Authoring and verification of clinical guidelines: A model driven approach

ObjectivesThe goal of this research is to provide a framework to enable authoring and verification of clinical guidelines. The framework is part of a larger research project aimed at improving the representation, quality and application of clinical guidelines in daily clinical practice.MethodsThe verification process of a guideline is based on (1) model checking techniques to verify guidelines against semantic errors and inconsistencies in their definition, (2) combined with Model Driven Development (MDD) techniques, which enable us to automatically process manually created guideline specifications and temporal-logic statements to be checked and verified regarding these specifications, making the verification process faster and cost-effective. Particularly, we use UML statecharts to represent the dynamics of guidelines and, based on this manually defined guideline specifications, we use a MDD-based tool chain to automatically process them to generate the input model of a model checker. The model checker takes the resulted model together with the specific guideline requirements, and verifies whether the guideline fulfils such properties.ResultsThe overall framework has been implemented as an Eclipse plug-in named GBDSSGenerator which, particularly, starting from the UML statechart representing a guideline, allows the verification of the guideline against specific requirements. Additionally, we have established a pattern-based approach for defining commonly occurring types of requirements in guidelines. We have successfully validated our overall approach by verifying properties in different clinical guidelines resulting in the detection of some inconsistencies in their definition.ConclusionsThe proposed framework allows (1) the authoring and (2) the verification of clinical guidelines against specific requirements defined based on a set of property specification patterns, enabling non-experts to easily write formal specifications and thus easing the verification process.     

A Delphi-based consensus clinical practice protocol for the diagnosis and management of 3-methylcrotonyl CoA carboxylase deficiency

3-MCC deficiency is among the most common inborn errors of metabolism identified on expanded newborn screening (1:36,000 births). However, evidence-based guidelines for diagnosis and management of this disorder are lacking. Using the traditional Delphi method, a panel of 15 experts in inborn errors of metabolism was convened to develop consensus-based clinical practice guidelines for the diagnosis and management of 3-MCC screen-positive infants and their mothers. The Oxford Centre for Evidence-based Medicine system was used to grade the literature review and create recommendations graded from A (evidence level of randomized clinical trials) to D (expert opinion).Panelists reviewed the initial evaluation of the screen-positive infant–mother dyad, diagnostic guidelines, and management of diagnosed patients. Grade D consensus recommendations were made in each of these three areas. The panel did not reach consensus on all issues. This consensus protocol is intended to assist clinicians in the diagnosis and management of screen-positive newborns for 3-MCC deficiency and to encourage the development of evidence-based guidelines.     

Electronic implementation of guidelines in the EsPeR system: a knowledge specification method

Despite initiatives to standardize methods for the development of clinical guidelines, several barriers hinder their integration in daily clinical practice: failure to fulfil quality criteria, poor effectiveness of their dissemination. Computerization of guidelines can favor their dissemination. The initial step of computerization is the knowledge specification from the text of the guideline. We describe the method of knowledge specification, which is used in EsPeR (Personalized Estimate of Risks), a web-based decision support system in preventive medicine, which allows, for a given person, to estimate risks and access recommendations, based on clinical profile. This method is based on a structured and systematic analysis of text allowing detailed specification of a decision tree. We use decision tables to validate the decision algorithm and decision trees to specify this algorithm, along with elementary messages of recommendation. Editing tools are used to facilitate the process of validation and the workflow between expert physicians and computer scientists. Applied to eleven different guidelines, the method allows a quick and valid computerization and integration in the EsPeR system. The method used for computerization could help to define a framework usable at the initial step of guideline development in order to produce guidelines ready for electronic implementation.     

Development of clinical guidelines for inborn errors of metabolism: Commentary

This is one of an occasional series of articles commenting on trends, advances, and challenges in understanding and treating inborn errors of metabolism (IEMs). Previously, we have called attention to the critical lack of a clinical trial infrastructure to routinely evaluate new therapies for IEMs and the adverse effect of this deficit (Vockley and Vockley, 2010 [1]). In this article, we highlight the role of therapeutic guidelines in implementing best practice for IEMs and the processes used to generate them. Current conventions for evidence-based guidelines are best applied to studies involving significantly more subjects than is feasible for IEMs, and can lead to relative weak-appearing recommendations when applied to rare disorders. We propose a guideline development process that maintains the use of conventional methodologies but adapts to unique features and inherent difficulties dealing with rare conditions such as IEMs. Such guidelines will consist of a hybrid between evidence and consensus based processes. Implementation of these recommendations and subsequent therapeutic guidelines for IEMs provides an opportunity to define current knowledge as well as starting points for future clinical trials.     

Development of patient versions of guidelines in Chinese mainland: A systematic survey of current practices and methods

ObjectivesTo review current practices and methods underlying the development of patient versions of guidelines (PVGs) in Chinese mainland.MethodsWe systematically searched for PVGs created or published between January 2010 and February 2022. We conducted a framework analysis for the development process and assessed the compliance of PVGs using the Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG).ResultsWe identified 26 PVGs developed by 16 PVG-working teams. In accordance with the Guidelines International Network (GIN), only two PVGs were translated using one clinical practice guideline (CPG) provided by the CPG-working group source. Several CPGs and other information sources were integrated and translated into a single PVG by other PVG teams. Moreover, we identified various practices described by different PVG teams that could be structured into six steps. Out of the 17 RIGHT-PVG items, five items were fully reported in all PVGs, while two items (“Provide a summary of the PVG” and “Provide a list of terms and abbreviations”) were not reported in any of the PVGs.Conclusions and practical implicationsA relatively small number of PVGs were developed in Chinese mainland. The development of a PVG requires comprehensive methodological guidance based on several CPGs and other sources of information as opposed to only using one.     

A comprehensive model of factors affecting adoption of clinical practice guidelines in Korea

This study aims to investigate the factors related to the adoption of clinical practice guidelines in clinical settings in Korea; it also aims to determine how these factors differ depending on the specific situation of health care system and professional climate. The research sample comprised physicians who are board members of academic societies with experiences in development of clinical practice guidelines using a convenient sampling. We analyzed 324 physicians with pooling two-year sample of 2007 and 2008. From all the respondents, 48.8% stated that they followed Clinical Practice Guidelines, and 93.4% agreed with the content in the Clinical Practice Guidelines. With regard to the item on the self-efficacy of practicing guidelines, 90.3% of the respondents selected 'low level'. In the regression analysis, the factors associated with implementation were level of recognition, agreement and self-efficacy and positive attitude towards practice guidelines. Although the health care system in Korea differs from those in Western countries, our results revealed that the factors related to the adoption of practice guidelines were similar to the research results of Western countries. These results suggest that professionals' attitudes towards clinical practice guidelines are universal, and implementation strategies should be developed globally.     

Approaches for creating computer-interpretable guidelines that facilitate decision support

During the last decade, studies have shown the benefits of using clinical guidelines in the practice of medicine. Although the importance of these guidelines is widely recognized, health care organizations typically pay more attention to guideline development than to guideline implementation for routine use in daily care. However, studies have shown that clinicians are often not familiar with written guidelines and do not apply them appropriately during the actual care process. Implementing guidelines in computer-based decision support systems promises to improve the acceptance and application of guidelines in daily practice because the actions and observations of health care workers are monitored and advice is generated whenever a guideline is not followed. Such implementations are increasingly applied in diverse areas such as policy development, utilization management, education, clinical trials, and workflow facilitation. Many parties are developing computer-based guidelines as well as decision support systems that incorporate these guidelines. This paper reviews generic approaches for developing and implementing computer-based guidelines that facilitate decision support. It addresses guideline representation, acquisition, verification and execution aspects. The paper describes five approaches (the Arden Syntax, GuideLine Interchange Format (GLIF), PROforma, Asbru and EON), after the approaches are compared and discussed.     

The integration of information across lexical and sublexical processes in spelling

We report on a brain-injured subject, LAT, who made phonologically plausible errors in word spelling (e.g., "bouquet" spelled as BOUKET). Although many of his errors are phonologically plausible they contained low-frequency (yet lexically correct) spellings (/ei/ spelled as ET in BOUK ET). Because these errors are phonologically plausible they do not appear to have been generated by the lexical process, yet because they contain low probability, lexically correct elements they do not appear to be have been generated by the sublexical process. We present analyses that specifically support the conclusion that many of LAT's phonologically plausible responses to word stimuli consist of the integrated output of elements generated by both the lexical and sublexical processes. This evidence constitutes strong support for the notion that lexical and sublexical processes share information during the course of spelling a familiar word.     

Evidence-based group psychotherapy: using AGPA's practice guidelines to enhance clinical effectiveness

Practice guidelines represent a useful approach to facilitate the delivery of evidence-based mental health care. In this article, we detail group psychotherapy practice guidelines developed by the American Group Psychotherapy Association (AGPA). Combining the research literature with expert consensus, the AGPA has created a resource that should prove useful for psychotherapists, administrators, and patients. We illustrate the guidelines through a series of clinical dilemmas and challenges.     

Improving clinical decisions and outcomes with information: a review

The clinical information available to clinicians is expanding rapidly. It can enhance clinical decision-making, but it can also confuse the process. To be most useful, information should be available at the time and place it is needed and be specific to the task at hand. In the new paradigm of medicine, one based on continuous quality improvement, useful information must be relevant to both the processes and outcomes of care. Clinical practice guidelines have become increasingly popular for improving the quality of health care. The field of medical informatics can bring cogent information to the point where decisions are being made to augment quality improvement activities in general, and practice guidelines in particular. However, such innovations are dependent on the type, quantity, and quality of information available. This article discusses when guidelines can enhance the quality and outcomes of care and how medical informatics can help achieve these goals. In particular, the barriers to the broad implementation of electronic medical records in a variety of health care settings are explored.     

Guidelines for management of epilepsy--commentary on Scottish ("SIGN") guidelines

The choice of AED (antiepileptic drug), worldwide and in Croatia, is been still based on the physician's subjective decision, personal experience, knowledge and marketing pressure made by big pharmaceutical industries. Therefore, according to some opinions, there is a need of treatment guidelines for epilepsy that would provide relevant information based on scientific evidence on the efficacy, tolerability and safety of AEDs. The guidelines, published by a competent source, should be designed as to allow for easy access to the information on the best practice in specific cases. An extensive background literature review was made to identify such a type of guidelines for the management of epilepsy. The literature review revealed a number of references with the recommendations for treating epilepsy in different groups of patients and from various, specific aspects of epilepsy treatment. However, only one comprehensive set of guidelines for the diagnosis and treatment of epilepsy treatment was found, i.e. the evidence-based guidelines published by the Scottish Intercollegiate Guidelines Network (SIGN). The development of this set of guidelines is quite extensively described in order to illustrate how rigorous and long-lasting the process was, including a great number of health professionals at the national level. Such a type of well designed guidelines facilitates access to highest educational standards for all professionals involved in the primary and secondary care of people with epilepsy. However, it is clear that guidelines can fully replace the standards of clinical practice based on critical evaluation and integration of all clinical data of each individual patient. No guidelines can replace the physician's obligation to keep informed of the novel achievements in the epileptology either.     

Ocular Reduction in EEG Signals Based on Adaptive Filtering,Regression and Blind Source Separation

Quantitative electroencephalographic (EEG) analysis is very useful for diagnosing dysfunctional neural states and for evaluating drug effects on the brain, among others. However, the bidirectional contamination between electrooculographic (EOG) and cerebral activities can mislead and induce wrong conclusions from EEG recordings. Different methods for ocular reduction have been developed but only few studies have shown an objective evaluation of their performance. For this purpose, the following approaches were evaluated with simulated data: regression analysis, adaptive filtering, and blind source separation (BSS). In the first two, filtered versions were also taken into account by filtering EOG references in order to reduce the cancellation of cerebral high frequency components in EEG data. Performance of these methods was quantitatively evaluated by level of similarity, agreement and errors in spectral variables both between sources and corrected EEG recordings. Topographic distributions showed that errors were located at anterior sites and especially in frontopolar and lateral–frontal regions. In addition, these errors were higher in theta and especially delta band. In general, filtered versions of time-domain regression and of adaptive filtering with RLS algorithm provided a very effective ocular reduction. However, BSS based on second order statistics showed the highest similarity indexes and the lowest errors in spectral variables.     

Representation primitives,process models and patient data in computer-interpretable clinical practice guidelines: a literature review of guideline representation models

Representation of clinical practice guidelines in a computer-interpretable format is a critical issue for guideline development, implementation, and evaluation. We studied 11 types of guideline representation models that can be used to encode guidelines in computer-interpretable formats. We have consistently found in all reviewed models that primitives for representation of actions and decisions are necessary components of a guideline representation model. Patient states and execution states are important concepts that closely relate to each other. Scheduling constraints on representation primitives can be modeled as sequences, concurrences, alternatives, and loops in a guideline's application process. Nesting of guidelines provides multiple views to a guideline with different granularities. Integration of guidelines with electronic medical records can be facilitated by the introduction of a formal model for patient data. Data collection, decision, patient state, and intervention constitute four basic types of primitives in a guideline's logic flow. Decisions clarify our understanding on a patient's clinical state, while interventions lead to the change from one patient state to another.     

Mitigation of adverse interactions in pairs of clinical practice guidelines using constraint logic programming

We propose a new method to mitigate (identify and address) adverse interactions (drug–drug or drug–disease) that occur when a patient with comorbid diseases is managed according to two concurrently applied clinical practice guidelines (CPGs). A lack of methods to facilitate the concurrent application of CPGs severely limits their use in clinical practice and the development of such methods is one of the grand challenges for clinical decision support. The proposed method responds to this challenge.We introduce and formally define logical models of CPGs and other related concepts, and develop the mitigation algorithm that operates on these concepts. In the algorithm we combine domain knowledge encoded as interaction and revision operators using the constraint logic programming (CLP) paradigm. The operators characterize adverse interactions and describe revisions to logical models required to address these interactions, while CLP allows us to efficiently solve the logical models – a solution represents a feasible therapy that may be safely applied to a patient.The mitigation algorithm accepts two CPGs and available (likely incomplete) patient information. It reports whether mitigation has been successful or not, and on success it gives a feasible therapy and points at identified interactions (if any) together with the revisions that address them. Thus, we consider the mitigation algorithm as an alerting tool to support a physician in the concurrent application of CPGs that can be implemented as a component of a clinical decision support system. We illustrate our method in the context of two clinical scenarios involving a patient with duodenal ulcer who experiences an episode of transient ischemic attack.     

Clinical guidelines: their implementation in general practice.

In recent years the development of clinical guidelines has received increasing attention from medical educators and those involved in standard setting, and has been initiated at both central and local levels. This review article outlines the current state of knowledge with regard to clinical guideline implementation in medical practice. It deals with the main aspects of the current guideline debate, such as, clinical freedom and doctor autonomy, the importance of ownership in guideline implementation, the effectiveness of guidelines in changing practice and, in particular, the strategies needed to implement clinical guidelines in general practice. Mechanisms of behavioural change that have been recognized as being important for implementation are also discussed. If implementation strategies are not treated as an integral part of the development process then clinical guidelines may fail to achieve their potential in changing clinical practice.     

Benchmarking using simulated clinical scenarios: a feasibility project.

'Benchmarking' clinical practice and integrating such data with national guidelines offers a way of establishing standards for use in clinical governance. We report on a feasibility project for benchmarking clinical practice in one topic area (otitis media) using simulated clinical scenarios. Consistency and variations in clinical management were identified for different scenarios. Participants perceived the process likely to reflect actual practice and effect change in clinical management.     

Development and Regulation of Biosimilars: Current Status and Future Challenges

Biologic medicinal products developed via rDNA technology as recombinant protein-based medicines that have been in clinical use since the early 1980s as original biopharmaceuticals have greatly contributed to the therapy of severe metabolic and degenerative diseases. The recent expiration of the data protection or patents for most of them created opportunities for the development of copy versions of original biopharmaceuticals with similar biologic activity (termed biosimilars). Production of these new products is expected to meet worldwide demand, promote market competition, maintain the incentives for innovation, and sustain the healthcare systems. The licencing of these products, however, relies on the experience gained with the original biopharmaceuticals. Critical issues related to this class of medicinal products include their terminology (to avoid confusion with generics and non-innovator copy versions that have not been tested according to the biosimilar guidelines), manufacturing, and regulation. The European Union (EU) has been the first to establish a regulatory framework for marketing authorization application (MAA) and has named these products biosimilars, a term also recently adopted by the US FDA. Unlike the conventional, more common small molecular weight human medicines and chemical generics, protein-based medicines exhibit higher molecular weight, complexity in structure and function that can be affected by changes in the manufacturing process. Therefore, biosimilars represent a relatively heterogeneous class of medicinal products that make their regulation quite challenging. According to the current understanding in the EU, a biosimilar is a copy version of an already authorized biopharmaceutical (or reference product) with similar biologic activity, physicochemical characteristics, efficacy, and safety, based on a full comparability exercise at quality, preclinical and clinical level to ensure similar efficacy and safety. Guidance has been provided through several Committee for Medicinal Products for Human Use (CHMP) guidelines as well as individual scientific advice requested from the European Medicines Agency (EMA) by various companies for the development and regulation of biosimilars. This review is mainly focused on the current status of regulation of biosimilars in the EU as well as on future challenges lying ahead for the improvement of the requirements needed for the marketing authorization of biosimilars. Emphasis is given on the quality requirements concerning these medicinal products (biologics).     

遗传与基因组医学专科临床实践指南写作的指导原则

建立遗传与基因组学医学专科的临床实践指南,是将基础和临床遗传学研究转化为循证与精准临床服务的关键步骤。本文简要阐述了撰写高质量、高可信度临床实践指南的基本原则,并根据这些原则叙述了医学遗传专科指南的管理架构、写作流程、审核程序和应用评估,重点介绍了通过系统回顾相关文献总结特定遗传病筛査、诊断、咨询、治疗和预防方法的循证依据,以及高质量医学遗传专业指南写作和审核的具体要求。这些指导原则和具体要求可以保证指南写作的循证方法和建议内容符合现行的国际标准,并具备特定临床目的、适用范围和时效追踪。指南的实施可以促进基础和临床遗传研究成果的转化,推进医学遗传专科的科研合作和多学科跨专业临床实践指南的协同,为遗传病患者和亲属提供有效和安全的临床服务。     

Multiple hierarchical classification of free-text clinical guidelines

OBJECTIVE: Manual classification of free-text documents within a predefined hierarchy, commonly required in the medical domain, is highly time consuming task. We present an approach based on supervised learning to automate the classification of clinical guidelines into predefined hierarchical conceptual categories. METHODS AND MATERIAL: Given a set of hierarchically categorized documents in the training stage the learning algorithm exploits the hierarchical structure of the concepts in order to overcome the low number of training examples. The classification task is thus decomposed into a continuous decision process, unlike searching within a decision tree, which follows the concept hierarchy and makes a single decision at each node on the path, multiple paths can be chosen. Classification is based on applying a similarity function at each concept. Several evaluation measures were used, based on the intended use of the hierarchy. In addition, conservative and aggressive stop-criterion strategies for stopping the search through the concept hierarchy were formulated. An evaluation of the approach, including several training methods and multiple evaluation measures, has been performed using a training set of 1136 guidelines from the National Guideline Clearing House set. RESULTS: Based on a test collection consisting of 1038 clinical practice guidelines (CPGs) classified along two hierarchies, of roughly 5000 concepts, in which each CPG was classified by a mean of 10 concepts, a variable precision was observed from 44% to 60% depending on the settings of the training methods. CONCLUSION: These results demonstrate the feasibility of the approach, especially when considering the low ratio of guidelines to classification indices (concepts) in the evaluation data set used here.