There will be four phases:
-
Phase 1: Identifying trials and establishing the Trialist Steering Committee (TSC)
-
Phase 2: Creating the repository, preparing data and pooling individual trial datasets
-
Phase 3: Analysis of pooled data to inform DACHA study objectives
-
Phase 4: Preparing for migration to Virtual Trials Archive and operation as VICHTA
Phase 1: Identifying trials and establishing the Trialist Steering Committee
To be included in the proposed repository, trials must meet the following eligibility criteria {10}:
-
Examination of any intervention conducted exclusively in an adult care home setting
-
Minimum dataset of 100 participants
-
Completed since 2010
-
Trial conducted in the UK {9}
-
Documented entry criteria
-
Documented participant consent or assent following Health Research Authority approved procedure
-
Monitoring procedures exist to validate data
Internationally, there is significant heterogeneity in the terminology used in practice and research to describe the settings in which long-term care is delivered [27, 28]. We have used the term ‘care home’ to describe care facilities that provide 24-h care to their residents, including those with and without on-site registered nursing staff.
Identifying trials
A scoping review identified potential care home trials for inclusion. As part of preparatory work, we contacted a small number of trialists who had completed RCTs in UK care homes to date. Based on provisional agreement from five of these trialists, we anticipate the repository will initially combine trial data for over 4200 residents from 250 care homes across the UK. Through an ongoing scoping review, we have identified a further thirteen potential trials, representing an additional 6000 residents from approximately 500 care homes. We anticipate this will increase further as the project develops, including the recruitment of international studies in the legacy dataset. Additional trials will be identified through an ongoing Google Scholar alert, systematically through concurrent reviews (Prospero: CRD42020155923), by contacting all trialists listed in the NIHR ‘Advancing Care’ Themed Review [10] (44 studies featured), the CLAHRC National Work stream Report [29] (32 studies featured), and snowballing techniques utilising the DACHA project management team, study steering committees and their professional networks.
Approaching/inviting trialists to share their data
We have created a database to track potentially eligible trials, where we will record how IPD are requested, collected and managed, and log of all contact with trialists. We will write to original trialists explaining the purpose of the repository and how it will operate. A reminder email will be sent 2 weeks after the initial contact if the trialist has not responded. If the trialist declines or does not respond, we will log this dataset as unavailable. Following a positive response, we will set up a meeting (phone, Zoom or face to face depending on trialist preference) to outline the project in more detail. If a trialist agrees to participate, they will be asked to sign a data transfer agreement that covers the transfer, use and storage of their trial data (see Terms of Reference, Appendix 1).
Establishing Trialist Steering Committee (TSC)
Contributing trialists will make up the TSC to oversee sharing, combining and repurposing of the pooled trial data. Whilst day-to-day co-ordination will be led by the DACHA co-ordinator at University of Hertfordshire (LI) and latterly the Virtual Trials Archive (MA), the TSC will agree on Terms of Reference for the collaboration, including the approval process for data requests, and will have the ultimate responsibility for all decisions regarding strategy, confidentiality, scientific matters and determining publication policy. This system mirrors the VTA, to which the care home repository will ultimately migrate.
The main role of the TSC during the DACHA-funded phase will be to provide advice on trial-specific details to aid with the pooling of datasets and better understanding of original data. Key information will be drawn from the original trial protocol, funders report and standard study documentation such as case report form templates and statistical analysis plans, but if any issues are not dealt with from those sources, we will seek clarification from the original trial team.
Phase 2: Creating repository, preparing data and pooling individual trial datasets
Contributing trial data to repository
Once an agreement has been made to contribute data, trial data managers (e.g. within clinical trials units (CTU)) will be engaged to prepare datasets. As standard practice with individual participant data sharing models [30], only completely anonymised data will be held in the repository, to minimise the risk of reidentification. We will request that all data received will be fully de-personalised (such as converting ‘date of birth’ to ‘age at randomisation’). Full instructions on de-identification and how to transfer securely will be provided if necessary.
Additional documents to support datasets will be requested, including the trial protocol and data dictionary. Optional supporting documents will include blank, annotated case report forms, statistical analysis plans, relevant published outputs or grey literature about the trial. We will request evidence of ethical approval and consent procedure (e.g. blank consent and/or assent forms).
Repository data storage
The Virtual Trials Archive team have developed a DACHA data contribution form [16] where trialists can record information about the trial and complete a data sharing agreement. Following this, the trial dataset and all accompanying files will be transferred in a zipped, password-protected folder to the University of Glasgow’s RCB, using the University of Glasgow’s File Transfer Protocol, where it will be held securely for the duration of the DACHA study and beyond. As it does for other VTA repositories, the RCB will act as an independent data host, providing common format and access mechanisms. All data will remain on their server and analysed through their secure analysis platform, in accordance with standard conventions for data sharing initiatives. During the development stage, access to the data will be restricted to the core team (LI, JB and MA), who have undergone necessary data protection and confidentiality training. At the end of the DACHA project, the VTA will act as custodians of the data under the terms of the data transfer agreement.
Data preparation and quality checks
When trial data are submitted to the repository, the DACHA co-ordinator (LI) at the University of Hertfordshire (UH) will access the server remotely via a secure virtual private network. A data checking analysis plan will be developed, outlining procedures and decision rules for data pooling, according to established principles [30]. We will query any anomalies, including checks for invalid, out-of-range or inconsistent items with the trialist (or their nominated study contact) to ensure that the data are represented accurately. Trials may use the same outcome measure but administer it differently. If a measure could be completed, e.g. face-to-face with a member of the research team, or as self-report or as proxy-response from care staff, we will ensure this data are coded in a standardised way. Decisions on the standardisation will be made by consensus decisions with the wider TSC or delegated groups, e.g. trial statisticians. Where possible, we will request all individual domain scores for outcome measures as opposed to the single, composite scores. All trial datasets will be cross-checked against their respective protocol and statistical analysis plan to confirm how each composite outcome was derived. If the scoring was modified, we will seek clarification from the respective trialists in the TSC for their advice and interpretation on whether the composite outcome data should be removed or amended to enable pooling with other trial datasets. We will record the number and timing of measurement points and ensure all time points are labelled consistently.
We anticipate there will be a strong opportunity for methodological research to look at groups of measures, e.g. cognitive assessments, to attempt mapping or potentially harmonising similar variables [31, 32]. We would encourage external researchers to look at this in the operational phase; however, in the development phase, we will not attempt to harmonise non-matched data.
We anticipate most RCTs with an economic evaluation component will use a variant of the Client Service Receipt Inventory (CSRI) [33] to record information on resource use and costs alongside the trial. We will request all health service use questionnaires used in the trials and look for differences which may potentially impact the findings. Due to differences in price years and interpretation of unit costs, we will focus on resource use (e.g. number of GP contacts) as opposed to costs (e.g. total cost of GP contacts over the follow-up period). We will request datasets to include missing values where possible and not the imputed values. In developing the repository, we will not perform any missing data imputation.
Database of trial summaries
We have collated aggregate data available in each trial (generated through protocol papers and funders reports) and will build on this database as new trials are published. A summary of available data will be published on the VTA website, allowing viewers to identify what outcome measures have been collected multiple times, how care home characteristics have been recorded and contextual aspects of each trial, e.g. sample size and follow-up points.
The repository will host trials with a range of clinical focus—it is therefore likely that some measures will be unique to single trials. However, a combination of several key outcome measures—e.g. Barthel, Mini-Mental State Examination (MMSE), European Quality of Life Scale (EQ 5D) and Quality of Life assessment in Dementia (DEMQoL) [34,35,36,37], is used in almost all RCTs conducted in care homes. Additionally, clinical indicators such as hospitalisations, falls and death rates are routinely reported (see Table 1 in Appendix 2: examples of data available from each trial.)
Phase 3: Analysis of pooled data to inform DACHA study objectives
When the initial set of trials has been added and variables prepared for pooling, we will temporarily lock the repository to allow two pre-specified analyses:
-
1.
Identification of key resident characteristics and outcomes from within the trial repository, which could be used to inform the development of a minimum dataset (MDS) for care homes
-
2.
Comparison of the pooled individual participant data with point estimates from administrative sources to assess the generalisability of RCT data
We will prepare a detailed research plan for each analysis, outlining the purpose of the request, objective/research question, plan for statistical analysis and repository variables requested. This research plan will then be circulated to the TSC for approval, as per future data requests from external analysts.
Informing development of a prototype minimum dataset (MDS) for care homes
Briefly, we will expand focus on what clinical, demographic and outcomes data from trials may be appropriate to include in a care homes MDS framework. We will categorise outcome measures into broad areas, e.g. cognition, anxiety and depression, pain, mobility, activities of daily living (ADLs) and specific clinical measures, and will focus on pre-specified outcome measures, in part identified through existing work on evidence reviews (PROSPERO CRD42020155923 and CRD42020171323). This identification and critique of relevant outcome measures within existing trials will help inform the development of a prototype MDS [26]. We will develop a quality assessment criterion to assess proposed outcome measures in terms of the following:
-
What has been measured—baseline, processes of care, outcomes
-
How data were collected (resident notes, researcher observation/assessment, use of routine data sources)
-
Completeness of the data and where data are incomplete, what is the nature of this (i.e. death, unavailable, withdrawn consent, unable to complete, unclear)
-
Where outcomes are measured across multiple studies, what are the range of values
-
Where outcomes are measured over time, what is their sensitivity to detect change
-
What information may be derived from collected data, e.g. comorbidity scoring based on medication usage
Generalisability of trial data
Briefly, we will conduct an evidence synthesis of key care home demographic information, by collating data from administrative sources, e.g. UK Census, Care Quality Commission. We will report baseline characteristics about care homes and residents as derived from all pooled trial data, tabulated for each individual trial and the pooled dataset. We will then compare point estimates from administrative sources with point estimates from the pooled IPD trial data, to evaluate how generalisable the repository data are, compared to alternative data sources.
Phase 4: Preparing migration to Virtual Trials Archive
The VICHTA repository will be a legacy output of the DACHA project—a valuable source of high-quality, anonymised IPD to inform the development of future research, testing of hypotheses and optimisation of study design issues. We took an early decision to store all trial data solely on the University of Glasgow secure server, where the VTA is also housed. This means the repository will already have a permanent ‘home’ when the DACHA study ends. Management of the repository will be transferred from the DACHA team at the University of Hertfordshire (LI, CG) to the VTA team at the University of Glasgow (principally the VTA co-ordinator, MA). The VTA will maintain and update the VICHTA repository, and manage requests to access its data, in conjunction with the existing TSC.
Following formal migration to the VTA, external researchers may apply for data extracts, by submitting a project proposal (for review and approval by the TSC) and agreeing to the predefined VTA data sharing terms and conditions (see Appendix 1). At the proposal stage, TSC members may declare an interest in joining the analysis team of a proposed project and take an active role, thereby meeting the ICMJE criteria for authorship. All completed analyses will be forwarded to the TSC before submission for presentation or publication for review (see the data processing flowchart). The TSC is acknowledged on all publications using ‘on behalf of VICHTA collaborators’ by-line. Active involvement from each TSC member is encouraged but not essential, as data request decisions will be made by a quorum (see Table 2 in Appendix 3: summary of development and operational phases).