MR756: Knee Arthroplasty Trial (KAT)

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

Datasets: + HES-ID to MPS-ID HES Admitted Patient Care

Objective for processing

[1 paragraph unchanged] Both Pfizer and Zimmer Biomet are mentioned as funders in the latest KAT Study protocol (version 8). These organisations are not listed as data controller or data processor in this Agreement as they do not make any decisions regarding the data collected, neither do they have access to any data or any outputs other than the aggregated results with small number suppressed. This project is funded by the NIHR Health Technology Assessment programme. Similarly, the The protocol names a Professor based at the University of Bristol as one [32 words unchanged] and will not make any decisions regarding the data under this Agreement. A Project Management Group was set up consisting of the principal grant [22 words unchanged] concerning the data collected and will not have access to either NHS Digital England data nor participant reported data. They will only have access to the [5 words unchanged] suppressed) following analysis and they are involved in dissemination of the results. [3 paragraphs unchanged] In total 1,704 participants are currently flagged on NHS Digital's England's system and as recruitment has ended the cohort will not be added to. Information on knee-related hospital re-admissions and further surgery is collected directly from [5 words unchanged] 3-months and 1-year post-randomisation and annually thereafter up to 20 years post-randomisation. Collection of outcome data on annual questionnaires is therefore ongoing and trial participants are between 17 and 20 years post-randomisation. In order to better evaluate these newer forms of arthroplasty, in terms [18 words unchanged] participant reported data will be supplemented with routinely collected information from NHS Digital England in England and Information Services Division (ISD) in Scotland. The data requested [13 words unchanged] basis and a one-off drop of HES Admitted Patient Care historic data. Eight Three years of HES Admitted Patient Care data are requested under this agreement. HES data has already been requested and supplied on two three previous occasions (2008 (2008, 2012 and 2012) and will be further requested until 2020). As all participants have reached 20 years now completed 20-years of follow-up. follow-up, no further requests are planned. For information, a A further one-off of HES data will also be has been requested again in 2023 towards the end of the study. However, this will be subject to a further application with NHS Digital. [1 paragraph unchanged] 1) Permission to retain the knee related hospital readmission data already provided by NHS Digital England in 2008 2008, 2012 and 2012. 2020. This permission will also extend to the death notifications previously received on [38 words unchanged] are kept for at least 5 years after a trial has ended. 2) Continuation of permission to use the NHS Digital’s patient tracking service to receive notifications on participants’ deaths. This will allow the KAT team to manage the process of sending postal questionnaires and to reduce the risk of causing distress by sending questionnaires to deceased participants. Under this Agreement the research team are requesting quarterly notifications of demographics data. The cohort identifiers are already held by NHS Digital, and latest demographics data will be provided to University of Aberdeen using the unique study ID and the date of birth. All other identifiers will not be returned to University of Aberdeen in order to minimise the amount of data requested as much as possible. 2) Permission to retain data previously received demographics data. No additional data is required. 3) Permission for NHS Digital England to link the KAT cohort to HES data and supply further knee-related hospital readmissions for the period 2011 2020 to March 2020. December 2022. The University of Aberdeen have supplied the identifying details of the participants to NHS Digital England to facilitate the data linkage exercise. The identifying details included NHS Number, [63 words unchanged] unspecified joint; Amputation; Other knee operations, and Other knee re-admissions (no operation). The data controllers have considered the moral and ethical issues raised by [17 words unchanged] All participants are aware that their details will be shared with NHS Digital England for data linkage purposes and the data controllers consider this to be [6 words unchanged] consent noting that participants can withdraw from the study at any point. [1 paragraph unchanged] • Confidential data is processed by the University of Aberdeen. The University of Aberdeen shares identifying data with NHS Digital England and receives identifying data from NHS Digital. England. This data is processed solely at the University of Aberdeen. [2 paragraphs unchanged] • There is a second clinical co-ordinator based at the University of [11 words unchanged] to the data. However, the University of Dundee has not met NHS Digital’s England’s requirements to be included as a data processor in this DSA and so access to this individual and organisation will be prohibited under this DSA. [1 paragraph unchanged] Quarterly cohort event notifications (informal date of death; formal date of death) is not being requested as part of this renewal application as direct participant contact is not required after 30/04/2022. Cause of death reports are not being requested in this renewal application and have not been requested or received since 2017.

Processing activities

1. Patient tracking service to receive notifications on participants’ death: 1. Knee-related hospital re-admissions: The University of Aberdeen have previously supplied will supply the participants' identifying details to NHS Digital (Name, NHS England (NHS Number, Date of Birth, Sex, Gender, Postcode and a Unique Participant ID) to allow NHS Digital England to flag link the cohort on its computer system. Quarterly Cohort Event notifications within to the study population have previously been supplied and under this Agreement, this service would be reactivated. Fact and date of death are required along with HES data. The linked HES data-set containing details of participants' exits further knee replacements or re-entries into the NHS in England or Wales. Data episodes relating to further knee complications will be returned containing supplied to the Unique Participant ID and supplied date University of birth. The date of birth field is requested in order to help researchers identify a participant more easily than using only Aberdeen, including the Unique Participant ID. The supplied file will be securely stored within the University of Aberdeen's storage servers inside the Edward Wright building. The data file supplied by NHS England will be securely stored in the University of Aberdeen’s storage servers. KAT researchers at the University of Aberdeen will then analyse the NHS England data to identify any knee related hospital re-admissions not already reported by the trial participants on their postal questionnaires. This new information will then be electronically captured and stored on the secure KAT trial database which already contains the participant reported outcomes. The KAT Trial database will be accessed by the University of Aberdeen. Access to this web-based application is controlled by user name and password and only those personnel identified by the Trial Manager as working on the KAT study will be allowed access to the website and appropriate data. The Aberdeen Business School data centre will be a primary network storage location. The data replicates constantly between the data centres and a file saved in the Edward Wright Building would replicate to the Aberdeen Business School seconds later. Although the Aberdeen Business School data centre is located within a Robert Gordon University building, the data centre itself is operated and maintained by a University of Aberdeen, Robert Gordon University and North East Scotland College partnership. No staff employed by Robert Gordon University and North East Scotland College will have access to the NHS Digital data. The death notification data is primarily used to manage the process of mailing out participant questionnaires (by the study team at the University of Aberdeen) to reduce the risk of causing distress by contacting deceased participants. 2. Knee-related hospital re-admissions: The University of Aberdeen will supply the participants' identifying details to NHS Digital (NHS Number, Date of Birth, Gender, Postcode and a Unique Participant ID) to allow NHS Digital to link the cohort to the HES data. The linked HES data-set containing details of further knee replacements or episodes relating to further knee complications will be supplied to the University of Aberdeen, including the Unique Participant ID. The data file supplied by NHS Digital will be securely stored in the University of Aberdeen’s storage servers. KAT researchers at the University of Aberdeen will then analyse the NHS Digital data to identify any knee related hospital re-admissions not already reported by the trial participants on their postal questionnaires. This new information will then be electronically captured and stored on the secure KAT trial database which already contains the participant reported outcomes. The KAT Trial database will be accessed by the University of Aberdeen. Access to this web-based application is controlled by user name and password and only those personnel identified by the Trial Manager as working on the KAT study will be allowed access to the website and appropriate data. [1 paragraph unchanged] Another clinical co-ordinator with the same role as the co-ordinator in Oxford is based at the University of Dundee. Under this Agreement, no access to NHS Digital England data may be granted to the University of Dundee or its employees. [1 paragraph unchanged] 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 - i.e. employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

[1 paragraph unchanged] Further follow-up of the KAT participants is therefore ongoing, and the ongoing. The intention is to analyse the data at two further time-points – once when all participants have reached 15 years of follow-up and when they have reached 20 years of follow-up. At follow-up, at which point both time-points a clinical effectiveness and cost-effectiveness analysis will be conducted. The primary outcome [30 words unchanged] and cost-effectiveness (the last three outcomes will include information provided by NHS Digital). The 15-year publication has not been released yet as the KAT clinical coordinator in Oxford is currently obtaining further information from the hospital where the knee-related readmission occurred. Once this further data has been analysed the 15 year publication can be released. Target date: Winter 2021 England). The findings will be submitted to peer reviewed journals and will be of great interest to the orthopaedic community, in terms of 1) the size of the trial, 2) the number of years of follow-up and 3) collection of participant reported and clinical (re-admissions/further surgery) outcomes. The outputs including both the clinical and cost-effectiveness analyses for the 15-year publication was published in 2020 and the date of the 20-year publication is expected in 2023. At the final time-point, a report will also be submitted to funder to be included in the NIHR Journals Library. Research conducted by the HTA programme serves a variety of stakeholders including decision-makers in local government, policy makers (including NICE), researchers, NHS health professionals, other NIHR stakeholders and the general public. These outputs are expected to be completed with the support of the final request of data for HES APC. Once data is received from NHS England a accurate completion of analysis date will be able to be established. The findings will be submitted to peer reviewed journals and will be of great interest to the orthopaedic community, in terms of 1) the size of the trial, 2) the number of years of follow-up and 3) collection of participant reported and clinical (re-admissions/further surgery) outcomes. The outputs include both the clinical and cost-effectiveness analyses of the 20-year follow-up data and is expected to be published in the summer of 2023. Research conducted by the HTA programme serves a variety of stakeholders including decision-makers in local government, policy makers (including NICE), researchers, NHS health professionals, other NIHR stakeholders and the general public. [10 paragraphs unchanged] The quarterly cohort event notifications will be used to mitigate the risk of attempting to contact participants who have died or are lost to follow up. The remaining participants can then receive questionnaires and future information about the study via newsletters. The primary benefit of receiving quarterly cohort event notifications was to reduce the risk of attempting to contact deceased study members thereby causing distress to living relatives. Quarterly cohort event notifications (informal date of death; formal date of death) is not being requested as part of this renewal application as direct participant contact is not required after 30/04/2022. Please note: cause of death reports are not being requested in this renewal application and have not been requested or received since 2017.

Expected measurable benefits

[3 paragraphs unchanged] The primary benefit of receiving quarterly cohort event notifications is that it will was to reduce the risk of attempting to contact deceased study members thereby causing distress to living relatives.

Benefits reported

[7 paragraphs unchanged] The work from KAT has therefore already influenced surgical practice as it [63 words unchanged] However, there were trends suggesting that there might be substantial differences at 15 20 years. It is therefore expected that the 15-year 20-year results will show differences which will have major implications for knee replacement. Additional benefits are expected to be realised for the 20 year point after the approval of this version (4.3) is approved.

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

Datasets: + MRIS - Cause of Death Report

Objective for processing

[1 paragraph unchanged] Both Pfizer and Zimmer Biomet are mentioned as funders in the latest KAT Study protocol (version 8). These organisation organisations are not listed as data controller or data processor in this Agreement [19 words unchanged] or any outputs other than the aggregated results with small number suppressed. [11 paragraphs unchanged] 2) Continuation of permission to use the NHS Digital’s patient tracking service [24 words unchanged] risk of causing distress by sending questionnaires to deceased participants. Under this agreement Agreement the research team are requesting quarterly notifications of mortality demographics data. The cohort identifiers are already held by NHS Digital, and latest death demographics data will be provided to University of Aberdeen using the unique study [18 words unchanged] order to minimise the amount of data requested as much as possible. 3) Permission for NHS Digital to link the KAT cohort to HES data and supply further knee-related hospital readmissions for the period 2011 to present. March 2020. The University of Aberdeen will supply have supplied the identifying details of the participants to NHS Digital to facilitate the data linkage exercise. The identifying details will include included NHS Number, Date of Birth, Sex, Postcode and a Unique Participant ID. The linked data to be returned will contain contains the Unique Study ID as the only identifier. The HES data will be is filtered to specific codes related to: Knee arthroplasty; Hybrid knee replacement; Knee [24 words unchanged] unspecified joint; Amputation; Other knee operations, and Other knee re-admissions (no operation). [1 paragraph unchanged] There are multiple types of processing involved in this Agreement: • Confidential data is processed by the University of Aberdeen. The University of Aberdeen shares identifying data with NHS Digital and receives identifying data from NHS Digital. This data is processed solely at the University of Aberdeen. • The data can be remotely accessed by a clinical co-ordinator at the University of Oxford but the data does not leave the University of Aberdeen’s servers. The role of the clinical co-ordinators is that of a data processor on behalf of the data controller(s). • Clinical co-ordinators need access to the data as this alerts them of any knee-related hospital admissions that occur which had not already been reported to the study from other sources so that the co-ordinators can contact the hospital to obtain further information regarding the relevant hospital admission. • There is a second clinical co-ordinator based at the University of Dundee to whom the applicant would wish to grant remote access to the data. However, the University of Dundee has not met NHS Digital’s requirements to be included as a data processor in this DSA and so access to this individual and organisation will be prohibited under this DSA. • A pseudonymised subset of the data is periodically transferred to the University of Oxford where researchers undertake a health economic evaluation. This does not involve any transfer of confidential data. Health economic evaluations took place in 2012 and 2020. A final evaluation in planned in 2023 when the study ends.

Processing activities

1. Retention of data already supplied: 1. Patient tracking service to receive notifications on participants’ death: This data will be securely stored but not otherwise processed. 2. Patient tracking service to receive notifications on participants’ death: [1 paragraph unchanged] The supplied file will be securely stored on the University of Aberdeen’s Sensitive Research Data Store (SRDS). This is a separate system from the main University’s data storage facility and was purposely built to meet the requirement of NHS Digital in terms of data storage. The supplied file will be securely stored within the University of Aberdeen's storage servers inside the Edward Wright building. The Aberdeen Business School data centre will be a primary network storage location. The data replicates constantly between the data centres and a file saved in the Edward Wright Building would replicate to the Aberdeen Business School seconds later. Although the Aberdeen Business School data centre is located within a Robert Gordon University building, the data centre itself is operated and maintained by a University of Aberdeen, Robert Gordon University and North East Scotland College partnership. No staff employed by Robert Gordon University and North East Scotland College will have access to the NHS Digital data. [1 paragraph unchanged] 3. 2. Knee-related hospital re-admissions: [1 paragraph unchanged] The data file supplied by NHS Digital will be securely stored on in the University of Aberdeen’s Sensitive Research Data Store (SRDS). storage servers. KAT researchers at the University of Aberdeen will then analyse the NHS [80 words unchanged] KAT study will be allowed access to the website and appropriate data. A clinical co-ordinator based at the Nuffield Department of Orthopaedics, Rheumatology and [86 words unchanged] not physically transferred elsewhere. It is strictly stored and processed in the SRDS at the University of Aberdeen. Aberdeen's storage servers and will be constantly replicated to the Aberdeen Business School. [3 paragraphs unchanged]

Expected output

[1 paragraph unchanged] Further follow-up of the KAT participants is therefore ongoing, and the intention [74 words unchanged] cost-effectiveness (the last three outcomes will include information provided by NHS Digital). The 15-year publication has not been released yet as the KAT clinical coordinator in Oxford is currently obtaining further information from the hospital where the knee-related readmission occurred. Once this further data has been analysed the 15 year publication can be released. Target date: Winter 2021 The findings will be submitted to peer reviewed journals and will be [23 words unchanged] and 3) collection of participant reported and clinical (re-admissions/further surgery) outcomes. The date of the 15-year publication (which is likely to include outputs including both the clinical and cost-effectiveness analyses) is dependent on receipt of analyses for the linked data requested 15-year publication was published in this application, but it is anticipated to occur in 2020 and the summer of 2020. The date of the 20-year publication is expected in 2023. At the final [36 words unchanged] NICE), researchers, NHS health professionals, other NIHR stakeholders and the general public. [4 paragraphs unchanged] The following manuscripts, all of which contained hospital readmission data obtained from participants and/or HES and ISD data have now been published: Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D for the KAT Trial Group. Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement. Bone Joint J 2013; 95-B(4):486-92 Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D, KAT Trial Group. Patellar resurfacing in total knee replacement: five year clinical and economic results of a large randomised controlled trial. Journal of Bone and Joint Surgery 2011;93:1473-1481 Murray DW, MacLennan GS, Breeman S, Dakin HA, Johnston L, Campbell MK, et al. A randomised controlled trial of the clinical effectiveness and cost-effectiveness of different knee prostheses: the Knee Arthroplasty Trial (KAT). Health Technol Assess 2014;18(19). Johnston L, MacLennan G, McCormack K, Ramsay C, Walker A. The Knee Arthroplasty Trial (KAT) design features, baseline characteristics, and two-year functional outcomes after alternative approaches to knee replacement. J Bone Joint Surg Am 2009;91(1)134-41. Data was fully anonymised in all publications which contained only aggregate level data with small numbers suppressed in line with the HES Analysis Guide. Further publications are planned as outlined in the outputs section. The quarterly cohort event notifications will be used to mitigate the risk of attempting to contact participants who have died or are lost to follow up. The remaining participants can then receive questionnaires and future information about the study via newsletters.

Benefits reported

The work has already influenced surgical practice as it is one of the key sources for the American Academy of Orthopaedic Surgeons surgical management of osteoarthritis of the knee evidence-based clinical practice guidelines. As a result it has probably benefited patients. The 10 year results did however not show major advantages for one treatment approach over another. However, there were trends suggesting that there might be substantial differences at 15 years. It is therefore expected that the 15 year results will show differences which will have major implications for knee replacement. The (median) ten-year clinical and economic results have already been published for the first three comparisons (patellar resurfacing, mobile bearings and metal backing) which demonstrated that: The following manuscripts, all of which contained hospital readmission data obtained from participants and/or HES and ISD data have now been published: • Participants had poor functional status and quality of life before undergoing knee replacement, although all study groups showed marked improvement within three months of surgery. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D for the KAT Trial Group. Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement. Bone Joint J 2013; 95-B(4):486-92 • Around 15% of patients were readmitted to hospital regarding their knee or underwent additional knee surgery within 10 years of their primary operation. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D, KAT Trial Group. Patellar resurfacing in total knee replacement: five year clinical and economic results of a large randomised controlled trial. Journal of Bone and Joint Surgery 2011;93:1473-1481 • There were no statistically significant differences between randomised groups in terms of functional status, quality of life or complications over the first 10 years after total knee replacement. Murray DW, MacLennan GS, Breeman S, Dakin HA, Johnston L, Campbell MK, et al. A randomised controlled trial of the clinical effectiveness and cost-effectiveness of different knee prostheses: the Knee Arthroplasty Trial (KAT). Health Technol Assess 2014;18(19). • Patella resurfacing dominated no resurfacing, non-significantly improving quality of life and decreasing cost. Johnston L, MacLennan G, McCormack K, Ramsay C, Walker A. The Knee Arthroplasty Trial (KAT) design features, baseline characteristics, and two-year functional outcomes after alternative approaches to knee replacement. J Bone Joint Surg Am 2009;91(1)134-41. • Metal backing improved quality of life at a small cost, costing £35 per QALY gained compared with all polyethylene. Data was fully anonymised in all publications which contained only aggregate level data with small numbers suppressed in line with the HES Analysis Guide. Further publications are planned as outlined in the outputs section. • Mobile bearings were also associated with increased cost and small improvements in quality of life and cost £1,666 per QALY gained, although there was substantial uncertainty around this conclusion. The quarterly cohort event notifications will be used to mitigate the risk of attempting to contact participants who have died or are lost to follow up. The remaining participants can then receive questionnaires and future information about the study via newsletters. The work from KAT has therefore already influenced surgical practice as it is one of the key sources for the American Academy of Orthopaedic Surgeons surgical management of osteoarthritis of the knee evidence-based clinical practice guidelines. As a result, it has probably benefited patients worldwide as they will have received a treatment that has been shown to be more effective. The 10-year results did however not show major advantages for one treatment approach over another. However, there were trends suggesting that there might be substantial differences at 15 years. It is therefore expected that the 15-year results will show differences which will have major implications for knee replacement.

Unchanged: Expected measurable benefits.

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

Data controllers: + UNIVERSITY OF OXFORD

Datasets: + Demographics

Objective for processing

Hospital Episode Statistics and Mortality data were supplied to the University of Aberdeen by ONS and subsequently by the Health and Social Care Information Centre (now known as NHS Digital) for the purpose of a research study known as the Knee Arthroplasty Trial (KAT). The University of Aberdeen and the University of Oxford are joint data controllers for the Knee Arthroplasty Trial (KAT). Both institutions are publicly funded and conduct research which serves the interest of society as a whole. Therefore the legal basis for processing data according to the General Data Protection Regulations (GDPR) are Article 6 (1)(e) and 9(2)(j). University of Aberdeen and University of Oxford will both process the data under this Agreement. This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. Both Pfizer and Zimmer Biomet are mentioned as funders in the latest KAT Study protocol (version 8). These organisation are not listed as data controller or data processor in this Agreement as they do not make any decisions regarding the data collected, neither do they have access to any data or any outputs other than the aggregated results with small number suppressed. 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. Similarly, the protocol names a Professor based at the University of Bristol as one of 6 'investigators'. The University of Bristol is neither controller nor processor of the data under this Agreement. This individual will only access data which has been aggregated with small numbers suppressed and will not make any decisions regarding the data under this Agreement. The following information provides background information on the purpose of the original study: The University of Aberdeen and the University of Oxford are joint data controllers for the Knee Arthroplasty Trial (KAT). Both institutions are publicly funded and conduct research which serves the interest of society as a whole. Therefore the legal basis for processing data according to the General Data Protection Regulations (GDPR) are Article 6 (1)(e) and 9(2)(j). Both University of Aberdeen and University of Oxford will process the data under this agreement. Both Pfizer and Zimmer Biomet are mentioned in the KAT Study protocol, however these organisations are not data controllers as they do not make any decisions regarding the data collected, nor do they have access to any data or to any outputs other than the aggregated results with small number suppressed. Similarly the protocol (version 8) names an investigator employed by the University of Bristol. This individual will only access data which has been aggregated with small numbers suppressed and will not make any decisions regarding the data under this Agreement. Therefore, the University of Bristol is not listed as either a data controller or data processor in this Agreement. [1 paragraph unchanged] A Steering Committee made up of the principal grant holders and a [32 words unchanged] for any reason. The Steering Committee met until the end of recruitment. However, However the Steering Committee made no decisions on nor have any access in relation to the data requested under this agreement. Agreement. The trial has involved clinical co-ordinators at centres in Dundee (University of Dundee, Department of Orthopaedics and Trauma Surgery) and Oxford (University of Oxford, Nuffield Orthopaedics Centre). [4 paragraphs unchanged] In order to better evaluate these newer forms of arthroplasty, in terms [6 words unchanged] further treatment, and to achieve the overall objectives of the KAT trial, the intention is to supplement participant reported data will be supplemented with routinely collected information from NHS Digital in England and Information Services Division (ISD) in Scotland. The data requested will include a Cohort Event Notification report to be disseminated on a quarterly basis and a one-off drop of HES Admitted Patient Care historic data. Eight years of HES Admitted Patient Care data are requested under this agreement. HES data has already been requested and supplied on two previous occasions (2008 and 2012) and will be further requested until all participants have reached 20 years of follow-up. For information, a further one-off of HES data will also be requested again in 2023 towards the end of the study. However, this will be subject to a further application with NHS Digital. There are three main purposes of this Agreement: 1) Permission to retain the knee related hospital readmission data already provided by NHS Digital in 2008 and 2012. This permission will also extend to the death notifications previously received on a quarterly basis. This request is to comply with The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 and the Department of Health’s guidance in “Research involving the NHS: retention of records” which requires that essential documents are kept for at least 5 years after a trial has ended. 2) Continuation of permission to use the NHS Digital’s patient tracking service to receive notifications on participants’ deaths. This will allow the KAT team to manage the process of sending postal questionnaires and to reduce the risk of causing distress by sending questionnaires to deceased participants. Under this agreement the research team are requesting quarterly notifications of mortality data. The cohort identifiers are already held by NHS Digital, and latest death data will be provided to University of Aberdeen using the unique study ID and the date of birth. All other identifiers will not be returned to University of Aberdeen in order to minimise the amount of data requested as much as possible. 3) Permission for NHS Digital to link the KAT cohort to HES data and supply further knee-related hospital readmissions for the period 2011 to present. The University of Aberdeen will supply the identifying details of the participants to NHS Digital to facilitate the data linkage exercise. The identifying details will include NHS Number, Date of Birth, Sex, Postcode and a Unique Participant ID. The linked data to be returned will contain the Unique Study ID as the only identifier. The HES data will be filtered to specific codes related to: Knee arthroplasty; Hybrid knee replacement; Knee revision; Hybrid knee revision; Resurfacing of Patella; Other knee resurfacing; Excision arthroplasty; Arthroplasty to knee or unspecified joint; Excision revision; Revision to knee or unspecified joint; Amputation; Other knee operations, and Other knee re-admissions (no operation). The data controllers have considered the moral and ethical issues raised by the proposed dissemination. Risks to participants' confidentiality are managed as only aggregate level data will be published. All participants are aware that their details will be shared with NHS Digital for data linkage purposes and the data controllers consider this to be in line with participants' expectations and consent noting that participants can withdraw from the study at any point.

Processing activities

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. 1. Retention of data already supplied: The study data, including data provided by NHS Digital under previous agreements, are currently held by the University of Aberdeen. Under this interim extension all portable devices containing data must be securely locked away in a locked cabinet at the University of Aberdeen storage address specified in this Agreement. This data will be securely stored but not otherwise processed. This Data Sharing Agreement strictly prohibits any data sharing outside of the University of Aberdeen including with the University of Oxford and the University of Dundee. 2. Patient tracking service to receive notifications on participants’ death: The following provides background on the processing activities undertaken for the original study: The University of Aberdeen have previously supplied participants' identifying details to NHS Digital (Name, NHS Number, Date of Birth, Sex, Postcode and a Unique Participant ID) to allow NHS Digital to flag the cohort on its computer system. Quarterly Cohort Event notifications within the study population have previously been supplied and under this Agreement, this service would be reactivated. Fact and date of death are required along with details of participants' exits or re-entries into the NHS in England or Wales. Data will be returned containing the Unique Participant ID and supplied date of birth. The date of birth field is requested in order to help researchers identify a participant more easily than using only the Unique Participant ID. The University of Aberdeen have previously supplied the participant identifiers to NHS Digital (Name, NHS Number, Date of Birth, Sex, Postcode and a Unique Participant ID) to allow NHS Digital to flag the cohort on its computer system. Quarterly Cohort Event notifications within the study population have previously been supplied. Fact and date of death were required along with details of participants' exits or re-entries into England. The data returned included the unique participant ID and supplied date of birth. The date of birth field was required in order to help researchers identify a participant more easily than using only the Unique Participant ID. The supplied file will be securely stored on the University of Aberdeen’s Sensitive Research Data Store (SRDS). This is a separate system from the main University’s data storage facility and was purposely built to meet the requirement of NHS Digital in terms of data storage. The supplied files are be securely stored on the University of Aberdeen’s Sensitive Research Data Store (SRDS). This is a separate system from the main University’s data storage facility and was purposely built to meet the requirement of NHS Digital in terms of data storage. The death notification data is primarily used to manage the process of mailing out participant questionnaires (by the study team at the University of Aberdeen) to reduce the risk of causing distress by contacting deceased participants. NHS Digital have previously supplied linked HES data containing details of further knee replacements or episodes relating to further knee complications to the University of Aberdeen, including the Unique Participant ID and no other identifiers. 3. Knee-related hospital re-admissions: The data file supplied by NHS Digital is be securely stored on the University of Aberdeen’s Sensitive Research Data Store (SRDS). KAT researchers at the University of Aberdeen analysed the NHS Digital data to identify any knee related hospital re-admissions not already reported by the trial participants on their postal questionnaires. This new information was then electronically captured and stored on the secure KAT trial database which already contains the participant reported outcomes. The University of Aberdeen will supply the participants' identifying details to NHS Digital (NHS Number, Date of Birth, Gender, Postcode and a Unique Participant ID) to allow NHS Digital to link the cohort to the HES data. The linked HES data-set containing details of further knee replacements or episodes relating to further knee complications will be supplied to the University of Aberdeen, including the Unique Participant ID. 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 i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). The data file supplied by NHS Digital will be securely stored on the University of Aberdeen’s Sensitive Research Data Store (SRDS). KAT researchers at the University of Aberdeen will then analyse the NHS Digital data to identify any knee related hospital re-admissions not already reported by the trial participants on their postal questionnaires. This new information will then be electronically captured and stored on the secure KAT trial database which already contains the participant reported outcomes. The KAT Trial database will be accessed by the University of Aberdeen. Access to this web-based application is controlled by user name and password and only those personnel identified by the Trial Manager as working on the KAT study will be allowed access to the website and appropriate data. A clinical co-ordinator based at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (University of Oxford) has remote access to the patient-identifiable data in the KAT trial database at the University of Aberdeen. They are alerted when knee-related hospital re-admissions are reported (either directly from the participant or through data linkage to HES) and contact the relevant treatment centre for further details (e.g. hospital based records and hard copy CRF forms at the time of the readmission). This information is then electronically captured and stored on the KAT trial database. This database in its identifiable form is not physically transferred elsewhere. It is strictly stored and processed in the SRDS at the University of Aberdeen. Another clinical co-ordinator with the same role as the co-ordinator in Oxford is based at the University of Dundee. Under this Agreement, no access to NHS Digital data may be granted to the University of Dundee or its employees. In 2020 and again in 2023 (when all participants have reached 20 years of follow-up), a pseudonymised copy of the KAT database will be supplied to the KAT Health Economists (Department of Population Health, University of Oxford) to undertake the health economic analysis while the KAT statisticians (Health Services Research Unit, University of Aberdeen) will undertake the statistical analyses. This dataset will contain data which has been processed and verified by the hospital sites where the respective treatments occurred. This dataset is in pseudonymised form and contains no identify details. 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 - i.e. employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

No new outputs will be produced under this Data Sharing Agreement. The analysis of the ten-year follow-up data from KAT participants is now complete and has gone a long way towards providing a substantially firmer evidence base to guide answers to the questions addressed by the randomisations within KAT. However, knee failures due to many causes such as component loosening, polyethylene wear, and osteolysis tend to occur more frequently in the second decade than the first. Therefore, any design features, such as patella resurfacing, mobile bearings and metal backing of the tibia, that influence these failure mechanisms are likely to have a greater effect on revision rates in the second decade than the first. Therefore, further follow-up to a minimum of fifteen and twenty years and analysis of this data should result in stronger conclusions which should provide the basis for more detailed, stronger and complete recommendations for patients, clinicians and policy makers. In any future application, the applicant will be required to provide details any future outputs planned. Further follow-up of the KAT participants is therefore ongoing, and the intention is to analyse the data at two further time-points – once all participants have reached 15 years of follow-up and when they have reached 20 years of follow-up. At both time-points a clinical effectiveness and cost-effectiveness analysis will be conducted. The primary outcome measure will be the functional status of the knee measured using the Oxford Knee Score. Other outcome measures include quality of life (SF-12 and EQ-5D), need for additional surgery, cost and cost-effectiveness (the last three outcomes will include information provided by NHS Digital). Three manuscripts from the study - based on analyses of the HES and ISD data as well as information obtained from directly participants - were published between 2011 and 2014: The findings will be submitted to peer reviewed journals and will be of great interest to the orthopaedic community, in terms of 1) the size of the trial, 2) the number of years of follow-up and 3) collection of participant reported and clinical (re-admissions/further surgery) outcomes. The date of the 15-year publication (which is likely to include both the clinical and cost-effectiveness analyses) is dependent on receipt of the linked data requested in this application, but it is anticipated to occur in the summer of 2020. The date of the 20-year publication is expected in 2023. At the final time-point, a report will also be submitted to funder to be included in the NIHR Journals Library. Research conducted by the HTA programme serves a variety of stakeholders including decision-makers in local government, policy makers (including NICE), researchers, NHS health professionals, other NIHR stakeholders and the general public. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D, KAT Trial Group. Patellar resurfacing in total knee replacement: five year clinical and economic results of a large randomised controlled trial. Journal of Bone and Joint Surgery 2011;93:1473-1481 To further ensure full dissemination to the clinical community, the findings will be presented at scientific conferences attended by the Chief Investigator. Conferences include the British Orthopaedic Association Annual Congress and the American Academy of Orthopaedic Surgeons Annual Meeting. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D for the KAT Trial Group. Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement. Bone Joint J 2013; 95-B(4):486-92 In addition, as with the ten-year findings, the University of Aberdeen anticipates providing a summary of the trial results to the KAT participants (traditionally this has been in the form of a Newsletter) and providing relevant information in lay terms for members of the public. Previously this involved writing an NIHR externally commissioned ‘Research Summary for the Public’ article. Murray DW, MacLennan GS, Breeman S, Dakin HA, Johnston L, Campbell MK, et al. A randomised controlled trial of the clinical effectiveness and cost-effectiveness of different knee prostheses: the Knee Arthroplasty Trial (KAT). Health Technol Assess 2014;18(19). It is the intention that a lay summary of the trial results will be written for inclusion on the study websites. These websites are publicly available platforms. The trials unit also have an active Public Partnership Group which is an independent group consisting of members of the public led by a dedicated PPI co-ordinator. The remit of this group is to contribute a public perspective on a number of research activities, including dissemination of results to the public. This resource will therefore be utilised to support the development of the lay summary, which may include an infographic, and any further distribution to interested parties. Data was fully anonymised in all publications which contained only aggregate level data with small numbers suppressed in line with the HES Analysis Guide. Further publications are planned as outlined in the outputs section. All outputs will only contain results in highly aggregated format and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party. All outputs only contain results in highly aggregated format and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.

Expected measurable benefits

[2 paragraphs unchanged] Continuing follow-up to 20 completed years (which includes the collection of hospital readmission data) will provide long term data on the clinical and cost effectiveness of the various design options on which strong recommendations for knee replacement practice will be based. If such data is not available then the opportunity to assess the long term stability of the 10 year KAT findings will be lost. The primary benefit of receiving quarterly cohort event notifications is that it will reduce the risk of attempting to contact deceased study members thereby causing distress to living relatives.

Benefits reported

The quarterly cohort event notifications have been used to mitigate the risk of attempting to contact participants who have died or are lost to follow up. The remaining participants can then receive questionnaires and future information about the study via newsletters. The work has already influenced surgical practice as it is one of the key sources for the American Academy of Orthopaedic Surgeons surgical management of osteoarthritis of the knee evidence-based clinical practice guidelines. As a result it has probably benefited patients. The 10 year results did however not show major advantages for one treatment approach over another. However, there were trends suggesting that there might be substantial differences at 15 years. It is therefore expected that the 15 year results will show differences which will have major implications for knee replacement. Various manuscripts have resulted from the processing The following manuscripts, all of the which contained hospital readmission data obtained from participants and/or HES and ISD data, and data have now been published. This includes secondary analyses of the original dataset. The publications are as follows: published: Dakin HA, Gray AM, MacLennan GS, Morris RW, Murray DW. Partial factorial trials: comparing methods for statistical analysis and economic evaluation. Trials. 2018;19(1):442. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D for the KAT Trial Group. Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement. Bone Joint J 2013; 95-B(4):486-92 Sanchez-Santos MT, Garriga C, Judge A, Batra RN, Price AJ, Liddle A,D, Javaid MK, Cooper C, Murray DW, Arden NK. Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery. Sci Rep. 2018;8(1):3381. Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D, KAT Trial Group. Patellar resurfacing in total knee replacement: five year clinical and economic results of a large randomised controlled trial. Journal of Bone and Joint Surgery 2011;93:1473-1481 Jiang Y, Sanchez-Santos MT, Judge AD, Murray DW, Arden NK. Predictors of Patient-Reported Pain and Functional Outcomes Over 10 Years After Primary Total Knee Arthroplasty: A Prospective Cohort Study. J Arthroplasty. 2017;32(1):92-100 [1 paragraph unchanged] Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D for the KAT Trial Group. Five-year results of a randomised controlled trial comparing mobile and fixed bearings in total knee replacement. Bone Joint J 2013; 95-B(4):486-92 Johnston L, MacLennan G, McCormack K, Ramsay C, Walker A. The Knee Arthroplasty Trial (KAT) design features, baseline characteristics, and two-year functional outcomes after alternative approaches to knee replacement. J Bone Joint Surg Am 2009;91(1)134-41. Dakin, H, Gray, A, Murray, D. (2012). Mapping analyses to estimate EQ-5D utilities and responses based on Oxford Knee Score. Qual Life Res. 2013;22(3):683-94. Rationing of total knee replacement: a cost-effectiveness analysis on a large trial data set. H Dakin, A Gray, R Fitzpatrick, G MacLennan, D Murray. BMJ open 2012;2(1) Breeman S, Campbell M, Dakin H, Fiddian N, Fitzpatrick R, Grant A, Gray A, Johnston L, MacLennan GS, Morris R, Murray D, KAT Trial Group. Patellar resurfacing in total knee replacement: five year clinical and economic results of a large randomised controlled trial. Journal of Bone and Joint Surgery 2011;93:1473-1481. M Campbell, N Fiddian, R Fitzpatrick, A Grant, A Gray, R Morris, D Murray, D Rowley, L Johnston, G MacLennan, K McCormack, C Ramsay, A Walker. The Knee Arthroplasty Trial (KAT) design features, baseline characteristics, and two-year functional outcomes after alternative approaches to knee replacement. J Bone Joint Surg Am, 2009;91(1):134-41 [1 paragraph unchanged] In addition, the results of the KAT trial have also been cited in the American Academy of Orthopaedic Surgeons surgical management of osteoarthritis of the knee evidence-based clinical practice guidelines. The quarterly cohort event notifications will be used to mitigate the risk of attempting to contact participants who have died or are lost to follow up. The remaining participants can then receive questionnaires and future information about the study via newsletters. The results of the KAT trial thus far have influenced medical guidelines in the UK and internationally.