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Developing a Dementia Research Registry: a descriptive case study from North Thames DeNDRoN and the EVIDEM programme

Developing a Dementia Research Registry: a descriptive case study from North Thames DeNDRoN and... Aim: To describe the development of a dementia research registry, outlining the conceptual, practical and ethical challenges, and to report initial experiences of recruiting people with dementia to it from primary and secondary care. Background: Women, the oldest old and ethnic minorities have been under-represented in clinical trials in dementia. Such under-representation biases estimates of absolute effect, absolute harm and cost-effectiveness. Research on dementia should include patient populations that more exactly reflect the population at risk. One of the impediments to this is the lack of a suitable tool for identification of patients suitable for studies. Construction & contents: A technology development methodology was used to develop a registry of people with dementia and their carers. This involved phases of modelling and prototype creation, ‘bench testing’ the prototype with experts and then ‘field testing’ the refined prototype in exemplar sites. The evaluation of the field testing described here is based on a case study methodology. Utility: This case study suggests that construction and population of a dementia research registry is feasible, but initial development is complex because of the ethical and organisational difficulties. Recruitment from primary care is particularly costly in terms of staff time and only identifies a very small number of people with dementia who were not already known to specialist services. Recruiting people with dementia through secondary care is a resource intensive process that takes up to six months to complete. Identifying the components of a minimum dataset was easy but its usefulness for pre-screening potential research populations has yet to be established. Acceptance rates are very high in the first clinic to recruit to the registry, but this may reflect the efforts of registry ‘champions’. Discussion and Conclusions: Easier recruitment may perpetuate potential selection biases and we are not yet able to assess the representativeness of the research-ready population recruited to the registry. The need to recruit from wider populations, through primary and social care, remains. The success of this registry will be measured by the proportion of people from it who are recruited to research projects, and its impact on overall accrual to studies. Background points in the illness trajectory, from diagnosis through UK government policy is to maintain people with to end of life care [2]. Further research is required to dementia syndromes in their own homes for as long as address the obstacles to the timely recognition of possible [1]. However, the needs of people with demen- dementia syndromes in primary care [3], the support for tia and their carers’ are inadequately addressed at all key people with dementia and their families after diagnosis, carer strain, what factors predict the transfer of people with dementia syndromes to institutional care, interven- * Correspondence: [email protected] 1 tions to manage incontinence and challenging symptoms Research Department of Primary Care & Population Health, University College London, Royal Free campus, Rowland Hill St., London NW3 2PF, UK [4] and the therapeutic options available to clinicians Full list of author information is available at the end of the article © 2011 Iliffe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 2 of 10 http://www.biomedcentral.com/1471-2288/11/9 which are currently sparse and insufficiently evaluated 2. Building on the research strengths already present [5]. in the UK as well as increasing general research capacity There are some treatments for people with Alzhei- in the field of dementia and neurodegeneration. mer’s disease shown in trials to be effective in modifying 3. Promoting collaboration between patients, carers, symptoms [6] and emerging therapies will need rigorous researchers, clinicians, academics, NHS Trusts, funders evaluation in large-scale trials. The next target for che- and industry, to enhance sharing of resources and motherapeutic approaches in Alzheimer’s disease is the expertise. development of disease-modifying drugs, but the design One of the impediments in accomplishing clinical trials for the treatment of dementia is the lack of a sui- of these trials raises many questions. Which populations should be studied, for how long and with which princi- table tool that would facilitate identification of patients pal and secondary endpoints? [7]. who might be recruited for studies. Registries for These questions may be difficult to answer. Difficulties patients with Motor Neurone disease and Huntington’s in ensuring that samples are representative have meant disease have been long established but to date there is that people with dementia included in clinical research no equivalent registry for such a large patient group, have been systematically younger than the general popu- those with dementia syndrome and earlier clinical, cog- lation of people with dementia and that women, the nitive manifestations of neurodegenerative disease in the oldest old and ethnic minorities have been under- UK. The problems of recruiting the appropriate popula- represented. Such under-representation may not always tions to trials prompted the DeNDRoN to test the con- affect the external validity of relative effect estimates, but cept of a research registry of people with dementia and measures of absolute effectiveness, absolute harm and cognitive impairment (presumed secondary to neurode- cost-effectiveness are associated with underlying risk generation) who would express an interest in participat- levels in different socio-demographic groups and current ing in dementia and cognitive impairment research in under-representation will bias absolute effect estimates general, rather than specific studies. [8]. Research on dementia could gain much from the study of patient populations that more appropriately Research registries reflect the population at risk [9]. This age differential is There is now considerable experience of developing significant given the potential delays in dementia diagno- research registries, particularly in North America. Many sis, progression of dementia and diminishing capacity to registries have been developed to facilitate epidemiological give informed consent to participate in a study. studies [12] but can also offer an organized and systematic Primary care-led studies could in theory address these way to maintain contact with participants from previous methodological problems because of the heterogeneity research and recruit an even more diverse pool of subjects of the community population and given the growing interested in participating in future studies [13]. expertise in trial design and implementation, but in However, there are difficulties in developing research practice we know from recent trials that recruitment to registries. Registries have been used in dementia studies on dementia through general practice is proble- research, to study the clinical expression of Alzheimer’s matic [10,11]. disease [14] and to improve the flow of information in order to increase research participation [15]. The US Promoting dementia research Consortium to Establish a Registry for Alzheimer’sdis- These difficulties in recruitment to dementia research ease (CERAD) [16] has functioned as a vehicle for a prompted the National Institute of Health Research to wide range of studies and as a mechanism for develop- establish the Dementia and Neurodegenerative Research ing and testing dementia-specific instruments. In 2008 Network (DeNDRoN). The Dementia and Neurodegen- the Leon Thal Symposium proposed the development of erative Research Network aims to improve the speed, a US National Registry and Database to meet the multi- quality, and integration of research in dementias and ple needs of the research field, including the develop- other neurodegenerative diseases, resulting in improve- ment of a a research programme on prevention [17]. ments in prevention, diagnosis, treatment and care for Similarly, the European Alzheimer’s Disease Consortium patients. DeNDRoN facilitates the development, conduct in 2010 proposed the construction of international and delivery of clinical trials and other well-designed research registries for studies of familial Alzheimer’s dis- studies by: ease and for therapeutic trials [18]. 1. Coordinating focused, effective investment in Whilst registries based on routinely collected data can National Health Service (NHS) research infrastructure offer opportunities for research they pose problems of to ensure that quality research, funded by both commer- data organisation and accuracy for researchers [19]. Pro- cial and non-commercial organizations, becomes spective collection of additional data requires organised outreach from the Registry to patients, providers and staff, embedded in clinical practice. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 3 of 10 http://www.biomedcentral.com/1471-2288/11/9 integration of the registry into pre-existing clinical rou- Health Research also proposed to create a cohort of up to tines and addition of reminder systems to workstations 2000 people with dementia and their carers, as the basis [20]. Unique challenges in recruiting and retaining partici- for recruiting individuals to studies on early diagnosis, con- pants with neurological disorders for research studies tinence management, management of behavioural and psy- include cognitive deficits in participants and the complex chological symptoms in dementia, end-of-life care and the ways in which many neurological conditions present [21]. application of new legislation about giving and obtaining The perceived advantages of a research registry were consent (the Mental Capacity Act 2005). that providing an opportunity for patients to show their interest in research could allow pre-screening of Registry design research- ready populations for different types of study, The development of the registry was based on a stan- allow more accurate assessments of study feasibility dard technology development methodology, originally (because the potential research population would be derived from the construction of decision support sys- known), and create the basis for cohort studies. This tems [24]. This involves phases of modelling and proto- paper describes a project to establish a dementia registry type creation, ‘bench testing’ and refining of the and reports initial experiences of recruiting people with prototype with experts and then ‘field testing’ of the dementia through primary and secondary care. refined prototype in exemplar sites. A co-design approach [25] was taken, bringing Construction and Contents together researchers (in the EVIDEM programme), Evaluation research network developers (in DeNDRoN) and people The evaluation of the field testing described here is with dementia and carers, through the Patient and Pub- based on a case study methodology. Case study methods lic Involvement arm of DeNDRoN. are appropriate when investigators desire or are forced The design team met on six occasions during 2008-9 by circumstances to define research topics broadly, to and held monthly teleconferences to review progress. cover contextual or complex multivariate conditions and The design team consisted of five members from the to rely on multiple sources of evidence [22]. The all- EVIDEM programme (SI, DL, GR, JW and KK) and two encompassing feature of a case study is its intense focus from North Thames DeNDRoN (CWR, LC) bringing on a single phenomenon within its real-life context [23]. together academic, clinical and research network exper- The research questions in this case study of the demen- tise. The design team developed a prototype registry, tia research registry are: ‘bench tested’ it with other experts in the field, and then 1) Is it feasible to develop and sustain a research regis- initiated recruitment to it, initially in one specialist pilot site but also in selected general practices. ter for people with dementia? 2) What are the actions and resources required to Expert advisors from the Centre for Health Infor- develop and implement a dementia research registry? matics at University College London were recruited to 3) What are the clinical data capture requirements for the design team to develop the electronic database for a dementia registry for the purpose of clinical trials the registry (AT, DK). The proposals for the registry recruitment? were discussed with DeNDRoN ’s patient and public 4) What are the likely recruitment rates to a dementia involvement working group (made up of DeNDRoN research registry? regional workers and members of third sector organisa- tions) and Forum (made up of people with neurodegen- Stakeholders erative diseases and their carers). DeNDRoN is funded by the UK National Institute of Health research (NIHR) and has specific objectives that Modelling, ‘bench testing’ and prototype development include increasing the number of principal investigators, The objectives agreed by the design team were: research sites and numbers of patients recruited to trials. North Thames DeNDRoN is one of the seven regional a) To identify people with dementia and their carers DeNDRoN networks and is a collaboration between through primary and secondary health care, social three universities [Imperial College London (ICL), Queen care, community care and voluntary sector organisa- Mary’s University of London (QMUL) and University tions in the North Thames DeNDRoN region. College London (UCL)] and 36 NHS Trusts covering b) To invite patients to join a research registry. all North London Boroughs plus areas of Essex, Hert- c) To gain consent for a minimum dataset of infor- fordshire and Bedfordshire (26 Acute Trusts, 10 Mental mation about patients to be held on the research Health Trusts). It is hosted by one NHS Trust. registry. The EVIDEM programme (Evidence-based Interventions d) To enable clinical research staff and registered in Dementia) funded by the English National Institute of research staff to search for patients relevant to a set Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 4 of 10 http://www.biomedcentral.com/1471-2288/11/9 of user-defined parameters, and then use that retrie- expert opinion about how best to explain the purpose of val set as the basis for making contact (through the the registry. Finally, the rigorous and well documented patients’ clinicians). consenting process that has to be followed as per the e) To enable the registry staff to maintain a list of granting of the ethics approval provides a clear and studies to which the patient has been invited, is auditable pathway from dissemination of information deciding about, has consented too or is participating regarding the registry through the information sheets in. for patients and carers, the assessment of capacity and f) To enable appropriate matching of registry mem- the storage of critical documents to defend against bers to research projects and further anonymised future challenges which may arise. analyses. It was also clear that recruitment of large numbers of g) To manage all such data securely, using role people with dementia and their carers would require based access and maintaining an audit log. Research Management and Governance approvals across multiple sites and sectors, and information management Recruitment to the Registry would occur in the geo- approvals for data storage. In addition, the team had to graphical area covered by the North Thames DeNDRoN. develop a minimum dataset and database, and devise Recruitment would occur through primary care, second- mechanisms for capturing data in primary and second- ary care, social care (e.g. care homes), community care ary care, and through other routes like care homes and (e.g. community nursing services, Admiral Nurses) and third sector organisations. third sector (voluntary) organisations (e.g. Alzheimer’s Society). Constructing the minimum dataset The target population was defined as people of any A minimum set was developed in three stages. In the age with any form of dementia residing in the commu- first stage written commentary on the secondary care nity or residential care within the defined geographical requirements of the dataset were gathered from the area. North Thames DeNDRoN’s executive board, supple- The inclusion criteria chosen were: People with either mented by individual discussions with researchers within a formal specialist (imaging/neuropsychological) or the local network. In the second stage face-to-face inter- informal generalist diagnosis of dementia as well as par- views with primary care clinicians were conducted to ticipants with cognitive impairment presumed secondary discuss the potential for using data from the General to an underlying neurodegenerative disease. The case Practice reimbursement mechanism (the ‘Quality & definition includes different types of dementia syndrome Outcomes Framework’) for dementia. In the third stage and people with dementia of differing severity (from members of North Thames DeNDRoN gave feedback on early to late dementia as well as the - much debated - the minimal dataset fields generated in the previous two Mild Cognitive Impairment). We agreed to include non stages and the dataset was refined based on this feed- ICD10-DSM-IV diagnoses, but the source and quality of back. Table 1 shows the contents and data fields of the the diagnosis would be a field within the registry to minimum dataset. allow prospective filtering to match the quality needs of We were aware that information recorded in notes later research projects. The exclusion criteria chosen would be variable across services and sites. This mini- were: 1) People who do not speak English for whom an mum dataset was based on data known to be routinely interpreter could not be located and 2) those whom collected in secondary care clinics assessing patients their clinician believed it would be inappropriate to with cognitive disorders and to a lesser extent in pri- approach, for specific reasons like receiving end-of-life mary care (for example, functional status data may not care, treatment for severe co-morbidity, or major beha- be routinely recorded in primary care notes). The design viour disturbance. group intended that the minimum dataset would evolve over time to be consistent amongst collaborating cen- Ethics committee approval tres, as far as pragmatically possible. Although the primary aim of the registry was to support research, the design team felt that it was essential to Confidentiality seek ethics committee approval, in part because dimin- A unique identifier is assigned to all participants on the ishing capacity to consent to participation in research is registry, so that data are held anonymously. A file link- a feature of dementia syndrome. In addition the Data ing name and unique identifier is stored separately and Protection Act requires that all patients who are identi- securely and in accordance with the Data Protection fied for research projects have given their consent to be Act. This will be held until the participant indicates that identified in this way, and the design team believed that s/he no longer wishes their data to be included on the an ethics committee would provide another layer of registry, and six monthly reviews will allow reaffirmation Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 5 of 10 http://www.biomedcentral.com/1471-2288/11/9 Table 1 The minimum dataset For all practices we will record Location (Primary Care Trust -PCT) Deprivation index score. For all clinics we will record Specialist Clinic location For other services we will record Location e.g. Nursing Home, Supported Accommodation, Elderly Mentally Infirm (EMI) home Key worker details For all participants in the registry the following information Demographic details (name, date of birth, gender, marital status, first language, (extracted from practice or clinic notes) is recorded where possible: ethnicity, address, postcode, housing status, National Health Service number) Carer information (name, date of birth, gender, address, postcode, relationship to person with dementia) Practice details (name, address) Specialist details (name, clinic details) Cognitive status (date of most recent test and score) Functional status (date of most recent test and score) Behavioural/Neuropsychiatric status Investigations (imaging and dates) Specific dementia medication Co-morbidity (e.g. depression, CVD, diabetes) History of participation in trials/studies of registry status. Six monthly reviews were chosen invitation of potential participants, judgement of capa- because of the relatively rapid health status changes that city, and obtaining both official permission and actual can occur in dementia syndrome. It is intended for the support from practitioners and administrators to recruit registry to be comprehensive and to be able to include through NHS services. all patients seen in the North Thames DeNDRoN region Identification of people with dementia from medical in order to be representative of the patient population. records complied with recommendations from the Patient Information Advisory Group (PIAG). These recommenda- Duplication tions allow only members of the patient’s usual clinical Information on whether the patient has been/or is cur- care team to pre-screen patient notes to identify those sui- rently participating in research studies will be included table for the registry. The lead clinician (or other member on the registry to avoid patients being approached for of the normal clinical team responsible for the patient’s care) would then make the first contact with the patients participation in multiple projects and registry managers will cross check key identifiers (name, date of birth, identified, either in a face-to-face meeting or by letter or NHS number) of potential new participants to ensure telephone. This contact would be only to inform the indi- that people and their carers are not approached vidual or their family about the registry; enrolment would repeatedly. usually take place separately from the clinical encounter in which the information about the registry was given. There Access are exceptions to this, as some people are keen to enrol National and regional researchers wanting to access the immediately rather than wait until their next appointment. Registry will need to approach North Thames DeNDRoN In cases where people feel they have had sufficient time to in the first instance. Prioritisation of studies within the consider their decision, their consent can be taken on the North Thames DeNDRoN portfolio by local researchers same day as they receive the information. Figure 1 shows is anticipated and access to the registry will reflect this the recruitment path and steps for an individual enrolled prioritisation. Governance of the Registry will be mana- through a memory clinic. This process is likely to vary ged through DeNDRoN’s national co-ordinating centre. slightly to reflect differing care pathways in different mem- ory clinic services. Utility Physical construction of the research registry and its use Judgement of Capacity at the first sites provided experience of the practical To ensure that people at all stages of the disease process problems involved in recruiting people with dementia to were able to join the registry required judgements about a research registry. These included identification and capacity. (This proved particularly difficult in primary Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 6 of 10 http://www.biomedcentral.com/1471-2288/11/9 care - see below). A recent analysis of ability to consent Recruitment in secondary care to research in a therapeutic trial of Gingko Biloba found Recruitment began in the first Mental Health Trust in approximately 70% of individuals with mild-moderate early March 2009, and three other Trusts began patient dementia could not give valid consent to research parti- recruitment in the next 12 months, with four more initi- cipation [26]. In the case of individuals who are not able ating involvement. Figure 2 shows the rates of invitation and recruitment to the registry, the numbers engaged to give informed consent, UK Medical Research Council through the registry in trials, over a one year period. and European Union-Good Clinical Practice guidelines Acceptance of the invitation was high, at over 90%, but and the principles of the UK Mental Capacity Act 2005 the rate of recruitment has been determined by the pat- were followed, and assent sought from a relevant con- sultee. This is also in accord with internationally tern of clinic attendances, with a gap of three to six accepted guidelines on research involving human sub- months between the invitation to join the registry and jects with dementia [27]. acceptance. Seeking Permissions Recruitment in primary care Research Management and Governance offices at each Tests of recruitment began with five practices that were NHS Trust were approached for permission to approach already part of the EVIDEM programme in autumn Trust staff and to engage them in the development of the 2009. Of 72 people with dementia identified from these database. Seeking multiple permissions across provider five general practices and sent information by post organisations in primary and secondary care proved to be about the research registry, three responded that they a lengthy process, taking up to five months. This process were not interested in research or finding out more and was not made easier by high staff turnover rates in the 18 respondedthattheywereinterestedand want to DeNDRoN research network itself and the time needed know more. Fifty one did not respond to the invitation. for training, Criminal Research Bureau checks and Amongst those expressing interest in the research reg- research passport applications for new study officers. The istry ten people were attending specialist clinics already steps required to engage a new clinical site as a recruit- working with the research registry, and their details ment site for the registry are summed up in Table 2. were passed onto the appropriate clinic. Three lived in Care Homes, and an assistant psychologist obtained the Recruitment of patients and carers to the research reg- carer’s agreement to gather data for one of them. She istry generated important lessons about sites of recruit- did not meet the patient to assess capacity, but both the ment, and about data governance. Clinician / delegate approaches patient in person Makes judgement of patient’s capacity to consent Interested: Not interested: Gives information sheets and consent Declined forms Consent forms can be signed on the day if (Option to phone local number & have patient/carer have had sufficient time to questions answered) consider the implications & have questions answered. Consented Patient Consent form and Carer Consent At next appointment – clinician / delegate form can be returned in the post asks if patient and carer want to consent. Answer any questions they have. Consented Want to sign: Consented Do not want to sign: Declined Figure 1 Recruiting patients and carers to the Dementia Registry. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 7 of 10 http://www.biomedcentral.com/1471-2288/11/9 Table 2 Getting a new specialist site to recruitment stage requires A principal investigator to act as champion for that site Local Research Management & Governance approval Resources for a local co-ordinator, who initially carries out and then coordinates data entry, acts as contact person for data queries and liaises with site staff about recruiting patients. To date the financial resources have come from different streams of research network funding. New staff may need to be recruited, or honorary contracts established for those already in other posts. Agreement from local IT departments who need to give new staff access to electronic databases, and to set up shared drives where none existed previously. The local information governance manager needs to be satisfied about data security. Service manager agreement to provide office space, promote the use of the registry to front line clinical staff, allow computer use and staff involvement in seeking consent, as well as facilitating best working practices for each site. Site team involvement in supporting the lead clinician in identification of patients to inform about the study GP and the Care Home manager judged that the resi- assistant psychologist was uncomfortable with home vis- dent lacked capacity for this decision. The data gathered its, so this individual’s expression of interest was not did not contain information about medication or MMSE pursued. score, and the psychologist extracting the data was Testing the process of recruitment in general practice unsure which of two documented diagnoses was correct. was undertaken by the EVIDEM team and in specialist For the other two individuals the assistant psychologist clinics by NT DeNDRoN, but responsibility for subse- had to meet with distant relatives as care home staff did quent six monthly follow-up and review did not clearly not feel able to give an opinion about participation in belong to either party and had to be decided through research. discussion. The situation was complicated by the organi- The assistant psychologist also arranged a meeting, at sation of research infrastructure in England, where three a hospital site, with two of the three who were not seen research networks may be involved in dementia in any other service. The remaining person not seen in research: DeNDRoN, the Primary Care Research net- any other service lived in an area distant from any ser- work (PCRN), which recruits general practitioners for vice that the psychologist could invite them to, and the research projects, and the Comprehensive Local Recruitment to the dementia registry PIS given out Patients Consented Patients + Carers Total Consented Patients Declined Date Figure 2 Recruitment to the registry 2009-2010. Number 31/03/2009 30/04/2009 31/05/2009 30/06/2009 31/07/2009 31/08/2009 30/09/2009 31/10/2009 30/11/2009 31/12/2009 31/01/2010 28/02/2010 31/03/2010 30/04/2010 31/05/2010 30/06/2010 31/07/2010 Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 8 of 10 http://www.biomedcentral.com/1471-2288/11/9 Research Network (CLRN), which funds the involve- and experience informs the process). However, early ment of practitioners in research work. These three investment of effort will ensure that not only will local types of network do not have the same boundaries, so clinical teams be invested in the process but it also trilateral negotiations were necessary in different geogra- ensures that data collected thereafter will be both accu- phical locations to allow the EVIDEM team to test rate and complete. The costs of developing and running recruitment to the registry through general practice. the registry are core service support costs and will therefore be borne by the NIHR Clinical Research Net- Data governance work. DeNDRoN proposes to fund the registry through existing funds, given the current financial climate, but A decision had to be made about who would ultimately hold and be responsible for the data collected in this it is also part of DeNDRoN ’s five year strategy way. The information sheets state that documents and (2010-2015) to develop a broad coalition to secure registry data would be stored by the registry team at appropriate funding arrangements for the registry in the North Thames DeNDRoN. However, North Thames longer term. DeNDRoN is not a legal entity. As such, documents and registry data are stored by West London Mental Health Clinical Data requirements Trust in accordance with agreements from North Identifying the components of a minimum dataset was Thames DeNDRoN for the prototype, and are only an early achievement of the design team, which is being accessible by the clinical and research staff within the tested as researchers begin to use the register to recruit involved NHS Trust’s boundaries. to studies. The effectiveness of the registry’s minimum dataset (as currently designed) as a device for pre- Discussion screening potential research populations has yet to be Feasibility established. The North Thames DeNDRoN dementia registry is a pioneering project in the United Kingdom. This case Recruitment study suggests that construction and population of a Acceptance rates are very high in the first clinic to dementia research registry is feasible, but that the initial recruit to the registry, but this may reflect the efforts of development is complex because of the ethical difficul- registry ‘champions’. We are monitoring recruitment in ties in dementia research and the organisational difficul- more recently recruited clinics where there may be less ties in embedding research projects in NHS clinical ownership and hence less commitment to registry devel- services. Recruitment from primary care has proved pro- opment; this will give us an estimate of the likely growth blematic; enrolment of patients is particularly costly in of a dementia research registry within usual NHS clini- terms of staff time especially given the very small num- cal practice. Easier recruitment may perpetuate potential ber of people with dementia identified who were not selection biases and we are not yet able to assess the already known to specialist services. The logistics of representativeness of the research-ready population recruitment in memory clinics was relatively easy to recruited to the registry; this is an issue that needs to be establish because of the concentration of patients and revisited in the next stages of registry development. The staff as well as the rigorous application of care pathways design team will need to reconsider ways of increasing into which the recruitment process can be embedded. recruitment through primary care, and through care Even then, given the timescale of clinic attendance and homes and social services, to offset biases inherent in the restrictions on obtaining informed consent, the clinic recruitment. recruitment process may take up to six months. Conclusions Resource issues We believe that the registry will assist in connecting Recruiting people with dementia to the registry through people with dementia and their carers with high quality secondary care is still a resource intensive process. research studies that will help us answer important Potential registry members need to be identified as sui- questions regarding the pathology, clinical pathways, table, informed about the registry, met again to obtain aetiology, experiences of and best treatments for neuro- consent and to capture information for the minimum degenerative disease. Only through careful scrutiny of dataset, and reviewed every six months to confirm their our processes in developing the registry and articulating continued interest and update their dataset. The preli- the problems faced will we deliver within the DeNDRoN minary steps in gaining the necessary permissions and research network a state-of-the-art recruitment tool. resources to establish the registry at a new site require The primary obstacle to the development of the regis- effort (a manager able to devote sufficient time) and up try has been the complexity of permission processes to five months of preparatory work (decreasing as time within the NHS, an experience noted by others [28]. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 9 of 10 http://www.biomedcentral.com/1471-2288/11/9 Funding. SI, JW, KK and DL were supported by the NIHR EVIDEM programme. This maychangeastheregistryis adoptedbyresearch EVIDEM has received financial support from the Department of Health sitesthatare notpartofthe designer group; therestaff National Institute for Health Research (DH/NIHR) Programme Grants for attitudes and clinical priorities may become more sali- Applied Research funding scheme. The views and opinions expressed here do not necessarily reflect those of the Department of Health or the NIHR. ent, as found in other registries [18]. A number of important characteristics of the registry are awaiting Author details evaluation, including the utility to researchers of the Research Department of Primary Care & Population Health, University College London, Royal Free campus, Rowland Hill St., London NW3 2PF, UK. minimum dataset, the representativeness of the popula- 2 3 West London Mental Health Trust, London, UK. Central & NW London NHS tion recruited to the registry and the cost per person Foundation Trust, London UK. Centre for Health Informatics and recruited to studies through the registry. Recruitment Multiprofessional Education University College London Holborn Union Building, Highgate Hill, London N19 5LW, London UK. West London NHS from sources other than specialist clinics needs further Mental Health Trust, London UK. investigation, to achieve a more representative popula- tion of research-ready people with dementia. Received: 21 October 2010 Accepted: 27 January 2011 Published: 27 January 2011 The success of this prototype will be measured by the proportion of people from the registry who participate in References research studies and the impact that the registry has on 1. Department of Health: National Dementia Strategy. HMSO London; 2009. overall accrual to portfolio studies. If these outcomes are 2. National Audit Office: Improving services and support for people with dementia. HMSO London; 2007. positive, and if recruitment to the registry becomes part of 3. Iliffe S, Robinson L, Brayne C, Goodman C, Rait G, Manthorpe J, Ashley P, for the activity of other research sites within North Thames, the DENDRON Primary Care Clinical Studies Group: Primary care & the methodology of the registry will be made available for dementia: 1 Diagnosis, screening and disclosure. Int J Geriatric Psychiatr 2009, 24(9):895-901. all local research networks within DeNDRoN. 4. Audit Commission: Forget me not 2002: Developing mental health services for older people in England. London: Audit Commission; 2002. Conflicts of interest 5. Warner JP, Butler RE, Wuntakal B: Dementia. In Clinical Evidence. Edited by: Tovey D. BMJ, London; 2006:. The authors declare that they have no competing 6. Burns A, O’Brien J, BAP Dementia Consensus group: Clinical practice with interests. anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol 2006, 20(6):732-55. 7. Vellas B, Andrieu S, Sampaio C, Wilcock G, European Task Force group: Contributions of authors Disease-modifying trials in Alzheimer’s disease: a European task force CR was one of original designers of the registry, contrib- consensus. Lancet Neurol 2007, 6(1):56-62. uted to protocol writing, and submission of ethics appli- 8. Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, Dieppe P: The causes and effects of socio-demographic exclusions from clinical cation, and is chair of the registry steering group. SI was trials. Health Technol Assess 2005, 9(38):iii-iv, ix-x, 1-152. one of original designers of the registry, contributed to 9. Schoenmaker N, Van Gool WA: The age gap between patients in clinical protocol writing and submission of the ethics applica- studies and in the general population: a pitfall for dementia research. Lancet Neurol 2004, 3(10):627-30, 2004 Oct;3(10):627-30. tion, and is CI for the EVIDEM programme. JW is a 10. Wilcock J, Bryans M, Turner S, Downs M, Iliffe S: Methodological problems in member of the registry steering group, piloted the mini- dementia research in primary care: a case study of a randomized mum dataset and recruitment of primary care practices, controlled trial. Primary Health Care Research & Development 2007, 8(01):12-21. 11. McCarney R, Warner J, Iliffe S, van Haselen R, Griffin M, van der Meulen J, is a member of NT Dendron steering group and also Fisher P: The Hawthorne effect: a randomised controlled trial. BMC Academic Research Manager for the EVIDEM pro- Research Methodology 2007, 7:30, (3 July 2007). gramme http://www.evidem.org.uk 12. Roos L, Nicol J: A research registry: Uses, development, and accuracy. Journal of Clinical Epidemiology 1999, 52:39-47. GR is a member of the EVIDEM cohort team, contrib- 13. Fitzgerald SG, Kelleher A, Teodorski E, Collins DM, Boninger M, Cooper RA: uted to protocol writing and the ethics application, and The development of a nationwide registry of wheelchair users. Disability is Primary Care Lead for North Thames DeNDRoN. DL & rehabilitation: Assistive technology 2007, 2(6):358-365. 14. Fritsch T, McClendon MJ, Smyth KA, Lerner AJ, Chen CH, Petot GJ, is the Trust-based project manager for EVIDEM, and Debanne SM, Soas A, Friedland RP: Effects of educational attainment on has contributed to the registry’s implementation. KK is the clinical expression of Alzheimer’s disease: Results from a research a member of the registry steering group and Academic registry. Am J Alzheimers Dis Other Demen 2001, 16(6):369-376. 15. Austrom MG, Bachman J, Altmeyer L, Gao S, Farlow M: A Collaborative Research Manager for the EVIDEM programme http:// Alzheimer Disease Research Exchange: Using a Community-based Helpline as www.evidem.org.uk. DKprovided IT support for the reg- aRecruitment Tool. Alzheimer Disease & Associated Disorders 2010, 24:S49-S53. istry’s development, as did AT. LC is the Dementia Reg- 16. The US Consortium to Establish a Registry for Alzheimer’s disease. [http://cerad.mc.duke.edu/], Accessed 20/6/2010. istry manager. 17. Katchachurian ZS, for Work Groups A & B of the Leon Thal Symposium All authors have read and approved the final 2008: A roadmap for the prevention of dementia II. Alzheimer’s& manuscript. Dementia 2009, 5:85-92. 18. Gauthier S, Garcia A, Sano M, Robert P, Senanarong V, Woodward M, Brodaty H: Priorities for research criteria in Alzheimer’s disease. Acknowledgements Alzheimer’s & Dementia 2010, 6:359-362. We would like to thank the primary care teams who helped with the 19. Roos LL, Mustard CA, Patrick NJ, Comm B, Mclerran DF, Malenka DJ, development of the minimum dataset and all those clinicians and other Young TK, Cohen MM: Registries and Administrative Data: Organization NHS staff who helped test recruitment to the registry. and Accuracy. Medical Care 1993, 31(3):201-212. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 10 of 10 http://www.biomedcentral.com/1471-2288/11/9 20. Bentley S, Melville J, Berry B, Katon W: Implementing a clinical and research registry in obstetrics: overcoming the barriers. General Hospital Psychiatry 2007, 29(3):192-8. 21. Newberry A, Sherwood P, Hricik A, Bradley S, Kuo J, Crago E, Hoffman LA, Given BA: Understanding Recruitment and Retention in Neurological Research. Journal of Neuroscience Nursing 2010, 42(1):47-57. 22. Yin RK: Applications of case study research. 2 edition. Sage, London; 2003, xi-xvii. 23. Yin RK: Enhancing the quality of case studies in health services research. Health Serv Res 1999, 34(5 Pt 2):1209-1224. 24. Wyatt J, Spiegelhalter D: Evaluating medical expert systems: what to test and how? Medical Informatics 1990, 15:205-217. 25. Kaulio M: Customer, consumer and user involvement in product development: a framework and a review of selected methods. Total Quality Management and Business Excellence 1998, 9(1):141-49. 26. McCarney R, Fisher P, Iliffe S, van Haselen R, Griffin M, van der Meulen J, Warner J: Gingko biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo- controlled trial. Int J Geriatr Psychiat 2008, 23(12):1222-30. 27. Brodaty H, Dresser R, Eisner M, Erkunjuntti T, Gauthier S, Graham N, Jonker C, Sachs G, Whitehouse P: Alzheimer’s Disease International and International Working Group for Harmonization of Dementia Drug Guidelines for research involving human subjects with dementia. Alz Dis Assoc Disord 1999, 13(2):71-9. 28. Rees M, Wells F: Falling research in the NHS. BMJ 2010. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2288/11/9/prepub doi:10.1186/1471-2288-11-9 Cite this article as: Iliffe et al.: Developing a Dementia Research Registry: a descriptive case study from North Thames DeNDRoN and the EVIDEM programme. BMC Medical Research Methodology 2011 11:9. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Medical Research Methodology Springer Journals

Developing a Dementia Research Registry: a descriptive case study from North Thames DeNDRoN and the EVIDEM programme

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Copyright © 2011 by Iliffe et al; licensee BioMed Central Ltd.
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Medicine & Public Health; Theory of Medicine/Bioethics; Statistical Theory and Methods; Statistics for Life Sciences, Medicine, Health Sciences
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Abstract

Aim: To describe the development of a dementia research registry, outlining the conceptual, practical and ethical challenges, and to report initial experiences of recruiting people with dementia to it from primary and secondary care. Background: Women, the oldest old and ethnic minorities have been under-represented in clinical trials in dementia. Such under-representation biases estimates of absolute effect, absolute harm and cost-effectiveness. Research on dementia should include patient populations that more exactly reflect the population at risk. One of the impediments to this is the lack of a suitable tool for identification of patients suitable for studies. Construction & contents: A technology development methodology was used to develop a registry of people with dementia and their carers. This involved phases of modelling and prototype creation, ‘bench testing’ the prototype with experts and then ‘field testing’ the refined prototype in exemplar sites. The evaluation of the field testing described here is based on a case study methodology. Utility: This case study suggests that construction and population of a dementia research registry is feasible, but initial development is complex because of the ethical and organisational difficulties. Recruitment from primary care is particularly costly in terms of staff time and only identifies a very small number of people with dementia who were not already known to specialist services. Recruiting people with dementia through secondary care is a resource intensive process that takes up to six months to complete. Identifying the components of a minimum dataset was easy but its usefulness for pre-screening potential research populations has yet to be established. Acceptance rates are very high in the first clinic to recruit to the registry, but this may reflect the efforts of registry ‘champions’. Discussion and Conclusions: Easier recruitment may perpetuate potential selection biases and we are not yet able to assess the representativeness of the research-ready population recruited to the registry. The need to recruit from wider populations, through primary and social care, remains. The success of this registry will be measured by the proportion of people from it who are recruited to research projects, and its impact on overall accrual to studies. Background points in the illness trajectory, from diagnosis through UK government policy is to maintain people with to end of life care [2]. Further research is required to dementia syndromes in their own homes for as long as address the obstacles to the timely recognition of possible [1]. However, the needs of people with demen- dementia syndromes in primary care [3], the support for tia and their carers’ are inadequately addressed at all key people with dementia and their families after diagnosis, carer strain, what factors predict the transfer of people with dementia syndromes to institutional care, interven- * Correspondence: [email protected] 1 tions to manage incontinence and challenging symptoms Research Department of Primary Care & Population Health, University College London, Royal Free campus, Rowland Hill St., London NW3 2PF, UK [4] and the therapeutic options available to clinicians Full list of author information is available at the end of the article © 2011 Iliffe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 2 of 10 http://www.biomedcentral.com/1471-2288/11/9 which are currently sparse and insufficiently evaluated 2. Building on the research strengths already present [5]. in the UK as well as increasing general research capacity There are some treatments for people with Alzhei- in the field of dementia and neurodegeneration. mer’s disease shown in trials to be effective in modifying 3. Promoting collaboration between patients, carers, symptoms [6] and emerging therapies will need rigorous researchers, clinicians, academics, NHS Trusts, funders evaluation in large-scale trials. The next target for che- and industry, to enhance sharing of resources and motherapeutic approaches in Alzheimer’s disease is the expertise. development of disease-modifying drugs, but the design One of the impediments in accomplishing clinical trials for the treatment of dementia is the lack of a sui- of these trials raises many questions. Which populations should be studied, for how long and with which princi- table tool that would facilitate identification of patients pal and secondary endpoints? [7]. who might be recruited for studies. Registries for These questions may be difficult to answer. Difficulties patients with Motor Neurone disease and Huntington’s in ensuring that samples are representative have meant disease have been long established but to date there is that people with dementia included in clinical research no equivalent registry for such a large patient group, have been systematically younger than the general popu- those with dementia syndrome and earlier clinical, cog- lation of people with dementia and that women, the nitive manifestations of neurodegenerative disease in the oldest old and ethnic minorities have been under- UK. The problems of recruiting the appropriate popula- represented. Such under-representation may not always tions to trials prompted the DeNDRoN to test the con- affect the external validity of relative effect estimates, but cept of a research registry of people with dementia and measures of absolute effectiveness, absolute harm and cognitive impairment (presumed secondary to neurode- cost-effectiveness are associated with underlying risk generation) who would express an interest in participat- levels in different socio-demographic groups and current ing in dementia and cognitive impairment research in under-representation will bias absolute effect estimates general, rather than specific studies. [8]. Research on dementia could gain much from the study of patient populations that more appropriately Research registries reflect the population at risk [9]. This age differential is There is now considerable experience of developing significant given the potential delays in dementia diagno- research registries, particularly in North America. Many sis, progression of dementia and diminishing capacity to registries have been developed to facilitate epidemiological give informed consent to participate in a study. studies [12] but can also offer an organized and systematic Primary care-led studies could in theory address these way to maintain contact with participants from previous methodological problems because of the heterogeneity research and recruit an even more diverse pool of subjects of the community population and given the growing interested in participating in future studies [13]. expertise in trial design and implementation, but in However, there are difficulties in developing research practice we know from recent trials that recruitment to registries. Registries have been used in dementia studies on dementia through general practice is proble- research, to study the clinical expression of Alzheimer’s matic [10,11]. disease [14] and to improve the flow of information in order to increase research participation [15]. The US Promoting dementia research Consortium to Establish a Registry for Alzheimer’sdis- These difficulties in recruitment to dementia research ease (CERAD) [16] has functioned as a vehicle for a prompted the National Institute of Health Research to wide range of studies and as a mechanism for develop- establish the Dementia and Neurodegenerative Research ing and testing dementia-specific instruments. In 2008 Network (DeNDRoN). The Dementia and Neurodegen- the Leon Thal Symposium proposed the development of erative Research Network aims to improve the speed, a US National Registry and Database to meet the multi- quality, and integration of research in dementias and ple needs of the research field, including the develop- other neurodegenerative diseases, resulting in improve- ment of a a research programme on prevention [17]. ments in prevention, diagnosis, treatment and care for Similarly, the European Alzheimer’s Disease Consortium patients. DeNDRoN facilitates the development, conduct in 2010 proposed the construction of international and delivery of clinical trials and other well-designed research registries for studies of familial Alzheimer’s dis- studies by: ease and for therapeutic trials [18]. 1. Coordinating focused, effective investment in Whilst registries based on routinely collected data can National Health Service (NHS) research infrastructure offer opportunities for research they pose problems of to ensure that quality research, funded by both commer- data organisation and accuracy for researchers [19]. Pro- cial and non-commercial organizations, becomes spective collection of additional data requires organised outreach from the Registry to patients, providers and staff, embedded in clinical practice. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 3 of 10 http://www.biomedcentral.com/1471-2288/11/9 integration of the registry into pre-existing clinical rou- Health Research also proposed to create a cohort of up to tines and addition of reminder systems to workstations 2000 people with dementia and their carers, as the basis [20]. Unique challenges in recruiting and retaining partici- for recruiting individuals to studies on early diagnosis, con- pants with neurological disorders for research studies tinence management, management of behavioural and psy- include cognitive deficits in participants and the complex chological symptoms in dementia, end-of-life care and the ways in which many neurological conditions present [21]. application of new legislation about giving and obtaining The perceived advantages of a research registry were consent (the Mental Capacity Act 2005). that providing an opportunity for patients to show their interest in research could allow pre-screening of Registry design research- ready populations for different types of study, The development of the registry was based on a stan- allow more accurate assessments of study feasibility dard technology development methodology, originally (because the potential research population would be derived from the construction of decision support sys- known), and create the basis for cohort studies. This tems [24]. This involves phases of modelling and proto- paper describes a project to establish a dementia registry type creation, ‘bench testing’ and refining of the and reports initial experiences of recruiting people with prototype with experts and then ‘field testing’ of the dementia through primary and secondary care. refined prototype in exemplar sites. A co-design approach [25] was taken, bringing Construction and Contents together researchers (in the EVIDEM programme), Evaluation research network developers (in DeNDRoN) and people The evaluation of the field testing described here is with dementia and carers, through the Patient and Pub- based on a case study methodology. Case study methods lic Involvement arm of DeNDRoN. are appropriate when investigators desire or are forced The design team met on six occasions during 2008-9 by circumstances to define research topics broadly, to and held monthly teleconferences to review progress. cover contextual or complex multivariate conditions and The design team consisted of five members from the to rely on multiple sources of evidence [22]. The all- EVIDEM programme (SI, DL, GR, JW and KK) and two encompassing feature of a case study is its intense focus from North Thames DeNDRoN (CWR, LC) bringing on a single phenomenon within its real-life context [23]. together academic, clinical and research network exper- The research questions in this case study of the demen- tise. The design team developed a prototype registry, tia research registry are: ‘bench tested’ it with other experts in the field, and then 1) Is it feasible to develop and sustain a research regis- initiated recruitment to it, initially in one specialist pilot site but also in selected general practices. ter for people with dementia? 2) What are the actions and resources required to Expert advisors from the Centre for Health Infor- develop and implement a dementia research registry? matics at University College London were recruited to 3) What are the clinical data capture requirements for the design team to develop the electronic database for a dementia registry for the purpose of clinical trials the registry (AT, DK). The proposals for the registry recruitment? were discussed with DeNDRoN ’s patient and public 4) What are the likely recruitment rates to a dementia involvement working group (made up of DeNDRoN research registry? regional workers and members of third sector organisa- tions) and Forum (made up of people with neurodegen- Stakeholders erative diseases and their carers). DeNDRoN is funded by the UK National Institute of Health research (NIHR) and has specific objectives that Modelling, ‘bench testing’ and prototype development include increasing the number of principal investigators, The objectives agreed by the design team were: research sites and numbers of patients recruited to trials. North Thames DeNDRoN is one of the seven regional a) To identify people with dementia and their carers DeNDRoN networks and is a collaboration between through primary and secondary health care, social three universities [Imperial College London (ICL), Queen care, community care and voluntary sector organisa- Mary’s University of London (QMUL) and University tions in the North Thames DeNDRoN region. College London (UCL)] and 36 NHS Trusts covering b) To invite patients to join a research registry. all North London Boroughs plus areas of Essex, Hert- c) To gain consent for a minimum dataset of infor- fordshire and Bedfordshire (26 Acute Trusts, 10 Mental mation about patients to be held on the research Health Trusts). It is hosted by one NHS Trust. registry. The EVIDEM programme (Evidence-based Interventions d) To enable clinical research staff and registered in Dementia) funded by the English National Institute of research staff to search for patients relevant to a set Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 4 of 10 http://www.biomedcentral.com/1471-2288/11/9 of user-defined parameters, and then use that retrie- expert opinion about how best to explain the purpose of val set as the basis for making contact (through the the registry. Finally, the rigorous and well documented patients’ clinicians). consenting process that has to be followed as per the e) To enable the registry staff to maintain a list of granting of the ethics approval provides a clear and studies to which the patient has been invited, is auditable pathway from dissemination of information deciding about, has consented too or is participating regarding the registry through the information sheets in. for patients and carers, the assessment of capacity and f) To enable appropriate matching of registry mem- the storage of critical documents to defend against bers to research projects and further anonymised future challenges which may arise. analyses. It was also clear that recruitment of large numbers of g) To manage all such data securely, using role people with dementia and their carers would require based access and maintaining an audit log. Research Management and Governance approvals across multiple sites and sectors, and information management Recruitment to the Registry would occur in the geo- approvals for data storage. In addition, the team had to graphical area covered by the North Thames DeNDRoN. develop a minimum dataset and database, and devise Recruitment would occur through primary care, second- mechanisms for capturing data in primary and second- ary care, social care (e.g. care homes), community care ary care, and through other routes like care homes and (e.g. community nursing services, Admiral Nurses) and third sector organisations. third sector (voluntary) organisations (e.g. Alzheimer’s Society). Constructing the minimum dataset The target population was defined as people of any A minimum set was developed in three stages. In the age with any form of dementia residing in the commu- first stage written commentary on the secondary care nity or residential care within the defined geographical requirements of the dataset were gathered from the area. North Thames DeNDRoN’s executive board, supple- The inclusion criteria chosen were: People with either mented by individual discussions with researchers within a formal specialist (imaging/neuropsychological) or the local network. In the second stage face-to-face inter- informal generalist diagnosis of dementia as well as par- views with primary care clinicians were conducted to ticipants with cognitive impairment presumed secondary discuss the potential for using data from the General to an underlying neurodegenerative disease. The case Practice reimbursement mechanism (the ‘Quality & definition includes different types of dementia syndrome Outcomes Framework’) for dementia. In the third stage and people with dementia of differing severity (from members of North Thames DeNDRoN gave feedback on early to late dementia as well as the - much debated - the minimal dataset fields generated in the previous two Mild Cognitive Impairment). We agreed to include non stages and the dataset was refined based on this feed- ICD10-DSM-IV diagnoses, but the source and quality of back. Table 1 shows the contents and data fields of the the diagnosis would be a field within the registry to minimum dataset. allow prospective filtering to match the quality needs of We were aware that information recorded in notes later research projects. The exclusion criteria chosen would be variable across services and sites. This mini- were: 1) People who do not speak English for whom an mum dataset was based on data known to be routinely interpreter could not be located and 2) those whom collected in secondary care clinics assessing patients their clinician believed it would be inappropriate to with cognitive disorders and to a lesser extent in pri- approach, for specific reasons like receiving end-of-life mary care (for example, functional status data may not care, treatment for severe co-morbidity, or major beha- be routinely recorded in primary care notes). The design viour disturbance. group intended that the minimum dataset would evolve over time to be consistent amongst collaborating cen- Ethics committee approval tres, as far as pragmatically possible. Although the primary aim of the registry was to support research, the design team felt that it was essential to Confidentiality seek ethics committee approval, in part because dimin- A unique identifier is assigned to all participants on the ishing capacity to consent to participation in research is registry, so that data are held anonymously. A file link- a feature of dementia syndrome. In addition the Data ing name and unique identifier is stored separately and Protection Act requires that all patients who are identi- securely and in accordance with the Data Protection fied for research projects have given their consent to be Act. This will be held until the participant indicates that identified in this way, and the design team believed that s/he no longer wishes their data to be included on the an ethics committee would provide another layer of registry, and six monthly reviews will allow reaffirmation Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 5 of 10 http://www.biomedcentral.com/1471-2288/11/9 Table 1 The minimum dataset For all practices we will record Location (Primary Care Trust -PCT) Deprivation index score. For all clinics we will record Specialist Clinic location For other services we will record Location e.g. Nursing Home, Supported Accommodation, Elderly Mentally Infirm (EMI) home Key worker details For all participants in the registry the following information Demographic details (name, date of birth, gender, marital status, first language, (extracted from practice or clinic notes) is recorded where possible: ethnicity, address, postcode, housing status, National Health Service number) Carer information (name, date of birth, gender, address, postcode, relationship to person with dementia) Practice details (name, address) Specialist details (name, clinic details) Cognitive status (date of most recent test and score) Functional status (date of most recent test and score) Behavioural/Neuropsychiatric status Investigations (imaging and dates) Specific dementia medication Co-morbidity (e.g. depression, CVD, diabetes) History of participation in trials/studies of registry status. Six monthly reviews were chosen invitation of potential participants, judgement of capa- because of the relatively rapid health status changes that city, and obtaining both official permission and actual can occur in dementia syndrome. It is intended for the support from practitioners and administrators to recruit registry to be comprehensive and to be able to include through NHS services. all patients seen in the North Thames DeNDRoN region Identification of people with dementia from medical in order to be representative of the patient population. records complied with recommendations from the Patient Information Advisory Group (PIAG). These recommenda- Duplication tions allow only members of the patient’s usual clinical Information on whether the patient has been/or is cur- care team to pre-screen patient notes to identify those sui- rently participating in research studies will be included table for the registry. The lead clinician (or other member on the registry to avoid patients being approached for of the normal clinical team responsible for the patient’s care) would then make the first contact with the patients participation in multiple projects and registry managers will cross check key identifiers (name, date of birth, identified, either in a face-to-face meeting or by letter or NHS number) of potential new participants to ensure telephone. This contact would be only to inform the indi- that people and their carers are not approached vidual or their family about the registry; enrolment would repeatedly. usually take place separately from the clinical encounter in which the information about the registry was given. There Access are exceptions to this, as some people are keen to enrol National and regional researchers wanting to access the immediately rather than wait until their next appointment. Registry will need to approach North Thames DeNDRoN In cases where people feel they have had sufficient time to in the first instance. Prioritisation of studies within the consider their decision, their consent can be taken on the North Thames DeNDRoN portfolio by local researchers same day as they receive the information. Figure 1 shows is anticipated and access to the registry will reflect this the recruitment path and steps for an individual enrolled prioritisation. Governance of the Registry will be mana- through a memory clinic. This process is likely to vary ged through DeNDRoN’s national co-ordinating centre. slightly to reflect differing care pathways in different mem- ory clinic services. Utility Physical construction of the research registry and its use Judgement of Capacity at the first sites provided experience of the practical To ensure that people at all stages of the disease process problems involved in recruiting people with dementia to were able to join the registry required judgements about a research registry. These included identification and capacity. (This proved particularly difficult in primary Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 6 of 10 http://www.biomedcentral.com/1471-2288/11/9 care - see below). A recent analysis of ability to consent Recruitment in secondary care to research in a therapeutic trial of Gingko Biloba found Recruitment began in the first Mental Health Trust in approximately 70% of individuals with mild-moderate early March 2009, and three other Trusts began patient dementia could not give valid consent to research parti- recruitment in the next 12 months, with four more initi- cipation [26]. In the case of individuals who are not able ating involvement. Figure 2 shows the rates of invitation and recruitment to the registry, the numbers engaged to give informed consent, UK Medical Research Council through the registry in trials, over a one year period. and European Union-Good Clinical Practice guidelines Acceptance of the invitation was high, at over 90%, but and the principles of the UK Mental Capacity Act 2005 the rate of recruitment has been determined by the pat- were followed, and assent sought from a relevant con- sultee. This is also in accord with internationally tern of clinic attendances, with a gap of three to six accepted guidelines on research involving human sub- months between the invitation to join the registry and jects with dementia [27]. acceptance. Seeking Permissions Recruitment in primary care Research Management and Governance offices at each Tests of recruitment began with five practices that were NHS Trust were approached for permission to approach already part of the EVIDEM programme in autumn Trust staff and to engage them in the development of the 2009. Of 72 people with dementia identified from these database. Seeking multiple permissions across provider five general practices and sent information by post organisations in primary and secondary care proved to be about the research registry, three responded that they a lengthy process, taking up to five months. This process were not interested in research or finding out more and was not made easier by high staff turnover rates in the 18 respondedthattheywereinterestedand want to DeNDRoN research network itself and the time needed know more. Fifty one did not respond to the invitation. for training, Criminal Research Bureau checks and Amongst those expressing interest in the research reg- research passport applications for new study officers. The istry ten people were attending specialist clinics already steps required to engage a new clinical site as a recruit- working with the research registry, and their details ment site for the registry are summed up in Table 2. were passed onto the appropriate clinic. Three lived in Care Homes, and an assistant psychologist obtained the Recruitment of patients and carers to the research reg- carer’s agreement to gather data for one of them. She istry generated important lessons about sites of recruit- did not meet the patient to assess capacity, but both the ment, and about data governance. Clinician / delegate approaches patient in person Makes judgement of patient’s capacity to consent Interested: Not interested: Gives information sheets and consent Declined forms Consent forms can be signed on the day if (Option to phone local number & have patient/carer have had sufficient time to questions answered) consider the implications & have questions answered. Consented Patient Consent form and Carer Consent At next appointment – clinician / delegate form can be returned in the post asks if patient and carer want to consent. Answer any questions they have. Consented Want to sign: Consented Do not want to sign: Declined Figure 1 Recruiting patients and carers to the Dementia Registry. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 7 of 10 http://www.biomedcentral.com/1471-2288/11/9 Table 2 Getting a new specialist site to recruitment stage requires A principal investigator to act as champion for that site Local Research Management & Governance approval Resources for a local co-ordinator, who initially carries out and then coordinates data entry, acts as contact person for data queries and liaises with site staff about recruiting patients. To date the financial resources have come from different streams of research network funding. New staff may need to be recruited, or honorary contracts established for those already in other posts. Agreement from local IT departments who need to give new staff access to electronic databases, and to set up shared drives where none existed previously. The local information governance manager needs to be satisfied about data security. Service manager agreement to provide office space, promote the use of the registry to front line clinical staff, allow computer use and staff involvement in seeking consent, as well as facilitating best working practices for each site. Site team involvement in supporting the lead clinician in identification of patients to inform about the study GP and the Care Home manager judged that the resi- assistant psychologist was uncomfortable with home vis- dent lacked capacity for this decision. The data gathered its, so this individual’s expression of interest was not did not contain information about medication or MMSE pursued. score, and the psychologist extracting the data was Testing the process of recruitment in general practice unsure which of two documented diagnoses was correct. was undertaken by the EVIDEM team and in specialist For the other two individuals the assistant psychologist clinics by NT DeNDRoN, but responsibility for subse- had to meet with distant relatives as care home staff did quent six monthly follow-up and review did not clearly not feel able to give an opinion about participation in belong to either party and had to be decided through research. discussion. The situation was complicated by the organi- The assistant psychologist also arranged a meeting, at sation of research infrastructure in England, where three a hospital site, with two of the three who were not seen research networks may be involved in dementia in any other service. The remaining person not seen in research: DeNDRoN, the Primary Care Research net- any other service lived in an area distant from any ser- work (PCRN), which recruits general practitioners for vice that the psychologist could invite them to, and the research projects, and the Comprehensive Local Recruitment to the dementia registry PIS given out Patients Consented Patients + Carers Total Consented Patients Declined Date Figure 2 Recruitment to the registry 2009-2010. Number 31/03/2009 30/04/2009 31/05/2009 30/06/2009 31/07/2009 31/08/2009 30/09/2009 31/10/2009 30/11/2009 31/12/2009 31/01/2010 28/02/2010 31/03/2010 30/04/2010 31/05/2010 30/06/2010 31/07/2010 Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 8 of 10 http://www.biomedcentral.com/1471-2288/11/9 Research Network (CLRN), which funds the involve- and experience informs the process). However, early ment of practitioners in research work. These three investment of effort will ensure that not only will local types of network do not have the same boundaries, so clinical teams be invested in the process but it also trilateral negotiations were necessary in different geogra- ensures that data collected thereafter will be both accu- phical locations to allow the EVIDEM team to test rate and complete. The costs of developing and running recruitment to the registry through general practice. the registry are core service support costs and will therefore be borne by the NIHR Clinical Research Net- Data governance work. DeNDRoN proposes to fund the registry through existing funds, given the current financial climate, but A decision had to be made about who would ultimately hold and be responsible for the data collected in this it is also part of DeNDRoN ’s five year strategy way. The information sheets state that documents and (2010-2015) to develop a broad coalition to secure registry data would be stored by the registry team at appropriate funding arrangements for the registry in the North Thames DeNDRoN. However, North Thames longer term. DeNDRoN is not a legal entity. As such, documents and registry data are stored by West London Mental Health Clinical Data requirements Trust in accordance with agreements from North Identifying the components of a minimum dataset was Thames DeNDRoN for the prototype, and are only an early achievement of the design team, which is being accessible by the clinical and research staff within the tested as researchers begin to use the register to recruit involved NHS Trust’s boundaries. to studies. The effectiveness of the registry’s minimum dataset (as currently designed) as a device for pre- Discussion screening potential research populations has yet to be Feasibility established. The North Thames DeNDRoN dementia registry is a pioneering project in the United Kingdom. This case Recruitment study suggests that construction and population of a Acceptance rates are very high in the first clinic to dementia research registry is feasible, but that the initial recruit to the registry, but this may reflect the efforts of development is complex because of the ethical difficul- registry ‘champions’. We are monitoring recruitment in ties in dementia research and the organisational difficul- more recently recruited clinics where there may be less ties in embedding research projects in NHS clinical ownership and hence less commitment to registry devel- services. Recruitment from primary care has proved pro- opment; this will give us an estimate of the likely growth blematic; enrolment of patients is particularly costly in of a dementia research registry within usual NHS clini- terms of staff time especially given the very small num- cal practice. Easier recruitment may perpetuate potential ber of people with dementia identified who were not selection biases and we are not yet able to assess the already known to specialist services. The logistics of representativeness of the research-ready population recruitment in memory clinics was relatively easy to recruited to the registry; this is an issue that needs to be establish because of the concentration of patients and revisited in the next stages of registry development. The staff as well as the rigorous application of care pathways design team will need to reconsider ways of increasing into which the recruitment process can be embedded. recruitment through primary care, and through care Even then, given the timescale of clinic attendance and homes and social services, to offset biases inherent in the restrictions on obtaining informed consent, the clinic recruitment. recruitment process may take up to six months. Conclusions Resource issues We believe that the registry will assist in connecting Recruiting people with dementia to the registry through people with dementia and their carers with high quality secondary care is still a resource intensive process. research studies that will help us answer important Potential registry members need to be identified as sui- questions regarding the pathology, clinical pathways, table, informed about the registry, met again to obtain aetiology, experiences of and best treatments for neuro- consent and to capture information for the minimum degenerative disease. Only through careful scrutiny of dataset, and reviewed every six months to confirm their our processes in developing the registry and articulating continued interest and update their dataset. The preli- the problems faced will we deliver within the DeNDRoN minary steps in gaining the necessary permissions and research network a state-of-the-art recruitment tool. resources to establish the registry at a new site require The primary obstacle to the development of the regis- effort (a manager able to devote sufficient time) and up try has been the complexity of permission processes to five months of preparatory work (decreasing as time within the NHS, an experience noted by others [28]. Iliffe et al. BMC Medical Research Methodology 2011, 11:9 Page 9 of 10 http://www.biomedcentral.com/1471-2288/11/9 Funding. SI, JW, KK and DL were supported by the NIHR EVIDEM programme. This maychangeastheregistryis adoptedbyresearch EVIDEM has received financial support from the Department of Health sitesthatare notpartofthe designer group; therestaff National Institute for Health Research (DH/NIHR) Programme Grants for attitudes and clinical priorities may become more sali- Applied Research funding scheme. The views and opinions expressed here do not necessarily reflect those of the Department of Health or the NIHR. ent, as found in other registries [18]. A number of important characteristics of the registry are awaiting Author details evaluation, including the utility to researchers of the Research Department of Primary Care & Population Health, University College London, Royal Free campus, Rowland Hill St., London NW3 2PF, UK. minimum dataset, the representativeness of the popula- 2 3 West London Mental Health Trust, London, UK. Central & NW London NHS tion recruited to the registry and the cost per person Foundation Trust, London UK. Centre for Health Informatics and recruited to studies through the registry. Recruitment Multiprofessional Education University College London Holborn Union Building, Highgate Hill, London N19 5LW, London UK. West London NHS from sources other than specialist clinics needs further Mental Health Trust, London UK. investigation, to achieve a more representative popula- tion of research-ready people with dementia. Received: 21 October 2010 Accepted: 27 January 2011 Published: 27 January 2011 The success of this prototype will be measured by the proportion of people from the registry who participate in References research studies and the impact that the registry has on 1. Department of Health: National Dementia Strategy. HMSO London; 2009. overall accrual to portfolio studies. If these outcomes are 2. National Audit Office: Improving services and support for people with dementia. HMSO London; 2007. positive, and if recruitment to the registry becomes part of 3. Iliffe S, Robinson L, Brayne C, Goodman C, Rait G, Manthorpe J, Ashley P, for the activity of other research sites within North Thames, the DENDRON Primary Care Clinical Studies Group: Primary care & the methodology of the registry will be made available for dementia: 1 Diagnosis, screening and disclosure. Int J Geriatric Psychiatr 2009, 24(9):895-901. all local research networks within DeNDRoN. 4. Audit Commission: Forget me not 2002: Developing mental health services for older people in England. London: Audit Commission; 2002. Conflicts of interest 5. Warner JP, Butler RE, Wuntakal B: Dementia. In Clinical Evidence. Edited by: Tovey D. BMJ, London; 2006:. The authors declare that they have no competing 6. Burns A, O’Brien J, BAP Dementia Consensus group: Clinical practice with interests. anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol 2006, 20(6):732-55. 7. Vellas B, Andrieu S, Sampaio C, Wilcock G, European Task Force group: Contributions of authors Disease-modifying trials in Alzheimer’s disease: a European task force CR was one of original designers of the registry, contrib- consensus. Lancet Neurol 2007, 6(1):56-62. uted to protocol writing, and submission of ethics appli- 8. Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, Dieppe P: The causes and effects of socio-demographic exclusions from clinical cation, and is chair of the registry steering group. SI was trials. Health Technol Assess 2005, 9(38):iii-iv, ix-x, 1-152. one of original designers of the registry, contributed to 9. Schoenmaker N, Van Gool WA: The age gap between patients in clinical protocol writing and submission of the ethics applica- studies and in the general population: a pitfall for dementia research. Lancet Neurol 2004, 3(10):627-30, 2004 Oct;3(10):627-30. tion, and is CI for the EVIDEM programme. JW is a 10. 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Rees M, Wells F: Falling research in the NHS. BMJ 2010. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2288/11/9/prepub doi:10.1186/1471-2288-11-9 Cite this article as: Iliffe et al.: Developing a Dementia Research Registry: a descriptive case study from North Thames DeNDRoN and the EVIDEM programme. BMC Medical Research Methodology 2011 11:9. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit

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Published: Jan 27, 2011

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