NHS Digital Data Release Register - reformatted
National CJD Surveillance Unit
Project 1 — DARS-NIC-148232-CPHLL
Opt outs honoured: Y, N, Yes - patient objections upheld (Section 251 NHS Act 2006)
Sensitive: Sensitive, and Non Sensitive
When: 2016/04 (or before) — 2021/03.
Legal basis: Section 251 approval is in place for the flow of identifiable data, Section 42(4) of the Statistics and Registration Service Act (2007) as amended by section 287 of the Health and Social Care Act (2012), Health and Social Care Act 2012 – s261(7), National Health Service Act 2006 - s251 - 'Control of patient information'.
- MRIS - Cause of Death Report
- MRIS - Cohort Event Notification Report
- MRIS - Scottish NHS / Registration
- MRIS - Flagging Current Status Report
- Civil Registration - Deaths
The data supplied by the NHS IC to National CJD Surveillance Unit will be used only for the approved Medical Research Project identified above.
Results from the vCJD arm of the project identified four instances of probable transfusion transmitted infection: in 3 cases of vCJD and a separate pre-clinical infection in a blood recipient. There have been no new cases of transfusion-associated vCJD since 2007. The last diagnosis of a transfusion-associated case was late 2006. The last diagnosis of a vCJD case (which was non transfusion-associated) was 2016. The identification of vCJD, the positing of a risk of blood-related secondary transmission of vCJD and the later actual identification of such transmission (of infection and disease) indicated that person-to-person spread of vCJD through blood and blood products was a real problem. This information and supporting data informed public health risk assessments and subsequent policy, allowing rational design and implementation of precautions that almost certainly prevented further transmissions and have critically limited the possibility of a self-sustaining blood-related secondary epidemic, including: • Withdrawal and recall of blood and associated products obtained from donors who develop vCJD (1997). • Importation of plasma for UK plasma fractionation (1998/1999) • Leucodepletion of all blood components (1998/1999) • Deferral of blood donors meeting certain criteria • The promotion of more appropriate blood/blood product use in the NHS. All of these policies are continually reviewed and currently remain in place – informed in part by data being provided by the NCJDRSU through the TMER study. Outputs achieved their stated purposes (and thus the benefits of processing). Examples of peer-reviewed publications resulting from the TMER study (available in the public domain) are as follows: 1. Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, Will RG. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363: 417-421. (This was the first recorded vCJD case who developed vCJD as a result of transfusion transmitted infection). 2. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364: 527-529 3. Health Protection Agency. New case of transfusion-associated variant-CJD. CDR Weekly 2006; 16(6). 4. Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology Review study. Vox Sanguinis 2006; 91: 221-230. 5. Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, Linehan JM, Brandner S, Wadsworth JD, Hewitt P, Collinge J. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006; 368: 2061-2067. 6. Health Protection Agency. Fourth case of transfusion-associated variant-CJD infection. Health Protection Report 2007; 1(3). 7. Gillies M, Chohan G, Llewelyn CA, Mackenzie J, Ward HJT, Hewitt PE, Will RG. A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions. Vox Sanguinis 2009; 97: 211-218. 8. Ward HJT, Mackenzie JM, Llewelyn CA, Knight RSG, Hewitt PE, Connor N, Molesworth A, Will RG. Variant Creutzfeldt-Jakob disease and exposure to fractionated products. Vox Sanguinis 2009; 97: 207-210. 9. Chohan G,Llewelyn C, Mackenzie J, Cousens S, Kennedy A, Will RG, Hewitt PE. Variant Creutzfeldt-Jakob disease in a transfusion recipient: coincidence or cause? Transfusion 2010; 50: 1003-1006. 10. Davidson LRR, Llewelyn CA, Mackenzie JM, Hewitt, PE, Will RG. Variant CJD and blood transfusion: are there additional cases? Vox Sanguinis 2014; 107(3): 220-225. 11. Urwin PJM, Mackenzie JM, Llewelyn CA, Will RG, Hewitt PE. Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study. Vox Sanguinis 2016; 110: 310-316. 12. Mackenzie JM, Turner M, Morris K, Field S, Molesworth AM, Pal S, Will RG, Llewelyn CA, Hewitt PE. Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study. Vox Sanguinis 2018; 113(5): 489-491. (This paper resulted in a proposal to change the study protocol to check all cases of CJD (as was already the case with vCJD) with the UK blood services, regardless of a reported history of blood donation. Previously only cases who had been reported by the relatives to have been blood donors were sent for checking). It is vital to continue studies such as the TMER so that any models can be ‘calibrated’ against actual observations and then risk assumptions potentially reconsidered. Results from all other types of CJD included in the project have not so far shown any evidence of transfusion transmission. The exact levels of infectivity in blood, the precise distribution of infection in the different blood components, and the details of how these might change over time in a given individual, in humans in either the preclinical or clinical stages of vCJD remain unknown. Assumptions have, however, been made (on the basis of available evidence) and used in risk assessments. It is vital to continue studies such as the TMER so as any models can be ‘calibrated’ against actual observations and then risk assumptions potentially reconsidered. As look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses, data from the TMER project were analysed to determine the accuracy of blood donation history provided by the relatives of cases. The results showed that only a small percentage of cases were found to be registered as donors on UKBS databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate. As there are potential public health implications of even a small percentage of CJD blood donors not being identified, a revision to the protocol of the CJD arm of the project has recently being made whereby all cases of CJD (definite and probable) will be notified to UKBS regardless of their reported donation history.
Output from the TMER study continues to inform public health decision making and transfusion guidelines contributing to national policy as well as adding to the evidence base on transfusion-associated transmission. This informs patients and the public as well as health care providers and professional societies and organisations. The identification of transfusion transmission of variant Creutzfeldt-Jakob disease (vCJD) through the Transfusion Medicine Epidemiology Review (TMER) has had profound implications for public health nationally and internationally It is crucial to determine whether there are further cases of transfusion transmission as this will inform public policy and serve the wider public interest. There are many unresolved questions including the risk to recipients, the level of infectivity of blood and the potential for a large population of infected donors that could lead to further cases. Methodology can assist future researchers in undertaking similar studies and helps direct further research and surveillance activity in this area, by providing the justification and relevant background to support funding applications. The monitoring of risks to public health, informing public health policy and adding to the evidence base in relation to transfusion-related transmission of infection is of considerable importance to public and patient health. Links between blood transfusion and CJD/vCJD have been established through this processing, publications have been written and presentations given to expert advisory panels and policy decision makers, informing public health decision making and enabling action to be taken to minimise the risk of further blood transfusion transmission. Data is processed in the public interest. This is an ongoing long term project and the data disseminated is required for the duration for public health purposes. This will help identify further instances where transfusion-related transmission of CJD/vCJD may occur in a timely manner, thus informing policy makers in the reassessment and quantification of risk. The outputs described provide a realistic and comprehensive framework for dissemination. Decisions regarding blood transfusion transmission risk mitigation are likely to happen as a result of outputs. This is a dissemination of public health importance and therefore relevant nationally and internationally, in helping to prevent transmission of CJD/vCJD through blood transfusion. This benefit is achieved by the NCJDRSU, working together with the UK national blood services and public health agencies, expert advisory panels and national Departments of Health. Absence of a CJD/vCJD epidemic associated with blood transfusion; low numbers of transfusion-associated cases in the general population. The timeframe of benefit is continuous and ongoing. To date the project has demonstrated that it is able to identify instances of probable transfusion transmitted infection, and it will remain vigilant to the possibility of further instances into the longer term.
Data from this project will be included in: a. Annual reports to Department of Health and Social Care and Scottish Government Health Department. b. The TMER section of the NCJDRSU website c. Submissions to peer reviewed journals resulting in research publications, in open-access format where possible. d. Presentations at conferences. The following articles have already been produced using the data from the TMER. •Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, Will RG. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363: 417-421. •Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364: 527-529. •Health Protection Agency. New case of transfusion-associated variant-CJD. CDR Weekly 2006; 16(6). •Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology Review study. Vox Sanguinis 2006; 91: 221-230. •Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, Linehan JM, Brandner S, Wadsworth JD, Hewitt P, Collinge J. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006; 368: 2061-2067. •Health Protection Agency. Fourth case of transfusion-associated variant-CJD infection. Health Protection Report 2007; 1(3). •Gillies M, Chohan G, Llewelyn CA, Mackenzie J, Ward HJT, Hewitt PE, Will RG. A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions. Vox Sanguinis 2009; 97: 211-218. •Ward HJT, Mackenzie JM, Llewelyn CA, Knight RSG, Hewitt PE, Connor N, Molesworth A, Will RG. Variant Creutzfeldt-Jakob disease and exposure to fractionated products. Vox Sanguinis 2009; 97: 207-210 •Chohan G,Llewelyn C, Mackenzie J, Cousens S, Kennedy A, Will RG, Hewitt PE. Variant Creutzfeldt-Jakob disease in a transfusion recipient: coincidence or cause? Transfusion 2010; 50: 1003-1006. •Davidson LRR, Llewelyn CA, Mackenzie JM, Hewitt, PE, Will RG. Variant CJD and blood transfusion: are there additional cases? Vox Sanguinis 2014 DOI: 10.1111/Vox 12161. •Urwin PJM, Mackenzie JM, Llewelyn CA, Will RG, Hewitt PE. Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study. Vox Sanguinis 2016; 110: 310-316. •Mackenzie JM, Turner M, Morris K, Field S, Molesworth AM, Pal S, Will RG, Llewelyn CA, Hewitt PE. Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER Study. Vox Sanguinis 2018; doi: 10.1111/vox 12661. All outputs will be aggregated with small numbers suppressed in line with the HES analysis guidance and no personal identifying information will be included in any outputs. Although the journal choice depends on the focus of the research question, NCJDRSU tries to make all peer-reviewed publications available in open-access. Blood donors are provided with information describing how their information may be used and information about the TMER study specifically is provided by NCJDRSU and NHSBT through their websites and privacy notices, and included in scientific publications. Donor information Prior to donation, when consenting to donate blood, donors are asked to read the donor welcome leaflet which describes how their data can be also used for purposes other than donation, including for research and surveillance activities: “to ensure the safety of all donors and patients and the traceability of donations…for research…this may include linkage of your information to your other NHS records”. The TMER study is just one of many possible projects that donor data may be used for and it is not feasible to provide detailed information for each and all of these. Instead the blood services have taken the approach of alerting donors to possible uses of their data through donor information and privacy notices, providing more project specific information on websites which are reviewed regularly by the respective organisations (information about the TMER study is made available on the NHSBT and NCJDRSU websites), and on demand. Websites NHS Blood & Transplant are co-investigators on this project which gives information on a number of national projects of which the TMER project is one. At the top of the NHSBT Donor facing Give Blood page there is a link taking readers to the research and surveillance pages with further information available. There are also annual reports on the SHOT (Serious Hazards of Transfusion) website. Chapter 20 relates to transfusion transmission infection (TTI) of which vCJD/prion disease is a category. Detail about the TMER study, including methods, results and publications are provided in the TMER section of the NCJDRSU website which is updated as new results become available. In addition, the TMER study management team comprising co-investigators, the study coordinator and supporting staff meet twice a year; all issues in relation to study management, progress and findings are discussed and the meeting is minuted. A report to the funding body is produced annually. Submissions to peer reviewed journals, conferences and updates to website will occur when new results are available. Under previous DSAs, previously stated target dates/deliverables have been realised. This agreement does not have any associated EU funding.
Flow of data into NHS Digital includes participant identifying information for recipients from, or donors to, CJD/vCJD cases. There is no health data attached to this cohort. NCJDRSU receives from NHS Digital NHS Number, Study ID, Supplied Identifiers, Latest Identifiers, Exits/Re-Entries, GP Practice Code, Fact/Date/Cause of Death for those individuals flagged in the cohort who have died. Data flow from NHS Digital will end at the NCJDRSU; information on place of death will be used to check the diagnosis in medical notes. No record level data will be shared with any organisation other than The University of Edinburgh. a) Transfer of data from NCJDRSU to NHS Digital. Details of recipients and donors will be sent by NCJDRSU to NHS Digital for flagging. The file will be sent in CSV format and follow the field format specified by NHS Digital. Data fields include study number, forename(s), surname(s), DOB, sex, address (if available), NHS number (if available). Data are not always available for every field requested but, as a minimum, name and date of birth are a mandatory requirement. This file is uploaded via a secure online Data Exchange Service (file transfer system, used for exchanging files between NHS Digital and external parties and for which the surveillance co-ordinator at NCJDRSU has been issued with a user name and password). b) Transfer of data from NHS Digital to NCJDRSU. A response file will be returned from NHS Digital to NCJDRSU via the secure online Data Exchange Service to the surveillance co-ordinator at NCJDRSU. The response file will include the current status of every patient supplied and traced. The data is encrypted to 256-bit AES when transmitted from NHS Digital. c) Electronic data storage. On receipt of information, the files will be downloaded onto an encrypted USB stick and transferred to the restricted space on the secure University of Edinburgh server supporting the NCJDRSU. Relevant information from the spreadsheets (date of death and cause of death) will be transferred onto the recipient and/or donor databases. The electronic data on the USB memory stick will then be deleted. A record of the date, place and cause of death is kept on the TMER study register of donors and recipients of CJD/vCJD implicated blood. This mortality data is not linked to any other datasets and is held on the secure University of Edinburgh server supporting the NCJDRSU. No further data linkages will be made with data supplied from NHS Digital and there will be no requirement or attempt to find out more information about the individuals concerned using the mortality data beyond the purpose for which it is requested. Mortality data from NHS Digital is held on the secure University of Edinburgh server supporting the NCJDRSU and is not linked to any datasets, other than the TMER register of donors and recipients to which the mortality data relates. Processing of mortality data extracts received from NHS Digital under the terms of the DSA will not be carried out by anyone who is not a substantive employee of the University of Edinburgh. Data will only be processed by NCJDRSU staff who have been appropriately trained in data protection, security and confidentiality. The information received from NHS Digital relates only to deceased individuals; the minimum data required is requested, this will be held securely and kept confidential by NCJDRSU, used only for the purposes of the study, analysed by staff trained in IG, not shared with any third parties and will be deleted once it has been processed. Study data will be processed exclusively in the UoE Data Safe Haven, which is a secure ISO 27001-certified environment using dedicated servers managed separately from the wider university network. The DSH has its own active directory where users are listed specific to each project; users gain access to the DSH via two-factor authentication, and only a limited number of TMER study team members have access to the data on a need to know basis. All are trained in IG. Data is securely held on University of Edinburgh premises and owned and managed by the University of Edinburgh. No data are stored outside University of Edinburgh premises. 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). There will be no data linkage undertaken with NHS digital data provided under this agreement that is not already noted in the agreement. Data will only be accessed and processed by substantive employees of University of Edinburgh and will not be accessed or processed by any other third parties not mentioned in this agreement. There will be no attempts made by University of Edinburgh to re-identify individuals involved in this project as there is no requirement to do so.