Detailed Clinical Modelling Approach to Data Extraction from Heterogeneous Data Sources for Clinical Research

Abstract

The reuse of routinely collected clinical data for clinical research is being explored as part of the drive to reduce duplicate data entry and to start making full use of the big data potential in the healthcare domain. Clinical researchers often need to extract data from patient registries and other patient record datasets for data analysis as part of clinical studies. In the TRANSFoRm project, researchers define their study requirements via a Query Formulation Workbench. We use a standardised approach to data extraction to retrieve relevant information from heterogeneous data sources, using semantic interoperability enabled via detailed clinical modelling. This approach is used for data extraction from data sources for analysis and for pre-population of electronic Case Report Forms from electronic health records in primary care clinical systems.

Full text

Detailed Clinical Modelling Approach to Data Extraction from Heterogeneous
Data Sources for Clinical Research
Sarah N. Lim Choi Keung, PhD1, Lei Zhao, MSc1, James Rossiter, PhD1, Mark
McGilchrist, PhD2, Frank Culross, MSc, BSc2, Jean-François Ethier, MD3, Anita Burgun,
MD, PhD3, Robert A. Verheij, PhD4, Nasra Khan, MSc4, Adel Taweel, PhD5, Vasa Curcin,
PhD6, Brendan C. Delaney, BM BCh, MD5, Theodoros N. Arvanitis, DPhil1
1Institute of Digital Healthcare, WMG, University of Warwick, UK;
2Health Informatics Centre, University of Dundee, UK;
3INSERM UMR_S 872, France;
4NIVEL Netherlands Institute for Health Services Research, The Netherlands;
5Department of Primary Care and Health Sciences, King’s College London, UK;
6Department of Computing, Imperial College London, UK
ABSTRACT
The reuse of routinely collected clinical data for clinical research is being explored as part of the drive to reduce
duplicate data entry and to start making full use of the big data potential in the healthcare domain. Clinical
researchers often need to extract data from patient registries and other patient record datasets for data analysis as
part of clinical studies. In the TRANSFoRm project, researchers define their study requirements via a Query
Formulation Workbench. We use a standardised approach to data extraction to retrieve relevant information from
heterogeneous data sources, using semantic interoperability enabled via detailed clinical modelling. This approach
is used for data extraction from data sources for analysis and for pre-population of electronic Case Report Forms
from electronic health records in primary care clinical systems.
INTRODUCTION
One of the challenges in healthcare is the efficient reuse of routinely collected data for secondary purposes, such as
clinical research. The main uses of electronic health records (eHRs) from patient registries or eHR systems in
clinical research are for data analysis and for pre-population of electronic Case Report Forms (eCRFs). While
existing patient records can sometimes fulfil all the requirements of a retrospective study analysis, the pre-
population of eCRFs from eHRs can cover between 30% and 50% of the requirements1, and integrated electronic
data capture for eCRFs and eHRs can have an even higher overlap, depending on the study2. These highlight the
potential of reusing clinical data while reducing the amount of redundant data entry (data recorded in clinical care
that can be directly used for clinical research). Our research aims to support the interoperability between the clinical
researcher tools and the clinical data within patient registries and eHR systems.
The TRANSFoRm project3 aims to develop rigorous and generic methods for the integration of primary care clinical
and research activities, to support patient safety and clinical research. The two clinical research support tools for
researchers are the Query Formulation Workbench (QFW) and the eCRF Data Collection Tool. The QFW helps
researchers to define studies with eligibility criteria sets for participants, build queries to identify eligible
participants, flag patients, and extract data for analysis. The eCRF Data Collection Tool will support primary care
practitioners to collect clinical study data and support the collection of patient reported outcome measures (PROMs)
via web and mobile methods. In TRANSFoRm, the challenge is to bridge the gap between user requirements in
terms of clinical study data items, and the execution of actual queries based on these requirements at the data
sources. We adopt a two-level modelling approach4-6 to separate out the more stable domain information from the
various schema implemented by the heterogeneous data sources. The detailed clinical modelling (DCM) approach
represents this accurately and will be described further in this paper.
The workflow and the involvement of the TRANSFoRm tools (specifically the QFW) and components are shown in
Figure 1, from the definition of the study data extraction requirements to the actual queries at the data sources. In
this paper, we focus on cohort identification. Taking the case of a researcher using the QFW to define a retrospective
study of patients with Diabetes Mellitus, Step 1 involves defining the data to be extracted from the data sources,
without needing to know the format or coding system used in individual data sources. In Steps 2 to 4, a number of
TRANSFoRm components are involved to convert the data extract definition into semantically interoperable queries
that can be executed at the respective data sources to return the requested data in the format defined by the user.

The remaining sections of this paper are structured as follows to describe DCM approach for semantic
interoperability. The Methods section describes the DCM approach as a two-level modelling based on an
information model and archetypes to constrain it. The Results section then demonstrates with examples how user
requirements are mapped to a specific patient registry schema for data extraction. Finally, we discuss the use of the
DCM approach in other TRANSFoRm tools, and finish with some conclusions and future work.
Figure 1. Conceptual workflow, from user definition of data extract requirements to actual queries at data source.
METHODS
Detailed Clinical Models (DCM) organise health information by combining knowledge, data element specification,
relationships between elements, and terminology into information models that allow deployment in different
technical formats7,8. DCM enables semantic interoperability by formalising or standardising clinical data elements
which are modelled independently of their technical implementations. The data elements and models can then be
applied in various technical contexts, such as eHR, messaging, data warehouses and clinical decision support
systems. Work on DCM is still at an early stage with a number of groups involved on an ISO standard for DCM9.
Within the TRANSFoRm project, the two-level modelling approach of DCM is depicted on the first level as an
information model, the Clinical Research Information Model (CRIM), which defines the workflow and data
requirements of the clinical research task, combined with the Clinical Data Integration Model (CDIM), an ontology
of clinical primary care domain that captures the structural and semantic variability of data representations across
data sources. This separation of the information model from the reference ontology has been previously described by
Smith and Ceusters10. At the second level, archetypes are used to constrain the domain concepts and specify the
implementation aspects of the data elements within eHR systems or patient registries. We use the Archetype
Definition Language (ADL) to define the constraints and combine them with CDIM concepts in specifying the
appropriate data types and range values. The two-level modelling approach, using the concept of archetype for
detailed clinical content modelling, has been adopted by ISO/CEN 1360611,12. This approach makes it possible to
separate specific clinical content from the software implementation. The technical design of the software is driven
by the first level information model which specifies the generic information structure of the domain. The archetype
defines the data elements that are required by specific application contexts e.g. different clinical studies.
The distributed query and data extraction infrastructure is a central component of the TRANSFoRm software
platform. This infrastructure facilitates patient identification and reuse of routine healthcare data for research
analysis. The TRANSForm platform interacts with disparate patient registries and eHR systems via the Data Node
Connector, which translates the user queries, such as a data extraction definition as part of a retrospective study, in
the form of archetypes to data source queries using the Semantic Mediator. The Semantic Mediator ensures the
semantic translation queries from the Query Formulation Workbench to individual data source schema with the help

of data source models (DSM) and mappings to CDIM (CDIM-DSM)13,14. The transformed query can then be
executed at the data source side and results are returned to the user. While specific DSM and CDIM-DSM mappings
are required for each data source, these have to be built only once per data source. Additionally, the detailed clinical
model is flexible enough to enable researchers to query heterogeneous datasets without any knowledge of the
underlying structure, as they themselves do not use the DSM and CDIM-DSM mappings directly.
RESULTS
The data extraction for analysis was carried out for a Diabetes study, using a patient registry sample. In this section,
we demonstrate how the data extract definition was processed, from the user at the Query Formulation Workbench,
via the TRANSFoRm DCM to the data source. Following the steps in the conceptual workflow in Figure 1, we
describe one specific data extract requirement – prescription dates for Metformin medication – for illustration. The
clinical researcher defines what data to extract using the Query Formulation Workbench. In the case where the
researcher wants to extract all the instances when patients have been prescribed Metformin (Figure 2), the data
elements Medication and Prescription date are selected for extraction, and the constraint on the Medication concept
is specified as part of the archetype specification. For example, the researcher can choose Metformin with the ATC
code ‘A10BA02’ from the TRANSFoRm terminology service15. The resulting archetype definition in ADL is shown
in Figure 3.
Figure 2: Data extract definition using the Query Formulation Workbench
Figure 3: Medication archetype definition in ADL.

The translation of archetypes into a computable form at the data source includes the use of a DSM (Figure 4a) and
the CDIM-DSM mappings for the data source (Figure 4b). The DSM defines how the data source organises the
medication prescription information, while the CDIM-DSM mappings express information in the form of triplets
(CDIM concept; operator; terminology code). For instance, for Metformin with ATC code ‘A10BA02’, the
information triplet is represented as (medication agent; =; ‘A10BA02’). Following the transformations, an SQL
query is generated to enable the specified data to be extracted from the data source (Figure 5).
Figure 4: (a) Part of DSM definition (b) Part of CDIM-DSM for medication.
Figure 5: SQL query generated for data source schema.
DISCUSSION
Different solutions have been developed internationally to support a more rapid translation of scientific discoveries
into clinical practice, notably i2b216. i2b2 is a data warehousing system that extracts, transforms and loads data
into a common schema. In comparison, the TRANSFoRm infrastructure adopts a model-based mediation
approach, allowing the querying of heterogeneous data repositories without needing them to be in a single
common schema. The TRANSFoRm project also aims to support clinical research with the reuse of eHR data
within eCRFs, to avoid duplicate data collection. A minimisation of transcription errors and time-saving are added
benefits for the reuse of routinely-collected clinical data. For instance, Köpcke et al.17 report that the pre-population
of case report forms decreased the time for data collection by nine-fold, from a median of 255 to 30 s. The DCM
approach can be used in a similar way for the automatic pre-population of eCRFs from eHR systems as for the data
extraction for retrospective studies from patient registries. The pre-populated data can be exported in the Operational
Data Model (ODM) format18, a standard for the interchange of data and metadata for clinical research, especially
data collected from multiple sources. This will make the pre-populated data compatible with the remaining eCRF
and PROM data that are collected as part of a study.
TRANSFoRm uses archetypes in the current implementation as ADL is a user-friendly language and can be easily
understood by clinical researchers. HL7 templates, which constrain the HL7 clinical statement pattern, provide an
alternative way to implement DCM in the context of HL78. Future improvements to the TRANSFoRm GUI tools
can include an authoring tool to assist users in defining new data elements. Referring to the medication archetype
definition in Figure 2, currently, a user cannot directly update the archetype structure, for example to add the
constraint of the dosage of the medication. Additionally, the tool can support various data element specification
formats, such as HL7 templates and archetypes, for interoperation with systems that use these technologies.

CONCLUSION
The reuse of routinely collected data from clinical care in clinical research is an important goal of the TRANSFoRm
project. The approach is to retrieve relevant data elements from the data sources (patient registries and eHR systems)
without using a common structure to enable interoperability. Researchers can use the TRANSFoRm tools to define
their studies without being aware of the underlying structure of the heterogeneous datasets. We have presented how
a detailed clinical modelling approach is used to enable semantic interoperability between the researcher-defined
queries and the individual data sources. The two-level modelling supports the flexibility of specifying new
archetypes, as well as to add new data sources, while keeping the information model stable. Therefore, the DCM
approach facilitates the bridging of the gap between clinical research and clinical care. The next steps include the
validation of this approach and the related TRANSFoRm tools and components. Validation is being planned based
on two use cases, a retrospective genotype-phenotype diabetes study and a prospective study for the gastro-
oesophageal reflux disease randomised control trial.
Acknowledgements
The TRANSFoRm project is partially funded by the European Commission under the 7th Framework Programme
(Grant Agreement 247787).
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