Whitehall Study of London Civil Servants

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Benefits reported

[3 paragraphs unchanged] The study team are currently writing a report on the prolonged effects [20 words unchanged] writing reports on (i) associations of alcohol consumption with deaths in old age and age, (ii) on marital status with mortality. mortality and (iii) the role of lipids on CVD risk in older ages. [2 paragraphs unchanged]

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits.

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Benefits reported

The study has provided made a major contribution to the identification of cardiovascular risk factors in middle [13 words unchanged] blood cholesterol, elevated blood pressure and diabetes for heart disease death rates is were lower compared with upper employment grades which were not fully explained by established risk factors. The work of the Prospective Studies Collaboration has helped to guide guided NICE guidelines in the UK, European Society of Cardiology guidelines, American Heart Association guidelines on use of blood pressure lowering treatment for prevention of cardiovascular disease. diseases. [2 paragraphs unchanged] The study has provided unique data on causes of death in old age in relation to very prolonged differences in cardiovascular risk factors and socioeconomic circumstances in middle and old age. These reports have guided public health policy on the provision of health services to reduce the risks of death and disability in older people in the UK and elsewhere. The study highlights the importance of modifiable risk factors for avoidable disability in old age using information collected in both middle and old age. The study team are currently writing a report on the prolonged effects of cigarette smoking and cause-specific mortality taking account of quitting smoking over the follow-up period. The study team are also writing reports on (i) associations of alcohol consumption with deaths in old age and (ii) on marital status with mortality. The study has provided unique data on causes of death in old age in relation to very prolonged differences in cardiovascular risk factors and socioeconomic circumstances recorded in middle and old age. These reports have guided public health policy on the provision of health services to reduce the risks of death and disability in older people in the UK and elsewhere. The study highlights the importance of modifiable risk factors for avoidable disability in old age using information collected in both middle and old age. [1 paragraph unchanged] As the follow-up study continues, the data previously disseminated under a previous version of this agreement has yet to be analysed and therefore, no additional yielded benefits have been realised to date.

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits.

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

Objective for processing

The Whitehall Study-1, carried out by the Department of Medical Statistics & Epidemiology at the School was a longitudinal health survey of the Civil Service, 1967-1970. The study screened over 18,000 men, aged 45-60, based in the London area primarily for cardiovascular and respiratory conditions. High-risk individuals were then selected for a series of controlled trials on smoking cessation, weight loss and reducing blood sugar. The survey cohort was also monitored with all forms of mortality recorded. By 1982, investigators were able to show that the lower the status of the job held, the worse the health status. The findings led to the establishment of the second Whitehall Study in 1985, to further investigate the social inequalities of health, and continues to the present day. The University of Oxford, University College London, and London School of Hygiene and Tropical Medicine, require access to NHS England data for the purpose of the following research project: Whitehall Study of London Civil Servants. Following a successful pilot study in 1995 a resurvey was conducted of all surviving 8448 participants in this cohort during 1997-98, after approval by the relevant ethics committees of the participating institutions. Data were collected for the resurvey using mailed questionnaires seeking details of previous medical history (diagnoses of heart attack, angina, or stroke), medications taken in the past month, smoking status, and last known civil service employment grade. Participants who reported a prior history of heart attack, angina, or stroke were defined as having prior cardiovascular disease. All respondents (83%) were subsequently sent a blood collection kit and asked to attend their local surgery to have a sample collected and measurements of blood pressure, height, and weight to be recorded. Data on questionnaires and blood results were available on over 5500 men. The following is a summary of the aims of the research project provided by the University of Oxford: The vital status and cause-specific mortality will be sought on all participants who were originally surveyed in 1967-1970 for this study. While surviving participants were re-surveyed in 1997, no additional participants have been recruited into the study since 1969-1970. 1. To determine the combined influence on cause-specific mortality in old age of lifestyle, socioeconomic circumstances, and cardiovascular disease (CVD) risk factors measured both in middle and in old age. The aims of the Whitehall-1 resurvey were (i) to determine the combined influence on cause-specific mortality in old age of lifestyle, socioeconomic circumstances and cardiovascular disease (CVD) risk factors measured both in middle and in old age; (ii) to provide reliable estimates of mortality risks associated with these factors and plasma markers when measured in old age alone; (iii) to ascertain whether mortality differentials by employment grade before retirement persist into old age and assess whether these are modified by additional circumstances measured in old age alone; (iv) to examine the associations between characteristics measured at the original survey and morbidity 25 years later including CVD morbidity, and self-assessment of physical and mental health. 2. To provide reliable estimates of mortality risks associated with these factors and plasma markers when measured in old age alone. The University of Oxford, University College London and the London School of Hygiene and Tropical Medicine (LSHTM) are public authorities and are processing data under Article 6(1)(e). 3. To ascertain whether mortality differentials by employment grade before retirement persist into old age and assess whether these are modified by additional circumstances measured in old age alone. Processing of personal data that is necessary for the performance of a task carried out in the public interest or in the exercise of the controller’s official authority includes processing of personal data that is necessary for… (c) the exercise of a function conferred on a person by an enactment or rule of law." 4. To examine the associations between characteristics measured at the original survey and morbidity 25 years later including CVD morbidity, and self-assessment of physical and mental health. The University of Oxford has a queen-in-council statute which states: “The principal objects of the University are the advancement of learning by teaching and research and its dissemination by every means”. The Whitehall study 1 screened 19,019 men aged 40-69 years between September 1967 and January 1970, based in the London area, and employed in Civil Service roles. Results showed that the lower the status of the job held, the worse the health status. University College London has a royal charter which states "3. The objects of the College shall be to provide education [...] and to encourage research". LSHTM has a royal charter which states "There shall be one Body Corporate and Politic under the name of the London School of Hygiene and Tropical Medicine (“London School”) for the purpose of and with the objects of promoting original research, consultancy and the study of and education in public health and tropical medicine and such other academic subjects". As both royal charters specifically refer to undertaking research as a key purpose of the established organisation, University College London and LSHTM are therefore both considered to be exercising a function of the Crown in undertaking research. The findings led to the establishment of the second Whitehall study in 1985 to further investigate the social inequalities of health and continues to the present day. All data controllers are processing data under Article 9(2)(j) as the data are required for research purposes. The ways in which the processing of data will be of benefit to the public – thereby demonstrating that the processing is in the public interest – are described in section ‘5d. ii. Expected Measurable Benefits to Health and/or Social Care Including Target Date’. The following NHS England data will be accessed: Participants in the study were initially flagged for cancers and deaths with the Office for National Statistics (ONS) record linkage for supplying information for Whitehall study. Cause-specific mortality data including names, dates of birth and region that the records were held, had been provided at three-monthly intervals and entered into the study database. In 2016 the study received ethics (NHS REC) and Section 251 (CAG) support for the retention of the identifier Date of Birth. Up to June 2018 the University of Oxford held identifiable reports (containing mortality and cancer registration data) disseminated by NHS Digital’s predecessor organisations, but these have since been securely destroyed with a data destruction certificate provided. The University of Oxford now only have access to pseudonymised data on deaths and cancer registrations on all participants that were provided by NHS Digital in Autumn 2020. • Civil Registrations of Death The initial study questionnaires are stored at LSHTM and the resurvey questionnaires are stored at the University of Oxford. NHS Digital holds details of identifiable data (name, date of birth, NHS number and postcode) on all Whitehall study participants and they provide the University of Oxford with identifiable information on health outcomes on all study participants. The information on health outcomes includes vital status, cancer registrations and date and cause of death for any participants who may have died. This information is used to discover more about the long-term effects of factors recorded in middle and old age on cancer incidence and causes of death in old age. • Cancer Registrations The University of Oxford obtains identifiable information on health outcomes on study participants from NHS Digital and processes these in order to conduct statistical analyses of the determinants of cancer incidence and cause-specific mortality. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL for collaborative research. • Demographics All information is stored securely by the University of Oxford and kept confidential. All questionnaires are stored in secure locations, with authorised access by swipe card only. Likewise, any electronic copies of pseudonymised data held by LSHTM and UCL are stored securely and kept confidential. Access to the computer databases are by a unique combination of usernames and passwords. No individual participants will be identified in any analyses or included in any study reports. The above datasets provide information on health outcomes including vital status, cancer registrations and date and cause of death for any participants who may have died. This information is used to discover more about the long-term effects of factors recorded in middle and old age on cancer incidence and causes of death in old age. The University of Oxford requires continued access to the above NHS England datasets to provide information on health outcomes on study participants and process these in order to conduct statistical analyses of the determinants of cancer incidence and cause-specific mortality for a 50-year follow-up report of these participants, and will include data collected at the resurvey at 25 years after baseline. In addition, the study is conducting analyses of changes in cigarette smoking patterns and their association with cause-specific mortality by age and risk and social class over the 50 year follow-up of this study population. The Whitehall Study of London Civil Servants is led by the University of Oxford, and also has in place a Steering Committee involving all three institutions who have historically been involved, London School of Hygiene and Tropical Medicine (LSHTM) University College London Medical School (UCL), and University of Oxford. The level of the data held is pseudonymised. As LSHTM and UCL are key collaborators with input into the decision making for the use of data in this study, these three organisations are therefore joint data controllers for the data disseminated under this Agreement. The data is minimised as: The study was originally set up at LSHTM assisted by a Statistician from UCL. In 1997 the University of Oxford conducted a resurvey of surviving participants and contributed and maintained updated mortality analyses on the study on behalf of the collaboration. Over the past 20 years, electronic data on dates of death and causes of death were sent every three months by NHS Digital to LSHTM and then passed onto the University of Oxford by secure email to process on behalf of the study steering committee. • Limited to data for a study cohort of 19,019 The study is ongoing, and is funded by the Medical Research Council and British Heart Foundation. The funding is in place until 31 December 2025. • Limited to pseudonymised data only for analysis purposes. The University of Oxford, University College London and The London School of Hygiene and are joint controllers as the organisations responsible for ensuring that the data will only be processed for the purpose described above. The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The study is funded by the Medical Research Council and British Heart Foundation. The funding is specifically for the Whitehall Study of London Civil Servants described. Funding is in place until March 2024. Data processing is only carried out by substantive employees of the University of Oxford, University College London and the London School of Hygiene and Tropical Medicine who have been appropriately trained in data protection and confidentiality.

Processing activities

No data will flow during this version of the Agreement. Previously, the cohorts were flagged by NHS Digital under an earlier data sharing Agreement (DARS-NIC-148044-RGS7W-v0.0), when NHS Digital provided updates on participant events, including removals and re-entries to NHS Registration, cancer registrations and deaths including cause of death details. No data will flow to NHS England for the purposes of this Agreement. Participants in the Whitehall study were flagged for mortality and cancer registration at the Office for National Statistics (England), which provided the date (mm/yyyy) and cause (including International Classification of Disease (ICD) codes) of all deaths. Cause-specific mortality is coded using ICD-9 up to August 2002 and ICD-10 subsequently. The applicant will continue to conduct analyses on all of the study participants and assess the causes of death and dates of death for all study participants. No data will flow out of NHS England for the purposes of this Agreement. Under previous iterations of this Agreement, NHS England and it’s predecessors, provided the relevant records from the mortality, demographics, and cancer data sets. The data does not contain any direct identifying data items. The data is pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient. In the past, mortality data and cancer registration data were provided electronically at 3-monthly intervals to the London School of Hygiene and Tropical Medicine. The data were sent to University of Oxford by encrypted email. The University of Oxford incorporated these data into the Whitehall database but in summer 2018 the data provided by NHS Digital was securely destroyed. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL for collaborative research. The participants in this study have agreed to prolonged follow-up via central registries via patient consent, with the patient information sheet and consent form making reference to the fact that information about health and lifestyle and causes of death could be collected for medical research purposes. Due to the age of the consent involved, Section 251 support was also obtained to cover the continued use of identifiable data. Study data is stored in secure electronic files at University of Oxford. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL for collaborative research. All questionnaires are stored in secure locations, with authorised access by swipe card only. Pseudonymised data held by University of Oxford, LSHTM and UCL are stored on secure servers and kept confidential. The Whitehall study database held by the University of Oxford contains identifiable data for the study participants, including date of birth and name if this was provided by participants in response to questionnaires. A senior statistician at the Clinical Trial Service Unit (CTSU) links the data, using study ID, with the study participants questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. The data is backed-up on servers at the University of Oxford, LSTHM, and UCL only. No other organisations store the data. All information is stored securely by the University of Oxford and kept confidential. All questionnaires are stored in secure locations, with authorised access by swipe card only. Likewise, any electronic copies of pseudonymised data held by LSHTM and UCL are stored securely and kept confidential. Access to the computer databases are by a unique combination of usernames and passwords. No individual participants will be identified in any analyses or included in any study reports. The data will be accessed by authorised personnel via remote access. The data will remain on the servers at University of Oxford, University College London Medical School and London School of Hygiene at all times. 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 study will not share any record level data supplied by NHS Digital with any other institution or individual outside the study of the University of Oxford, London School of Hygiene, or UCL. Personnel are prohibited from downloading or copying data to local devices. Data processing is only carried out by substantive employees of the University of Oxford, University College London and the London School of Hygiene and Tropical Medicine who have been appropriately trained in data protection and confidentiality. The data will not leave England at any time. Access is restricted to substantive employees or agents of the University of Oxford, University College London, and the London School of Hygiene and Tropical Medicine only. All personnel accessing the data have been appropriately trained in data protection and confidentiality. Data from NHS England has been linked to study participant data but will not be linked to any other data. There will be no requirement and no attempt to reidentify individuals when using the data. The identifying details are stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Expected output

The chief aim of the study is to assess mortality risks in old age in relation to cardiovascular risk factors measured in middle and old age, and assess life expectancy and lifetime risks of cardiovascular risk factors measured in middle and old age in 2021-2023. The previously disseminated data will also be used to generate reports on cardiovascular and non-vascular causes of death in relation to socioeconomic circumstances measured in both middle and old age. The University of Oxford’s Nuffield Department of Population Health (NDPH) has a communications team that provides regular electronic updates on news items to coincide with publications of reports by academic staff in topics of Public Health interest. For some reports, academics write a lay summary for a press release that is posted on the NDPH website. Some of these are picked up by media and are thereby disseminated to the general public. For important work, the communications team at NDPH will work with the study sponsors (MRC or BHF) and the stories are covered on their websites. The results Results of analyses of the Whitehall study have been presented at national and [9 words unchanged] the European Society of Cardiology and American Heart Association annual scientific sessions. The results of planned analyses have been submitted for publication and may also be presented at national and international meetings. Likewise, results of some analyses will be posted on the Nuffield Department of Population Health (a department within the University of Oxford) website. The target time frame for publication of the results of the planned analyses is ongoing. An archive collection has been established by the LSHTM Library & Archives Service between January and September 2017, with funding provided by a Wellcome Trust Research Resources grant. The catalogue description is now available on the London School of Hygiene and Tropical Medicine online catalogue and open for consultation in the Archives reading room. This archive provides an invaluable resource of the data collection, monitoring work and analysis conducted on the original Whitehall Study. The results of analyses have been submitted for publication and may also be presented at national and international meetings. Examples of publications are: Results of some analyses will be posted on the Nuffield Department of Population Health (a department within the University of Oxford) website. Clarke R, Shipley M, Collins R, Marmot M, Peto R. Am J Epidemiol.1999;150:341-353. An archive collection was established by the London School of Hygiene and Tropical Medicine Library & Archives Service between January and September 2017. The catalogue description is now available on the LSHTM online catalogue and open for consultation in the Archives reading room. This archive provides an invaluable resource of the data collection, monitoring work and analysis conducted on the original Whitehall Study. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. The study plans to conduct analyses for a series of scientific publications on the causes of mortality, particularly focusing on determinants of cardiovascular disease in old age in relation to cardiovascular risk factors measured in middle and old age. Importantly, the study contributed to a 2021 meta-analysis which showed significant associations of Vitamin D deficiency with CVD mortality and all-cause mortality. Clarke R, Breeze E, Youngman L, Sherliker P, Bell P, Shah S, Shipley M, Collins R, Leon D, Marmot M, Fletcher A. J Cardiovasc Risk. 2000;7:251-257. The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up. Outputs have, and will continue to be disseminated or otherwise communicated using the following: Breeze E, Fletcher AE, Leon DA, Marmot MG, Clarke R, Shipley MJ. Am J Publ Health. 2001;91:277-283. • Presentations at national and international conferences including Society of Social Medicine and the European Society of Cardiology and American Heart Association annual scientific sessions. Socioeconomic disadvantage persists into old age: self-reported morbidity in a 29 year follow-up of the Whitehall Study. • Communications informing public bodies such as NHS, Food Standards Agency, Public Health England. Breeze E, Clarke R, Shipley MJ, Marmot MG, Fletcher AE. • Publication on website: Nuffield Department of Population Health (a department within the University of Oxford). Int J Epidemiol. 2006;35:169-178. • Publications in peer reviewed scientific publications. Cause-specific mortality in relation to body mass index in middle age in old age. Three papers are planned for publication throughout 2023: Clarke R, Emberson J, Armitage J, Shipley M, Clark S, Linksted P , Fletcher A, Collins R. Arch Intern Med. 2007;167:1373-1378. 1. Lifetime risks of cardiovascular disease mortality in relation to risk factors in middle and old age in the Whitehall Study. Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men. 2. Socioeconomic differentials in smoking and cause-specific mortality in 50-year follow-up in the Whitehall Study. Survival in relation to angina symptoms and diagnosis among men aged 70-90 years: the Whitehall Study. 3. Cardiovascular risk factors in middle age and frailty in old age in the Whitehall Study. Clarke R, Shipley M, Breeze E, Collins R, Marmot M, Halsey J, Fletcher A, Hemingway H. Eur J Cardiovasc Prev Rehabil. 2007;14:280-286. Survival in relation to angina symptoms and diagnosis among men aged 70-90 years: the Whitehall Study. Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley M J. BMJ. 2009;339:b3513. doi: 104136/bmj.63513 Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19000 men in the Whitehall Study. Batty GB, Kivimaki M, Morrison D, Huxley R, Smith GD, Clarke R, Marmot M, Shipley MJ. Risk factors for pancreatic cancer mortality: extended follow-up of the original Whitehall Study. Cancer Epidemiol Biomarkers Prev. 2009;18:673-675. Clarke R, Shipley M, Armitage J, Collins R, Harris W. Br J Nutr. 2009; 102:279 284. Plasma phospholipid fatty acids and CHD in older men: Whitehall study of London civil servants. Clarke R, Shipley MJ. BMJ. 2009;339:b5097. Whitehall Study Authors’ reply. Batty GD, Shipley MJ, Gunnell D, Smith GD, Ferrie JE, Clarke R, Marmot MG, Kivimaki M. J Epidemiol Comm Health. 2011;65:461-464. Height loss and future coronary heart disease in London: the Whitehall II study. Batty GD, Kivimäki M, Clarke R, Davey Smith G, Shipley MJ. Cancer Causes Control. 2011;22:311-318. Modifiable risk factors for prostate cancer mortality in London: forty years of follow-up in the Whitehall study. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Eur Heart J. 2013;34:1365-74 Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Influence on guidelines for the management of hypertension and blood lipids: The 2002 report of the Prospective Studies Collaboration report on blood pressure and stroke and heart disease (Lewington et al, Lancet 2002), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies (Clarke et al, Am J Epidemiol 1999). Likewise, the 2007 report of the Prospective Studies Collaboration report on blood cholesterol and stroke and heart disease (Lewington et al, Lancet 2007), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies. These reports influenced JNC7 Guidelines on the Detection and Treatment of Hypertension in the USA and NICE guidelines for the management of hypertension and blood lipids in the UK in addition to the European Society of Cardiology reports on prevention of heart disease (Piepolo 2016) and detection and management of blood lipids (Capetano, 2016) and American Heart Association reports for prevention of heart disease over the last 15 years. References for benefits of study Lewington S, Clarke R, Quizilbash N, Peto R, Collins R for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: One million adults in 61 prospective studies. Lancet. 2002;360:1903-1913. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R on behalf of the Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual participant data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829-1839. Piepolo MF, Hoes AW, Agewal S, Albus C, Brotons C, Catapano AL, Cooney MT. 2016 guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37 (29): 2315-81. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37: 2999-3058. In addition to peer-reviewed scientific publications, the University of Oxford has also communicated with NHS and other organisations (Food Standards Agency) or Public Health England where outputs from the study will provide information needed for health strategies using up-to-date evidence on effects of cardiovascular risk factors on risk of death. These data will improve provision of health care delivery and health services in response to demands on health and social care in the present and the future. Lastly, data on blood levels of vitamin D (25(OH)D) in this study have guided policy on the relevance of vitamin D and specifically for testing for vitamin D for prediction of vascular and non-vascular causes of death in the UK. The study plans to conduct analyses for a series of scientific publications on the causes of mortality, particularly focusing on determinants of cardiovascular disease in old age in relation to cardiovascular risk factors measured in middle and old age. Importantly, the study contributed to a 2021 meta-analysis which showed significant associations of Vitamin D deficiency with CVD mortality and all-cause mortality. All outputs and publications contain only aggregated data with small numbers suppressed in line with HES Analysis Guide.

Expected measurable benefits

The analyses of the Whitehall study has provided data on life expectancy, [25 words unchanged] risk factors recorded in both middle and old-age. It is expected that he the results will highlight the range in survival by levels of cardiovascular risk [37 words unchanged] 12-14 years, between low and high levels of cardiovascular disease risk factors. It is expected that analysis of 50-year follow-up data disseminated under a previous version of this agreement, will be completed by 30th September 2023. It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

Benefits reported

The study already made has provided a major contribution to the identification of cardiovascular risk factors in middle [65 words unchanged] guidelines on use of blood pressure lowering treatment for prevention of cardiovascular disease disease. The study has provided unique data on causes of death in old age in relation to very prolonged differences in cardiovascular risk factors and socioeconomic circumstances in middle and old age. These reports will guide public health policy on the provision of health services to reduce the risks of death and disability in older people in the UK and elsewhere. The study will highlight the importance of modifiable risk factors for avoidable disability in old age using information collected in both middle and old age. Data on blood levels of vitamin D (25(OH)D) in this study have guided public health policy on the relevance of vitamin D for vascular and non-vascular causes of death in the UK. Derived data from this study were incorporated in the Prospective Studies Collaboration meta-analysis which guided public health policy on detection and treatment of elevated blood pressure and of elevated cholesterol levels in the UK and worldwide. Data from the resurvey on blood lipids and CHD mortality have helped to clarify the relevance of lipids for prediction of death from vascular disease in old age. No further data will be shared under this Agreement for meta-analysis, or for any other purpose, unless the level of derivation has been has been assessed and permitted by NHS Digital. Through analysis of mortality data, in 1982 it was revealed that lower grade employees were a third more like to die from various mortality causes than those employed at higher grades. This finding showed a clear social gradient in mortality and led to a second Whitehall Study being created in 1985 that focused directly on the extent and causes of the social gradient, to further investigate the social inequalities of health, and continues to the present day. The study has provided unique data on causes of death in old age in relation to very prolonged differences in cardiovascular risk factors and socioeconomic circumstances in middle and old age. These reports have guided public health policy on the provision of health services to reduce the risks of death and disability in older people in the UK and elsewhere. The study highlights the importance of modifiable risk factors for avoidable disability in old age using information collected in both middle and old age. [1 paragraph unchanged] By 1982, investigators were able to show that the lower the status of the job held, the worse the health status. The findings led to the establishment of the second Whitehall Study in 1985, to further investigate the social inequalities of health, and continues to the present day. As the follow-up study continues, the data previously disseminated under a previous version of this agreement has yet to be analysed and therefore, no additional yielded benefits have been realised to date. Through analysis of mortality data it was revealed that lower grade employees were a third more like to die from various mortality causes than those employed at higher grades. This finding showed a clear social gradient in mortality and led to a second Whitehall Study being created that focused directly on the extent and causes of the social gradient. As the follow-up study continues, the data previously disseminated in DARS-NIC-148044-RGS7W-v3.2 has yet to be analysed and therefore, no additional yielded benefits have been realised at he present.

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

Objective for processing

The Whitehall-1 study, also known as Health of Civil Servants study, is a prospective study of 19,019 male civil servants who were working in London at the time of recruitment in 1967-1970. Following a successful pilot study in 1995 a resurvey was conducted of all surviving 8448 participants in this cohort during 1997-98, after approval by the relevant ethics committees of the participating institutions. Data were collected for the resurvey using mailed questionnaires seeking details of previous medical history (diagnoses of heart attack, angina, or stroke), medications taken in the past month, smoking status, and last known civil service employment grade. Participants who reported a prior history of heart attack, angina, or stroke were defined as having prior cardiovascular disease. All respondents (83%) were subsequently sent a blood collection kit and asked to attend their local surgery to have a sample collected and measurements of blood pressure, height, and weight to be recorded. Data on questionnaires and blood results were available on over 5500 men. The Whitehall Study-1, carried out by the Department of Medical Statistics & Epidemiology at the School was a longitudinal health survey of the Civil Service, 1967-1970. The study screened over 18,000 men, aged 45-60, based in the London area primarily for cardiovascular and respiratory conditions. High-risk individuals were then selected for a series of controlled trials on smoking cessation, weight loss and reducing blood sugar. The survey cohort was also monitored with all forms of mortality recorded. By 1982, investigators were able to show that the lower the status of the job held, the worse the health status. The findings led to the establishment of the second Whitehall Study in 1985, to further investigate the social inequalities of health, and continues to the present day. The aims of the study are (i) to determine the combined influence on cause-specific mortality in old age of lifestyle, socioeconomic circumstances and cardiovascular risk factors measured both in middle and in old age; (ii) to provide reliable estimates of mortality risks associated with these factors and plasma or genetic markers when measured in old age alone; (iii) to determine whether mortality differentials by employment grade before retirement persist into old age and determine whether these are modified by additional circumstances measured in old age alone; (iv) to examine the associations between characteristics measured at the original survey and morbidity 25 years later including CVD morbidity, and self-assessment of physical and mental health. Following a successful pilot study in 1995 a resurvey was conducted of all surviving 8448 participants in this cohort during 1997-98, after approval by the relevant ethics committees of the participating institutions. Data were collected for the resurvey using mailed questionnaires seeking details of previous medical history (diagnoses of heart attack, angina, or stroke), medications taken in the past month, smoking status, and last known civil service employment grade. Participants who reported a prior history of heart attack, angina, or stroke were defined as having prior cardiovascular disease. All respondents (83%) were subsequently sent a blood collection kit and asked to attend their local surgery to have a sample collected and measurements of blood pressure, height, and weight to be recorded. Data on questionnaires and blood results were available on over 5500 men. The vital status and cause-specific mortality will be sought on all participants who were originally surveyed in 1967-1970 for this study. While surviving participants were re-surveyed in 1997, no additional participants have been recruited into the study since 1969-1970. The aims of the Whitehall-1 resurvey were (i) to determine the combined influence on cause-specific mortality in old age of lifestyle, socioeconomic circumstances and cardiovascular disease (CVD) risk factors measured both in middle and in old age; (ii) to provide reliable estimates of mortality risks associated with these factors and plasma markers when measured in old age alone; (iii) to ascertain whether mortality differentials by employment grade before retirement persist into old age and assess whether these are modified by additional circumstances measured in old age alone; (iv) to examine the associations between characteristics measured at the original survey and morbidity 25 years later including CVD morbidity, and self-assessment of physical and mental health. [1 paragraph unchanged] Processing of personal data that is necessary for the performance of a [30 words unchanged] function conferred on a person by an enactment or rule of law." The University of Oxford has a queen-in-council statute which states: “The principal objects of the University are the advancement of learning by teaching and research and its dissemination by every means”. University College London has a royal charter which states "3. The objects of the College shall be to provide education [...] and to encourage research". LSHTM have a royal charter which states "There shall be one Body Corporate and Politic under the name of the London School of Hygiene and Tropical Medicine (“London School”) for the purpose of and with the objects of promoting original research, consultancy and the study of and education in public health and tropical medicine and such other academic subjects". As both royal charters specifically refer to undertaking research as a key purpose of the established organisation, University College London and LSHTM are therefore both considered to be exercising a function of the Crown in undertaking research. The University of Oxford has a queen-in-council statute which states: “The principal objects of the University are the advancement of learning by teaching and research and its dissemination by every means”. University College London has a royal charter which states "3. The objects of the College shall be to provide education [...] and to encourage research". LSHTM has a royal charter which states "There shall be one Body Corporate and Politic under the name of the London School of Hygiene and Tropical Medicine (“London School”) for the purpose of and with the objects of promoting original research, consultancy and the study of and education in public health and tropical medicine and such other academic subjects". As both royal charters specifically refer to undertaking research as a key purpose of the established organisation, University College London and LSHTM are therefore both considered to be exercising a function of the Crown in undertaking research. [1 paragraph unchanged] Participants in the study were initially flagged for cancers and deaths with [91 words unchanged] securely destroyed with a data destruction certificate provided. The University of Oxford continues now only have access to hold identifiable pseudonymised data collected directly from on deaths and cancer registrations on all participants under consent and Section 251 support. that were provided by NHS Digital in Autumn 2020. The Whitehall Study of London Civil Servants is led by the University of Oxford, and also has in place a Steering Committee involving all three institutions who have historically been involved, London School of Hygiene and Tropical Medicine (LSHTM) University College London Medical School (UCL), and University of Oxford. As LSHTM and UCL are key collaborators with input into the decision making for the use of data in this study, these three organisations are therefore joint data controllers for the data disseminated under this agreement. The study was originally set up at LSHTM assisted by a Statistician from UCL. In 1997 the University of Oxford conducted a resurvey of surviving participants and contributed and maintained updated mortality analyses on the study on behalf of the collaboration. Over the past 20 years, electronic data on dates of death and causes of death were sent every three months by NHS Digital to LSHTM and then passed onto the University of Oxford by secure email to process on behalf of the study steering committee. To simplify the process and minimise the flow of identifiable data, only pseudonymised data on deaths and cancer registrations will now be sent at six-monthly intervals by NHS Digital directly to University of Oxford who will incorporate these data into the study database. The initial study questionnaires are stored at LSHTM and the resurvey questionnaires are stored at the University of Oxford. NHS Digital holds details of identifiable data (name, date of birth, NHS number and postcode) on all Whitehall study participants and they provide the University of Oxford with identifiable information on health outcomes on all study participants. The information on health outcomes includes vital status, cancer registrations and date and cause of death for any participants who may have died. This information is used to discover more about the long-term effects of factors recorded in middle and old age on cancer incidence and causes of death in old age. Data are being sought on vital status, date and causes of death (death certificates) and cancer registrations for all participants in the Whitehall study (Health of Civil Servants study). The study has already made a very valuable contribution to the understanding of major risk factors for heart disease and stroke in the UK and the extent to which such risk factors explained social class differences in death rates in the UK population. The University of Oxford obtains identifiable information on health outcomes on study participants from NHS Digital and processes these in order to conduct statistical analyses of the determinants of cancer incidence and cause-specific mortality. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL for collaborative research. The study is ongoing, and funding is in place until 2020. All information is stored securely by the University of Oxford and kept confidential. All questionnaires are stored in secure locations, with authorised access by swipe card only. Likewise, any electronic copies of pseudonymised data held by LSHTM and UCL are stored securely and kept confidential. Access to the computer databases are by a unique combination of usernames and passwords. No individual participants will be identified in any analyses or included in any study reports. The Whitehall Study of London Civil Servants is led by the University of Oxford, and also has in place a Steering Committee involving all three institutions who have historically been involved, London School of Hygiene and Tropical Medicine (LSHTM) University College London Medical School (UCL), and University of Oxford. As LSHTM and UCL are key collaborators with input into the decision making for the use of data in this study, these three organisations are therefore joint data controllers for the data disseminated under this Agreement. The study was originally set up at LSHTM assisted by a Statistician from UCL. In 1997 the University of Oxford conducted a resurvey of surviving participants and contributed and maintained updated mortality analyses on the study on behalf of the collaboration. Over the past 20 years, electronic data on dates of death and causes of death were sent every three months by NHS Digital to LSHTM and then passed onto the University of Oxford by secure email to process on behalf of the study steering committee. The study is ongoing, and is funded by the Medical Research Council and British Heart Foundation. The funding is in place until 31 December 2025.

Processing activities

The No data will flow during this version of the Agreement. Previously, the cohorts were flagged by NHS Digital under an earlier data sharing agreement (DARS-NIC-148044-RGS7W-v0.0). Agreement (DARS-NIC-148044-RGS7W-v0.0), when NHS Digital will provide provided updates on participant events, including removals and re-entries to NHS Registration, cancer registrations and deaths including cause of death details. Participants in the Whitehall study were flagged for mortality and cancer registration at the Office for National Statistics (England), which provided the date (mm/yyyy) and cause (including International Classification of Disease (ICD) codes) of all deaths. Cause-specific mortality is coded using ICD-9 up to August 2002 and ICD-10 subsequently. In the past, mortality data and cancer registration data were provided electronically at 3-monthly intervals to the London School of Hygiene and Tropical Medicine. The data were sent to University of Oxford by encrypted email. The University of Oxford incorporated these data into the Whitehall database but in summer 2018 the data provided by NHS Digital was securely destroyed. The participants in this study have agreed to prolonged follow-up via central registries via patient consent, with the patient information sheet and consent form making reference to the fact that information about health and lifestyle and causes of death could be collected for medical research purposes. Due to the age of the consent involved, Section 251 support was also obtained to cover the continued use of identifiable data. All data on the study will be stored in secure electronic files at University of Oxford. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL to maintain the 3-way collaboration for supervision of the study. Participants in the Whitehall study were flagged for mortality and cancer registration at the Office for National Statistics (England), which provided the date (mm/yyyy) and cause (including International Classification of Disease (ICD) codes) of all deaths. Cause-specific mortality is coded using ICD-9 up to August 2002 and ICD-10 subsequently. The applicant will continue to conduct analyses on all of the study participants and assess the causes of death and dates of death for all study participants. The Whitehall study database held by the University of Oxford contains identifiable data for the study participants, including date of birth and name if this was provided by participants in response to questionnaires. The data disseminated by NHS Digital will be in a pseudonymised format using a Study ID, but once received by the University of Oxford the data will be combined with the identifiable study data already held. For the purposes of this agreement the data disseminated by NHS Digital is therefore considered to be identifiable. A senior statistician at the Clinical Trial Service Unit (CTSU) links the data, using study ID, with the study participants questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. All such subsets are customised for specific analyses intended for specific purposes. In the past, mortality data and cancer registration data were provided electronically at 3-monthly intervals to the London School of Hygiene and Tropical Medicine. The data were sent to University of Oxford by encrypted email. The University of Oxford incorporated these data into the Whitehall database but in summer 2018 the data provided by NHS Digital was securely destroyed. 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 study will not share any data supplied by NHS Digital with any other institution or individual outside the study of the University of Oxford, London School of Hygiene, or UCL. The participants in this study have agreed to prolonged follow-up via central registries via patient consent, with the patient information sheet and consent form making reference to the fact that information about health and lifestyle and causes of death could be collected for medical research purposes. Due to the age of the consent involved, Section 251 support was also obtained to cover the continued use of identifiable data. Study data is stored in secure electronic files at University of Oxford. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL for collaborative research. The Whitehall study database held by the University of Oxford contains identifiable data for the study participants, including date of birth and name if this was provided by participants in response to questionnaires. A senior statistician at the Clinical Trial Service Unit (CTSU) links the data, using study ID, with the study participants questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. All information is stored securely by the University of Oxford and kept confidential. All questionnaires are stored in secure locations, with authorised access by swipe card only. Likewise, any electronic copies of pseudonymised data held by LSHTM and UCL are stored securely and kept confidential. Access to the computer databases are by a unique combination of usernames and passwords. No individual participants will be identified in any analyses or included in any study reports. 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 study will not share any record level data supplied by NHS Digital with any other institution or individual outside the study of the University of Oxford, London School of Hygiene, or UCL. Data processing is only carried out by substantive employees of the University of Oxford, University College London and the London School of Hygiene and Tropical Medicine who have been appropriately trained in data protection and confidentiality.

Expected output

The chief aim of the study is to assess mortality risks in [18 words unchanged] and lifetime risks of cardiovascular risk factors measured in middle and old age in 2021-2023. The previously disseminated data will also be used to generate reports on cardiovascular and non-vascular causes of death in relation to socioeconomic circumstances measured in both middle and old age. All outputs and publications contain only aggregated data with small numbers suppressed in line with HES Analysis Guide. The results of analyses of the Whitehall study have been presented at national and international meetings, including the Society of Social Medicine and the European Society of Cardiology and American Heart Association annual scientific sessions. The results of planned analyses have been submitted for publication and may also be presented at national and international meetings. Likewise, results of some analyses will be posted on the Nuffield Department of Population Health (a department within the University of Oxford) website. The target time frame for publication of the results of the planned analyses is ongoing. The results of analyses of the Whitehall study have been presented at national and international meetings, including the Society of Social Medicine and the European Society of Cardiology and American Heart Association annual scientific sessions. The results of planned analyses will be submitted for publication and some may also be presented at national and international meetings. Likewise, results of some analyses will be posted on the Nuffield Department of Population Health (a department within the University of Oxford) website. The target time frame for publication of the results of the planned analyses is during 2018-2020. An archive collection has been established by the LSHTM Library & Archives Service between January and September 2017, with funding provided by a Wellcome Trust Research Resources grant. The catalogue description is now available on the London School of Hygiene and Tropical Medicine online catalogue and open for consultation in the Archives reading room. This archive provides an invaluable resource of the data collection, monitoring work and analysis conducted on the original Whitehall Study. [1 paragraph unchanged] Clarke R, Shipley M, Collins R, Marmot M, Peto R. Am J Epidemiol.1999;150:341-353. [1 paragraph unchanged] Clarke R, Breeze E, Youngman L, Sherliker P, Bell P, Shah S, Shipley M, Collins R, Leon D, Marmot M, Peto R. Fletcher A. J Cardiovasc Risk. 2000;7:251-257. Am J Epidemiol. 1999;150:341-353. [1 paragraph unchanged] Breeze E, Fletcher AE, Leon DA, Marmot MG, Clarke R, Breeze E, Youngman L, Sherliker P, Bell P, Shah S, Shipley M, Collins R, Leon D, Marmot M, Fletcher A. MJ. Am J Publ Health. 2001;91:277-283. J Cardiovasc Risk. 2000;7:251-257. [1 paragraph unchanged] Breeze E, Fletcher AE, Leon DA, Marmot MG, Clarke R, Shipley MJ. Am J Publ Health. 2001;91:277-283. Cause-specific mortality in relation to body mass index in middle age in old age. [2 paragraphs unchanged] Cause-specific mortality in relation to body mass index in middle age in old age. Clarke R, Emberson J, Armitage J, Shipley M, Clark S, Linksted P , Fletcher A, Collins R. Arch Intern Med. 2007;167:1373-1378. [1 paragraph unchanged] Clarke R, Emberson J, Armitage J, Shipley M, Clark S, Linksted P , Fletcher A, Collins R. Arch Intern Med. 2007;167:1373-1378. [1 paragraph unchanged] Clarke R, Shipley M, Breeze E, Collins R, Marmot M, Halsey J, Fletcher A, Hemingway H. Eur J Cardiovasc Prev Rehabil. 2007;14:280-286. Eur J Cardiovasc Prev Rehabil. 2007;14:280-286. Survival in relation to angina symptoms and diagnosis among men aged 70-90 years: the Whitehall Study. Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley M J. BMJ. 2009;339:b3513. doi: 104136/bmj.63513 [1 paragraph unchanged] Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley M J. Batty GB, Kivimaki M, Morrison D, Huxley R, Smith GD, Clarke R, Marmot M, Shipley MJ. BMJ. 2009;339:b3513. doi: 104136/bmj.63513 [1 paragraph unchanged] Batty GB, Kivimaki M, Morrison D, Huxley R, Smith GD, Clarke R, Marmot M, Shipley MJ. [1 paragraph unchanged] Clarke R, Shipley M, Armitage J, Collins R, Harris W. Br J Nutr. 2009; 102:279 284. [1 paragraph unchanged] Clarke R, Shipley M, Armitage J, Collins R, Harris W. Clarke R, Shipley MJ. BMJ. 2009;339:b5097. Whitehall Study Authors’ reply. Br J Nutr. 2009; 102:279-284. Batty GD, Shipley MJ, Gunnell D, Smith GD, Ferrie JE, Clarke R, Marmot MG, Kivimaki M. J Epidemiol Comm Health. 2011;65:461-464. Whitehall Study Authors’ reply. Clarke R, Shipley MJ. BMJ. 2009;339:b5097. [1 paragraph unchanged] Batty GD, Shipley MJ, Gunnell D, Smith GD, Ferrie JE, Clarke R, Marmot MG, Kivimaki M. Batty GD, Kivimäki M, Clarke R, Davey Smith G, Shipley MJ. Cancer Causes Control. 2011;22:311-318. J Epidemiol Comm Health. 2011;65:461-464. [1 paragraph unchanged] Batty GD, Kivimäki M, Clarke R, Davey Smith G, Shipley MJ. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Eur Heart J. 2013;34:1365-74 Cancer Causes Control. 2011;22:311-318. Vitamin D and risk of death from vascular and non-vascular causes in the Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Influence on guidelines for the management of hypertension and blood lipids: Eur Heart J. 2013;34:1365-74 The 2002 report of the Prospective Studies Collaboration report on blood pressure and stroke and heart disease (Lewington et al, Lancet 2002), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies (Clarke et al, Am J Epidemiol 1999). Likewise, the 2007 report of the Prospective Studies Collaboration report on blood cholesterol and stroke and heart disease (Lewington et al, Lancet 2007), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies. These reports influenced JNC7 Guidelines on the Detection and Treatment of Hypertension in the USA and NICE guidelines for the management of hypertension and blood lipids in the UK in addition to the European Society of Cardiology reports on prevention of heart disease (Piepolo 2016) and detection and management of blood lipids (Capetano, 2016) and American Heart Association reports for prevention of heart disease over the last 15 years. References for benefits of study Lewington S, Clarke R, Quizilbash N, Peto R, Collins R for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: One million adults in 61 prospective studies. Lancet. 2002;360:1903-1913. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R on behalf of the Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual participant data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829-1839. Piepolo MF, Hoes AW, Agewal S, Albus C, Brotons C, Catapano AL, Cooney MT. 2016 guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37 (29): 2315-81. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37: 2999-3058. In addition to peer-reviewed scientific publications, the University of Oxford has also communicated with NHS and other organisations (Food Standards Agency) or Public Health England where outputs from the study will provide information needed for health strategies using up-to-date evidence on effects of cardiovascular risk factors on risk of death. These data will improve provision of health care delivery and health services in response to demands on health and social care in the present and the future. Lastly, data on blood levels of vitamin D (25(OH)D) in this study have guided policy on the relevance of vitamin D and specifically for testing for vitamin D for prediction of vascular and non-vascular causes of death in the UK. The study plans to conduct analyses for a series of scientific publications on the causes of mortality, particularly focusing on determinants of cardiovascular disease in old age in relation to cardiovascular risk factors measured in middle and old age. Importantly, the study contributed to a 2021 meta-analysis which showed significant associations of Vitamin D deficiency with CVD mortality and all-cause mortality. All outputs and publications contain only aggregated data with small numbers suppressed in line with HES Analysis Guide.

Expected measurable benefits

The study will conduct medical research into the causes of death in this sample of the UK population. It is anticipated that the results of the planned analysis will be published in peer review medical journals. The results from this study have helped to inform UK response to the epidemic of deaths from heart disease and stroke in 1970’s and 1980’s and the extent to which mortality from both of these diseases have declined thereafter. The analyses of the Whitehall study has provided data on life expectancy, and proportions of study participants dying at age 50-59, 60-69, 70-79, 80-89, 90-99 years, overall and for those with low and high levels of cardiovascular risk factors recorded in both middle and old-age. It is expected that he results will highlight the range in survival by levels of cardiovascular risk factors in middle and old age. Such information has guided public health strategies on the importance of awareness of control of common cardiovascular disease risk factors in routine clinical practice, which may influence differences in survival by 12-14 years, between low and high levels of cardiovascular disease risk factors. Anonymised data from this study were incorporated in the Prospective Studies Collaboration meta-analysis which guided public health policy on detection and treatment of elevated blood pressure and of elevated cholesterol levels in the UK and worldwide. Data from the resurvey on blood lipids and CHD mortality have helped to clarify the relevance of lipids for prediction of death from vascular disease in old age. Lastly, data on blood levels of vitamin D (25(OH)D) in this study have guided policy on the relevance of vitamin D and specifically for testing for vitamin D for prediction of vascular and non-vascular causes of death in the UK. The study will generate a series of scientific publications on the causes of mortality, particularly focusing on determinants of cardiovascular disease in old age in relation to cardiovascular risk factors measured in middle and old age. It will also generate reports on cardiovascular and non-vascular causes of death in relation to socioeconomic circumstances measured in both middle and old age. As well as peer-reviewed scientific publications, the University of Oxford will also communicate with NHS and other organisations (Food Standards Agency) or Public Health England where outputs from the study will provide information needed for health strategies using up-to-date evidence on effects of cardiovascular risk factors on risk of death. This will improve provision of health care delivery and health services in response to demands on health and social care in the present and the future.

Benefits reported

The study already made a major contribution to the identification of cardiovascular [17 words unchanged] blood cholesterol, elevated blood pressure and diabetes for heart disease death rates in is lower compared with upper employment grades which were not fully explained by established risk factors. The access work of the Prospective Studies Collaboration has helped to lifestyle and medical information guide NICE guidelines in both middle and old age allowed assessment the UK, European Society of prolonged differences in such risk factors Cardiology guidelines, American Heart Association guidelines on use of blood pressure lowering treatment for life expectancy and causes prevention of death in old age. cardiovascular disease [1 paragraph unchanged] Influence on guidelines for the management of hypertension and blood lipids: Derived data from this study were incorporated in the Prospective Studies Collaboration meta-analysis which guided public health policy on detection and treatment of elevated blood pressure and of elevated cholesterol levels in the UK and worldwide. Data from the resurvey on blood lipids and CHD mortality have helped to clarify the relevance of lipids for prediction of death from vascular disease in old age. No further data will be shared under this Agreement for meta-analysis, or for any other purpose, unless the level of derivation has been has been assessed and permitted by NHS Digital. The 2002 report of the Prospective Studies Collaboration report on blood pressure and stroke and heart disease (Lewington et al, Lancet 2002), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies (Clarke et al, Am J Epidemiol 1999). Likewise, the 2007 report of the Prospective Studies Collaboration report on blood cholesterol and stroke and heart disease (Lewington et al, Lancet 2007), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies. The study has conducted medical research into the causes of death in this sample of the UK population. The results have been published in peer review medical journals. The results from this study have helped to inform UK response to the epidemic of deaths from heart disease and stroke in 1970’s and 1980’s and the extent to which mortality from both of these diseases have declined thereafter. These reports influenced JNC7 Guidelines on the Detection and Treatment of Hypertension in the USA and NICE guidelines for the management of hypertension and blood lipids in the UK in addition to the European Society of Cardiology reports on prevention of heart disease (Piepolo 2016) and detection and management of blood lipids (Capetano, 2016) and American Heart Association reports for prevention of heart disease over the last 15 years. By 1982, investigators were able to show that the lower the status of the job held, the worse the health status. The findings led to the establishment of the second Whitehall Study in 1985, to further investigate the social inequalities of health, and continues to the present day. References for benefits of study Through analysis of mortality data it was revealed that lower grade employees were a third more like to die from various mortality causes than those employed at higher grades. This finding showed a clear social gradient in mortality and led to a second Whitehall Study being created that focused directly on the extent and causes of the social gradient. Lewington S, Clarke R, Quizilbash N, Peto R, Collins R for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: One million adults in 61 prospective studies. Lancet. 2002;360:1903-1913. As the follow-up study continues, the data previously disseminated in DARS-NIC-148044-RGS7W-v3.2 has yet to be analysed and therefore, no additional yielded benefits have been realised at he present. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R on behalf of the Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual participant data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829-1839. Piepolo MF, Hoes AW, Agewal S, Albus C, Brotons C, Catapano AL, Cooney MT. 2016 guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37 (29): 2315-81. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37: 2999-3058.

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

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits, Benefits reported.