Whitehall II

University College London (UCL) requires access to NHS England data for the purpose of the following research project: The Stress and Health Study. Also known as Whitehall II, this study was established to investigate the importance of social class for health. Looking towards the future, the study seeks to answer questions about how previous and current circumstances affect health and quality of life in an ageing cohort. Older people form the largest - and growing - age group in the UK, and the more UCL can find out from study participants, the better health policy, prevention and provision can be informed.

The aim of the study is to examine the interrelationships between biological, psychosocial and behavioural factors in the ageing process, and identify key determinants of late life depression, cognitive decline, chronic disease, and physical functioning. The study's healthy ageing cohort is an ideal platform for studying primary prevention of vascular disease (CHD, stroke) and diabetes. The cohort is now aged 62-84 years (2023 figure) and is measured for age-related physical and cognitive functioning and mental health. The study contributes to the evidence on the potential for preventing functional decline through therapeutic risk factor reduction and behavioural interventions.

The second purpose of the Whitehall II is; Public health research studies undertaken within the scope of the Whitehall II study, which aim to answer specific questions.

The Whitehall II Data Sharing Committee discuss and approve draft funding applications prior to submission. Proposals should conform to the core research themes published on UCL’s website (https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii) - “Our new research model integrates observational (the Stress and Health study), interventional and clinical approaches (other studies in the department) to address common research areas, such as physical and cognitive functioning, old-age mental health, age-related physical diseases and multimorbidity."

Only Whitehall II study Principal Investigators are permitted to submit proposals for public health research studies. The Data Sharing Committee review and approve draft applications. There is a UCL internal review prior to the submission of research applications. All applications are submitted to funding bodies which provide an independent peer-reviewed assessment of the applications. On average 1-2 applications made by the Whitehall II principal investigators is approved and subsequently funded each year.

The following are examples of approved research studies conducted by UCL researchers;

i) Prevention of Dementia by targeting risk factors, funded by the Medical Research Council (MRC) which focuses on understanding drivers of neurodegeneration and confusion of the causes and consequences of the disease due to the long latent phase of dementia have been a major contributor to a large number of unsuccessful drug and lifestyle trials for dementia

ii) Education, socioeconomic status and Aging: transitions from multimorbidity to functional limitations and mortality funded by NIH National Institute on Aging, using longitudinal data on the same set of persons followed prospectively over 30 years in the Whitehall study to identify how socioeconomic circumstances affect stages of ageing and underlying mechanisms. Examining the role of socioeconomic factors in the onset of chronic disease, progression to multimorbidity, to disability, and death using multi-state models which allow analysis of all these transitions.

iii) COVID-19 and Alzheimer's Disease & Related Dementias: a longitudinal approach funded by NIH National Institute on Aging. Age is the primary risk factor for severe COVID-19 and Alzheimer’s disease and related dementias (ADRD) the most common comorbidity in COVID-19 deaths in older deaths. Examining the intersection of ADRD and COVID-19 using the Whitehall study where risk factors (social, behavioural, biologic, and health-related), functioning (cardiovascular, cognitive, motor), and cognitive status (cognitive impairment and ADRD) have been perfectly characterized since 1985 using repeat clinical assessments.

iv) Role of mid- and late-life risk factors in social inequalities in Alzheimer's Disease and Related Dementias funded by NIH National Institute on Aging. This study is examining the role of environmental, sociocultural, behavioural, and biological factors in explaining social inequalities in ADRD.

v) Taking the long view: Identification of plasma protein biomarkers for dementia risk funded by The Wellcome Trust. The overarching goal of this collaborative project is to make a step change in knowledge of dementia biomarkers by focusing on the plasma proteome

The Whitehall II study website has a section which details all data sharing applications and approved applications https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/research/collaborations-and-consortia

The following NHS England data will be accessed:

· Demographics Data,

· Cancer Registrations

· Civil Registration Deaths

· HES Admitted Patient Care

· HES Outpatient

· HES Accident and Emergency

· Emergency Care Data Set (ECDS)

· Mental Health : Mental Health and Learning Disabilities Data Set, Mental Health Minimum Data Set, Mental Health Services Data Set

· Diagnostic Imaging Dataset

· COVID-19 Second Generation Surveillance System (SGSS)

· COVID-19 Vaccination Status

Whitehall II researchers require access to Hospital Episode Statistics (HES) data, Mental Health data, demographics, mortality, and cancer data for use within the programme of research aimed at assessing a number of factors associated with the ageing process and their effects on the physiological functions of participants in later life, identifying health outcomes of participants for analysis.

Demographics and mortality data are also used to ascertain status of participants to minimise the risk of causing distress by writing to deceased participants.

In addition, access to SGSS and Vaccination Status data sets are necessary because the eighth wave of clinical data collection was underway when COVID-19 became a pandemic. Data collection was halted and UCL are keen to resume this process in order to complete data collection at this wave. Before UCL can start data collection, it would be important to know the COVID-19 status of the study participants. This would ensure that the data can be used for addressing research questions on risk and prognostic factors. The uniqueness of this study is to be able to examine a wide range of social, biological and behavioural factors. In addition, it would allow UCL to handle contact with participants affected by COVID-19 with tact, given prior information.

The level of data will be identifiable – necessary to enable linkage of the data with data collected from other sources, including the participants themselves.

The data will be minimised as follows:

· Limited to data for a study cohort of 10,308 civil servants recruited to the cohort in 1985

· Limited to data between 2015/16- 2022/23.

University College London is the sponsor and controller as the organisation responsible for ensuring that the data will only be processed for the purposes 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”.

UCL School of Life and Medical Sciences facilitates research for the benefit of health and social care, specifically the Whitehall II study which aims to explore the relationship between risk factors, socio-economic status, physical and mental functioning and disease and mortality to provide an insight into the effects of life factors on areas of health to help improve services within the health and social care system - these objectives require processing of the data for reasons of public interest in the area of public health

The funding comes from multiple sources. Funders include:

· Medical Research Council (MRC, UK)

· National Institute on Aging (NIA, US)

· The Wellcome Trust

Funding to continue the work described will be sought on an ongoing basis.

Amazon Web Services provides cloud hosting services to UCL and will store the data as contracted by UCL.

VIRTUS Data Centre provides offsite back-up services but does not process the data.

UCL stores data on the Cloud provided by Amazon Web Services.

A focus group was instigated in 2016 involving 11 participants from the Stress & Health Study (Whitehall II Study). The day was divided into four separate topics focussing on:

1. Participant Experience

2. Operational Procedures

3. Data Quality

4. Future Participation

Regarding Future Participation it was reported that: “It was felt to be valuable now and for the future. It was considered to be worthwhile and of benefit to future generations as well as taking responsibility for one’s own health.” And “It made participants more aware of their own health as well as making a contribution to social welfare and the health of the nation.”

The expected outputs of the processing will be:

• Submissions to peer-reviewed journals

• Presentations at scientific conferences

All publications are listed on the Whitehall II study website. See: https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/publications

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.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Public events – scientific conferences

• Posters displayed at scientific conferences

• Press/media engagement

• Participant newsletters

The key benefit to the public/patients is that linkage to English and Welsh records is helping expand the knowledge base to which the Whitehall II study has already contributed. UCL’s analyses will continue to generate evidence to improve public health policies, clinical guidelines, health care professionals, workplaces and promote healthier lifestyles in the general public for the benefit of patients and the healthcare system.

Outputs from the Whitehall II study have also gained substantial standing with several policymakers in the development of clinical guidelines and policy documents. Whitehall II findings have been used as primary evidence in documents such as the European Guideline for cardiovascular disease prevention, the National Institute for Health and Care Excellence (NICE) Guideline of dementia prevention and the World Health Organisation (WHO) Social Determinants of health policy.

Whitehall II has contributed evidence to current clinical guidelines, such as the ‘European Guidelines on Cardiovascular Prevention in Clinical Practice’ (see Eur Heart J 2012;33:1635-1701 and Eur Heart J 2016;37:2315-2381) and the ‘Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association’ (see Stroke. 2014;45:2160-2236). UCL have used Whitehall II data in their state-of-the-art reviews on prediabetes (Tabak A,Kivimaki M. Lancet 2013; 379:2279-2290) and stress (Kivimaki M, Steptoe A. Nature Reviews Cardiology 2018;15:215-229) to inform health professionals and policymakers in the UK and elsewhere.

The Whitehall II study has contributed evidence to the World Health Organization (WHO) policy documents for reducing social inequalities in health globally (Commission of Social Determinants in Health 2008) and the European and the UK reviews of inequalities and working conditions (Review of Social Determinants and the Health Divide in the WHO European Region, updated in 2014 and Fair Society, Healthy Lives, 2010) and developed a guide for evidence-based public health in a project led by the UK National Institute of Clinical Excellence (NICE, Killoran 2009). In addition, the study has provided evidence to European Union Occupational Safety and Health recommendations and contributed to priority settings in occupational health research at a European level.

Furthermore, the Whitehall II study has contributed evidence to the American Heart Association prevention policy, which in turn influences UK policy (American Heart Association Behavior Change Committee of the Council on Epidemiology and Prevention, Council on Lifestyle and Cardiometabolic Health, Council for High Blood Pressure Research, and Council on Cardiovascular and Stroke Nursing. ‘Better population Health through behaviour change in adults: a call to action’ Circulation. 2013 Nov5;128(19):2169-76). The paper on long working hours and stroke (Lancet. 2015 Oct 31;386(10005):1739-46) was referenced by WHO (Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. World Health Organization. http://www.who.int/iris/handle/10665/204585) and received widespread media coverage (rated the 12th in the 100 in the world Altmetric ratings).

Two Whitehall papers contributed evidence to NICE guidelines on Dementia (NG16) published in October 2015. The papers were referenced in “Dementia, disability and frailty in later life – mid-life approaches to delay or prevent onset”. (Sabia S, Singh‑Manoux A, Hagger‑Johnson G et al. (2012) Influence of individual and combined healthy behaviours on successful ageing. Canadian Medical Association Journal doi: 10.1503/cmaj.121080; Singh‑Manoux A, Marmot MG, Glymour M et al. (2011) Does cognitive reserve shape cognitive decline? Annals of Neurology 70: 296–304)

More recently, a number of Whitehall’s papers on dementia have found a home in high-impact journals. An example is the paper on alcohol consumption and cognitive decline ‘Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: a longitudinal cohort study’ (BMJ 2017;357:j2353) received widespread media coverage, demonstrating the neurotoxicity of alcohol consumption (the paper was rated in the top 5% of all outputs scored by Altmetric). Taken together, these papers contribute to advances in understanding optimal time frames for intervention on risk factors for dementia.

The Whitehall II study was set up in 1985 as a prospective cohort project to explore the relationship between socioeconomic status, stress and cardiovascular disease. The study, based at University College London (UCL), recruited civil servants working in London. The participants were sent a self-completion questionnaire covering a wide range of topics, and underwent a comprehensive clinical examination.

Since 1985 there have been twelve phases of data collection of similar nature. These data have always been collected on the original cohort recruited in 1985, and no additional recruitment of participants has taken place since then. In addition to cardiovascular measures, the Whitehall II study has over the years focused on all chronic diseases and also added further measures to test physical functioning, cognitive functioning, mental health, measures of cortisol levels and new cardiovascular tests such as Heart Rate Variability (HRV) and Pulse Wave Velocity (PWV).

1. The GDPR Legal Basis is Article 6(1)(e) Task in the public interest and Article 9(2)(j):

- Public authority: The Data Protection Act 2018 defines 'public authority' as that defined under the Freedom of Information (FOI) Act 2000.

- Necessary for the performance of the task: As part of the application process, the requirement for the data requested has been assessed and NHS Digital is content that it is appropriate, necessary and proportionate for the performance of the task described in the purpose statement and that there is no other reasonable and less intrusive means for the data processor to achieve their purpose.

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 data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

UCL’s purpose is to expand knowledge within fields of study by conducting and promoting research within such branches, including Life and Medical Sciences, through its fulfilment of the obligation to provide an environment in which research that benefits branches of learning can take place. Research projects conducted within the different courses of study receive backing from organisations working within the specific fields where the use of results could benefit this area. In the instance of the Whitehall II study, funding has been received from organisations such as the Medical Research Council, the British Heart Foundation, the US NIH National Institute for Aging and the National Heart, Lung and Blood Institute. Processing of the data being requested is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the data controller. To achieve this purpose and the obligations of the data controller (sub-article 6(1)(e)) UCL School of Life and Medical Sciences facilitates research for the benefit of health and social care, specifically the Whitehall II study which aims to explore the relationship between risk factors, socio-economic status, physical and mental functioning and disease and mortality to provide an insight into the effects of life factors on areas of health to help improve services within the health and social care system - these objectives require processing of the data for reasons of public interest in the area of public health (sub-article 9(2)(j)).

There are three distinct aspects to the study:

1) The compilation of research data, which consists of the collection of self-completion questionnaires and medical examination data from the Whitehall II cohort participants. Medical data and mortality data from this cohort are also obtained through data linkage with external data sources such as NHS Digital. The totality of these data are compiled into the Whitehall II research database for use as a research resource;

2) Public health research studies undertaken within the scope of the Whitehall II study, which aim to answer specific questions and are primarily funded by grants from the Medical Research Council and the British Heart Foundation. Further studies have been funded by the European Commission Horizon 2020 and the Economic and Social Research Council. No raw or record level NHS Digital data is shared with funders.

3) Making pseudonymised data available to the scientific community for use in UCL-approved research studies beyond the scope of the Whitehall II study. Any data supplied to third parties, whether as part of the EU-funded LIFEPATH project or for any other purpose will comprise of:

a. Self-reported data provided voluntarily by the participants; and/or

b. Variables derived from the Civil Registration data. Specifically ‘yes’ or ‘no’ indicators to indicate if the participant is deceased and, if so, if specific causes of death were applicable or not; and/or

c. Clinical events derived from a set of diagnoses in the form of ‘yes’ or ‘no’ variables to indicate if the participant has had a specific clinical event such as a stroke, cancer or CHD episode.

HES derived variables created by the study team indicates whether a medical condition is present based on the HES ICD-10 codes (e.g. HES_CHD, HES_STROKE, etc with values ‘yes’ or ‘no’) are also shared. As an example, if a participant self-reported a stroke, the applicant would cross-check the data with the derived HES data to verify the diagnosis. If verified, the research data that could potentially be made available to third parties would include a ‘yes’ or ‘no’ indicator confirming the self-reported stroke.

Whitehall II researchers require access to identifiable Hospital Episode Statistics (HES) data, Diagnostic Imaging Data, Mental Health data, mortality and cancer data for use within the programme of research aimed at assessing a number of factors associated with the ageing process and their effects on the physiological functions of participants in later life, identifying health outcomes of participants for analysis. The required data will be minimised by being restricted to the cohort submitted for tracing. Whitehall II researchers require access to latest available data for each of the data products (2017/18 & 2018/19 periods for HES data) in order to effectively access health outcomes in participants in recent years.

The data will be used for public health research purposes. Based on 30 years of follow-up, the aim is to examine the interrelationships between biological, psychosocial and behavioural factors in the ageing process, and identify key determinants of late life depression, cognitive decline, chronic disease, and physical functioning. The study’s healthy ageing cohort is an ideal platform for studying primary prevention of vascular disease (CHD, stroke) and diabetes. The cohort is now aged 62-84 years and is measured for age-related physical and cognitive functioning and mental health. The study contributes to the evidence on the potential for preventing functional decline through therapeutic risk factor reduction and behavioural interventions.

As part of the current NIH funded research programme, the research programme will:

i. demonstrate socioeconomic disparities and underlying mechanisms in chronic diseases, transitions to multimorbidity and mortality

ii. establish whether socioeconomic factors buffer the association of multimorbidity with disability, and that of disability with mortality and identify underlying mechanisms

iii. assess the role of socioeconomic status in shaping the association of functional impairment (subjective and objective assessments) with mortality, and its role in terminal decline, i.e. accelerated decline in function prior to death by 31/05/2023.

In the MRC-funded research programme, the research programme will:

i. confirm or refute the hypothesised associations of the Lancet 2017 Commission risk factors with cognitive decline, clinically-verified Alzheimer's disease and dementia

ii. determine how trajectories of diseases over the adult lifecourse shape risk of dementia

iii. test proteomic and metabolite biomarkers, singly and in combination, as early predictors of cognitive function, Alzheimer's disease and dementia, by 31/01/2022.

The BHF-funded research programme allows the research team to determine how arterial stiffening, a proxy of vascular ageing, is associated with the development and progression of cardiometabolic diseases by 31/08/2021. In addition, the team's international collaborative work will reveal how social, occupational and health related determinants affect working life expectancy and whether exposure to work-related adverse social behaviours are likely to have long-term impacts on health, by the end of 2022. Furthermore, over the next 5 years the research team's international omics consortia will identify new genetic variants and metabolomic and proteomic factors that contribute to a range of different diseases.

The aim is to follow-up participants across transitions from a healthy state to pre-clinical and manifest disease, multi morbidity and death. Due to the longitudinal nature of the study, the aim is to actively collect questionnaire and clinical data until 2030. After this date, passive follow-up will continue until all cohort members have died. Once the Whitehall participants cannot be followed up anymore, their identifiable data will be destroyed and the study will move to using pseudonymised data only. The research analysis will need to continue for as long as the study is active. In accordance with the principles and guidelines on good research practice of the MRC (the main funder), the research data and related material will need to be retained for a minimum of 10 years after the study has been completed.

Self-reported clinical events data are open to major limitations of bias, including missing responses and attrition. Therefore, since 1997, UCL have supplemented the self-reported events with information extracted from GP and paper hospital notes, and also with data provided by NHS Digital.

The Whitehall II MRC grant (MR/R024227/1 - The Whitehall II study: A core resource for ageing research) has dementia, disability and depression as the outcome variables. In order to be able to study these outcomes in older individuals it is crucial to have complete data from all possible sources. Data on psychiatric conditions are important outcomes in their own right, but it is also needed to study other conditions. For example, the diagnosis of dementia involves ruling out major psychiatric disorder as an underlying condition for the observed clinical phenotype. In order to do so, external data on psychiatric conditions is required. This cannot possibly be achieved without access to the Mental Health and Learning Disabilities Data Set (MHLDDS). In addition, information on clinical procedures, such as brain MRI or CT, is important to evaluate the validity of dementia diagnosis and changes in diagnostic testing over time, a potential source of bias that needs to be considered longitudinal analyses. For this reason, records from the Digital Imaging Dataset are also needed for the Whitehall II dementia project.

University College London are the sole data controller for this agreement and the processing of data is conducted solely by researchers within the University College London School of Medical Sciences.

All published outputs will be aggregate with cells with small numbers supressed or aggregated in line with the HES Analysis Guide.

The Whitehall II researchers will use peer-review journals to report the contribution of midlife inflammatory, vascular, and metabolic factors to chronic disease, depression, cognitive impairment, dementia and functional health in later life. They will also assess whether the adoption of healthy lifestyle even at older ages modifies functional trajectories, and aim to develop multi-factorial predictive algorithms, like those developed for cardiovascular diseases, to facilitate early identification of adverse ageing outcomes.

The study dissemination plan, which has been very successful up to now (please see examples below), involves publications in high impact scientific journals, scientific meetings, briefing papers for policy makers, regular and ad hoc meetings with interested parties such as Public Health England.

A research dataset will be created for the UCL study researchers named in the Data Sharing Agreement. It will contain all records with all directly identifiable data removed. It will include the study ID but no personal variables. Any sensitive variables that might identify a participant (such as hospital dates or full ICD-10 codes) will never be published, reported or provided to third parties.

The scientific conclusions of the Whitehall II study will be published in international peer-reviewed journals starting from a few months after the data are available. UCL aim to continue publishing the analyses in journals with high coverage and high impact factor and UCL’s preference is journals with an open access option (web version of the paper available free of charge). Some examples of journals where the Whitehall II researchers have published their results since 2017 are Lancet, British Medical Journal, PLoS Medicine, JAMA Psychiatry, European Heart Journal, Alzheimer's & Dementia, etc.

A full list of the project publications to date is published on the Whitehall II website

(https://www.ucl.ac.uk/iehc/research/epidemiology-and-public-health/research/whitehall-ii/publications).

Outputs from the Whitehall II study have also gained a substantial standing with several policymakers in the development of clinical guidelines and policy documents. Whitehall II findings have been used as primary evidence in documents such as the European Guideline for cardiovascular disease prevention, National Institute for Health and Care Excellence (NICE) Guideline of dementia prevention and the World Health Organisation (WHO) Social Determinants of health policy.

UCL distribute outputs regularly throughout the year, aiming to publish multiple scientific papers, several conferences and key notes per year. Such outputs for 2020 so far can be seen listed on the publication webpage linked above. UCL has also regularly published health-related advice via its website, accessible to the public, aiming to expand practical channels for outputs to be communicated with the public. For future outputs, SLMS researchers plan to publish analyses of novel biomarkers and lifestyle factors predicting neurodegeneration, frailty, disability and multi-morbidity. UCL will be looking to replicate previous outputs focused around these areas, distributing results via multiple channels such as scientific peer-reviewed journals, website publications offering health-related advice, books and social media.

The key benefit to the public/patients is that linkage to English and Welsh records is helping expand the knowledge base to which the Whitehall II study has already contributed. UCL’s analyses will continue to generate evidence to improve public health policies, clinical guidelines, health care professionals, workplaces and promote healthier lifestyles in the general public for the benefit of patients and the healthcare system.

Evidence from previous benefits:

Whitehall II have contributed evidence to current clinical guidelines, such as the ‘European Guidelines on Cardiovascular Prevention in Clinical Practice’ (see Eur Heart J 2012;33:1635-1701 and Eur Heart J 2016;37:2315-2381) and the ‘Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association’ (see Stroke. 2014;45:2160-2236). UCL have used Whitehall II data in their state-of-the-art reviews on prediabetes (Tabak A,Kivimaki M. Lancet 2013; 379:2279-2290) and stress (Steptoe A, Kivimaki, M. Nature Reviews Cardiology 2012;9(6):360-70 and Steptoe A, Kivimaki, M . Annu Rev Public Health 2013;34:337-54.) to inform health professionals and policy makers in the UK and elsewhere.

The Whitehall II study has contributed evidence to the World Health Organization (WHO) policy documents for reducing social inequalities in heath globally (Commission of Social Determinants in Health 2008) and the European and the UK reviews of inequalities and working conditions (Review of Social Determinants and the Health Divide in the WHO European Region, updated in 2014 and Fair Society, Healthy Lives, 2010) and developed a guide for evidence-based public health in a project led by the UK National Institute of Clinical Excellence (NICE, Killoran 2009). In addition, the study has provided evidence to European Union Occupational Safety and Health recommendations and contributed to priority settings in occupational health research at a European level (https://osha.europa.eu/en/tools-andpublications/publications/e-facts/efact18/view; https://osha.europa.eu/en/tools-andpublications/publications/reports/management-psychosocial-risks-esener;https://osha.europa.eu/en/tools andpublications/publications/reports/summary-priorities-for-osh-research-in-eu-for-2013-20).

Furthermore, the Whitehall II study has contributed evidence to the American Heart Association prevention policy, which in turn influences UK policy (American Heart Association Behavior Change Committee of the Council on Epidemiology and Prevention, Council on Lifestyle and Cardiometabolic Health, Council for High Blood Pressure Research, and Council on Cardiovascular and Stroke Nursing. ‘Better population Health through behaviour change in adults: a call to action’ Circulation. 2013 Nov5;128(19):2169-76). The paper on long working hours and stroke (Lancet. 2015 Oct 31;386(10005):1739-46) was referenced by WHO (Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. World Health Organization. http://www.who.int/iris/handle/10665/204585) and received widespread media coverage (rated the 12th in the 100 in the world Altmetric ratings).

Two Whitehall papers contributed evidence to NICE guidelines on Dementia (NG16) published in October 2015. The papers were referenced in “Dementia, disability and frailty in later life – mid-life approaches to delay or prevent onset”. (Sabia S, Singh‑Manoux A, Hagger‑Johnson G et al. (2012) Influence of individual and combined healthy behaviours on successful aging. Canadian Medical Association Journal doi: 10.1503/cmaj.121080; Singh‑Manoux A, Marmot MG, Glymour M et al. (2011) Does cognitive reserve shape cognitive decline? Annals of Neurology 70: 296–304)

More recently, a number of our papers on dementia have found a home in high impact journals. An example is the paper on alcohol consumption and cognitive decline ‘Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study’ (BMJ 2017;357:j2353) received widespread media coverage, demonstrating the neurotoxicity of alcohol consumption (the paper was rated in the top 5% of all outputs scored by Altmetric). Taken together, these papers contribute to advances in understanding optimal time frames for intervention on risk factors for dementia.

The Whitehall II study was set up in 1985 as a prospective cohort project to explore the relationship between socioeconomic status, stress and cardiovascular disease. The study, based at University College London (UCL), recruited civil servants working in London. The participants were sent a self-completion questionnaire covering a wide range of topics, and underwent a comprehensive clinical examination.

Since 1985 there have been twelve phases of data collection of similar nature. These data have always been collected on the original cohort recruited in 1985, and no additional recruitment of participants has taken place since then. In addition to cardiovascular measures, the Whitehall II study has over the years focused on all chronic diseases and also added further measures to test physical functioning, cognitive functioning, mental health, measures of cortisol levels and new cardiovascular tests such as Heart Rate Variability (HRV) and Pulse Wave Velocity (PWV).

1. The GDPR Legal Basis is Article 6(1)(e) Task in the public interest and Article 9(2)(j):

- Public authority: The Data Protection Act 2018 defines 'public authority' as that defined under the Freedom of Information (FOI) Act 2000.

- Necessary for the performance of the task: As part of the application process, the requirement for the data requested has been assessed and NHS Digital is content that it is appropriate, necessary and proportionate for the performance of the task described in the purpose statement and that there is no other reasonable and less intrusive means for the data processor to achieve their purpose.

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 data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

UCL’s purpose is to expand knowledge within fields of study by conducting and promoting research within such branches, including Life and Medical Sciences, through its fulfilment of the obligation to provide an environment in which research that benefits branches of learning can take place. Research projects conducted within the different courses of study receive backing from organisations working within the specific fields where the use of results could benefit this area. In the instance of the Whitehall II study, funding has been received from organisations such as the Medical Research Council, the British Heart Foundation, the US NIH National Institute for Aging and the National Heart, Lung and Blood Institute. Processing of the data being requested is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the data controller. To achieve this purpose and the obligations of the data controller (sub-article 6(1)(e)) UCL School of Life and Medical Sciences facilitates research for the benefit of health and social care, specifically the Whitehall II study which aims to explore the relationship between risk factors, socio-economic status, physical and mental functioning and disease and mortality to provide an insight into the effects of life factors on areas of health to help improve services within the health and social care system - these objectives require processing of the data for reasons of public interest in the area of public health (sub-article 9(2)(j)).

There are three distinct aspects to the study:

1) The compilation of research data, which consists of the collection of self-completion questionnaires and medical examination data from the Whitehall II cohort participants. Medical data and mortality data from this cohort are also obtained through data linkage with external data sources such as NHS Digital. The totality of these data are compiled into the Whitehall II research database for use as a research resource;

2) Public health research studies undertaken within the scope of the Whitehall II study, which aim to answer specific questions and are primarily funded by grants from the Medical Research Council and the British Heart Foundation. Further studies have been funded by the European Commission Horizon 2020 and the Economic and Social Research Council. No raw or record level NHS Digital data is shared with funders.

3) Making pseudonymised data available to the scientific community for use in UCL-approved research studies beyond the scope of the Whitehall II study. Any data supplied to third parties, whether as part of the EU-funded LIFEPATH project or for any other purpose will comprise of:

a. Self-reported data provided voluntarily by the participants; and/or

b. Variables derived from the Civil Registration data. Specifically ‘yes’ or ‘no’ indicators to indicate if the participant is deceased and, if so, if specific causes of death were applicable or not; and/or

c. Clinical events derived from a set of diagnoses in the form of ‘yes’ or ‘no’ variables to indicate if the participant has had a specific clinical event such as a stroke, cancer or CHD episode.

HES derived variables created by the study team indicates whether a medical condition is present based on the HES ICD-10 codes (e.g. HES_CHD, HES_STROKE, etc with values ‘yes’ or ‘no’) are also shared. As an example, if a participant self-reported a stroke, the applicant would cross-check the data with the derived HES data to verify the diagnosis. If verified, the research data that could potentially be made available to third parties would include a ‘yes’ or ‘no’ indicator confirming the self-reported stroke.

Whitehall II researchers require access to identifiable Hospital Episode Statistics (HES) data, Diagnostic Imaging Data, Mental Health data, mortality and cancer data for use within the programme of research aimed at assessing a number of factors associated with the ageing process and their effects on the physiological functions of participants in later life, identifying health outcomes of participants for analysis. The required data will be minimised by being restricted to the cohort submitted for tracing. Whitehall II researchers require access to latest available data for each of the data products (2017/18 & 2018/19 periods for HES data) in order to effectively access health outcomes in participants in recent years.

The data will be used for public health research purposes. Based on 30 years of follow-up, the aim is to examine the interrelationships between biological, psychosocial and behavioural factors in the ageing process, and identify key determinants of late life depression, cognitive decline, chronic disease, and physical functioning. The study’s healthy ageing cohort is an ideal platform for studying primary prevention of vascular disease (CHD, stroke) and diabetes. The cohort is now aged 62-84 years and is measured for age-related physical and cognitive functioning and mental health. The study contributes to the evidence on the potential for preventing functional decline through therapeutic risk factor reduction and behavioural interventions.

As part of the current NIH funded research programme, the research programme will:

i. demonstrate socioeconomic disparities and underlying mechanisms in chronic diseases, transitions to multimorbidity and mortality

ii. establish whether socioeconomic factors buffer the association of multimorbidity with disability, and that of disability with mortality and identify underlying mechanisms

iii. assess the role of socioeconomic status in shaping the association of functional impairment (subjective and objective assessments) with mortality, and its role in terminal decline, i.e. accelerated decline in function prior to death by 31/05/2023.

In the MRC-funded research programme, the research programme will:

i. confirm or refute the hypothesised associations of the Lancet 2017 Commission risk factors with cognitive decline, clinically-verified Alzheimer's disease and dementia

ii. determine how trajectories of diseases over the adult lifecourse shape risk of dementia

iii. test proteomic and metabolite biomarkers, singly and in combination, as early predictors of cognitive function, Alzheimer's disease and dementia, by 31/01/2022.

The BHF-funded research programme allows the research team to determine how arterial stiffening, a proxy of vascular ageing, is associated with the development and progression of cardiometabolic diseases by 31/08/2021. In addition, the team's international collaborative work will reveal how social, occupational and health related determinants affect working life expectancy and whether exposure to work-related adverse social behaviours are likely to have long-term impacts on health, by the end of 2022. Furthermore, over the next 5 years the research team's international omics consortia will identify new genetic variants and metabolomic and proteomic factors that contribute to a range of different diseases.

The aim is to follow-up participants across transitions from a healthy state to pre-clinical and manifest disease, multi morbidity and death. Due to the longitudinal nature of the study, the aim is to actively collect questionnaire and clinical data until 2030. After this date, passive follow-up will continue until all cohort members have died. Once the Whitehall participants cannot be followed up anymore, their identifiable data will be destroyed and the study will move to using pseudonymised data only. The research analysis will need to continue for as long as the study is active. In accordance with the principles and guidelines on good research practice of the MRC (the main funder), the research data and related material will need to be retained for a minimum of 10 years after the study has been completed.

Self-reported clinical events data are open to major limitations of bias, including missing responses and attrition. Therefore, since 1997, UCL have supplemented the self-reported events with information extracted from GP and paper hospital notes, and also with data provided by NHS Digital.

The Whitehall II MRC grant (MR/R024227/1 - The Whitehall II study: A core resource for ageing research) has dementia, disability and depression as the outcome variables. In order to be able to study these outcomes in older individuals it is crucial to have complete data from all possible sources. Data on psychiatric conditions are important outcomes in their own right, but it is also needed to study other conditions. For example, the diagnosis of dementia involves ruling out major psychiatric disorder as an underlying condition for the observed clinical phenotype. In order to do so, external data on psychiatric conditions is required. This cannot possibly be achieved without access to the Mental Health and Learning Disabilities Data Set (MHLDDS). In addition, information on clinical procedures, such as brain MRI or CT, is important to evaluate the validity of dementia diagnosis and changes in diagnostic testing over time, a potential source of bias that needs to be considered longitudinal analyses. For this reason, records from the Digital Imaging Dataset are also needed for the Whitehall II dementia project.

University College London are the sole data controller for this agreement and the processing of data is conducted solely by researchers within the University College London School of Medical Sciences.

All published outputs will be aggregate with small number supressed in line with the HES Analysis Guide.

The Whitehall II researchers will use peer-review journals to report the contribution of midlife inflammatory, vascular, and metabolic factors to chronic disease, depression, cognitive impairment and functional health in later life. They will also assess whether the adoption of healthy lifestyle even at older ages modifies functional trajectories, and aim to develop multi-factorial predictive algorithms, like those developed for cardiovascular diseases, to facilitate early identification of

adverse ageing outcomes.

The study dissemination plan, which has been very successful up to now (please see examples below), involves publications in high impact scientific journals, scientific meetings, briefing papers for policy makers, regular and ad hoc meetings with interested parties such as Public Health England.

A research dataset will be created for the UCL study researchers named in the Data Sharing Agreement. It will contain all records with all directly identifiable data removed. It will include the study ID but no personal variables. Any sensitive variables that might identify a participant (such as hospital dates or full ICD-10 codes) will never be published, reported or provided to third parties.

The scientific conclusions of the Whitehall II study will be published in international peer-reviewed journals starting from a few months after the data are available. UCL aim to continue publishing the analyses in journals with high coverage and high impact factor and UCL’s preference is journals with an open access option (web version of the paper available free of charge). Some examples of journals where the Whitehall II researchers have published their results in 2017 and 2018 are Lancet, British Medical Journal, PLoS Medicine, JAMA Psychiatry, European Heart Journal, Alzheimer's & Dementia, etc.

A full list of the project publications to date is published on the Whitehall II website

(https://www.ucl.ac.uk/iehc/research/epidemiology-and-public-health/research/whitehall-ii/publications).

Outputs from the Whitehall II study have also gained a substantial standing with several policymakers in the development of clinical guidelines and policy documents. Whitehall II findings have been used as primary evidence in documents such as the European Guideline for cardiovascular disease prevention, National Institute for Health and Care Excellence (NICE) Guideline of dementia prevention and the World Health Organisation (WHO) Social Determinants of health policy.

UCL distribute outputs regularly throughout the year, aiming to publish multiple scientific papers, several conferences and key notes per year. Such outputs for 2019 so far can be seen listed on the publication webpage linked above. UCL has also regularly published health-related advice via its website, accessible to the public, aiming to expand practical channels for outputs to be communicated with the public. For future outputs, SLMS researchers plan to publish analyses of novel biomarkers and lifestyle factors predicting neurodegeneration, frailty, disability and multi-morbidity. UCL will be looking to replicate previous outputs focused around these areas, distributing results via multiple channels such as scientific peer-reviewed journals, website publications offering health-related advice, books and social media.

The key benefit to the public/patients is that linkage to English and Welsh records is helping expand the knowledge base to which the Whitehall II study has already contributed. UCL’s analyses will continue to generate evidence to improve public health policies, clinical guidelines, health care professionals, workplaces and promote healthier lifestyles in the general public for the benefit of patients and the healthcare system.

Evidence from previous benefits:

Whitehall II have contributed evidence to current clinical guidelines, such as the ‘European Guidelines on Cardiovascular Prevention in Clinical Practice’ (see Eur Heart J 2012;33:1635-1701 and Eur Heart J 2016;37:2315-2381) and the ‘Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association’ (see Stroke. 2014;45:2160-2236). UCL have used Whitehall II data in their state-of-the-art reviews on prediabetes (Tabak A,Kivimaki M. Lancet 2013; 379:2279-2290) and stress (Steptoe A, Kivimaki, M. Nature Reviews Cardiology 2012;9(6):360-70 and Steptoe A, Kivimaki, M . Annu Rev Public Health 2013;34:337-54.) to inform health professionals and policy makers in the UK and elsewhere.

The Whitehall II study has contributed evidence to the World Health Organization (WHO) policy documents for reducing social inequalities in heath globally (Commission of Social Determinants in Health 2008) and the European and the UK reviews of inequalities and working conditions (Review of Social Determinants and the Health Divide in the WHO European Region, updated in 2014 and Fair Society, Healthy Lives, 2010) and developed a guide for evidence-based public health in a project led by the UK National Institute of Clinical Excellence (NICE, Killoran 2009). In addition, the study has provided evidence to European Union Occupational Safety and Health recommendations and contributed to priority settings in occupational health research at a European level (https://osha.europa.eu/en/tools-andpublications/publications/e-facts/efact18/view; https://osha.europa.eu/en/tools-andpublications/publications/reports/management-psychosocial-risks-esener;https://osha.europa.eu/en/tools andpublications/publications/reports/summary-priorities-for-osh-research-in-eu-for-2013-20).

Furthermore, the Whitehall II study has contributed evidence to the American Heart Association prevention policy, which in turn influences UK policy (American Heart Association Behavior Change Committee of the Council on Epidemiology and Prevention, Council on Lifestyle and Cardiometabolic Health, Council for High Blood Pressure Research, and Council on Cardiovascular and Stroke Nursing. ‘Better population Health through behaviour change in adults: a call to action’ Circulation. 2013 Nov5;128(19):2169-76). The paper on long working hours and stroke (Lancet. 2015 Oct 31;386(10005):1739-46) was referenced by WHO (Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. World Health Organization. http://www.who.int/iris/handle/10665/204585) and received widespread media coverage (rated the 12th in the 100 in the world Altmetric ratings).

Two Whitehall papers contributed evidence to NICE guidelines on Dementia (NG16) published in October 2015. The papers were referenced in “Dementia, disability and frailty in later life – mid-life approaches to delay or prevent onset”. (Sabia S, Singh‑Manoux A, Hagger‑Johnson G et al. (2012) Influence of individual and combined healthy behaviours on successful aging. Canadian Medical Association Journal doi: 10.1503/cmaj.121080; Singh‑Manoux A, Marmot MG, Glymour M et al. (2011) Does cognitive reserve shape cognitive decline? Annals of Neurology 70: 296–304)

More recently, a Whitehall II paper on alcohol consumption and cognitive decline ‘Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study’ (BMJ 2017;357:j2353) received widespread media coverage, demonstrating the neurotoxicity of alcohol consumption (the paper was rated in the top 5% of all outputs scored by Altmetric).

The Whitehall II study was set up in 1985 as a prospective cohort project to explore the relationship between socioeconomic status, stress and cardiovascular disease. The study, based at University College London (UCL), recruited civil servants working in London. The participants were sent a self-completion questionnaire covering a wide range of topics, and underwent a comprehensive clinical examination.

Since 1985 there have been twelve phases of data collection of similar nature. These data have always been collected on the original cohort recruited in 1985, and no additional recruitment of participants has taken place since then. In addition to cardiovascular measures, the Whitehall II study has over the years focused on all chronic diseases and also added further measures to test physical functioning, cognitive functioning, mental health, measures of cortisol levels and new cardiovascular tests such as Heart Rate Variability (HRV) and Pulse Wave Velocity (PWV).

1. The GDPR Legal Basis is Article 6(1)(e) Task in the public interest and Article 9(2)(j):

- Public authority: The Data Protection Act 2018 defines 'public authority' as that defined under the Freedom of Information (FOI) Act 2000.

- Necessary for the performance of the task: As part of the application process, the requirement for the data requested has been assessed and NHS Digital is content that it is appropriate, necessary and proportionate for the performance of the task described in the purpose statement and that there is no other reasonable and less intrusive means for the data processor to achieve their purpose.

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 data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

UCL’s purpose is to expand knowledge within fields of study by conducting and promoting research within such branches, including Life and Medical Sciences, through its fulfilment of the obligation to provide an environment in which research that benefits branches of learning can take place. Research projects conducted within the different courses of study receive backing from organisations working within the specific fields where the use of results could benefit this area. In the instance of the Whitehall II study, funding has been received from organisations such as the Medical Research Council, the British Heart Foundation, the US NIH National Institute for Aging and the National Heart, Lung and Blood Institute. Processing of the data being requested is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the data controller. To achieve this purpose and the obligations of the data controller (sub-article 6(1)(e)) UCL School of Life and Medical Sciences facilitates research for the benefit of health and social care, specifically the Whitehall II study which aims to explore the relationship between risk factors, socio-economic status, physical and mental functioning and disease and mortality to provide an insight into the effects of life factors on areas of health to help improve services within the health and social care system - these objectives require processing of the data for reasons of public interest in the area of public health (sub-article 9(2)(j)).

There are three distinct aspects to the study:

1) The compilation of research data, which consists of the collection of self-completion questionnaires and medical examination data from the Whitehall II cohort participants. Medical data and mortality data from this cohort are also obtained through data linkage with external data sources such as NHS Digital. The totality of these data are compiled into the Whitehall II research database for use as a research resource;

2) Public health research studies undertaken within the scope of the Whitehall II study, which aim to answer specific questions and are primarily funded by grants from the Medical Research Council and the British Heart Foundation. Further studies have been funded by the European Commission Horizon 2020 and the Economic and Social Research Council. No raw or record level NHS Digital data is shared with funders.

3) Making pseudonymised data available to the scientific community for use in UCL-approved research studies beyond the scope of the Whitehall II study. Any data supplied to third parties, whether as part of the EU-funded LIFEPATH project or for any other purpose will comprise of:

a. Self-reported data provided voluntarily by the participants; and/or

b. Variables derived from the Civil Registration data. Specifically ‘yes’ or ‘no’ indicators to indicate if the participant is deceased and, if so, if specific causes of death were applicable or not; and/or

c. Clinical events derived from a set of diagnoses in the form of ‘yes’ or ‘no’ variables to indicate if the participant has had a specific clinical event such as a stroke, cancer or CHD episode.

HES derived variables created by the study team indicates whether a medical condition is present based on the HES ICD-10 codes (e.g. HES_CHD, HES_STROKE, etc with values ‘yes’ or ‘no’) are also shared. As an example, if a participant self-reported a stroke, the applicant would cross-check the data with the derived HES data to verify the diagnosis. If verified, the research data that could potentially be made available to third parties would include a ‘yes’ or ‘no’ indicator confirming the self-reported stroke.

Whitehall II researchers require access to identifiable Hospital Episode Statistics (HES) data, Diagnostic Imaging Data, Mental Health data, mortality and cancer data for use within the programme of research aimed at assessing a number of factors associated with the ageing process and their effects on the physiological functions of participants in later life, identifying health outcomes of participants for analysis. The required data will be minimised by being restricted to the cohort submitted for tracing. Whitehall II researchers require access to latest available data for each of the data products (2017/18 & 2018/19 periods for HES data) in order to effectively access health outcomes in participants in recent years.

The data will be used for public health research purposes. Based on 30 years of follow-up, the aim is to examine the interrelationships between biological, psychosocial and behavioural factors in the ageing process, and identify key determinants of late life depression, cognitive decline, chronic disease, and physical functioning. The study’s healthy ageing cohort is an ideal platform for studying primary prevention of vascular disease (CHD, stroke) and diabetes. The cohort is now aged 62-84 years and is measured for age-related physical and cognitive functioning and mental health. The study contributes to the evidence on the potential for preventing functional decline through therapeutic risk factor reduction and behavioural interventions.

As part of the current NIH funded research programme, the research programme will:

i. demonstrate socioeconomic disparities and underlying mechanisms in chronic diseases, transitions to multimorbidity and mortality

ii. establish whether socioeconomic factors buffer the association of multimorbidity with disability, and that of disability with mortality and identify underlying mechanisms

iii. assess the role of socioeconomic status in shaping the association of functional impairment (subjective and objective assessments) with mortality, and its role in terminal decline, i.e. accelerated decline in function prior to death by 31/05/2023.

In the MRC-funded research programme, the research programme will:

i. confirm or refute the hypothesised associations of the Lancet 2017 Commission risk factors with cognitive decline, clinically-verified Alzheimer's disease and dementia

ii. determine how trajectories of diseases over the adult lifecourse shape risk of dementia

iii. test proteomic and metabolite biomarkers, singly and in combination, as early predictors of cognitive function, Alzheimer's disease and dementia, by 31/01/2022.

The BHF-funded research programme allows the research team to determine how arterial stiffening, a proxy of vascular ageing, is associated with the development and progression of cardiometabolic diseases by 31/08/2021. In addition, the team's international collaborative work will reveal how social, occupational and health related determinants affect working life expectancy and whether exposure to work-related adverse social behaviours are likely to have long-term impacts on health, by the end of 2022. Furthermore, over the next 5 years the research team's international omics consortia will identify new genetic variants and metabolomic and proteomic factors that contribute to a range of different diseases.

The aim is to follow-up participants across transitions from a healthy state to pre-clinical and manifest disease, multi morbidity and death. Due to the longitudinal nature of the study, the aim is to actively collect questionnaire and clinical data until 2030. After this date, passive follow-up will continue until all cohort members have died. Once the Whitehall participants cannot be followed up anymore, their identifiable data will be destroyed and the study will move to using pseudonymised data only. The research analysis will need to continue for as long as the study is active. In accordance with the principles and guidelines on good research practice of the MRC (the main funder), the research data and related material will need to be retained for a minimum of 10 years after the study has been completed.

Self-reported clinical events data are open to major limitations of bias, including missing responses and attrition. Therefore, since 1997, UCL have supplemented the self-reported events with information extracted from GP and paper hospital notes, and also with data provided by NHS Digital.

The Whitehall II MRC grant (MR/R024227/1 - The Whitehall II study: A core resource for ageing research) has dementia, disability and depression as the outcome variables. In order to be able to study these outcomes in older individuals it is crucial to have complete data from all possible sources. Data on psychiatric conditions are important outcomes in their own right, but it is also needed to study other conditions. For example, the diagnosis of dementia involves ruling out major psychiatric disorder as an underlying condition for the observed clinical phenotype. In order to do so, external data on psychiatric conditions is required. This cannot possibly be achieved without access to the Mental Health and Learning Disabilities Data Set (MHLDDS). In addition, information on clinical procedures, such as brain MRI or CT, is important to evaluate the validity of dementia diagnosis and changes in diagnostic testing over time, a potential source of bias that needs to be considered longitudinal analyses. For this reason, records from the Digital Imaging Dataset are also needed for the Whitehall II dementia project.

University College London are the sole data controller for this agreement and the processing of data is conducted solely by researchers within the University College London School of Medical Sciences.

All published outputs will be aggregate with small number supressed in line with the HES Analysis Guide.

The Whitehall II researchers will use peer-review journals to report the contribution of midlife inflammatory, vascular, and metabolic factors to chronic disease, depression, cognitive impairment and functional health in later life. They will also assess whether the adoption of healthy lifestyle even at older ages modifies functional trajectories, and aim to develop multi-factorial predictive algorithms, like those developed for cardiovascular diseases, to facilitate early identification of

adverse ageing outcomes.

The study dissemination plan, which has been very successful up to now (please see examples below), involves publications in high impact scientific journals, scientific meetings, briefing papers for policy makers, regular and ad hoc meetings with interested parties such as Public Health England.

A research dataset will be created for the UCL study researchers named in the Data Sharing Agreement. It will contain all records with all directly identifiable data removed. It will include the study ID but no personal variables. Any sensitive variables that might identify a participant (such as hospital dates or full ICD-10 codes) will never be published, reported or provided to third parties.

The scientific conclusions of the Whitehall II study will be published in international peer-reviewed journals starting from a few months after the data are available. UCL aim to continue publishing the analyses in journals with high coverage and high impact factor and UCL’s preference is journals with an open access option (web version of the paper available free of charge). Some examples of journals where the Whitehall II researchers have published their results in 2017 and 2018 are Lancet, British Medical Journal, PLoS Medicine, JAMA Psychiatry, European Heart Journal, Alzheimer's & Dementia, etc.

A full list of the project publications to date is published on the Whitehall II website

(https://www.ucl.ac.uk/iehc/research/epidemiology-and-public-health/research/whitehall-ii/publications).

Outputs from the Whitehall II study have also gained a substantial standing with several policymakers in the development of clinical guidelines and policy documents. Whitehall II findings have been used as primary evidence in documents such as the European Guideline for cardiovascular disease prevention, National Institute for Health and Care Excellence (NICE) Guideline of dementia prevention and the World Health Organisation (WHO) Social Determinants of health policy.

UCL distribute outputs regularly throughout the year, aiming to publish multiple scientific papers, several conferences and key notes per year. Such outputs for 2019 so far can be seen listed on the publication webpage linked above. UCL has also regularly published health-related advice via its website, accessible to the public, aiming to expand practical channels for outputs to be communicated with the public. For future outputs, SLMS researchers plan to publish analyses of novel biomarkers and lifestyle factors predicting neurodegeneration, frailty, disability and multi-morbidity. UCL will be looking to replicate previous outputs focused around these areas, distributing results via multiple channels such as scientific peer-reviewed journals, website publications offering health-related advice, books and social media.

The key benefit to the public/patients is that linkage to English and Welsh records is helping expand the knowledge base to which the Whitehall II study has already contributed. UCL’s analyses will continue to generate evidence to improve public health policies, clinical guidelines, health care professionals, workplaces and promote healthier lifestyles in the general public for the benefit of patients and the healthcare system.

Evidence from previous benefits:

Whitehall II have contributed evidence to current clinical guidelines, such as the ‘European Guidelines on Cardiovascular Prevention in Clinical Practice’ (see Eur Heart J 2012;33:1635-1701 and Eur Heart J 2016;37:2315-2381) and the ‘Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association’ (see Stroke. 2014;45:2160-2236). UCL have used Whitehall II data in their state-of-the-art reviews on prediabetes (Tabak A,Kivimaki M. Lancet 2013; 379:2279-2290) and stress (Steptoe A, Kivimaki, M. Nature Reviews Cardiology 2012;9(6):360-70 and Steptoe A, Kivimaki, M . Annu Rev Public Health 2013;34:337-54.) to inform health professionals and policy makers in the UK and elsewhere.

The Whitehall II study has contributed evidence to the World Health Organization (WHO) policy documents for reducing social inequalities in heath globally (Commission of Social Determinants in Health 2008) and the European and the UK reviews of inequalities and working conditions (Review of Social Determinants and the Health Divide in the WHO European Region, updated in 2014 and Fair Society, Healthy Lives, 2010) and developed a guide for evidence-based public health in a project led by the UK National Institute of Clinical Excellence (NICE, Killoran 2009). In addition, the study has provided evidence to European Union Occupational Safety and Health recommendations and contributed to priority settings in occupational health research at a European level (https://osha.europa.eu/en/tools-andpublications/publications/e-facts/efact18/view; https://osha.europa.eu/en/tools-andpublications/publications/reports/management-psychosocial-risks-esener;https://osha.europa.eu/en/tools andpublications/publications/reports/summary-priorities-for-osh-research-in-eu-for-2013-20).

Furthermore, the Whitehall II study has contributed evidence to the American Heart Association prevention policy, which in turn influences UK policy (American Heart Association Behavior Change Committee of the Council on Epidemiology and Prevention, Council on Lifestyle and Cardiometabolic Health, Council for High Blood Pressure Research, and Council on Cardiovascular and Stroke Nursing. ‘Better population Health through behaviour change in adults: a call to action’ Circulation. 2013 Nov5;128(19):2169-76). The paper on long working hours and stroke (Lancet. 2015 Oct 31;386(10005):1739-46) was referenced by WHO (Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. World Health Organization. http://www.who.int/iris/handle/10665/204585) and received widespread media coverage (rated the 12th in the 100 in the world Altmetric ratings).

Two Whitehall papers contributed evidence to NICE guidelines on Dementia (NG16) published in October 2015. The papers were referenced in “Dementia, disability and frailty in later life – mid-life approaches to delay or prevent onset”. (Sabia S, Singh‑Manoux A, Hagger‑Johnson G et al. (2012) Influence of individual and combined healthy behaviours on successful aging. Canadian Medical Association Journal doi: 10.1503/cmaj.121080; Singh‑Manoux A, Marmot MG, Glymour M et al. (2011) Does cognitive reserve shape cognitive decline? Annals of Neurology 70: 296–304)

More recently, a Whitehall II paper on alcohol consumption and cognitive decline ‘Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study’ (BMJ 2017;357:j2353) received widespread media coverage, demonstrating the neurotoxicity of alcohol consumption (the paper was rated in the top 5% of all outputs scored by Altmetric).