Computers in Biology and Medicine 41 (2011) 575–586

Contents lists available at ScienceDirect

Computers in Biology and Medicine

0010-48

doi:10.1

n Corr

Medicin

Street, L

fax: þ4

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journal homepage: www.elsevier.com/locate/cbm

Development of an advanced database for clinical trials integrated with anelectronic patient record system

Alexander C. Newsham a,b, Colin Johnston a,b, Geoff Hall a,e, Michael G. Leahy a,f, Adam B. Smith c,Aditya Vikram a, Aine M. Donnelly a, Galina Velikova a,b, Peter J. Selby a,b, Sheila E. Fisher b,d,n

a Cancer Research UK Clinical Centre, University of Leeds, St James’s Institute of Oncology, Beckett Street, Leeds, West Yorkshire, LS9 7TF, United Kingdomb Leeds Institute of Molecular Medicine, Faculty of Medicine & Health, University of Leeds, St. James’s University Hospital, Beckett Street, Leeds, West Yorkshire,

LS9 7TF, United Kingdomc Centre for Health & Social Care, Leeds Institute of Health Sciences, Charles Thackrah Building, University of Leeds, Leeds, LS2 9JT, United Kingdomd School of Health Studies, University of Bradford, West Yorkshire, United Kingdome St. James’s Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Beckett Street, Leeds, West Yorkshire, LS9 7TF, United Kingdomf The Christie Hospital NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, United Kingdom

a r t i c l e i n f o

Article history:

Received 9 June 2010

Accepted 28 April 2011

Keywords:

Electronic clinical records

Clinical trials

Electronic databases

Internet technologies

Healthcare workflow

Integrated care technologies

Touch-screen technologies

Head and neck cancer

Oncology

Electronic questionnaires

25/$ - see front matter & 2011 Elsevier Ltd. A

016/j.compbiomed.2011.04.014

esponding author at: Leeds Institute of Mo

e & Health, University of Leeds, St. James’s

eeds, West Yorkshire, LS9 7 TF, United Kingd

4 113 343 6165.

ail addresses: s.e.fisher@doctors.org.uk, s.e.fis

a b s t r a c t

Secondary use of patient databases is essential in healthcare if clinical trials are to progress efficiently

to planned time and target and imperative if the planned UK expansion of research and development

(R&D) at point of care is to be achieved. Integration of effective databases primarily designed to

facilitate patient care with R&D requirements is needed but represents a complex challenge.

We present a system that achieves an integrated approach with online management of complex

datasets for clinical trials within care records using a specific study as an example to show functionality

in practice; illustrating how this system provides an ideal resource to meet the needs of both clinicians

and researchers.

& 2011 Elsevier Ltd. All rights reserved.

1. Introduction

In recent years there has been a huge drive from both withinand outside the National Health Service (NHS) to develop andrefine Information Technology systems for healthcare. In an evermore complex global setting, advances in care depend on wellconducted and robust clinical trials. This close relationshipbetween the needs of healthcare professionals and researchersgives impetus to the use of health information technology that canprovide integrated systems to facilitate the organisation and day today management of clinical trials and to disseminate findings intoclinical care. Provision of access for clinical researchers to patientdata that protects individual interests and allows research toproceed effectively is a core recommendation of the Academy of

ll rights reserved.

lecular Medicine, Faculty of

University Hospital, Beckett

om. Tel.: þ44 113 268 7348;

her@leeds.ac.uk (S.E. Fisher).

Medical Sciences review of regulation and governance of healthresearch [1].

The UK government set up a national information technologyprogramme (NPfIT) in 2002, into which they agreed to invest£18bn over the following 10 years [2] which aims to provide acomprehensive electronic records infrastructure. Electronicpatient records, created at the point of care, will be accessibleto authorised users in primary, secondary, tertiary and commu-nity care as well as to patients themselves, making necessaryinformation available at a time and place convenient to allinvolved. The database of patients created by Spine (NPfIT) willhave almost 50 million patients; this will create one of the largestdatabases of patients in the world [3].

Although primarily used to facilitate coordination of the carepathway, this system can also be of enormous value in the area ofresearch and clinical trials. The commitment to clinical researchin an NHS setting has been confirmed by the creation of theNational Institute for Health Research (NIHR) [4], which bringscoordinated research support and infrastructure to clinical trialsin all areas of medicine and which is tasked with delivery of

A.C. Newsham et al. / Computers in Biology and Medicine 41 (2011) 575–586576

clinical research to time and to target. The NHS Constitution hasfurther affirmed its commitment to innovation and the conductof research to improve the current and future health of thepopulation [5].

Integration of patient care and clinical trial databases wouldachieve much to support these ambitious goals in advancinghealthcare through robust clinical research. A reliable and accep-table technology platform for both clinical and research commu-nities is essential if the aims of the NIHR and NHS Constitution areto be realised.

Current strategy reviews in cancer care highlight the promiseof new therapies but also the potential burden of their adop-tion [6]. As the clinical environment in which care is givenbecomes ever more complex, the Department of Health (DH) iscommitted to gathering robust data for benchmarking and servicedevelopment. The Improving Outcomes: A Strategy for Cancerreport emphasises the place of the patient at the core in thedelivery of healthcare, healthcare innovation and research [7].

Integration with a clinical trials record will be helpful, especially inmulti-centre studies where the investigators and researchers needaccess to patient details in a convenient way. For cancer research it isestimated that 25% of UK patients will access healthcare, andpotentially cIinical research, through the emergency care pathway;therefore, information must be available about involvement inresearch, especially trials of new therapeutic agents to enable safemanagement at the point of care. In Leeds, UK, the Patient PathwayManager (PPM) system (developed in Leeds and described below) isnow being used routinely as an integrated resource.

The system developed in response to need to bridge the gap inknowledge between informatics and researchers, as most soft-ware is fairly difficult to use. The software and the system,described in this paper, have been designed to be user friendlyand provide real time data. Though some training is required, theinterface can be easily understood; allowing seamless integrationof patient records and research data, which can be analysed. Thedata can be obtained in different ways, i.e. through online or onstand-alone systems, which can then be synchronized with themain data on the server.

The data technology system was initially developed to supportoncology clinical research but has now been rolled out to embrace allclinical disciplines. LTHT is the largest NHS Trust in the UK with aconsiderable cancer related workload allied to a strong researchprogramme across all aspects of cancer diagnosis, treatment andpatient and carer support. In accordance with the National Institutefor Health and Clinical Excellence (NICE) national guidelines forimproving outcomes [8], patients are managed by a team combiningall relevant medical specialist expertise and that of nurses and alliedhealth professionals, the multidisciplinary cancer team (MDT). PatientPathway Manager (PPM) is now the core resource for integratingcancer care across various Trust sites. The patient ‘‘pathway’’ refers toall the key stages in a patient’s care episode from initial referralthrough diagnosis and treatment to follow-up and outcomes, includ-ing reports of clinical tests, chemotherapy prescriptions, imaging andpathology reports to provide a comprehensive record of care.

At all points in the pathway, there is potential for recruitmentto a clinical trial. Managing such activity in isolation carries anumber of generic risks:

�

Patients may be approached for entry after they have alreadyrefused. � Patients may be asked to take part in more than one clinical

trial, with ethical implications as well as governance issueswhen trials conflict.

� Health professionals in both hospital and primary care settings

may not know that a patient has been entered into a trial, anevent which might affect their management.

Integration of clinical trial management with the care pathwaycan overcome these practical problems.

To assess the place of PPM as a research database linked toclinical practise initial feasibility work was undertaken with theCancer Research UK funded Psychosocial Oncology and ClinicalPractise Research Group in Leeds. This research team has under-taken substantial research into the use of touch-screen computersin health related quality of life (HRQoL) research, successfullycapturing data from patients in an acceptable and reliableway [9]. The use of touch-screen technology has proved verysuccessful in investigating HRQoL in patient populations. Theability to rapidly collect and automatically score data allows thedoctor easy access to information about present and cumulativeHRQoL [10]. This intervention resulted in an increase in thenumber of issues discussed at consultation and patients consid-ered questionnaires a useful tool to inform their doctors abouttheir problems. The benefit of making HRQoL scores readilyavailable at clinic through availability of touch-screen data, interms of identification of issues and patient satisfaction, has beendemonstrated by randomised control trials [11,12]. This workopened the path to a full clinical/research electronic databasecombining the clinical pathway, clinical trials management anddirect entry of patient generated data that has revolutionised theway study participants are recruited by the clinical team andquestionnaire data is gathered and stored by the clinical research-ers. With the use of new generation on-line touch screen datacollection systems since January 2006 eligible patients can beeasily identified on PPM by clinicians and drawn directly into thepathway for invitation to enter studies, thus meeting the require-ments of the NHS Constitution whereby clinical teams have aduty to inform their patients of clinical trials which they areeligible to enter [5]. Once successful completion of the interactivetouch screen questionnaires has taken place, data collected can beeither automatically or retrospectively uploaded into PPM.

To illustrate this system and to allow a description of thepractical functionality, from a user perspective, we report a studyassessing HRQoL in head and neck (H&N) cancer patients, carriedout at a number of geographical sites within LTHT; showing thebenefits provided by a system, which electronically links clinicsand uploads and downloads data to and from a secure site.

2. The electronic database

2.1. Patient pathway manager (PPM)

The Patient Pathway Manager (PPM) is an integrated informa-tion and data management system. It is the Cancer InformationSystem for Leeds Teaching Hospital Trust (LTHT) and, with theencouragement of the Yorkshire Cancer Network, instances ofPPM are now running live beyond LTHT, in the Calderdale,Bradford, York and the Mid-Yorkshire Trusts and is also nowbeing deployed to other, non-cancer related services.

PPM has been built around a standard SQL Server 2005infrastructure and is viewed and administered via a user interfaceapplication constructed and developed using Visual Basic. At thecentre of PPM’s architecture is a relational database structure,using a synchronisation methodology, which utilises SQL 2005Merge Replication. This enables locally hosted instances of PPM(in Leeds, Bradford and Calderdale for instance), known as‘Subscribers’ to pass locally registered patient data via VPNencryption on N3 to the central PPM system, known as the‘Publisher’. The Publisher determines which of the Subscriberorganisations share the data based upon the data entered (e.g.referral events, letters, contacts etc.) on the various Subscribersystems. Once a patient’s data is deemed as shared between

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organisations, then all the relevant data is synchronised to therelevant subscriber systems, ensuring that each Unit can accesstheir own instance of PPM regardless of the state of the N3connection.

Each local subscriber interfaces to local clinical and adminis-trative systems. All non-LTHT subscriber systems utilise interfacemechanisms created by the PPM development team, and employ-ing HL7, to standardise imports between different subscribers,importing all the related activity from a source system when apatient already exists on the PPM subscriber or registering thepatient when related activity is deemed relevant to existingPPM data.

At the user level, the system employs thick client technologyto deliver the application to a variety of user desktops, using acombination of MS Windows and SQL Server security technolo-gies to manage user authentication on a secure NHS Trustnetwork of servers.

PPM integrates all the information relating to the care, treat-ment and management of patients seen within the Trust, present-ing this information through a variety of the thick client views,called ‘browsers’, which include a Patient Pathway browser, aSearch browser, a Trial browser, Clinics browser, and an MDTmeeting browser, thus enabling a variety of activities to bemanaged through PPM. The information is presented as a ‘‘path-way’’ of patient-specific events, listed chronologically, in the formof an expandable list or tree of events and (where applicable)sub-events (See Fig. 1). When each event/sub-event on display isclicked, the relevant data is displayed in a series of tabbed formssituated in the right-hand portion of the computer screen. This issupported by on-screen access to the electronic patient annotatednotes for clinical staff providing a full history of the patient’streatment, though we must emphasise that this facility does notreplace the hand-written, hard-copy patient notes, it merelyintegrates them. A summary screen for each patient, detailingcurrent treatment and indicating their current trial activity,together with on-screen access (where appropriate) to clinical trialprotocols, enables authorised healthcare staff to have an up-to-date picture of the patient’s treatment past and current. A small

Fig. 1. Pathway of

icon flags the fact that the patient is enroled in a clinical trial.Researchers have access to data associated with their trial, personalinformation being anonymised by the automatic generation of aunique identifying number.

The data detailing each event are obtained from a variety ofsources both integral and external to the system. Informationfrom the external data sources is refreshed every few minutes toensure information is current and up-to-date.

External data sources include the NHS Trust Patient Adminis-tration System (PAS), a master index for patients who have beentreated at any of the hospitals within the LTHT, which providesdemographic, outpatient clinic, and in-patient attendance informa-tion. Other external sources include the LTHT Results Server (bywhich clinicians routinely access test results data), an oncologychemotherapy prescribing system providing details of a patient’schemotherapy regimens and administrations, the Trust radiother-apy database, a pathology database, as well as data feeds for anyoncology-related surgery the patients have undergone in the Trust.All these data sources feed tables integral to the system which aresupplemented by data collected manually via PPM itself.

Also integral to PPM is the PPM trial browser and trialsdatabase, which is the repository for information about any ofthe trials (clinical and psychosocial) conducted within or incollaboration with the Trust and its related academic depart-ments. At present PPM does not hold patient trial-specific casereport form (CRF) data completed for clinical trials (this data isheld in trial-specific databases, such as in-house academic studydatabases). As regards patient assessment visits for clinical trials,PPM simply collects the administrative details of the patient-specific trial events themselves, not the assessment data specificto the trial visit. Though PPM does have the potential to collectand store data entered on CRFs, as it stores patient trial events in avisit-related trial structure, the format and scope of individualtrial assessment data proves too variable across studies to enableintegration with PPM.

It is important that clinicians are aware and can access dataabout trial involvement. Governance issues require differentaccess levels for clinical staff and clinical researchers, and a Trial

patient events.

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browser specific security structure is now in place to administerthis. Research staff require anonymised recruitment records foranalysis, and the PPM provides these in the form of authorised,scheduled exports of anonymised data utilising the secure SQL

Fig. 2. (a) Defining assessment properties (including defau

Server Data Transfer Service (DTS). A reporting server hosted withLTHT provides for the reporting of data and its graphical output toregistered users via PPM, a secure web facility, or by a scheduledautomated email service (within the secure NHS LTHT mail

lt item responses). (b) Defining the item’s properties.

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service). These interfaces are essential for the integration ofclinical and research care, ensuring acceptable standards ofconfidentiality.

2.2. The trial browser and touch-screen

Interacting dynamically with the PPM Trial Browser is the PPMTouch-screen (TS) application. This is an application built inVisual Basic 6.0, which can be used both live, on the Trustnetwork, communicating in real time with PPM, or, alternatively,as a detachable off-line application on a stand-alone machine,which can be used for patient assessments outside the clinic, forinstance, to enter data collected at visits to patients’ homes. Ifdata is collected off-line, then the TS application works with alocal copy of the PPM database that simulates the live system.Once the consultation has been completed, the stand-alonemachine can be reconnected to the network in order to synchro-nise the data with the on-line PPM system.

Patients can be selected directly by duly authorised clinicalpersonnel with substantive or honorary NHS contracts throughPPM using a whole a variety of listings, including clinic listings, orvia the patient browser, or the PPM system’s search browser. Theprocess of selecting patients is called ‘‘watching’’. Once patientsare watched, they can be reselected directly via the TS from a‘‘Watched by User’’ or ‘‘Watched by Team’’ option on the Clinicdrop down box on the TS. This proves useful for the off-lineversion of the TS application, where patients may not be attend-ing a specific clinic. In such instances it is necessary to downloadthe watched list of patients from the network prior to going off-line; this can be done via the on-line networked TS at the touch ofa button. Alternatively, if the user is working directly with thelive, networked version of PPM, the patient can be selected on theTS directly from a clinic appointments list.

Fig. 3. Self-select list of questionnaires (showing ordering toggle button and groups

indicated by the numbered columns below).

Once a patient is selected on the TS, they can be enroled andentered onto a study and complete assessments directly via theTS in a single session.

2.2.1. Setting up touch-screen (TS) study assessments on PPM

All assessment packages are defined in advance via the PPMUser Interface (UI). Each TS assessment is created in advance onPPM, including advanced features such as randomisation of studyinterventions and branched assessments. The format of the studyassessment, each of its individual items and their properties aredefined manually via the PPM UI and are then associated witha trial visit structure under the specific trial that has beenpre-added onto PPM. If item response values and codes are uniformthese only need be defined once in the item response definitionfields on the assessment properties screen. If the item responsevalues vary throughout the assessment, then these can be definedindividually under the assessment item’s properties (See Fig. 2a). Ifthe item response values are mostly uniform for an assessment thenthey can be defined as the default item response in the assessmentproperties screen, and for those items where they vary, the defaultmay be overridden and separately defined on the item’s propertiesscreen (See Fig. 2b), saving time and labour.

Each visit may contain a multiple number of assessments toallow for consultations where more than one assessment is to becompleted in accordance with the trial protocol. If the definitionof an assessment is standard in type, it need only be defined onceon PPM and can then be re-used on any number of trials, simplyby first creating the visit and then adding the pre-defined assess-ment to the visit by selecting the assessment from a self-selectlist. The user can also pre-define the style and format of the visitas it is delivered on the TS, creating introductory screens to thevisit and individual assessments, and item format.

of randomised questionnaires—internally randomised groups of Assessments are

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The TS user pre-defines the order or sequence in which theassessments appear on the TS, via PPM, by using a toggle buttonin the assessment self-select list window (see Fig. 3). This facilityalso allows for randomising the order in which the assessments

Fig. 4. Assessment properties scre

Fig. 5. The TS initia

appear. Assessments can be randomised as a whole or as intern-ally randomising groups of assessments, enabling randomisationfor some of the assessments while others in the sequence canprecede or follow the randomised group in a fixed ordinal

en displaying item branching.

l entry screen.

Fig. 6. Selecting patient groups from the ‘clinic’ drop down list.

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position in the sequence of questionnaires for that particularvisit (see Fig. 3). The defined visits (or suite of time-pointspecific assessments) are then delivered directly to the TS forthe relevant trial.

PPM also enables the user to pre-define branching structuresfor the sequence of assessment items. This enables the user to additems with conditional responses, which allows certain items orgroups of items to appear or be skipped according to the responseprovided to a preceding question presented on the TS. Forinstance, the Closed Persons Questionnaire (CPQ) asks the ques-tion ‘‘Is there another person who you are close to?’’ If answered‘Yes’, the person completing the assessment simply moves torespond to the next question (assessment item No. 17). However,if this question is answered ‘No’, the TS will skip to assessmentitem No. 32 (see Fig. 4).

This arrangement provides a versatility, which ensures thatthe technology meets the needs of the clinical study.

2.2.2. Using the touch-screen (TS)

Having defined their trial visits, the user, being an authorisedmember of the research team, is then ready to use the TS to carryout assessments.

The user simply needs to load the TS application, and oncetheir user identity is authenticated they will be taken to the TSinitial entry screen (see Fig. 5).

That user will then choose the relevant study from the TS’sinitial entry screen, select the patient who has consented to enteronto their trial from the clinic list or list of ‘Watched’ patients viathe ‘Clinics’ drop down list (Fig. 6), and choose a trial arm if

applicable (this option is only relevant for patients attending theirfirst trial visit).

The TS then calculates the relevant trial visit according towhich stage the patient has reached on the trial, and thenpresents the relevant trial visit for selection (see Fig. 7).

Once selected, the user elects to continue. At this point the TSproceeds to the visit’s first assessment introductory screen,delivering the assessments to the user in the pre-defined way.The TS security controls allow a patient to complete assessmentswithout gaining access to the initial entry screen, thus ensuringdata protection and patient confidentiality.

On some trials there is also an option to print off a fullyformatted copy of the assessment’s item responses, though theauthorised user may elect not to do so at this stage, preferring toreview them retrospectively via the PPM UI.

3. The clinical setting

Head and neck (H&N) cancer represents a global healthcarechallenge [13] with oral cancer alone accounting for 220,000 newcases in males and 90,000 in females annually worldwide,representing 5% and 2%, respectively, of new cancer diagnoses.In the USA, 36,234 new cases of H&N cancer were reported in2003 [14] and in England, 6036 cases in 2006 [15]. The complex-ity of management of this cancer with challenges to key functionssuch as speech and eating as well as aesthetic morbidity makes aH&N clinical trial a challenging model to test the efficacy of theintegrated database. The clinical care pathway involves a numberof surgical and non-surgical disciplines, requiring appointments

Fig. 7. Selecting the relevant trial visit.

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at a number of sites, making a central record imperative for safecare and requiring a similarly dependable and robust system tomanage research. The study reported resulted from collaborationbetween the H&N clinical team and the Cancer Research UKPsychosocial Oncology and Clinical Practice Research Group andillustrates well the way the integrated database is used in practiceand its acceptability to the clinical team.

4. How we use the electronic database

4.1. Patient identification and clinical records

The introduction of PPM as a base for the clinical record allowsstaff to log on, identify a patient and access medical notes,diagnostic summaries, reports and annotations. The use of a coredataset for generic data for clinical care and research avoids errorsin entry and completion of a separate and potentially less secureset of records. As well as integrating care and research recordswithin the MDT, other teams can access essential informationwhen the patient has other problems, an example being admis-sion for an unrelated acute surgical event when the previous H&Ntherapy may render airway management hazardous.

4.2. Patient identification for clinical trials

We used the integrated database in a study designed to seekpatient opinion on the content and wording of questionnairesused in the assessment of health related quality of life (HRQoL).The study population included patients undergoing follow upafter treatment with curative intent for H&N cancer.

The trial was set up on PPM as described in Section 2 of thispaper, and given a unique identifier to access a secure passwordprotected file in which records were stored. The trials database is

placed within the secure encrypted area of the Trust Networkappropriate to the trial’s setting.

PPM was used to identify all eligible patients, i.e. those aliveand free of disease one year after treatment. Study data wasentered on a laptop computer, allowing mobility between loca-tions and clinics. When a patient was not be identified prior to aclinic but chose to enter the trial, online synchronisation via anetwork access point allowed their records to be downloaded.If an access point was not available, then the patient could beentered manually onto PPM and synchronisation performed later.

4.3. Study entry and management

Eligible patients were approached by their clinician andinvited to enter the study by the clinically led research team.

Once a participant was recruited, the system automaticallyloaded the data on to the screen and the questionnaire, or otherstudy material, was presented in an ordered fashion. In this study,a series of questionnaires (attitude to consultation, general statusquestionnaires, head and neck specific questionnaires and apsychological screening tool) were presented in random order,stratified by content, i.e. general questionnaires in random orderfollowed by head and neck questionnaires in random order, anddata was entered using the touch-screen (see Fig. 8).

The screen is designed in such a way that questions are clearlyvisible and there is a pause between screens, which we havefound avoids errors in data entry.

In order to ensure that data collected is of the highest qualityand that patient confidentiality is maintained, a quiet space inwhich to complete questionnaires and conduct interviews isnecessary. The busy clinic environment often makes it difficultto reserve a private room for data collection purposes. The currentuse of mobile touch-screen technology overcomes this practicalconsideration by enabling data collection to be carried out

Fig. 8. TS: presentation of questions on screen.

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wherever a quiet space is available. For this study the recruitmenttarget of 150 patients was achieved and despite the burden ofdata collection, full records were completed in the target time of1 h. This level and speed of data recording would not have beenpossible using paper based records.

On completion of a clinic, the laptop was immediatelysynchronised with the Trust Network ensuring security andback-up of study data.

4.4. Data exploration and analysis

One key advantage of the integrated system is the ability todirectly correlate demographic and clinical material (age, sex,diagnosis, staging, therapy, time of treatment) with study mate-rial, including advanced data comparison. An additional require-ment of the study was the analysis of a taped consultation andcomparison with the clinic annotation to determine which patientneeds were not discussed or managed through routine consulta-tions. The clinic record and annotation, together with the analysisform, was managed through the integrated database, giving a verydetailed, semi-quantitative capacity, an increasingly importantfeature as clinical management and the trials which seek toexplore efficacy become more complex.

For standard quantitative statistical analyses, queries can beperformed using anonymised datasets transferred from PPMnightly to the University network and downloaded from SQLServer in a format as required by the research team, in thisinstance to a standard Microsoft Access database.

4.5. Using generated data in a clinical setting

The system can be programmed to issue reports in a standar-dised fashion and in this way be presented to the doctor orhealthcare professional during the patient’s attendance, either inrespect to clinical data or research data. The interest for our groupwill be to explore the effect of making longitudinal comparisondata on HRQoL available to MDTs and to determine the impact onquality of care.

5. Discussion

In view of recent plans for and massive investment in modernNHS recording and communication systems, the incorporation ofthe PPM system into clinical services at the LTHT has been mosttimely. Furthermore, the integration of this system with ongoingresearch within the CR-UK Oncology Psychosocial and ClinicalPractice Research Group is very much in line with the majornational recommendations for bringing together clinical researchand clinical care. The advantages of using new generation touchscreen data collection systems, which are directly linked toelectronic patient records, are considerable and wholly compa-tible with national priorities as outlined in the paper.

Well-designed clinical trials are imperative in assessment andimprovement in patient care. The commitment to this throughthe NHS Constitution with the personal support of the Secretaryof State for Health and backed by a highly integrated commis-sioning and funding structure through the NIHR is very welcometo clinicians and clinical research teams. It is essential thattechnology, of the design and level of integration described inthis paper is made available to those teams if the aims of thestrategy documents are to be brought to practical reality inclinical and research practice.

Traditionally, in clinical trials of all types, paper based datasets ofvarying but often significant complexity have been entered at acentral management centre, requiring much time as well as poten-tial for error in entry or transcription. Such challenges have madethe incorporation of clinical trials into routine care very difficult.

Communication between health professionals in terms of clin-ical status and current treatment and support issues are ever morecritical and, as the new biological agents, which offer much forcancer care move into large clinical trials, it is envisaged that thetrials themselves may be hosted jointly by primary and secondarycare. The traditional separation of patient care and clinical trialsdata cannot be supported in such a model of healthcare.

HRQoL studies such as the H&N study used in this paperto illustrate the database in practice are concerned with thepsychosocial and emotional impact of diagnosis and treatmentfor groups as a whole and on the individual. This is of particularsignificance where patients receive treatments that affect key

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functions, result in distressing aesthetic changes and/or social andfinancial challenges. Understanding the impact of clinical condi-tions through research requires analysis in a number of ways;statistical, thematic and both cross-sectional and longitudinal.The system can be equally applied to other datasets in all areas ofhealthcare.

For multi-site and complex studies the use of the PPM clinicaltrials database is a significant advance in conducting health research.The approach outlined in this paper overcomes geographical andpoint of care limitations; the only requirement for data transmissionand receipt being a suitably configured network point. It is particu-larly suited to community based studies where the ability to use amobile data collection device, such as a laptop is important.

Measuring HRQoL is fundamental in understanding the patientexperience and improving patient care by aiding optimal treat-ment decisions especially when these have functional, emotionalor psychological consequences. Such a patient centred approach isconducive to producing health research that relates directlyto clinical practice, improves patient care and is highly compa-tible with the IT system currently in use. The close relationshipbetween patient reported outcomes measures (PROMs) andclinical benefit has recently been recognised by the Federal DrugAdministration (FDA) who now require PROM to be includedin submissions for regulatory approval [16]. Simple effectivesystems to collect this data will become increasingly importantas quality of life becomes a major and potentially the mainparameter in randomised clinical trials.

However in common with all systems, the interrogationfunction relies on the quality of data entry. We have found thisto be the limiting factor as PPM is relatively new and, for manyeligible participants, a full clinical and diagnostic retrospectivedataset had not been completed. As PPM is rolled out as thedefinitive record to all clinics, and data prospectively entered,this problem will be overcome. Despite this current limitation,potentially eligible patients have been found reliably, by manualsearching on an opportunistic basis when patients present to theclinic, much reducing the requirement to search blindly throughclinic lists and medical records.

Future work includes the facility to set up entry for individualswho are not already registered as patients (for trials of acuteinterventions in A&E, for example) and the management of controlas well as participant groups. Such a feature would allow manualentry of patients even if the parent system were closed for main-tenance or technical reasons. Work is in progress towards makingavailable stand-alone systems to facilitate collaborations with otherresearch organisations. We are currently looking into developing aportable web-enabled version of the system that would enablegreater flexibility in the way we distribute the technology andcollect data from beyond the Trust network. This will expedite datacollection and reporting for multi-centre studies (i.e. outside thetrust network) via the touch-screen application in real-time, thuseliminating the current necessity of physically connecting a client toa Trust network point in order to synchronise data collected atlocations outside the Trust network with the live system.

If this system is to gain widespread recognition, compatibilitywith the requirements of external regulatory bodies will be animportant element. Consideration of the ethical aspects of datasharing is important and systems for clinical research must meetthe legal and governance standards, which we have outlined above.For some trials, especially of new medicinal products, healthprofessionals may need to access information for patient safetyas the trial may well impact directly on the care episode. However,some trials are of a sensitive nature, where participants may wishaccess to their records to be restricted. It is likely that this will needto be addressed on a trial by trial basis, covered in the consentform for the trial. At present, in the UK, the accepted research

governance policy is that identifiable information should be sharedonly with the patient’s permission. PPM is restricted to authorisedusers, wider sharing of a web-based system will require carefulconsideration of who can have access and at what level. Security interms of restriction of access, encryption and of data backuprepresents an advance over stand alone systems. Firewall consid-erations where an external body, regulatory or commercial partnerrequires data access are important in this context.

Integration of records for clinical care with secondary use hasthe potential to facilitate entry into trials, correlate trial and clinicaldata and provide a secure and dependable data store in line withthe requirements of good clinical practice. It can act as a repositoryfor information required during external quality assurance inspec-tions and its secure nature protects against data loss or accidentaldestruction. We believe that this system has the flexibility andreliability to meet the needs of clinicians and can be a valuableadvance in the secondary use of primary care databases.

6. Summary

This paper presents a practical example of use of an integrateddatabase for primary and secondary purposes. This developmentis fundamental to the future of research and development inhealthcare and to the ever increasing wish to integrate clinicalcare between the community and hospital based settings.

It aims to bring awareness of the issues to be addressed inachieving integration and outlines practical solutions. The mate-rial presented is part of an evolving research and clinical pro-gramme, using the collaborative resources made availablethrough the NHS and University partnerships to enhance patientcare and to develop clinical research.

The technology is constantly evolving in line with develop-ments in electronic record systems and the impetus to breakdown barriers in healthcare. Work towards stand alone and web-enabled systems will ensure that the trials database described inthis paper will continue to meet the needs of clinicians andresearchers.

The system has proved highly suitable for the clinic environ-ment and its portability is ideal for community based research orresearch including visits to environments remote from the Uni-versity and Hospital bases, such as patients’ homes. Futuredevelopments are planned to build on this framework to enhancecompatibility with other systems and confidential data exchangeas part of multi-centre studies.

Conflict of interest statement

Our involvement in this study was as noted. Colin Johnston,Geoff Hall and Michael Leahy, as inventors of the PPM systemmay have a commercial interest should it be adopted more widelyin healthcare. The other authors confirm that we have no conflictof interest arising from this paper.

Acknowledgements

The authors wish to acknowledge the support of the Psycho-social Oncology and Clinical Practice Research Group through aCancer Research UK Programme Award and support for the Headand Neck Cancer study from the British Association of Oral &Maxillofacial Surgeons and the Charitable Trustees of the LeedsTeaching Hospitals NHS Trust, the THOR (Translational Headand Neck Oncology Research) Group, University of Leeds, theclinicians and the patients.

A.C. Newsham et al. / Computers in Biology and Medicine 41 (2011) 575–586 585

The sponsor for the clinical study is the University of Leeds, UK.The study was conducted according to the standards of the GoodClinical Practice guidelines and was approved by a UK Research EthicsCommittee (Leeds West REC ref 05/Q1205/26). Neither the sponsornor the REC had any direct input into the study design or conduct norinvolvement in this submission for which responsibility lies with theresearch team as represented by the authors of this paper.

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Alexander C. Newsham, has over eleven years’ worth of experience as a DataManager, Programmer and Database Developer. Having previously worked as aClinical Data Scientist and Clinical Data Management Team Leader in the Pharma-ceutical industry, Alex has spent the last five years working in various fields ofcancer research. His current position as the CR-UK Senior Data Manager andDatabase Developer at the Cancer Medicine Research Unit, CR-UK Clinical Centrein Leeds, involves developing systems and providing data and programmingsolutions for a wide range of academic and translational oncology research activitiesas well as contributing to departmental research papers. Immediately prior to histime at Leeds, Alex held a similar role with Professor Leslie Fallowfield’s Psycho-social Oncology Group at the University of Sussex. He was awarded an MA withdistinction from Birkbeck College, University of London, in 2000.

Colin Johnston, has been the driver for the development of the PPM system.A statistician by background, he has been aware of the potential for electronicrecords to revolutionise health care and health research. Working with clinical

colleagues in the Section of Oncology at the University of Leeds and with the LeedsTeaching Hospitals NHS Trust, he has been primarily responsible for the creationof the electronic records system which now forms the core of oncology care in thehospital and which links seamlessly to the partner and University based clinicaltrials system as described in this paper.

Geoff Hall, is a Senior Lecturer in Medical Oncology at the University of Leeds.He received his medical degree from the University of Sheffield in 1990, a Ph.D.from the University of Leeds in 1993 and completed specialist training in MedicalOncology in 2001. As an Honorary Consultant at the St James’s Institute ofOncology, Leeds, his clinical practice focuses on the care of women withgynaecological malignancies and is part of an academic research group assessingthe efficacy of targeted therapy in gynaecological malignancies. Since startingwork in oncology, he has had a particular interest in the use of Informatics toenhance patient care. He is now the Clinical Lead and Chair of the PPM SeniorManagement Board and helps guide the overall development and delivery of thiscomprehensive clinical database/electronic patient record which collates informa-tion on all cancer patients treated within St James’s Institute of Oncology andassociated cancer units across the Yorkshire Cancer network. He has recently beenappointed as the Lead Clinician for Cancer at the Leeds Teaching Hospitals Trust.

Michael Leahy, is a full time medical oncologist in sarcoma, germ cell cancer andteenagers and young adults with cancer. He trained in London and Manchesterand was appointed as Senior Lecturer/Consultant in Medical Oncology in Leedsbetween 1998 and 2005 and is now working at The Christie in Manchester. He hasno academic qualification in IT but has been involved in database design andmanagement with particular reference to clinical data since medical school andhas attended a number of relevant training courses. He has used these skills tosupport his clinical and research practice throughout his career.

Adam B. Smith, previously worked for the CR-UK Psychosocial and ClinicalPractice Research Group at Leeds for over ten years where he was involved inthe original design and development of the touch-screen computer systems forcollecting quality of life information from patients and more recently as a lecturerin quantitative methods at the Leeds Institute for Health Sciences. His mainresearch interest lies in the application of modern psychometric methods such asRasch and Item-response Models to health data. Adam’s research has focused ondeveloping and assessing computer-assisted questionnaires to measure and assessquality-of-life and psychological well-being. His recent work has involved thedevelopment of item banks and computer-adaptive tests for screening forpsychological distress.

Aditya Vikram, is a dentist by clinical discipline whose research interests focus onQuality of Life in Head and Neck Cancer patients. He holds a PostgraduateQualification (MFD) from the Royal College of Surgeons in Ireland. He has aninterest in Head and Neck cancer and has worked as a clinician in Oral &Maxillofacial Surgery. He has clinical experience as a Senior House Officer in Oral& Maxillofacial Surgery in a number of UK hospitals, giving insight into the care ofHead and Neck cancer patients. His recent post was Research Assistant in theUniversity of Leeds working towards the development of a ‘Patient specificQuestionnaire for Head and Neck Cancer patients’.

Aine M. Donnelly, was a Research Assistant in the Psychosocial Oncology Group atthe University of Leeds. Her role involved managing data collection and the day-to-day management of research looking at Quality of Life assessment as part ofroutine care in Head and Neck cancer patients. She was awarded a Masters Degreein Health Psychology from the University of Bath where she conducted researchinvestigating Quality of Life in Heart and Lung transplant candidates.

Galina Velikova, Professor Velikova obtained her medical degree from the MedicalInstitute, Varna, Bulgaria in 1986 and a specialty degree in Internal Medicine inBulgaria in 1994. She completed specialist training in Medical Oncology in UK in2001. She obtained a PhD from the University of Leeds 2001 for a research degreeproject ‘‘Quality of life measurement in daily oncology practice’’. Prof Velikovaleads a research group funded by a Cancer Research UK programme grant in

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psycho-social oncology to study the implementation of routine measurement ofpatient-reported outcomes and quality of life in oncology practice. She is aConsultant in Medical Oncology and a Senior Lecturer at the University of Leeds.Her clinical work focuses on systemic treatment of breast cancer patients. Sheleads the quality of life sub-studies of large national trials in breast cancer. ProfVelikova is chair of British Psychosocial Oncology Society (BPOS) and a member ofUK National Cancer Research Institute Psychosocial Oncology Study Group. She ischair of EORTC Quality of Life Group and Board member of International Society ofQuality of Life research.

Peter J. Selby, was, until 2010, Joint Director of the National Institute for HealthResearch Clinical Research Network with Professor Janet Darbyshire. Peter isProfessor of Cancer Medicine, Director of the Leeds Institute of Molecular Medicineand a Consultant Physician at St James’s University Hospital. Before taking up thatpost he was at the Royal Marsden Hospital and Institute of Cancer Research inLondon and the Ontario Cancer Institute, Toronto. His research interests includebiomarkers and biological therapy and clinical trials and his clinical work is

mainly with urological cancer patients. Peter was formerly the Director of theNational Cancer Research Network and is President of the Association of CancerPhysicians.

Sheila E. Fisher, is Associate Director for Patient and Public Involvement at theNational Cancer Research Institute and National Cancer Research Network andClinical Research Fellow, University of Leeds. Her surgical practice centred on thecare of patients with head and neck cancer and facial trauma and she wasappointed Consultant Maxillofacial Surgeon to the University Hospital, Notting-ham in 1992. In 2000 she moved to the University of Leeds as Senior Lecturer/HonConsultant in Maxillofacial Surgery, where her research interests include newdiagnostic and therapeutic interventions in the care of patients with head andneck cancer and assessment of quality of life as part of routine care. She holds aSenior Research Fellowship at the University of Bradford. She has been a memberof a number of Department of Health strategy groups for H&N Cancer care and amember of the National Cancer Research Institute (NCRI) H&N Clinical StudiesGroup and Chair of the Survivorship subgroup.