United States’ Largest Integrated Health System. Archives of Pathology & Laboratory Medicine, 144(4), 478-484. doi:10.5858/arpa.2019-0055-oaLee, D., de Keizer, N., Lau, F., & Cornet, R. (2014). Literature review of SNOMED CT use. Journal of the American Medical Informatics Association, 21(e1), e11-e19. doi:10.1136/amiajnl-2013-001636TROTTI, A., COLEVAS, A., SETSER, A., RUSCH, V., JAQUES, D., BUDACH, V., … COLEMAN, C. (2003). CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Seminars in Radiation Oncology, 13(3), 176-181. doi:10.1016/s1053-4296(03)00031-6Daniel, C., & Kalra, D. (2019). Clinical Research Informatics: Contributions from 2018. Yearbook of Medical Informatics, 28(01), 203-205. doi:10.1055/s-0039-1677921Marco-Ruiz, L., Pedrinaci, C., Maldonado, J. A., Panziera, L., Chen, R., & Bellika, J. G. (2016). Publication, discovery and interoperability of Clinical Decision Support Systems: A Linked Data approach. Journal of Biomedical Informatics, 62, 243-264. doi:10.1016/j.jbi.2016.07.011Marcos, C., González-Ferrer, A., Peleg, M., & Cavero, C. (2015). Solving the interoperability challenge of a distributed complex patient guidance system: a data integrator based on HL7’s Virtual Medical Record standard. Journal of the American Medical Informatics Association, 22(3), 587-599. doi:10.1093/jamia/ocv003Wulff, A., Haarbrandt, B., Tute, E., Marschollek, M., Beerbaum, P., & Jack, T. (2018). An interoperable clinical decision-support system for early detection of SIRS in pediatric intensive care using openEHR. Artificial Intelligence in Medicine, 89, 10-23. doi:10.1016/j.artmed.2018.04.012Chen, C., Chen, K., Hsu, C.-Y., Chiu, W.-T., & Li, Y.-C. (Jack). (2010). A guideline-based decision support for pharmacological treatment can improve the quality of hyperlipidemia management. Computer Methods and Programs in Biomedicine, 97(3), 280-285. doi:10.1016/j.cmpb.2009.12.004Anani, N., Mazya, M. V., Chen, R., Prazeres Moreira, T., Bill, O., Ahmed, N., … Koch, S. (2017). Applying openEHR’s Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study. BMC Medical Informatics and Decision Making, 17(1). doi:10.1186/s12911-016-0401-5Eddy, D. M. (1982). Clinical Policies and the Quality of Clinical Practice. New England Journal of Medicine, 307(6), 343-347. doi:10.1056/nejm198208053070604Guyatt, G. H. (1990). Then-of-1 Randomized Controlled Trial: Clinical Usefulness. Annals of Internal Medicine, 112(4), 293. doi:10.7326/0003-4819-112-4-293CHALMERS, I. (1993). The Cochrane Collaboration: Preparing, Maintaining, and Disseminating Systematic Reviews of the Effects of Health Care. Annals of the New York Academy of Sciences, 703(1 Doing More Go), 156-165. doi:10.1111/j.1749-6632.1993.tb26345.xWoolf, S. H., Grol, R., Hutchinson, A., Eccles, M., & Grimshaw, J. (1999). Clinical guidelines: Potential benefits, limitations, and harms of clinical guidelines. BMJ, 318(7182), 527-530. doi:10.1136/bmj.318.7182.527Grading quality of evidence and strength of recommendations. (2004). BMJ, 328(7454), 1490. doi:10.1136/bmj.328.7454.1490Guyatt, G. H., Oxman, A. D., Vist, G. E., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., & Schünemann, H. J. (2008). GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 336(7650), 924-926. doi:10.1136/bmj.39489.470347.adHill, J., Bullock, I., & Alderson, P. (2011). A Summary of the Methods That the National Clinical Guideline Centre Uses to Produce Clinical Guidelines for the National Institute for Health and Clinical Excellence. Annals of Internal Medicine, 154(11), 752. doi:10.7326/0003-4819-154-11-201106070-00007Qaseem, A. (2012). Guidelines International Network: Toward International Standards for Clinical Practice Guidelines. Annals of Internal Medicine, 156(7), 525. doi:10.7326/0003-4819-156-7-201204030-00009Rosenfeld, R. M., Nnacheta, L. C., & Corrigan, M. D. (2015). Clinical Consensus Statement Development Manual. Otolaryngology–Head and Neck Surgery, 153(2_suppl), S1-S14. doi:10.1177/0194599815601394De Boeck, K., Castellani, C., & Elborn, J. S. (2014). Medical consensus, guidelines, and position papers: A policy for the ECFS. Journal of Cystic Fibrosis, 13(5), 495-498. doi:10.1016/j.jcf.2014.06.012Clinical Practical Guidelineshttp://www.openclinical.org/guidelines.htmlHaynes, A. B., Weiser, T. G., Berry, W. R., Lipsitz, S. R., Breizat, A.-H. S., Dellinger, E. P., … Gawande, A. A. (2009). A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population. New England Journal of Medicine, 360(5), 491-499. doi:10.1056/nejmsa0810119Grigg, E. (2015). Smarter Clinical Checklists. Anesthesia & Analgesia, 121(2), 570-573. doi:10.1213/ane.0000000000000352Hales, B., Terblanche, M., Fowler, R., & Sibbald, W. (2007). Development of medical checklists for improved quality of patient care. International Journal for Quality in Health Care, 20(1), 22-30. doi:10.1093/intqhc/mzm062Greenfield, S. (2017). Clinical Practice Guidelines. JAMA, 317(6), 594. doi:10.1001/jama.2016.19969Vegting, I. L., van Beneden, M., Kramer, M. H. H., Thijs, A., Kostense, P. J., & Nanayakkara, P. W. B. (2012). How to save costs by reducing unnecessary testing: Lean thinking in clinical practice. European Journal of Internal Medicine, 23(1), 70-75. doi:10.1016/j.ejim.2011.07.003Drummond, M. (2016). Clinical Guidelines: A NICE Way to Introduce Cost-Effectiveness Considerations? Value in Health, 19(5), 525-530. doi:10.1016/j.jval.2016.04.020Prior, M., Guerin, M., & Grimmer-Somers, K. (2008). The effectiveness of clinical guideline implementation strategies - a synthesis of systematic review findings. Journal of Evaluation in Clinical Practice, 14(5), 888-897. doi:10.1111/j.1365-2753.2008.01014.xWatts, C. G., Dieng, M., Morton, R. L., Mann, G. J., Menzies, S. W., & Cust, A. E. (2014). Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. British Journal of Dermatology, 172(1), 33-47. doi:10.1111/bjd.13403Woolf, S., Schünemann, H. J., Eccles, M. P., Grimshaw, J. M., & Shekelle, P. (2012). Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations. Implementation Science, 7(1). doi:10.1186/1748-5908-7-61Legido-Quigley, H., Panteli, D., Brusamento, S., Knai, C., Saliba, V., Turk, E., … Busse, R. (2012). Clinical guidelines in the European Union: Mapping the regulatory basis, development, quality control, implementation and evaluation across member states. Health Policy, 107(2-3), 146-156. doi:10.1016/j.healthpol.2012.08.004Rashidian, A., Eccles, M. P., & Russell, I. (2008). Falling on stony ground? A qualitative study of implementation of clinical guidelines’ prescribing recommendations in primary care. Health Policy, 85(2), 148-161. doi:10.1016/j.healthpol.2007.07.011Yang, W.-S., & Hwang, S.-Y. (2006). A process-mining framework for the detection of healthcare fraud and abuse. Expert Systems with Applications, 31(1), 56-68. doi:10.1016/j.eswa.2005.09.003Kose, I., Gokturk, M., & Kilic, K. (2015). An interactive machine-learning-based electronic fraud and abuse detection system in healthcare insurance. Applied Soft Computing, 36, 283-299. doi:10.1016/j.asoc.2015.07.018Pryor, T. A., Gardner, R. M., Clayton, P. D., & Warner, H. R. (1983). The HELP system. Journal of Medical Systems, 7(2), 87-102. doi:10.1007/bf00995116Shahar, Y., Miksch, S., & Johnson, P. (1998). The Asgaard project: a task-specific framework for the application and critiquing of time-oriented clinical guidelines. Artificial Intelligence in Medicine, 14(1-2), 29-51. doi:10.1016/s0933-3657(98)00015-3Boxwala, A. A., Peleg, M., Tu, S., Ogunyemi, O., Zeng, Q. T., Wang, D., … Shortliffe, E. H. (2004). GLIF3: a representation format for sharable computer-interpretable clinical practice guidelines. Journal of Biomedical Informatics, 37(3), 147-161. doi:10.1016/j.jbi.2004.04.002Terenziani, P., Molino, G., & Torchio, M. (2001). A modular approach for representing and executing clinical guidelines. Artificial Intelligence in Medicine, 23(3), 249-276. doi:10.1016/s0933-3657(01)00087-2Sutton, D. R., & Fox, J. (2003). The Syntax and Semantics of the PROformaGuideline Modeling Language. Journal of the American Medical Informatics Association, 10(5), 433-443. doi:10.1197/jamia.m1264Musen, M. A., Tu, S. W., Das, A. K., & Shahar, Y. (1996). EON: A Component-Based Approach to Automation of Protocol-Directed Therapy. Journal of the American Medical Informatics Association, 3(6), 367-388. doi:10.1136/jamia.1996.97084511Ciccarese, P., Caffi, E., Quaglini, S., & Stefanelli, M. (2005). Architectures and tools for innovative Health Information Systems: The Guide Project. International Journal of Medical Informatics, 74(7-8), 553-562. doi:10.1016/j.ijmedinf.2005.02.001Shiffman, R. N., & Greenes, R. A. (1994). Improving Clinical Guidelines with Logic and Decision-table Techniques. Medical Decision Making, 14(3), 245-254. doi:10.1177/0272989x9401400306Peleg, M., Tu, S., Bury, J., Ciccarese, P., Fox, J., Greenes, R. A., … Stefanelli, M. (2003). Comparing Computer-interpretable Guideline Models: A Case-study Approach. Journal of the American Medical Informatics Association, 10(1), 52-68. doi:10.1197/jamia.m1135Karadimas, H., Ebrahiminia, V., & Lepage, E. (2018). User-defined functions in the Arden Syntax: An extension proposal. Artificial Intelligence in Medicine, 92, 103-110. doi:10.1016/j.artmed.2015.11.003Peleg, M., Keren, S., & Denekamp, Y. (2008). Mapping computerized clinical guidelines to electronic medical records: Knowledge-data ontological mapper (KDOM). Journal of Biomedical Informatics, 41(1), 180-201. doi:10.1016/j.jbi.2007.05.003German, E., Leibowitz, A., & Shahar, Y. (2009). An architecture for linking medical decision-support applications to clinical databases and its evaluation. Journal of Biomedical Informatics, 42(2), 203-218. doi:10.1016/j.jbi.2008.10.007Marcos, M., Maldonado, J. A., Martínez-Salvador, B., Boscá, D., & Robles, M. (2013). Interoperability of clinical decision-support systems and electronic health records using archetypes: A case study in clinical trial eligibility. Journal of Biomedical Informatics, 46(4), 676-689. doi:10.1016/j.jbi.2013.05.004Marco-Ruiz, L., Moner, D., Maldonado, J. A., Kolstrup, N., & Bellika, J. G. (2015). Archetype-based data warehouse environment to enable the reuse of electronic health record data. International Journal of Medical Informatics, 84(9), 702-714. doi:10.1016/j.ijmedinf.2015.05.016Gooch, P., & Roudsari, A. (2011). Computerization of workflows, guidelines, and care pathways: a review of implementation challenges for process-oriented health information systems. Journal of the American Medical Informatics Association, 18(6), 738-748. doi:10.1136/amiajnl-2010-000033Quaglini, S., Stefanelli, M., Cavallini, A., Micieli, G., Fassino, C., & Mossa, C. (2000). Guideline-based careflow systems. Artificial Intelligence in Medicine, 20(1), 5-22. doi:10.1016/s0933-3657(00)00050-6Schadow, G., Russler, D. C., & McDonald, C. J. (2001). Conceptual alignment of electronic health record data with guideline and workflow knowledge. International Journal of Medical Informatics, 64(2-3), 259-274. doi:10.1016/s1386-5056(01)00196-4González-Ferrer, A., ten Teije, A., Fdez-Olivares, J., & Milian, K. (2013). Automated generation of patient-tailored electronic care pathways by translating computer-interpretable guidelines into hierarchical task networks. Artificial Intelligence in Medicine, 57(2), 91-109. doi:10.1016/j.artmed.2012.08.008Shabo, A., Parimbelli, E., Quaglini, S., Napolitano, C., & Peleg, M. (2016). Interplay between Clinical Guidelines and Organizational Workflow Systems. Methods of Information in Medicine, 55(06), 488-494. doi:10.3414/me16-01-0006Mulyar, N., van der Aalst, W. M. P., & Peleg, M. (2007). A Pattern-based Analysis of Clinical Computer-interpretable Guideline Modeling Languages. Journal of the American Medical Informatics Association, 14(6), 781-787. doi:10.1197/jamia.m2389Grando, M. A., Glasspool, D., & Fox, J. (2012). A formal approach to the analysis of clinical computer-interpretable guideline modeling languages. Artificial Intelligence in Medicine, 54(1), 1-13. doi:10.1016/j.artmed.2011.07.001Kaiser, K., & Marcos, M. (2015). Leveraging workflow control patterns in the domain of clinical practice guidelines. BMC Medical Informatics and Decision Making, 16(1). doi:10.1186/s12911-016-0253-zMartínez-Salvador, B., & Marcos, M. (2016). Supporting the Refinement of Clinical Process Models to Computer-Interpretable Guideline Models. Business & Information Systems Engineering, 58(5), 355-366. doi:10.1007/s12599-016-0443-3Decision Model and Notation Version 1.0https://www.omg.org/spec/DMN/1.0Ghasemi, M., & Amyot, D. (2016). Process mining in healthcare: a systematised literature review. International Journal of Electronic Healthcare, 9(1), 60. doi:10.1504/ijeh.2016.078745Rebuge, Á., & Ferreira, D. R. (2012). Business process analysis in healthcare environments: A methodology based on process mining. Information Systems, 37(2), 99-116. doi:10.1016/j.is.2011.01.003Rovani, M., Maggi, F. M., de Leoni, M., & van der Aalst, W. M. P. (2015). Declarative process mining in healthcare. Expert Systems with Applications, 42(23), 9236-9251. doi:10.1016/j.eswa.2015.07.040Rojas, E., Munoz-Gama, J., Sepúlveda, M., & Capurro, D. (2016). Process mining in healthcare: A literature review. Journal of Biomedical Informatics, 61, 224-236. doi:10.1016/j.jbi.2016.04.007Lenkowicz, J., Gatta, R., Masciocchi, C., Casà, C., Cellini, F., Damiani, A., … Valentini, V. (2018). Assessing the conformity to clinical guidelines in oncology. Management Decision, 56(10), 2172-2186. doi:10.1108/md-09-2017-0906Fernández-Llatas, C., Benedi, J.-M., García-Gómez, J., & Traver, V. (2013). Process Mining for Individualized Behavior Modeling Using Wireless Tracking in Nursing Homes. Sensors, 13(11), 15434-15451. doi:10.3390/s131115434Qu, G., Liu, Z., Cui, S., & Tang, J. (2013). Study on Self-Adaptive Clinical Pathway Decision Support System Based on Case-Based Reasoning. Frontier and Future Development of Information Technology in Medicine and Education, 969-978. doi:10.1007/978-94-007-7618-0_95Van de Velde, S., Roshanov, P., Kortteisto, T., Kunnamo, I., Aertgeerts, B., Vandvik, P. O., & Flottorp, S. (2015). Tailoring implementation strategies for evidence-based recommendations using computerised clinical decision support systems: protocol for the development of the GUIDES tools. Implementation Science, 11(1). doi:10.1186/s13012-016-0393-