Publications

For publications of Protocure I project, visit this page.

A Constraint-based Approach to Medical Guidelines and Protocols.
A. Hommersom, P. Groot, P. Lucas, M. Marcos, and B. Martínez-Salvador.
Published in Computer-based Medical Guidelines and Protocols: A Primer and Current Trends, Vol. 139, pages 213-222, 2008.
Medical guidelines and protocols are documents aimed at improving the quality of medical care by offering support in medical decision making in the form of management recommendations based on scientific evidence. Whereas medical guidelines are intended for nation-wide use, and thus omit medical management details that may differ among hospitals, medical protocols are aimed at local use, e.g., within hospitals, and, therefore, include more detailed information. Although a medical guideline and an associated protocol concerning the management of a particular disorder are related to each other, one question is to what extent they are different. Formal methods are applied to shed light on this issue. A Dutch medical guideline regarding the treatment of breast cancer, and a Dutch protocol based on it, are taken as an example.

Maintaining Formal Models of Living Guidelines Efficiently.
Andreas Seyfang, Begoña Martínez-Salvador, Radu Serban, Jolanda Wittenberg, Silvia Miksch, Mar Marcos, Annette ten Teije, and Kitty Rosenbrand.
Published in 11th European Conference on Artificial Intelligence in Medicine (AIME-07), pages 441-445, Jul 2007.
Translating clinical guidelines into formal models is beneficial in many ways, but expensive. The progress in medical knowledge requires clinical guidelines to be updated at relatively short intervals, leading to the term living guideline. This causes potentially expensive, frequent updates of the corresponding formal models. When performing these updates, there are two goals: The modelling effort must be minimised and the links between the original document and the formal model must be maintained. In this paper, we describe our solution, using tools and techniques developed during the Protocure II project.

Extraction and use of linguistic patterns for modelling medical guidelines.
Radu Serban, Annette ten Teije, Frank van Harmelen, Mar Marcos, and Cristina Polo.
Published in Artificial Intelligence in Medicine, Vol. 39 (2), pages 137-149, Feb 2007.
Objective: The quality of knowledge updates in evidence-based medical guidelines can be improved and the effort spent for updating can be reduced if the knowledge underlying the guideline text is explicitly modelled using the so-called linguistic guideline patterns, mappings between a text fragment and a formal representation of its corresponding medical knowledge. Methods and material: Ontology-driven extraction of linguistic patterns is a method to automatically reconstruct the control knowledge captured in guidelines, which facilitates a more effective modelling and authoring of medical guidelines. We illustrate by examples the use of this method for generating and instantiating linguistic patterns in the text of a guideline for treatment of breast cancer, and evaluate the usefulness of these patterns in the modelling of this guideline. Results: We developed a methodology for extracting and using linguistic patterns in guideline formalization, to aid the human modellers in guideline formalization and reduce the human modelling effort. Using automatic transformation rules for simple linguistic patterns, a good recall (between 72% and 80%) is obtained in selecting the procedural knowledge relevant for the guideline model, even though the precision of the guideline model generated automatically covers only between 20% and 35% of the human-generated guideline model. These results indicate the suitability of our method as a pre-processing step in medical guideline formalization. Conclusions: Modelling and authoring of medical texts can benefit from our proposed method. As pre-requisites for generating automatically a skeleton of the guideline model from the procedural part of the guideline text, to aid the human modeller, the medical terminology used by the guideline must have a good overlap with existing medical thesauri and its procedural knowledge must obey linguistic regularities that can be mapped into the control constructs of the target guideline modelling language.

Construction of a Process Model for the Integration of Formal Methods in the Development of Medical Guidelines.
M. Marcos, J.C. Galán, J. Wittenberg, J. van Croonenborg, K. Rosenbrand, and B. Martínez-Salvador.
Published in Exploiting the Knowledge Economy: Issues, Applications and Case Studies, pages 886-892, Oct 2006.
The development of medical guidelines is a complex process through which the best empirical evidence available at a point in time is systematically collected, analysed and processed, with the aim of producing a document encompassing high-quality recommendations for the management of patients with a particular clinical condition. Because of the problems associated with documenting guidelines, the idea of using IT techniques and tools is gaining acceptance among guideline developers. In particular, the use of formal methods from software engineering and artificial intelligence would allow the development of medical guidelines in a more structured and systematic way. Nevertheless, major process changes would be needed to make the full integration of formal methods possible. As a first step in this direction, we have built a process model describing the way in which various support tools for the development of computerised guidelines can be used in conjunction with established guideline development activities. For this task we have used a well-known language for business process modelling in combination with a methodology specifically devised for our purpose. Using the resulting process model as a guide, we expect that guideline developers will be able to take advantage of the benefits that IT techniques and tools can offer them.

A Constraint-based Approach to Medical Guidelines and Protocols.
A. Hommersom, P. Groot, P. Lucas, M. Marcos, and B. Martínez-Salvador.
Published in Workshop on AI techniques in healthcare: evidence-based guidelines and protocols, 17th European Conference on Artificial Intelligence (ECAI-06), Aug 2006.
Medical guidelines and protocols are documents aimed at improving the quality of medical care by offering support in medical decision making in the form of management recommendations based on scientific evidence. Whereas medical guidelines are intended for nation-wide use, and thus omit medical management details that may differ among hospitals, medical protocols are aimed at local use within hospitals and, therefore, include detailed information. Although a medical guideline and protocol concerning the management of a particular disorder are related to each other, one question is to what extent they are different. Formal methods are applied to shed light on this issue. A Dutch medical guideline regarding the treatment of breast cancer, and a Dutch protocol based on it, are taken as an example.

Bridging the Gap between Informal and Formal Guideline Representations.
A. Seyfang, S. Miksch, M. Marcos, J. Wittenberg, C. Polo-Conde, and K. Rosenbrand.
Published in 17th European Conference on Artificial Intelligence (ECAI-06), pages 447-451, Aug 2006.
Clinical guidelines are important means to improve quality of health care while limiting cost and supporting the medical staff. They are written as free text with tables and figures. Transforming them into a formal, computer-processable representation is a difficult task requiring both computer scientist skills and medical knowledge. To bridge this gap, we designed an intermediate representation (or ontology) which serves as a mediator between the original text and different formal guideline representations. It is easier to use than the latter, structures the original prose and helps to spot missing information and contradictions. In this paper we describe the representation and a practical evaluation thereof through the modelling of a real-world clinical guideline.

Interactive Verification of Medical Guidelines.
J. Schmitt, A. Hoffmann, M. Balser, W. Reif, and M. Marcos.
Published in 14th Symposium on Formal Methods (FM-06), pages 32-47, Aug 2006.
In the medical domain, there is a tendency to standardize health care by providing medical guidelines as summary of the best evidence concerning a particular topic. Based on the assumption that guidelines are similar to software, we try to carry over techniques from software engineering to guideline development. In this paper, we show how to apply formal methods, namely interactive verification to improve the quality of guidelines. As an example, we have worked on a guideline from the American Academy of Pediatrics for the management of jaundice in newborns. Contributions of this paper are as follows: (I) a formalized model of a nontrivial example guideline, (II) an approach to verify properties of medical guidelines interactively, and (III) verification of a first example property.

Improving medical protocols by formal methods.
A. ten Teije, M. Marcos, M. Balser, J. van Croonenborg, C. Duelli, F. van Harmelen, P. Lucas, S. Miksch, W. Reif, K. Rosenbrand, A. Seyfang.
Published in Artificial Intelligence in Medicine, Vol. 36 (3), pages 193-209, Mar 2006.
Objectives: During the last decade, evidence-based medicine has given rise to an increasing number of medical practice guidelines and protocols. However, the work done on developing and distributing protocols outweighs the efforts on guaranteeing their quality. Indeed, anomalies like ambiguity and incompleteness are frequent in medical protocols. Recent efforts have tried to address the problem of protocol improvement, but they are not sufficient since they rely on informal processes and notations. Our objective is to improve the quality of medical protocols. Approach: The solution we suggest to the problem of quality improvement of protocols consists in the utilisation of formal methods. It requires the definition of an adequate protocol representation language, the development of techniques for the formal analysis of protocols described in that language and, more importantly, the evaluation of the feasibility of the approach based on the formalisation and verification of real-life medical protocols. For the first two aspects we rely on earlier work from the fields of knowledge representation and formal methods. The third aspect, i.e. the evaluation of the use of formal methods in the quality improvement of protocols, constitutes our main objective. The steps with which we have carried out this evaluation are the following: (1) take two real-life reference protocols which cover a wide variety of protocol characteristics; (2) formalise these reference protocols; (3) check the formalisation for the verification of interesting protocol properties; and (4) determine how many errors can be uncovered in this way. Results: Our main results are: a consolidated formal language to model medical practice protocols; two protocols, each both modelled and formalised; a list of properties that medical protocols should satisfy; verification proofs for these protocols and properties; and perspectives of the potentials of this approach. Our results have been evaluated by a panel of medical experts, who judged that the problems we detected in the protocols with the help of formal methods were serious and should be avoided. Conclusions: We have succeeded in demonstrating the feasibility of formal methods for improving medical protocols.

Assessment of MHB: an intermediate language for the representation of medical guidelines.
C. Polo-Conde, M. Marcos, A. Seyfang, J. Wittenberg, S. Miksch, and K. Rosenbrand.
Published in 10th Conference of the Spanish Association for Artificial Intelligence (CAEPIA-05), Vol. I, pages I-19--I-28, Oct 2005.
The goal of the study described in this research paper is the assessment of a recently developed intermediate representation language, called MHB (Many-Headed Bridge), as an intermediate step within the clinical guidelines formalisation process. We qualitatively assess (1) whether it makes easier the formalisation of the guideline and, (2) to which degree MHB covers written text guideline features. For the assessment, we apply a multi-step formalisation process. In this practical approach, we have based our work on the CBO evidencebased clinical guideline for the treatment of the breast carcinoma.

A business process model of evidence-based guideline development.
J.C. Galan, M. Marcos, J. Wittenberg, J. van Croonenborg, and K. Rosenbrand.
Published in 10th Conference of the Spanish Association for Artificial Intelligence (CAEPIA-05), Vol. I, pages I-273--I-282, Oct 2005.
During the last years, knowledge management has become one of the most important points in the enterprise field. A lot of knowledge, explicit and implicit, is disseminated through the organisations. A way to make explicit all the knowledge is to capture business processes into models and to analyze them, trying to discover that knowledge. In our case, we have modelled a process of medical guideline development, obtaining two models where knowledge is captured, allowing to discover all the implicit knowledge. Furthermore, this new unexpected knowledge has allowed to improve the medical guideline development.

Ontology-driven extraction of linguistic patterns for modelling clinical guidelines.
Radu Serban, Annette ten Teije, Frank van Harmelen, Mar Marcos, and Cristina Polo.
Published in 10th European Conference on Artificial Intelligence in Medicine (AIME-05), pages 191-200, Jul 2005.
Evidence-based clinical guidelines require frequent updates due to research and technology advances. The quality of guideline updates can be improved if the knowledge underlying the guideline text is explicitly modelled using the so-called guideline patterns (GPs), mappings between a text fragment and a formal representation of its corresponding medical knowledge. Ontology-driven extraction of linguistic patterns is a method to automatically reconstruct the control knowledge captured in guidelines, which facilitates a more e ective modelling and authoring of clinical guidelines. We illustrate by examples the use of a method for generating and searching for linguistic guideline patterns in the text of a guideline for treatment of breast cancer, and provide a general evaluation of usefulness of these patterns in the modelling of the guideline analyzed.

Design patterns for modelling medical guidelines.
Radu Serban, Annette ten Teije, Mar Marcos, Cristina Polo, Kitty Rosenbrand, Joyce van Croonenborg, and Jolanda Wittenberg.
Published in 10th European Conference on Artificial Intelligence in Medicine (AIME-05), pages 121-126, Jul 2005.
It is by now widely accepted that medical guidelines can help to significantly improve the quality of medical care. Unfortunately, constructing the required medical guidelines is a very labour intensive and costly process. The cost of guideline construction would decrease if guidelines could be built from a set of building blocks that can be reused across guidelines. Such reusable building blocks would also result in more standardised guidelines, facilitating their deployment. The goal of this paper is to identify a collection of patterns that can be used as guideline building blocks. We propose two different methods for finding such patterns We compare the collections of patterns obtained through these two methods, and experimentally validate some of the patterns by checking their usability in the actual modelling of a medical guideline for breastcancer treatment.

MHB - A Many-Headed Bridge between Informal and Formal Guideline Representations.
Andreas Seyfang, Silvia Miksch, Cristina Polo, Jolanda Wittenberg, Mar Marcos, and Kitty Rosenbrand.
Published in 10th European Conference on Artificial Intelligence in Medicine (AIME-05), pages 146-150, Jul 2005.
Clinical guidelines become more and more important as a means to improve the quality of care by supporting the medical staff. Modeling guidelines in a computer-processable form is a prerequisite for various computer applications, to improve the quality of guidelines and to support their application. However, transforming the original text into a formal guideline representation is a difficult task requiring both computer scientist skills and medical knowledge. To bridge this gap, we designed an intermediate representation named MHB.

Formalising medical quality indicators to improve medical guidelines.
Marjolein van Gendt, Annette ten Teije, Radu Serban, Frank van Harmelen.
Published in Proceedings of the 10th Conference on Artificial Intelligence in Medicine (AIME-05), pages 201-211, Jul 2005.
Medical guidelines can significantly improve quality of medical care and reduce costs. But how do we get sound and well-structured guidelines? This paper investigates the use of quality indicators that are formulated by medical institutions to evaluate medical care. The main research questions are (i) whether it is possible to formalise those indicators in a specific knowledge representation language for medical guidelines, and (ii) whether it is possible to verify whether such guidelines do indeed satisfy these indicators. In a case study on two real-life guidelines (Diabetes and Jaundice) we have studied 35 indicators, that were developped independently from these guidelines. Of these 25 (71%!) suggested anomalies in one of the guidelines in our case study.

Protocure: Supporting the Development of Medical Protocols through Formal Methods.
M. Balser, O. Coltell, J. van Croonenborg, C. Duelli, F. van Harmelen, A. Jovell, P. Lucas, M. Marcos, S. Miksch, W. Reif, K. Rosenbrand, A. Seyfang and A. ten Teije.
Published in Symposium on Computerized Guidelines and Protocols (CGP-04), pages 103-107, Apr 2004.
This paper summarises the research activities in the framework of the Protocure project, with the aim of supporting the development of medical protocols through formal methods.