TRANSFoRm: Translational research and patient safety in Europe (TRANSFoRm)

Published on: 03/10/2013

TRANSFoRm aims to develop the technology that facilitates a learning healthcare system (Figure 1). It brings together a highly multidisciplinary consortium where three carefully chosen clinical ‘use cases’ will drive, evaluate and validate the approach to the ICT challenges. The project will build on existing work at international level in clinical trial information models (BRIDG and PCROM), service-based approaches to semantic interoperability and data standards (ISO11179 and controlled vocabulary), data discovery, machine learning and electronic health records based on open standards (openEHR).

TRANSFoRm will extend this work to interact with individual eHR systems as well as operate within the consultation itself providing both diagnostic support and support for the identification and follow up of subjects for research. The approach to system design will be modular and standards-based, providing services via a distributed architecture, and will be tightly linked with the user community. Four years of development and testing will end with a fifth year that will be dedicated to summative validation of the project deliverables in the Primary Care setting.

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Figure 1: Concept of TRANSFoRm

Policy Context

The EU has a longstanding strategy to promote greater safety and productivity for EU healthcare via advanced ICT, part of a broader strategy for growth and development via ICT known as i2010. This has been supported by several European Commission ‘Communications’ and a programme of scientific projects funded through the ‘Framework Programme’, currently FP7.

These include:

  • Cross-border interoperability (COM 3282)
  • Empowerment and evidence-based care (COM 630) “together for health”
  • There is also an intention to improve uptake and ease of use of the eHR, and to promote the development and adoption of international standards including Hl7, CDISC, BRIDG and CEN/ISO13606.

The TRANSFoRm project was funded under a competitive call from the ICT (Health) FP7 Work Programme, with the aims of:

  1. Enabling integration between eHR and research information systems.
  2. Enabling effective knowledge translation to support patient safety.

These two aims are best encapsulated by the term ‘The learning Healthcare System’.

Description of target users and groups

There are four groups of target users for TRANSFoRm, public research organisations, pharmaceutical industry, researchers and general practitioners. Each group has different interest in the three use cases, and all use cases contribute towards the overall aim of improving the quality and safety of clinical care.

For the Genotype-phenotype study, researchers with questions requiring large amounts of data will be able to collaborate with national or regional clinical database and genomic repositories held by research organisations. TRANSFoRm enables the secure semantic integration of these resources, as well as adding a standard approach to data quality and provenance. We are working with databases in England, Scotland, The Netherlands, Spain and Belgium.

For Randomised Controlled Trials, researchers and the pharmaceutical industry will be able to manage the whole RCT lifecycle via electronic health record systems of general practitioners. This includes feasibility and recruitment, including live, within-consultation, recruitment on incident criteria, live flagging of follow up requirements, semantically integrated electronic case reports deployed within the EHR system and smart-phone and web-captured patient related outcome measures. The EHR vendors can build a new business model around supporting research whilst supporting international standards (CDISC and IHE), and without the significant investment of building tools from scratch. Again provenance and privacy are handled by the TRANSFoRm system. We are working with electronic health record vendors in England, Poland, Netherlands, Greece and Belgium.

For knowledge translation we are building a prototype system to interact with the EHR system during the consultation between GP and patient to provide live diagnostic suggestions and alerts based on an updateable database of diagnostic evidence. We have shown that both differential diagnostic suggestions and prompts can improve diagnostic accuracy. We are working with InPS, an EHR vendor in the UK on this system.

Description of the way to implement the initiative

The basic concept of this project is that if data from research and clinical practice is to be integrated in support of patient safety, it is not sufficient to simply extract data from EHR systems, the data must be semantically enriched by the use of a live interface direct to the consultation. Similarly, automatic ‘translation’ of data is unreliable and a semantically aware workbench is needed to assist researchers in selecting appropriate codes. The core requirements for interoperability, semantically aware, dynamic interfaces and a rich ontology are common to all elements of research and knowledge translation, justifying their combination in this project and the ICT2009 workplan. TRANSFoRm will support clinical studies with potential patient safety value and directly support the use of evidence for diagnosis, reducing diagnostic error. Each WP will address one of the principal scientific objectives.

  • Clinical Use Cases: Three clinical use cases run throughout the project, supporting the ICT WPs in three phases: use case development, testing and validation, and evaluation. The three clinical use cases are representative of the two types of Translational Research [genotype=phenotype studies and RCTs] and one form of knowledge translation [diagnostic decision support].
  • User Requirements Analysis: Two work packages have developed the clinical use cases into highly detailed user requirements specifications in Legal, Privacy and Security, Decision Support rules.
  • Models and Standards: Another WP has taken the detailed requirements and developed extensions to models and standards, using a core Ontology for clinical concepts.
  • Development and Evaluation: Two work packages are developing the software and services based on the requirements, models and standards.
  • Validation, Demonstration, Dissemination and Exploitation: The software and services will be evaluated in the well-defined use cases.

The TRANSFoRm project will achieve its impact via exploitation of the principal study outputs listed below.  WP 9, Dissemination and exploitation will lead the engagement of exploitation partners throughout the project and be responsible for the creation and maintenance of an exploitation strategy, which was delivered at the 24m review, and will be updated at the end of the project.

Overall Project objectives aligned with the ICT 2009 Workplan are listed below:

SO1 Validation in well-defined research use cases: To develop and validate the software and services in the context of two representative research use cases (a genomic-phenotype study and an RCT).
SO2 Validation in a Decision Support use case: Diagnostic error is the major threat to patient safety in Primary Care.
SO3 Data protection: To ensure that systems to integrate clinical and research data are built in full compliance with all legal and ethical requirements at European level, a systems user-centred security policy is required.
SO4 Supporting learning and decision-making: To support the development of an active learning healthcare system, improving patient safety by decreasing diagnostic error, it is necessary to store, make available and maintain research knowledge about the predictive value of symptoms and signs.
SO5 Support semantically rich data capture in both research and clinical practice: For a system to adequately integrate data between clinical care and research it is necessary to be able to go beyond the simple coding of data in each type of system and to enhance the capture of meaning within both systems.
SO6 Communication between research and clinical systems: TRANSFoRm aims to establish semantic interoperability between EHR datasets and clinical research data requirements, including linkage to other data such as genomic data.     
SO7 Development of a modular set of tools and services:  A service and agent based distributed middleware will be developed to manage secure connectivity to clinical databases and electronic health record systems, and to manage distributed searches and data mining across the system.
SO8 Demonstration: To engage target users beyond the project consortium in planning for, testing and evaluating the systems for their user group.
SO9 Dissemination and exploitation: To develop and implement a strategy for the exploitation of the systems and tools.
SO10 Advanced, intelligent analysis of data. The existing project was required to provide use cases covering randomised controlled trials and epidemiological studies, and could not provide the effort to also integrate cohort studies for diagnosis, although this logically completes the learning cycle with the diagnostic decision support system. Extension of the project to encompass analysis of diagnostic data from the EHR is thus of significant value.
SO11 Mobile eHealth. Another objective of the project is to develop a mobile eHealth application for the delivery of patient-related outcome-measures online.
SO12 Interoperability of IT systems by means of middleware. The amount and profile of data gathered in the TRANSFoRm project requires specialized work on standardization and interoperability to make the co-operating IT systems compatible, especially for subsystems responsible for further data processing.

Technology solution

The TRANSFoRm software ecosystem consists of executable software components and non-executable models that the software tools are based on. The high-level overview of the software components is shown in Figure 2.

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Figure 2: High-level software components

Three basic configurations of the tools are evaluated in the project. The Epidemiological Study configuration (Figure 3) is used in the Diabetes use case and consists of tools and frameworks for secure, provenance-enabled design and execution of epidemiological studies, from query design to phenotypic and genotypic data retrieval from heterogeneous data sources. Queries are formulated using standardised elements, and using information about suitable practices obtained from the data quality tool and sent to the data sources, using a secure data transport mechanism that communicates with TRANSFoRm connector tools on the data source side.

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Figure 3: Epidemiological Study configuration

The Clinical Trial software configuration (Figure 4) is used in the GORD use case, and consists of components needed for design, deployment, and collection of trial data, backed by provenance and secure authentication framework. Trial data consists of Patient-Reported Outcome Measures (PROMs) and electronic Case Report Forms (eCRFs) that are collected using the web and mobile devices as well as from the EHR systems in the clinical institutions where the trials are taking place. Data collection is based on custom extensions to CDISC Organizational Data Model (ODM) that allow integration with EHR systems via TRANSFoRm’s CDIM model, and rendering capabilities necessary for web and mobile data collections.

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Figure 4: Clinical Trial configuration

The Diagnostic Support configuration (Figure 5) is evaluated in collaboration with industrial partners. It consists of tools for mining rules from health data sources, and managing their deployment into the knowledge base upon which an evidence service is operating to support clinician diagnostic support tool embedded into a local EHR system.

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Figure 5: Diagnostic support configuration

TRANSFoRm models form the backbone of the tools and ensure their interoperability both on the conceptual level, and for concrete data exchange tasks.

CRIM (Clinical Research Information model) underpins all software tools developed in the project and is necessary to integrate the clinical research workflow with TRANSFoRm software platform.

CDIM (Clinical Data Integration Model) is a global mediation model using the local-as-view approach, expressed as an ontology. The ontology includes concepts that are especially important to primary care (e.g. episode of care or reason for encounter), but also others to handle temporality in queries (e.g. start and beginning of processes). Other ontologies including BFO 1.1, OGMS and VSO are referenced in CDIM. The ontology is stored as OWL files and managed using Protégé 4.2. It is deployed using the LexEVS 6 platform.

DSM (Data Source Model) is a UML model that describes the internal structure of data sources such as RDBMS, XML documents and HL7 messages

CEM (Clinical Evidence Model) provides an ontology of clinical evidence to represent the clinical knowledge needed to provide diagnostic decision support. The general model of evidence allows us to represent relationships between presenting patient complaints, formal diagnoses, and the diagnostic cues that support those diagnoses.

We have introduced a novel concept of research provenance that creates model-based audit trails using a common graph syntax derived from the Open Provenance Model (OPM) standard, and uses bridging ontologies to map to the overall information model used in the research task.

PROV-CRIM is the bridging model that maps the key concepts from CRIM to the OPM.

PROV-CEM is the bridging model that maps the key concepts from CEM to the OPM.

Technology choice: Standards-based technology, Open source software

Main results, benefits and impacts

The anticipated impact of the project is to improve patient safety by speeding translational research, quicker and more economic recruitment and follow up of RCTs, and enhanced uptake of eHR systems that offer support for clinical care and research. TRANSFoRm is currently at the start of year 4 of a 5 year project.

More specifically, the outputs of the project will be:

  • Principles, innovative methods and approaches;
  • Models, policies and frameworks;
  • Models and software (both end user services and middleware) to support the learning healthcare system.

Impact 1. ICT challenge of interoperability and scalable, standardised linkage of clinical and research data goes well beyond the state of the art. Building on the consortium’s international expertise in the development of models-based standards for interoperability in clinical trial data management,

Impact 2. The identification method developed in TRANSFoRm will serve to develop and test the technical and semantic requirements of Commission Recommendation COM 3282 (2008) [Commission recommendation 2nd July 2008 on cross-border interoperability of EHRs C(2008) 3282 2008/594/EC] on cross-border interoperability of EHR data. A particularly important impact of TRANSFoRm will be to provide tools for clinicians and researchers to manage interoperability and integration WITHOUT having to create single, monolithic systems.

Impact 3. An open-source, standards-based approach to study data collection will enable considerable cost savings through reduction in paperwork and duplicative data entry. Existing state-of-the-art data standards repositories are being extended to include rules for data validation and enforcing study protocols, timelines and for the capture of data from existing clinical records. In addition, the aims of Together for Health: A strategic approach for the EU 2008-2013 COM(2007) 630 will be addressed by greater citizens empowerment - allowing subject-initiated capture of Patient Related Outcomes,  reducing inequalities and encouraging evidence-based clinical care – by recruiting subjects from far more diverse community settings than has been usual for clinical research.

Impact 4. Three well-defined use cases ensure direct user involvement in all stages of the project. The ICT challenges are being addressed in the context of three use cases covering the principal areas of the project, risk prediction and monitoring via genetic epidemiology, a Randomised Controlled Trial with large numbers and Patient related Outcomes, and support for diagnosis and monitoring in the EHR. The involvement of the European General Practice Research Network, the European Primary Care Gastroenterology Society and the European Clinical Research Infrastructures Network and Quintiles in leading these work packages ensures that users with direct needs will drive the project, and form a collaboration between the pharmaceutical industry, healthcare IT industry, academic institutions and healthcare providers.

Impact 5. Bridging the gap between clinical research and medical practice will enhance patient safety.  TRANSFoRm will specifically focus on the role of Computerised Decision Support for diagnosis in primary care. There will be direct benefits in a reduction in diagnostic error in primary care, with benefits to patients and to health care systems, with less litigation. In addition the new user interface and DSS technologies will drive accelerated adoption of electronic health record systems by enabling more accurate and speedier recording/coding of information in the EHR. Furthermore, the TRANSFoRm clinical trial management module will enable earlier detection of adverse events in clinical trials.

Impact 6. European and international standards bodies will benefit from extension of domain models and greater use of standards in health ICT systems. TRANSFoRm will support the use of global ‘open’ standards, including CDISC ODM and SDTM, EN13606, HL7, and ISO11179 in line with Commission Recommendation COM 3282 and CEN Mandate M 403. In addition, the development of archetypes, templates and controlled vocabulary, to enable the DSS and EHR interface will extend our understanding of the ICT challenges in delivering patient safety-enhancing technologies across the EU via an open standards interface on top of proprietary systems.

Impact 7. Reinforced cooperation and better exploitation of ICT R&D synergies across the enlarged European Union.

Among the current TRANSFoRm project participants there are nine EU member states already represented, predominantly from the north-western European region and Southern Europe. The cooperation of those is creating a synergy effect by combining the knowledge and experience of every project participant. The addition of Poland in year 2, extended the project into the eastern EU.

Impact 8. Wider participation in EU-supported ICT research projects across all Member States.

Poland as a new member of European Union is about to implement wide-scale intelligent ICT systems in the medical field. The extension of the TRANSFoRm project will increase the participation of a new Member State by sharing the expertise gained from currently going-on medical ICT projects in Poland.

Impact 9. Paving the way for strategic partnerships in view of gaining access to knowledge, developing standards and interoperable solutions and strengthening European competitiveness.

CSIOZ as a national organisation is a very influential partner when talking about EHR standards and WRUT will enhance the project by the ability to build agile solutions. Poland is particularly important, as it is a new adopter of ICT for health and as such is not held back by a long tail of legacy systems and data. Poland can act, via rapid adoption of the results of TRANSFoRm via CSIOZ, as a leader in the adoption of new ICT for health in the eastern European region.

Return on investment

Return on investment: Larger than €10,000,000

Track record of sharing

TRANSFoRm is still only part of the way through its 5 years, and exploitation will inevitably form a greater part of the final 2 years of the project. However learning from the project is a significant aspect of project exploitation. We have adopted the following strategy:

  1. Direct engagement with database owners, EHR vendors and researchers via the use case evaluations. As these are taking place in six different EU member states, this will act as an initial user-base for the system. In addition, the use cases require researchers, data owners, practices and vendors to work together on the evaluation. For example, in the UK, the Clinical Practice Research Datalink is working with the NIHR Primary Care Research Network on deploying TRANSFoRm tools.
  2. Development of an exploitation model with the vendor user group based on an open-source model of software licensing. There is a longstanding problem with exploitation of software produced by public projects. The ending of a research project funding stream can lead to a lack of maintenance and loss of the software. Alternatively, ‘privatisation’ of the software can lock out late adopters. We aim to create a ‘TRANSFoRm Consortium’ to look after the software and keep it free of use to exploters, who may incorporate it into their own commercial offerings. However, the principal outputs of the project are in the domain of methods, models and evaluations which will be published and disseminated. These are more important than software per-se, which is simply a reference implementation of these methods, which can be freely replicated. To this end we are working with a variety of international standards bodies and organisations, including CDISC and IHE.
  3. Direct dissemination activities at international conferences in informatics, health and computer science. In addition we are also collaborating closely with other EU projects and with the ‘Learning Healthcare Collaboration’ in the USA.

Lessons learnt

TRANSFoRm is in progress still, so it is too early to indicate ‘lessons learned’. However all project deliverables are made available to the public on the TRANSFoRm website.

Scope: Pan-European