Improving the safety and continuity of medicines management at care transitions (The ISCOMAT Programme) Work Packages 1 and 2

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. This Data Sharing Agreement permits Bradford Teaching Hospitals NHS Foundation Trust and the University of Leeds to continue to use NHS Digital data for a study to devise an underlying data linkage and data collection exercise to measure the effect of the intervention to better support people with heart failure manage their medication when they are discharge from hospital. This is part of the a programmer of work called "Improving the Safety and Continuity Of Medicines management at Transitions of care" (ISCOMAT). This study has received a favourable ethical opinion, is funded by the National Institute for Health Research (NIHR) and is performed by a public authority. Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated and destruction of the data will be required. Bradford Teaching Hospitals NHS Foundation Trust's and the University of Leeds' lawful bases for processing personal data and health data (defined as special category data) for the purposes of this project are: The following information provides background information on the purpose of the original study. No new data will be released under this version of the agreement, and this agreement allows the applicant to hold and not otherwise process, any further data that has already been disseminated. Article 6:1(e): Specific task in the ‘public interest’ or task that has a clear basis in law, and Improving the safety and continuity of medicines management at care transitions (ISCOMAT) is a series of interlinked work packages delivered by a multidisciplinary research collaboration between the Bradford Teaching Hospitals NHS Trust (BTHT) (as NHS lead and sponsor), the University of Bradford and University of Leeds. Each work package has designated lead(s) and is supported by researchers and collaborators from each of the organisations. Article 9:2(j): Special category data used for “Archiving in the public interest, scientific or historical research or statistical purposes”, with a basis in law. BTHT and the University of Leeds are acting as joint data controllers within this agreement. However, BTHT has overall responsibility for the delivery of the programme and delegates responsibilities to the University of Bradford and the University of Leeds in a collaborator agreement. Honorary contracts are in place between BTHT and the Chief Investigators for each of the work packages. Participants consented to have their personal data shared with NHS Digital, including personal details (initials, date of birth, postcode and NHS number) to be shared with NHS Digital for this project. The Chief Investigator for the work package related to this application is substantively employed by the University of Leeds, and has an honorary contract with BTHT. The Chief Investigator, consults with BTHT for all significant decisions in relation to the conduct of this work package, which includes information governance and data protection. The University of Bradford are not receiving any data as part of this application. The following information provides background information on the purpose of the study. No new data is required under this version of the Agreement. There has been a delay in analysis data held under this Agreement, as it was not possible to obtain data as intended from all intended sources, and scheduling of work during the COVID-19 pandemic. Improving the safety and continuity of medicines management at care transitions (ISCOMAT) is a series of interlinked work packages delivered by a multidisciplinary research collaboration between the Bradford Teaching Hospitals NHS Trust (BTHT) (as NHS lead and sponsor), the University of Bradford and University of Leeds. The programme is composed of four interlinked Work Packages. Each work package has designated lead(s) and is supported by researchers and collaborators from each of the organisations. Recruitment took place between 07/07/2016 and 14/03/2017-(53 participants). All participants in the cohort were included in the data linkage study, and a subset were also involved in the Patient Pathway study. These participants were involved in a study which involved interviews and data collection direct from the participants to obtain views about medicines when they leave hospital and again when back at home, and information on medicines once discharged from hospital. The objective of the programme is to look at and improve how patients with heart failure are supported with their medicines at points of NHS care transition (e.g. from hospital to home). Problems with medicines are common during such transitions, e.g. changes in medicines are not always followed through and doses are not always optimised adequately, both of which can lead to further health events. Patients with heart failure have been chosen for the programme as they are both an NHS priority and are particularly susceptible to medicine management problems, for a number of reasons including that they typically take multiple medicines. BTHT and the University of Leeds are acting as joint data controllers within this agreement. However, BTHT has overall responsibility for the delivery of the programme and delegates responsibilities to the University of Bradford and the University of Leeds in a collaborator agreement. Honorary contracts are in place between BTHT and the Chief Investigators for each of the work packages. The University of Bradford will not have access to any NHS Digital data other than aggregated data with small numbers suppressed. The Chief Investigator for the work package related to this application is substantively employed by the University of Leeds and has an honorary contract with BTHT for Work packages. The Chief Investigator consults with BTHT for all significant decisions in relation to the conduct of this work package, which includes information governance and data protection. The University of Bradford are not receiving any data under this Agreement and are not involved in any of the decisions relating to the processing of personal data held under this agreement. [4 paragraphs unchanged] 1. Map and evaluate current medicines management pathways across care transitions, describe the core characteristics of best practice and effective systems at each stage and compare with published evidence.(work evidence (work package 1a) [4 paragraphs unchanged] 6. Evaluate the effect and cost effectiveness of the intervention in a multi-centre cluster RCT (cRCT), in conjunction with a rigorous process evaluation. evaluation (work package 5) BACKGROUND-For Information only (brought forward from original application) This Agreement will facilitate objective 2 (data-linkage) which is a data linkage feasibility study and will construct the data linkage foundations for the cluster RCT (objective 6) (DARS-NIC-378185-P4L5Z). The day-to-day running of WP1a and WP1b is the responsibility of the programme manager employed by the University of Bradford. This includes co-coordinating the development of the research protocol, ethics submission and the identification of sites to identify, consent and recruit participants. The lead investigator for this work package 1 is based at the University of Leeds and the data linkage will be transferred, processed and analysed by researchers at the CTRU, University of Leeds. Accountability for decisions relating to WP1b sites with the Chief Investigator This agreement will facilitate objective 2 (data-linkage) which is a data linkage feasibility study and will construct the data linkage foundations for the cluster RCT (objective 6). A future application will be made to access data for objective 6 (multi-centre cluster RCT). The day-to-day running of WP1a and WP1b is the responsibility of the programme manager employed by the University of Bradford. This includes co-coordinating the development of the research protocol, ethics submission and the identification of sites to identify, consent and recruit participants. The lead investigator for this work package 1 is based at the University of Leeds and the data linkage will be transferred, processed and analysed by researchers at the CTRU, University of Leeds. The data linkage feasibility study recruited 53 patients from four hospitals. Patients were consented and recruited at the point of discharge from an in-hospital stay for heart failure, by a research nurse. The hospitals are Castle Hill Hospital in Hull, Leeds General Infirmary, Calderdale Royal Hospital and Royal Blackburn Hospital. The consent process included consent for information about their health conditions and prescribed medicines held by their hospital and GP to be accessed via the organisations (i.e. Data Providers) which hold this information, for example, NHS Digital, SystmOne, EMIS and the National Health Failure Audit (NICOR), along with community pharmacies. Data is processed, stored and analysed by the Clinical Trials Research Unit (CTRU) at the University of Leeds. No patient level data disseminated via NHS Digital under this Agreement will flow from CTRU to BTHT. The data linkage feasibility study recruited 53 patients from four hospitals. Patients were consented and recruited at the point of discharge from an in-hospital stay for heart failure, by a research nurse. The hospitals are Castle Hill Hospital in Hull, Leeds General Infirmary, Calderdale Royal Hospital and Royal Blackburn Hospital. The consent process included consent for information about their health conditions and prescribed medicines held by their hospital and GP to be accessed via the organisations (i.e. Data Providers) which hold this information, for example, NHS Digital, SystmOne, EMIS and the National Health Failure Audit (NICOR), along with community pharmacies. Data will be received, processed, stored and analysed by the by the Clinical Trials Research Unit (CTRU) at the University of Leeds. No patient level data disseminated via NHS Digital for this application will flow from CTRU to BTHT. The study team will use the data variables obtained from NHS Digital under this Agreement to inform the endpoints of the definitive cRCT (objective 6) to allow for assessment of the patient pathway and important co-morbidities and this will also allow for the study to meet the expectations of the participants who have agreed for their data to be processed and the requirements of the funder. Upon recruitment from four different hospitals the research nurse (or study research fellow) registered the patient with the CTRU and provided demographic details. Details about the patients study eligibility, admission and discharge medication were also recorded. Registration was via a secure online database at the CTRU. The data recorded at registration included patient’s name, date of birth, gender, NHS number and patient study ID. Beyond the analysis, to comply with Good Clinical Practice, the data will be securely archived to ensure it is possible to verify the conclusions published from this study. The study team have mapped the data variables available from each data provider onto the primary and secondary endpoints of the proposed definitive cRCT (objective 6) to allow for an accurate assessment of the patient pathway and important co-morbidities. This Agreement does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study. This will require the statisticians at the University of Leeds to re-run the previously analyses undertaken to verify that the published results were accurate. The primary endpoint for the definitive trial will be all-cause mortality + HF re-hospitalisation measured over 12 months from hospital discharge. The study team anticipate that the data required for this outcome will be obtained from HES and Civil Registration (Deaths) Data. The University of Leeds may not use the data to undertake different analyses to those undertaken during the original analysis, and this Agreement does not permit any onward sharing of the data with the exception that the data may be viewed for the purpose of an audit, for example by the sponsor or delegate, or verification of results. The key secondary endpoint is the number of patients prescribed the correct heart failure medications at 12 months post-discharge. The study anticipate that the data required for this outcome will be from NICOR, primary care and community outpatient pharmacy databases. Clinical and prognostic data such as diagnosis, comorbidities and discharge information, will be collected from the HES, NICOR, and primary care databases. If any further data processing is required in addition to the above purposes or if the data needs to be moved to a different location/organisation the applicant must submit an amendment request to NHS Digital before data is accessed. The findings of this data linkage study work package will inform the data variables required for the definitive cRCT and it is anticipated that a reduced dataset will be required for the subsequent DARS application for the cRCT. ISCOMAT is a NIHR Programme Grant for Applied Research (PGfAR) funded programme. It began in March 2016 and is scheduled to complete in 2022. The CTRU statisticians provided patient identifiers in line with the requirements of HES analysis Guide Requirements. This may include patients name, date of birth, gender, NHS number and patient study ID. The patient identifiers will be sent to NHS Digital for confirmation that there is a record for the patient in HES / Civil Registration (Deaths) data. NHS Digital will provide data extract to the CTRU. UPDATE The plan was for the above process to be performed with each of the Data Providers. However, data has only been successfully obtained from NHS Digital.

Processing activities

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. Clinical Trials Research Unit (CTRU) received patient identifiable data (including patient’s name, date of birth, gender, NHS number and patient study ID data) for each consenting participant from the participating site. The total number recruited was 53 participants. This data is processed by the trial data manager and statistician at the CTRU at the University of Leeds. Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated and destruction of the data will be required. The trial statistician provided NHS Digital with study ID, NHS number and date of birth for linkage to HES / Civil Registration (deaths) data. The NHS Digital have provided the linkage to HES APC, OP, A&E, CC and Civil Registration (Deaths) data for each study participant. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data)” Under this agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement. All transfer of data between the CTRU trial statistician and the NHS Digital took place via a secure file transfer system / secure data depot as agreed between the data provider and the data recipient. There will be no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement. Upon receipt of the data, data cleaning will be undertaken by CTRU statistician in accordance with internal Standard Operating Processes. This includes processes to ensure no duplicate episodes, no admission after date of death (if deceased). Additional data cleaning, analysis will be in accordance with a Statistical Analysis Plan. This will inform the derivation of endpoints of the definitive cRCT, and the extent to which NHS Digital data can be used to derive the primary and secondary outcomes of the cRCT. The CTRU statistician will also summarise the covariates that planned to be used in the analysis of the subsequent cRCT. The programmes developed as part of this work will be used to inform the analysis of the cRCT. BACKGROUND- For information only (brought forward from original application) CTRU received patient identifiable data (including patient’s name, date of birth, gender, NHS number and patient study ID data) for each consenting participant from the participating site. The total number recruited was 53 participants. This data is processed by the trial data manager and statistician at the CTRU at the University of Leeds. The trial statistician will provide NHS Digital with study ID, NHS number and date of birth for linkage to HES / Civil Registration (deaths) data. The NHS Digital will provide the linkage to HES APC, OP, A&E, CC and Civil Registration (Deaths) data for each study participant. All transfer of data between the CTRU trial statistician and the NHS Digital will take place via a secure file transfer system / secure data depot as agreed between the data provider and the data recipient. Upon receipt of the data, data cleaning will be undertaken by CTRU statistician in accordance with internal Standard Operating Processes. This includes processes to ensure no duplicate episodes, no admission after date of death (if deceased). Additional data cleaning, analysis and linkage across each dataset will be in accordance with a Statistical Analysis Plan. For this data linkage feasibility study, work will be undertaken to provide descriptive statistics which show the extent to which linkage was successful for each data source. No statistical modelling will be attempted. The study will summarise the extent to which can successfully obtain the primary and secondary outcomes of the cRCT. The CTRU statistician will also summarise the covariates that planned to be used in the analysis of the subsequent cRCT. Levels of missing data from will be summarised to demonstrate the acceptability of the data sources for the cRCT. It was anticipated that the study will be able to triangulate data from the various sources to produce a master patient record, and to report the agreement/disagreement between various data sources on common data items. However, this will not be possible as data has only been obtained from NHS Digital. [5 paragraphs unchanged] Update All organisations party to this Agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data)” The plan was for the CTRU trial statistician to subsequently link the HES / Civil Registration (Deaths) record level data to participant record level data from other primary care clinical systems (SystmOne and EMIS), a national cardiovascular specialist registry (National Institute of Cardiovascular Outcomes Research) and community pharmacy data. However, it was not possible to obtain data from these other data providers.Data will therefore only be linked to the ISCOMAT dataset held at the CTRU (consisting of the patient identifiers and details of patient’s study eligibility, admission and discharge medications). This will enable a data linkage algorithm to be developed for use in the main trial. The algorithm will not identify at the individual participants level, instead the outputs will identify the variables required to derive the primary endpoint, and key secondary endpoints as appropriate. There will be no data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement. For this data linkage feasibility study, work will be undertaken to provide descriptive statistics which show the extent to which linkage was successful for each data source. No statistical modelling will be attempted. The study will summarise the extent to which can successfully obtain the primary and secondary outcomes of the cRCT. The CTRU statistician will also summarise the covariates that planned to be used in the analysis of the subsequent cRCT. Levels of missing data from will be summarised to demonstrate the acceptability of the data sources for the cRCT. Data will only be accessed and processed by substantive employees of The University of Leeds and will not be accessed or processed by any other third parties not mentioned in this Agreement. It was anticipated that the study will be able to triangulate data from the various sources to produce a master patient record, and to report the agreement/disagreement between various data sources on common data items. However, this will not be possible as data has only been obtained from NHS Digital.

Expected output

BACKGROUND-For Information only (brought forward from original application) [1 paragraph unchanged] Pseudonymised HES and Civil Registration mortality data was supplied to the University of Leeds, by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study referred to as "Improving the safety and continuity of medicines management at care transitions ( The ISCOMAT Programme) Work Packages 1 and 2." The study team expect to have a data linkage algorithm by Q3 2021 and to publish this work in peer-reviewed journals (for example Health informatics) and present at relevant conferences to inform the wider research community on the lessons learned in data linkages (for example, 'Using electronic health records in clinical trials: rising to the challenge of developing a data linkage pipeline – experience from the ISCOMAT programme' was presented as an at the joint International Clinical Trials Methodology Conference / Society for Clinical Trials 2017 conference in Liverpool on May 7-10, 2017). This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. CTRU still intend to publish the work in a peer-reviewed journal, such as Health informatics. The output will also form part of the NIHR monograph. CTRU anticipate that outputs will be available in 2022, and the clinicians and hospital teams will be provided with an update and the trial website to share the study findings in various formats (e.g. lay summaries). The output of this work will also be useful to inform programming requirements for deriving outcomes assessed in the definitive clinical trial. Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated, and destruction of the data will be required. No further outputs of the data are permitted to be created under this version of the agreement. Outputs will only be permitted to be created once a new agreement that meets all of NHS Digital's legal, ethical and security requirements is in place. The below provides background on to what has already been produced, and what will be produced once data flow and permission to process resumes. ........................................................................................................... The study team expected to have a data linkage algorithm by the end of 2017 and to publish this work in peer-reviewed journals (for example Health informatics) and present at relevant conferences to inform the wider research community on the lessons learned in data linkages (for example, 'Using electronic health records in clinical trials: rising to the challenge of developing a data linkage pipeline – experience from the ISCOMAT programme' was presented as an at the joint International Clinical Trials Methodology Conference / Society for Clinical Trials 2017 conference in Liverpool on May 7-10, 2017). It has not been possible to obtain data from the other data providers (NICOR, SystmOne, EMIS). The plan is now to use the HES data obtained from NHS Digital only. CRTU still intend to publish the work in a peer-reviewed journal, such as Health informatics. The study will inform participants and involved clinicians and hospital teams and update the trial website to share the study findings in various formats (e.g. lay summaries).

Expected measurable benefits

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. No new data will be released under this version of the agreement, and this agreement allows the applicant to hold and not otherwise process any further data that has already been disseminated. The following information provides background information on the benefits of the original dissemination. Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated, and destruction of the data will be required. The benefit of this study is to understand the extent to which data from NHS Digital can be used to explore the intended and unintended outcomes of a transfer of care for people with heart failure. No further outputs of the data are permitted to be created under this version of the agreement. Outputs will only be permitted to be created once a new agreement that meets all of NHS Digital's legal, ethical and security requirements is in place. The following information provides background information on the benefits of the original dissemination. Pseudonymised HES and Civil Registration mortality data was supplied to the University of Leeds, by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study referred to as "Improving the safety and continuity of medicines management at care transitions ( The ISCOMAT Programme) Work Packages 1 and 2." ..................................................................................................................................... The benefit of this data linkage work is that it will allow the study to understand how linked data can be used to explore the intended and unintended outcomes of a transfer of care for people with heart failure. [1 paragraph unchanged] This It is expected that this work will allow the study to develop the capacity to understand how this linked data from NHS Digital can be used to measure important outcomes so that they can evaluate a co-designed intervention that improves patient care across a care transfer. The results of the data linkage work are expected to this study will inform the evaluation methods used in the definitive cRCT integrated care (Domain [45 words unchanged] for more effective optimisation of heart failure treatment, with associated health benefits. [1 paragraph unchanged]

Benefits reported

Delays have occurred in the access of data from other data sources (e.g. NICOR) and the organisation have has been unable to receive data direct from other data sources, Including NICOR and the primary care providers. Further delays incurred due to the COVID 19 pandemic and inability to continue to process the data. It is anticipated that the data linkage pipeline work this study will be complete by the end of 2020, March 2022 and will be based on data obtained directly from NHS Digital only.