MR487 - EPIC – European Prospective Investigation into Cancer in Norfolk

The European Prospective Investigation into Cancer (EPIC) is a long-standing research project that was established to examine the relationship between lifestyle (in particular, diet and physical activity), biological factors and health outcomes. EPIC is an international ten country collaboration, coordinated by the International Agency for Research into Cancer in Lyon, which is part of World Health Organisation, such that collaborating partners agreed on a core protocol for the collection and standardisation of data throughout EPIC. However, each individual cohort has also developed specialist areas for investigation. This Agreement relates to the Norfolk component of EPIC (EPIC-Norfolk) and the follow-up on approximately 30, 000 men and women aged 40-79 resident in Norfolk at the time of recruitment. Data provided by NHS Digital will not be shared with collaborating partners or any other organisation that is not listed in this Agreement except as aggregated data with small numbers suppressed (in line with the HES analysis guide).

The University of Cambridge is the sole Data Controller who also process the data for the purposes described in this Agreement. The EPIC-Norfolk Study is funded by the Medical Research Council (MC-UU_12015/1).

The scientific and public health strength of the population cohort is that through routine record linkage, the researchers of University of Cambridge are able to follow up the whole cohort who originally participated for health outcomes. Access to data only for the subset that, almost 25 years later are able to provide new signed informed consent will bias the follow up hugely and make subsequent follow up and results impossible to interpret. The substantial investment of effort by participants over nearly 2.5 decades in contributing to this research and increasingly valuable information from long-term follow-up of the whole population will be lost.

Section 251 approval was therefore obtained because reconsenting would reduce participation rates. Also, non-fatal disease is an important area of the research and access to linked HES data is essential to analyse. Many diseases cannot be studied using mortality data alone as the diseases do not cause a death and may only occasionally appear on death certificates. These would include diabetes, eye diseases such as glaucoma, bone diseases such as osteoporosis, frailty and sarcopenia, inflammatory bowel diseases and dementia. Hospital usage is another important area for future research.

Data from NHS Digital is restricted to the 30,445 EPIC-Norfolk participants recruited at inception of the study. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes.

Linkage strengthens the study by allowing the follow-up of participants who drop out of the study due to health reasons or death. It also allows the validation of self-reported conditions such as Parkinson's disease, dementia and stroke. Access to death data provides information on mortality but is also used for administrative purposes to prevent inappropriately mailing to participants who have died and thus avoiding unnecessary distress to family members. Events identified through record linkage will be documented and linked with data collected from individuals on lifestyle so that the University of Cambridge can assess associations between lifestyle and subsequent health outcomes.

The University of Cambridge has combined mortality data and Hospital Episode Statistics data to define outcomes for fatal and non-fatal incident diseases. For example, the University of Cambridge can define an outcome of heart disease using the same range of ICD 10 codes applied to both fatal events from death certificates and non-fatal events from hospital admissions. Data from NHS Digital is processed by a restricted number of trained staff within the Cambridge School of Clinical Medicine, Cambridge. NHS Digital data is not processed outside the UK, however outputs in the form of aggregated data with small numbers suppressed may be shared with collaborators worldwide. On-going updates of data are necessary for the accurate follow-up of participants.

Over 600,000 people in the UK suffer from dementia, costing over £17 billion a year. Dementia is an extremely important health issue. Figures released by the Office of National Statistics showed dementia replacing ischemic heart diseases as the leading cause of death registered in England and Wales in 2015. Several studies have shown the increased risk of mortality not only with dementia but also cognitive impairment. However, in an ageing population, understanding the influence of poor cognitive performance on mortality and health endpoints is also important in terms of advising on public health as this is likely to affect far more individuals than those with impaired cognition.

With the data collected over the past 2.5 decades, EPIC will be able to examine associations of a range of lifestyle factors and dementia outcomes and mortality. EPIC-Norfolk study is a partner of Dementia Platform UK (DPUK) to further develop understanding of predictors of dementia outcomes. From the latest 2016 updates from NHS Digital, 2 manuscripts are currently in progress:

1. Investigating Cognitive Performance as a Predictor of Mortality in EPIC-Norfolk and 2. Hospital use in the last year of life. The data analysis for both these papers were done by researchers with substantive contracts and approved users under the DSA. However even in these cases, the NHS Digital data used were in aggregated format, with small numbers suppressed.

Under version 5 of this Agreement, the University of Cambridge is requesting annual releases of HES Outpatients and HES Admitted Patient Care. In addition, quarterly releases of Civil Registration deaths and Demographic data and Annual Cancer Registration data.

This study also holds previous Mental Health data with the MHMDS being extremely important for dementia case ascertainment as dementia diagnoses cannot be adequately captured from the HES data. All aggregated data with small numbers suppressed (in line with the relevant guidance) will be provided to collaborating partners (including DPUK).

There are a number of scientific reasons as to why the earlier HES data is important. This data will allow validation of the self-report from the earliest point of the study allowing the identification of pre-existing conditions. Information on existing disease can also be used in the analysis to account for reverse causality and confounding. Furthermore, HES data gives national coverage of health whereas previously, when the study obtained health outcomes locally, this was only from local healthcare providers. Thus, participants receiving medical care or a diagnosis elsewhere would not always be included in available records.

Currently, information is missing on individuals who may have had treatment or diagnoses in other hospitals outside Norfolk. Having access to earlier HES years will provide information that is currently missing. Missing data can have serious impact on research, resulting in biased estimates, reduce statistical power and weaken findings that would be difficult to publish.

EPIC-Norfolk is an ongoing longitudinal study. The study continues to use outcome measures from HES data in publications and it is essential for the study to have up to date events for a number of reasons;

• Firstly, the statistical power of the analyses depends on the number of known events. Less common outcomes can only be studied with sufficiently long follow-up and event numbers.

• Secondly, EPIC-Norfolk has made multiple approaches to the cohort. Each approach is a new baseline and is necessary to have non-fatal events

• Thirdly, journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and their interpretation.

This Agreement also covers the retention of mental health data. These datasets contain the latest figures for dementia cases that are not held solely with the Mental Health Minimum Dataset (MHMDS). The reason for this is that it is extremely important to maximise on numbers and have the longest follow-up time from the cognitive measures taken between 2004-2011 for accurate analysis of the data. Combining the figures from MHMDS, MHSDS and MHLDDS will give better and more accurate estimates of dementia numbers.

Use of NHS Digital data has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes. EPIC Norfolk widely publicises its findings through a number of public channels, with key topics focused on lifestyle choices relevant to a large proportion of the public. The inclusion of NHS Digital data provides a number of statistical and scientific benefits to the study when investigating the relationships between lifestyle choices and health outcomes, highlighting positive correlations between the two to the public eye.

This study is part of the University of Cambridge and as such the legal basis to hold and use personal data is covered under the General Data Protection Regulation “Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest”. To hold special categories of personal data our lawful basis is for pursuing scientific research under “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 interest of the data subject.”

Outputs for participants and the public:

Equally important is the dissemination of results outside the research community. The University of Cambridge communicate the results to the research participants through newsletters. A list of recent newsletters can be found on the study website at

Information is also disseminated to the general public via printed and digital media. Examples of research results communicated to the public can be found at https://epic-norfolk.org.uk/newsletter_archive.shtml

The University of Cambridge also actively promotes participant involvement in this research. The University of Cambridge set up an advisory panel in 2010 to act as a consultation group to advise on the research. The EPIC-Norfolk Participant Advisory Panel (EPAP) has been involved in all aspects of the research project from designing health questionnaires, writing of lay summaries, participant information, dissemination of results and providing a lay perspective on potential projects being considered for the future.

At recent meetings the study group has discussed with the panel how they use their data and the appropriate use of stored samples. In October 2019, members from the participant panel as well as a researcher involved in the study appeared on a BBC Look East television broadcast discussing their involvement in the study. Further information on EPAP can be found at https://epic-norfolk.org.uk/participant_panel.shtml .

The University of Cambridge also shares results from this study via extensive public engagement activities including regular Science Festival events and lectures to the general public and charitable groups.

Outputs for the research/scientific community:

The University of Cambridge communicates research findings to members of the scientific community through publication in a broad range (both specialist and more general, scientific and medical based) of national and international peer-reviewed journals and at national and international conferences.

There have been over 1500 peer reviewed scientific publications from this study, with a number of findings making it into news. There are too many publications to list but can be found at the website at https://epic-norfolk.org.uk/publications.shtml with news articles found at https://epic-norfolk.org.uk/news.shtml.

Some specific recent publications using HES and mortality data as outputs:

- Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort (Luben R, Hayat S, Wareham N, et al, BMJ Open 2016)

- Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study (Basuetal., BMC Medicine2016)

- Accuracy of death certification and hospital record linkage for identification of incident stroke (Sinha, S., Myint, P.K., Luben, R.N. et al. BMC Med Res Methodol 2008)

To reiterate an earlier point, it is essential for the study to have up to date events as journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and its interpretation.

Outputs for collaborating researchers and PhD students:

Aggregated outputs from NHS Digital data (including mortality) may be shared with small numbers suppressed, with PhD students and researchers from recognised academic and research institutions (that are bound by the same conditions as the University of Cambridge) upon receiving a formal data request. No identifiable data is shared with collaborating researchers.

All publications are and will be open access, in line with the University of Cambridge open access policy and can be accessed by clinicians, academics, policy makers and interested members of the public. Outputs presented and/or reported will contain aggregate level data with small numbers suppressed in line with the HES analysis guide. No personal identifiable data will be released or published.

In 2020 the following publications were delivered:

Zheng JS, Sharp SJ, Imamura F, Chowdhury R, Gundersen TE, Steur M, Sluijs I, van der Schouw YT, Agudo A, Aune D, Barricarte A. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries. bmj. 2020 Jul 8;370.

Zamora-Ros R, Lujan-Barroso L, Achaintre D, Franceschi S, Kyrø C, Overvad K, Tjønneland A, Truong T, Lecuyer L, Boutron-Ruault MC, Katzke V. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The American Journal of Clinical Nutrition. 2020 Oct 6.

Yrjana KR, Neal SR, Soiza RL, Keevil V, Luben RN, Wareham NJ, Khaw KT, Myint PK. Baseline anticholinergic burden from medications predicts poorer baseline and long‐term health‐related quality of life in 16 675 men and women of EPIC‐Norfolk prospective population‐based cohort study. Pharmacoepidemiology and Drug Safety. 2020 Aug 5

Yates M, Luben R, Hayat S, Mackie SL, Watts RA, Khaw KT, Wareham NJ, MacGregor AJ. Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study. Rheumatology. 2020 Feb 1;59(2):319-23.

Trichia E, Luben R, Khaw KT, Wareham NJ, Imamura F, Forouhi NG. The associations of longitudinal changes in consumption of total and types of dairy products and markers of metabolic risk and adiposity: findings from the European Investigation into Cancer and Nutrition (EPIC)–Norfolk study, United Kingdom. The American Journal of Clinical Nutrition. 2020 May 1;111(5):1018-26.

Tong TY, Appleby PN, Key TJ, Dahm CC, Overvad K, Olsen A, Tjønneland A, Katzke V, Kühn T, Boeing H, Karakatsani A. The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries. European Heart Journal. 2020 Feb 24.

Tan MP, Tan GJ, Mat S, Luben RN, Wareham NJ, Khaw KT, Myint PK. Use of medications with anticholinergic properties and the long-term risk of hospitalization for falls and fractures in the EPIC-Norfolk Longitudinal Cohort Study. Drugs & Aging. 2020 Feb 1;37(2):105-14.

Sanikini H, Muller DC, Sophiea M, Rinaldi S, Agudo A, Duell EJ, Weiderpass E, Overvad K, Tjønneland A, Halkjær J, Boutron‐Ruault MC. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. International journal of cancer. 2020 Feb 15;146(4):929-42.

Pasdar Z, Gamble DT, Myint PK, Luben RN, Wareham NJ, Khaw KT, Bhattacharya S. Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study. Cancers. 2020 Nov;12(11):3100.

Ottaviani JI, Britten A, Lucarelli D, Luben R, Mulligan AA, Lentjes MA, Fong R, Gray N, Grace PB, Mawson DH, Tym A. Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk. Scientific reports. 2020 Oct 21;10(1):1-4.

Obón‐Santacana M, Luján‐Barroso L, Freisling H, Naudin S, Boutron‐Ruault MC, Mancini FR, Rebours V, Kühn T, Katzke V, Boeing H, Tjønneland A. Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition. International journal of cancer. 2020 Jan 1;146(1):76-84.

Naudin S, Solans Margalef M, Saberi Hosnijeh F, Nieters A, Kyrø C, Tjønneland A, Dahm CC, Overvad K, Mahamat‐Saleh Y, Besson C, Boutron‐Ruault MC. Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer. 2020 Mar 16

Luben R, Hayat S, Wareham N, Pharoah P, Khaw KT. Usual physical activity and subsequent hospital usage over 20 years in a general population: the EPIC-Norfolk cohort. BMC geriatrics. 2020 Dec;20:1-2.

Jakszyn P, Cayssials V, Buckland G, Perez‐Cornago A, Weiderpass E, Boeing H, Bergmann MM, Vulcan A, Ohlsson B, Masala G, Cross AJ. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer. 2020 Jan 16.

Ibsen DB, Steur M, Imamura F, Overvad K, Schulze MB, Bendinelli B, Guevara M, Agudo A, Amiano P, Aune D, Barricarte A. Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study. Diabetes care. 2020 Nov 1;43(11):2660-7.

Hayat SA, Luben R, Wareham N, Khaw KT, Brayne C. Cross-sectional and prospective relationship between occupational and leisure-time inactivity and cognitive function in an ageing population: the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study. International Journal of Epidemiology. 2020 Apr 2.

Gentiluomo M, Katzke VA, Kaaks R, Tjønneland A, Severi G, Perduca V, Boutron-Ruault MC, Weiderpass E, Ferrari P, Johnson T, Schulze MB. Mitochondrial DNA copy-number variation and pancreatic cancer risk in the prospective EPIC cohort. Cancer Epidemiology and Prevention Biomarkers. 2020 Mar 1;29(3):681-6.

Deschasaux M, Huybrechts I, Julia C, Hercberg S, Egnell M, Srour B, Kesse-Guyot E, Latino-Martel P, Biessy C, Casagrande C, Murphy N. Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries. bmj. 2020 Sep 16;370.

Barlas G, Luben RL, Neal SR, Wareham NJ, Khaw KT, Myint PK. Self-Reported Fatigue Predicts Incident Stroke in a General Population: EPIC-Norfolk Prospective Population-Based Study. Stroke. 2020 Apr;51(4):1077-84.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Understanding what the study can do to improve health and prevent disease and disability in ageing populations will have benefits for society and the general public nationally and internationally. Results have already and will continue to contribute to health and clinical policy. Clarification of the mechanisms underlying diseases will enable us to understand pathophysiological processes to support better prevention and treatment, understanding the risk profile for diseases will enable more targeted screening and prevention programmes and understanding and quantifying specific behaviours that influence functional health and healthy ageing will enable us to improve the health experience and quality of life in populations as they age.

University of Cambridge (EPIC-Norfolk Investigators) have contributed to national and international (e.g. WHO) clinical and public health guideline panels, Department of Health initiatives, and invited to provide evidence to Select Committees on health issues in the Houses of Parliament.

Results from this study have informed Department of Health public health initiatives, NICE and other clinical and public health policies and guidelines.

Examples include:

Research from EPIC-Norfolk quantifying the association between four health behaviours (not smoking, modest alcohol intake, physical activity and consumption of 5 servings of fruit and vegetable intake) were associated with a 14-year difference in life expectancy. This directly influenced the Department of Health "Small change big difference" national public health campaign launched from Downing Street, underpinned regional initiatives to promote health behaviour change and has been taken up in national guidance.

EPIC findings have been reported to meetings contributing European policies on ageing (invited presentations to the European Commission DG Health on Frailty in Old Age 2013) http://ec.europa.eu/dgs/health_consumer/dyna/enews/enews.cfm?al_id=1365

Results from EPIC have contributed to clinical guidelines on screening for osteoporosis using heel ultrasound measures, a low cost and safe feasible assessment ( Lewiecki EM et al, Official Positions for FRAX Bone Mineral Density and FRAX simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom. 2011 Jul-Sep;14(3):226-36).

Results from EPIC have also contributed to clinical guidelines on the use of glycated haemoglobin in the diagnosis of diabetes. (RydenL et al, ESC Guidelines on diabetes, prediabetes and cardiovascular diseases in collaboration with the EASD- Summary. Eur Heart J 2013;34: 3035; Anderson T et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidaemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167.

In addition general findings from EPIC-Norfolk have informed publications from charities (e.g. Cancer Research UK, British Heart Foundation, Stroke Association, AgeUK) on disease prevention and maintenance of health.

According to the Chief Executive of Public Health England (PHE), “Type 2 diabetes is one of the biggest health challenges of our time.” Data from EPIC-Norfolk was used in a large study to show the link between sugar-sweetened beverages and the risk of Type 2 Diabetes. Based on these results, University of Cambridge researchers have engaged with national and international policymakers and media to help shape the way that policy and decision-makers and the public understand and act upon these issues.Researchers have contributed to discussions on sugar reduction that were part of PHE’s Sugar Reduction: Responding to the Challenge document; and provided expert input and reviewed the Parliamentary Office on Science and Technology POSTNote on Sugar and Health.

This research was covered by the BBC's 'One Show' ( attracting an audience of over four million viewers), explaining the health impacts of sugary drinks.

The EPIC-Norfolk researchers recognise the importance of engagement with media, the general public and policymakers, tailoring the message according to the target audience.

The EPIC-Norfolk research team also recognises the value of public engagement and continue to make this an integral part of its research agenda. The primary objective is to raise awareness and inform the general public (all age ranges) on the high-quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at https://epic-norfolk.org.uk/publicevents.shtml.

The European Prospective Investigation into Cancer (EPIC) is a long-standing research project that was established to examine the relationship between lifestyle (in particular, diet and physical activity), biological factors and health outcomes. EPIC is an international ten country collaboration, coordinated by the International Agency for Research into Cancer in Lyon, which is part of World Health Organisation, such that collaborating partners agreed on a core protocol for the collection and standardisation of data throughout EPIC. However, each individual cohort has also developed specialist areas for investigation. This Agreement relates to the Norfolk component of EPIC (EPIC-Norfolk) and the follow-up on approximately 30, 000 men and women aged 40-79 resident in Norfolk at the time of recruitment. Data provided by NHS Digital will not be shared with collaborating partners or any other organisation that is not listed in this Agreement except as aggregated data with small numbers suppressed (in line with the HES analysis guide).

The University of Cambridge is the sole Data Controller who also process the data for the purposes described in this Agreement. The EPIC-Norfolk Study is funded by the Medical Research Council (MC-UU_12015/1).

The scientific and public health strength of the population cohort is that through routine record linkage, the researchers of University of Cambridge are able to follow up the whole cohort who originally participated for health outcomes. Access to data only for the subset that, almost 25 years later are able to provide new signed informed consent will bias the follow up hugely and make subsequent follow up and results impossible to interpret. The substantial investment of effort by participants over nearly 2.5 decades in contributing to this research and increasingly valuable information from long-term follow-up of the whole population will be lost.

Section 251 approval was therefore obtained because reconsenting would reduce participation rates. Also, non-fatal disease is an important area of the research and access to linked HES data is essential to analyse. Many diseases cannot be studied using mortality data alone as the diseases do not cause a death and may only occasionally appear on death certificates. These would include diabetes, eye diseases such as glaucoma, bone diseases such as osteoporosis, frailty and sarcopenia, inflammatory bowel diseases and dementia. Hospital usage is another important area for future research.

Data from NHS Digital is restricted to the 30,445 EPIC-Norfolk participants recruited at inception of the study. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes.

Linkage strengthens the study by allowing the follow-up of participants who drop out of the study due to health reasons or death. It also allows the validation of self-reported conditions such as Parkinson's disease, dementia and stroke. Access to death data provides information on mortality but is also used for administrative purposes to prevent inappropriately mailing to participants who have died and thus avoiding unnecessary distress to family members. Events identified through record linkage will be documented and linked with data collected from individuals on lifestyle so that the University of Cambridge can assess associations between lifestyle and subsequent health outcomes.

The University of Cambridge has combined mortality data and Hospital Episode Statistics data to define outcomes for fatal and non-fatal incident diseases. For example, the University of Cambridge can define an outcome of heart disease using the same range of ICD 10 codes applied to both fatal events from death certificates and non-fatal events from hospital admissions. Data from NHS Digital is processed by a restricted number of trained staff within the Cambridge School of Clinical Medicine, Cambridge. NHS Digital data is not processed outside the UK, however outputs in the form of aggregated data with small numbers suppressed may be shared with collaborators worldwide. On-going updates of data are necessary for the accurate follow-up of participants.

Over 600,000 people in the UK suffer from dementia, costing over £17 billion a year. Dementia is an extremely important health issue. Figures released by the Office of National Statistics showed dementia replacing ischemic heart diseases as the leading cause of death registered in England and Wales in 2015. Several studies have shown the increased risk of mortality not only with dementia but also cognitive impairment. However, in an ageing population, understanding the influence of poor cognitive performance on mortality and health endpoints is also important in terms of advising on public health as this is likely to affect far more individuals than those with impaired cognition.

With the data collected over the past 2.5 decades, EPIC will be able to examine associations of a range of lifestyle factors and dementia outcomes and mortality. EPIC-Norfolk study is a partner of Dementia Platform UK (DPUK) to further develop understanding of predictors of dementia outcomes. From the latest 2016 updates from NHS Digital, 2 manuscripts are currently in progress:

1. Investigating Cognitive Performance as a Predictor of Mortality in EPIC-Norfolk and 2. Hospital use in the last year of life. The data analysis for both these papers were done by researchers with substantive contracts and approved users under the DSA. However even in these cases, the NHS Digital data used were in aggregated format, with small numbers suppressed.

Under version 5 of this Agreement, the University of Cambridge is requesting annual releases of HES Outpatients and HES Admitted Patient Care. In addition, quarterly releases of Civil Registration deaths and Demographic data and Annual Cancer Registration data.

This study also holds previous Mental Health data with the MHMDS being extremely important for dementia case ascertainment as dementia diagnoses cannot be adequately captured from the HES data. All aggregated data with small numbers suppressed (in line with the relevant guidance) will be provided to collaborating partners (including DPUK).

There are a number of scientific reasons as to why the earlier HES data is important. This data will allow validation of the self-report from the earliest point of the study allowing the identification of pre-existing conditions. Information on existing disease can also be used in the analysis to account for reverse causality and confounding. Furthermore, HES data gives national coverage of health whereas previously, when the study obtained health outcomes locally, this was only from local healthcare providers. Thus, participants receiving medical care or a diagnosis elsewhere would not always be included in available records.

Currently, information is missing on individuals who may have had treatment or diagnoses in other hospitals outside Norfolk. Having access to earlier HES years will provide information that is currently missing. Missing data can have serious impact on research, resulting in biased estimates, reduce statistical power and weaken findings that would be difficult to publish.

EPIC-Norfolk is an ongoing longitudinal study. The study continues to use outcome measures from HES data in publications and it is essential for the study to have up to date events for a number of reasons;

• Firstly, the statistical power of the analyses depends on the number of known events. Less common outcomes can only be studied with sufficiently long follow-up and event numbers.

• Secondly, EPIC-Norfolk has made multiple approaches to the cohort. Each approach is a new baseline and is necessary to have non-fatal events

• Thirdly, journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and their interpretation.

This Agreement also covers the retention of mental health data. These datasets contain the latest figures for dementia cases that are not held solely with the Mental Health Minimum Dataset (MHMDS). The reason for this is that it is extremely important to maximise on numbers and have the longest follow-up time from the cognitive measures taken between 2004-2011 for accurate analysis of the data. Combining the figures from MHMDS, MHSDS and MHLDDS will give better and more accurate estimates of dementia numbers.

Use of NHS Digital data has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes. EPIC Norfolk widely publicises its findings through a number of public channels, with key topics focused on lifestyle choices relevant to a large proportion of the public. The inclusion of NHS Digital data provides a number of statistical and scientific benefits to the study when investigating the relationships between lifestyle choices and health outcomes, highlighting positive correlations between the two to the public eye.

This study is part of the University of Cambridge and as such the legal basis to hold and use personal data is covered under the General Data Protection Regulation “Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest”. To hold special categories of personal data our lawful basis is for pursuing scientific research under “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 interest of the data subject.”

Outputs for participants and the public:

Equally important is the dissemination of results outside the research community. The University of Cambridge communicate the results to the research participants through newsletters. A list of recent newsletters can be found on the study website at

Information is also disseminated to the general public via printed and digital media. Examples of research results communicated to the public can be found at https://epic-norfolk.org.uk/newsletter_archive.shtml

The University of Cambridge also actively promotes participant involvement in this research. The University of Cambridge set up an advisory panel in 2010 to act as a consultation group to advise on the research. The EPIC-Norfolk Participant Advisory Panel (EPAP) has been involved in all aspects of the research project from designing health questionnaires, writing of lay summaries, participant information, dissemination of results and providing a lay perspective on potential projects being considered for the future.

At recent meetings the study group has discussed with the panel how they use their data and the appropriate use of stored samples. In October 2019, members from the participant panel as well as a researcher involved in the study appeared on a BBC Look East television broadcast discussing their involvement in the study. Further information on EPAP can be found at https://epic-norfolk.org.uk/participant_panel.shtml .

The University of Cambridge also shares results from this study via extensive public engagement activities including regular Science Festival events and lectures to the general public and charitable groups.

Outputs for the research/scientific community:

The University of Cambridge communicates research findings to members of the scientific community through publication in a broad range (both specialist and more general, scientific and medical based) of national and international peer-reviewed journals and at national and international conferences.

There have been over 1500 peer reviewed scientific publications from this study, with a number of findings making it into news. There are too many publications to list but can be found at the website at https://epic-norfolk.org.uk/publications.shtml with news articles found at https://epic-norfolk.org.uk/news.shtml.

Some specific recent publications using HES and mortality data as outputs:

- Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort (Luben R, Hayat S, Wareham N, et al, BMJ Open 2016)

- Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study (Basuetal., BMC Medicine2016)

- Accuracy of death certification and hospital record linkage for identification of incident stroke (Sinha, S., Myint, P.K., Luben, R.N. et al. BMC Med Res Methodol 2008)

To reiterate an earlier point, it is essential for the study to have up to date events as journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and its interpretation.

Outputs for collaborating researchers and PhD students:

Aggregated outputs from NHS Digital data (including mortality) may be shared with small numbers suppressed, with PhD students and researchers from recognised academic and research institutions (that are bound by the same conditions as the University of Cambridge) upon receiving a formal data request. No identifiable data is shared with collaborating researchers.

All publications are and will be open access, in line with the University of Cambridge open access policy and can be accessed by clinicians, academics, policy makers and interested members of the public. Outputs presented and/or reported will contain aggregate level data with small numbers suppressed in line with the HES analysis guide. No personal identifiable data will be released or published.

In 2020 the following publications were delivered:

Zheng JS, Sharp SJ, Imamura F, Chowdhury R, Gundersen TE, Steur M, Sluijs I, van der Schouw YT, Agudo A, Aune D, Barricarte A. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries. bmj. 2020 Jul 8;370.

Zamora-Ros R, Lujan-Barroso L, Achaintre D, Franceschi S, Kyrø C, Overvad K, Tjønneland A, Truong T, Lecuyer L, Boutron-Ruault MC, Katzke V. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The American Journal of Clinical Nutrition. 2020 Oct 6.

Yrjana KR, Neal SR, Soiza RL, Keevil V, Luben RN, Wareham NJ, Khaw KT, Myint PK. Baseline anticholinergic burden from medications predicts poorer baseline and long‐term health‐related quality of life in 16 675 men and women of EPIC‐Norfolk prospective population‐based cohort study. Pharmacoepidemiology and Drug Safety. 2020 Aug 5

Yates M, Luben R, Hayat S, Mackie SL, Watts RA, Khaw KT, Wareham NJ, MacGregor AJ. Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study. Rheumatology. 2020 Feb 1;59(2):319-23.

Trichia E, Luben R, Khaw KT, Wareham NJ, Imamura F, Forouhi NG. The associations of longitudinal changes in consumption of total and types of dairy products and markers of metabolic risk and adiposity: findings from the European Investigation into Cancer and Nutrition (EPIC)–Norfolk study, United Kingdom. The American Journal of Clinical Nutrition. 2020 May 1;111(5):1018-26.

Tong TY, Appleby PN, Key TJ, Dahm CC, Overvad K, Olsen A, Tjønneland A, Katzke V, Kühn T, Boeing H, Karakatsani A. The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries. European Heart Journal. 2020 Feb 24.

Tan MP, Tan GJ, Mat S, Luben RN, Wareham NJ, Khaw KT, Myint PK. Use of medications with anticholinergic properties and the long-term risk of hospitalization for falls and fractures in the EPIC-Norfolk Longitudinal Cohort Study. Drugs & Aging. 2020 Feb 1;37(2):105-14.

Sanikini H, Muller DC, Sophiea M, Rinaldi S, Agudo A, Duell EJ, Weiderpass E, Overvad K, Tjønneland A, Halkjær J, Boutron‐Ruault MC. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. International journal of cancer. 2020 Feb 15;146(4):929-42.

Pasdar Z, Gamble DT, Myint PK, Luben RN, Wareham NJ, Khaw KT, Bhattacharya S. Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study. Cancers. 2020 Nov;12(11):3100.

Ottaviani JI, Britten A, Lucarelli D, Luben R, Mulligan AA, Lentjes MA, Fong R, Gray N, Grace PB, Mawson DH, Tym A. Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk. Scientific reports. 2020 Oct 21;10(1):1-4.

Obón‐Santacana M, Luján‐Barroso L, Freisling H, Naudin S, Boutron‐Ruault MC, Mancini FR, Rebours V, Kühn T, Katzke V, Boeing H, Tjønneland A. Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition. International journal of cancer. 2020 Jan 1;146(1):76-84.

Naudin S, Solans Margalef M, Saberi Hosnijeh F, Nieters A, Kyrø C, Tjønneland A, Dahm CC, Overvad K, Mahamat‐Saleh Y, Besson C, Boutron‐Ruault MC. Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer. 2020 Mar 16

Luben R, Hayat S, Wareham N, Pharoah P, Khaw KT. Usual physical activity and subsequent hospital usage over 20 years in a general population: the EPIC-Norfolk cohort. BMC geriatrics. 2020 Dec;20:1-2.

Jakszyn P, Cayssials V, Buckland G, Perez‐Cornago A, Weiderpass E, Boeing H, Bergmann MM, Vulcan A, Ohlsson B, Masala G, Cross AJ. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer. 2020 Jan 16.

Ibsen DB, Steur M, Imamura F, Overvad K, Schulze MB, Bendinelli B, Guevara M, Agudo A, Amiano P, Aune D, Barricarte A. Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study. Diabetes care. 2020 Nov 1;43(11):2660-7.

Hayat SA, Luben R, Wareham N, Khaw KT, Brayne C. Cross-sectional and prospective relationship between occupational and leisure-time inactivity and cognitive function in an ageing population: the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study. International Journal of Epidemiology. 2020 Apr 2.

Gentiluomo M, Katzke VA, Kaaks R, Tjønneland A, Severi G, Perduca V, Boutron-Ruault MC, Weiderpass E, Ferrari P, Johnson T, Schulze MB. Mitochondrial DNA copy-number variation and pancreatic cancer risk in the prospective EPIC cohort. Cancer Epidemiology and Prevention Biomarkers. 2020 Mar 1;29(3):681-6.

Deschasaux M, Huybrechts I, Julia C, Hercberg S, Egnell M, Srour B, Kesse-Guyot E, Latino-Martel P, Biessy C, Casagrande C, Murphy N. Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries. bmj. 2020 Sep 16;370.

Barlas G, Luben RL, Neal SR, Wareham NJ, Khaw KT, Myint PK. Self-Reported Fatigue Predicts Incident Stroke in a General Population: EPIC-Norfolk Prospective Population-Based Study. Stroke. 2020 Apr;51(4):1077-84.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Understanding what the study can do to improve health and prevent disease and disability in ageing populations will have benefits for society and the general public nationally and internationally. Results have already and will continue to contribute to health and clinical policy. Clarification of the mechanisms underlying diseases will enable us to understand pathophysiological processes to support better prevention and treatment, understanding the risk profile for diseases will enable more targeted screening and prevention programmes and understanding and quantifying specific behaviours that influence functional health and healthy ageing will enable us to improve the health experience and quality of life in populations as they age.

University of Cambridge (EPIC-Norfolk Investigators) have contributed to national and international (e.g. WHO) clinical and public health guideline panels, Department of Health initiatives, and invited to provide evidence to Select Committees on health issues in the Houses of Parliament.

Results from this study have informed Department of Health public health initiatives, NICE and other clinical and public health policies and guidelines.

Examples include:

Research from EPIC-Norfolk quantifying the association between four health behaviours (not smoking, modest alcohol intake, physical activity and consumption of 5 servings of fruit and vegetable intake) were associated with a 14-year difference in life expectancy. This directly influenced the Department of Health "Small change big difference" national public health campaign launched from Downing Street, underpinned regional initiatives to promote health behaviour change and has been taken up in national guidance.

EPIC findings have been reported to meetings contributing European policies on ageing (invited presentations to the European Commission DG Health on Frailty in Old Age 2013) http://ec.europa.eu/dgs/health_consumer/dyna/enews/enews.cfm?al_id=1365

Results from EPIC have contributed to clinical guidelines on screening for osteoporosis using heel ultrasound measures, a low cost and safe feasible assessment ( Lewiecki EM et al, Official Positions for FRAX Bone Mineral Density and FRAX simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom. 2011 Jul-Sep;14(3):226-36).

Results from EPIC have also contributed to clinical guidelines on the use of glycated haemoglobin in the diagnosis of diabetes. (RydenL et al, ESC Guidelines on diabetes, prediabetes and cardiovascular diseases in collaboration with the EASD- Summary. Eur Heart J 2013;34: 3035; Anderson T et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidaemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167.

In addition general findings from EPIC-Norfolk have informed publications from charities (e.g. Cancer Research UK, British Heart Foundation, Stroke Association, AgeUK) on disease prevention and maintenance of health.

According to the Chief Executive of Public Health England (PHE), “Type 2 diabetes is one of the biggest health challenges of our time.” Data from EPIC-Norfolk was used in a large study to show the link between sugar-sweetened beverages and the risk of Type 2 Diabetes. Based on these results, University of Cambridge researchers have engaged with national and international policymakers and media to help shape the way that policy and decision-makers and the public understand and act upon these issues.Researchers have contributed to discussions on sugar reduction that were part of PHE’s Sugar Reduction: Responding to the Challenge document; and provided expert input and reviewed the Parliamentary Office on Science and Technology POSTNote on Sugar and Health.

This research was covered by the BBC's 'One Show' ( attracting an audience of over four million viewers), explaining the health impacts of sugary drinks.

The EPIC-Norfolk researchers recognise the importance of engagement with media, the general public and policymakers, tailoring the message according to the target audience.

The EPIC-Norfolk research team also recognises the value of public engagement and continue to make this an integral part of its research agenda. The primary objective is to raise awareness and inform the general public (all age ranges) on the high-quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at https://epic-norfolk.org.uk/publicevents.shtml.

The European Prospective Investigation into Cancer (EPIC) is a long-standing research project that was established to examine the relationship between lifestyle, in particular, diet and physical activity, biological factors and health outcomes. EPIC is an international ten country collaboration, coordinated by the International Agency for Research into Cancer in Lyon, which is part of World Health Organisation, such that collaborating partners agreed on a core protocol for the collection and standardisation of data throughout EPIC. However, each individual cohort has also developed specialist areas for investigation. This agreement relates to the Norfolk component of EPIC (EPIC-Norfolk) and the follow-up on approximately 30, 000 men and women aged 40-79 resident in Norfolk at the time of recruitment. Data provided by NHS Digital will not be shared with collaborating partners or any other organisation that is not listed in this agreement except as aggregated data with small numbers suppressed (in line with the HES analysis guide).

The scientific and public health strength of the population cohort is that through routine record linkage, the researchers of University of Cambridge are able to follow up the whole cohort who originally participated for health outcomes. Access to data only for the subset that, almost 25 years later are able to provide new signed informed consent will bias the follow up hugely, and make subsequent follow up and results impossible to interpret. The substantial investment of effort by participants over nearly 2.5 decades in contributing to this research and increasingly valuable information from long-term follow-up of the whole population will be lost. S.251 approval was therefore obtained because reconsenting would reduce participation rates. Also, non-fatal disease is an important area of the research and access to linked HES data is essential to analyse. Many diseases cannot be studied using mortality data alone as the diseases do not cause a death and may only occasionally appear on death certificates. These would include diabetes, eye diseases such as glaucoma, bone diseases such as osteoporosis, frailty and sarcopenia, inflammatory bowel diseases and dementia. Hospital usage is another important area for future research.

EPIC-Norfolk is a flagging study and data from NHS Digital is restricted to the 30,445 EPIC-Norfolk participants recruited at inception of the study. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, and cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes.

Linkage strengthens the study by allowing the follow-up of participants who drop out of the study due to health reasons or death. It also allows the validation of self-reported conditions such as Parkinson's disease, dementia and stroke. Access to death data provides information on mortality but is also used for administrative purposes to prevent inappropriately mailing to participants who have died and thus avoiding unnecessary distress to family members. Events identified through record linkage will be documented and linked with data collected from individuals on lifestyle so that the University of Cambridge can assess associations between lifestyle and subsequent health outcomes.

The University of Cambridge has combined mortality data and Hospital Episode Statistics data to define outcomes for fatal and non-fatal incident diseases. For example, the University of Cambridge can define an outcome of heart disease using the same range of ICD 10 codes applied to both fatal events from death certificates and non-fatal events from hospital admissions. Data from NHS Digital is processed by a restricted number of trained staff within the EPIC-Norfolk team, Cambridge School of Clinical Medicine, Cambridge. Data is not accessed outside the UK. On-going updates of data are necessary for the accurate follow-up of participants.

Over 600,000 people in the UK suffer from dementia, costing over £17 billion a year. Dementia is an extremely important health issue. Figures released by the Office of National Statistics showed dementia replacing ischaemic heart diseases as the leading cause of death registered in England and Wales in 2015. Several studies have shown the increased risk of mortality not only with dementia but also cognitive impairment. However, in an ageing population, understanding the influence of poor cognitive performance on mortality and health endpoints is also important in terms of advising on public health as this is likely to affect far more individuals than those with impaired cognition. With the data collected over the past 2.5 decades, EPIC will be able to examine associations of a range of lifestyle factors and dementia outcomes and mortality. EPIC-Norfolk study is a partner of Dementia Platform UK (DPUK) to further develop understanding of predictors of dementia outcomes. From the latest 2016 updates from NHS Digital, 2 manuscripts are currently in progress 1/ Investigating Cognitive Performance as a Predictor of Mortality in EPIC-Norfolk and 2/ Hospital use in the last year of life. The data analysis for both these papers were done by researchers with substantive contracts and approved users under the DSA. However even in these cases, the NHS Digital data used were in aggregated format, with small numbers supressed.

This agreement relates to data already held and additional HES year, the Mental Health Minimum Dataset (MHMDS), and Mental Health and Learning Disabilities Data Set (MHLDDS) that have not been requested previously. The MHMDS is extremely important for dementia case ascertainment as dementia diagnoses cannot be adequately captured from the HES data. Having the MHMDS will give better and more accurate estimates of dementia numbers. Currently, dementia diagnoses are significantly underestimated with the data available to this study. Having the accurate figures is necessary for current work examining predictors of dementia outcomes. Again data provided by NHS Digital will only be shared with collaborating partners (including DPUK), as aggregated data with small numbers supressed (in line with the relevant guidance).

There are a number of scientific reasons as to why the earlier HES data is important. This data will allow validation of the self-report from the earliest point of the study allowing the identification of pre-existing conditions. Information on existing disease can also be used in the analysis to account for reverse causality and confounding. Furthermore, HES data gives national coverage of health whereas previously, when the study obtained health outcomes locally, this was only from local healthcare providers. Thus participants receiving medical care or a diagnosis elsewhere would not always be included in available records. Currently, information is missing on individuals who may have had treatment or diagnoses in other hospitals outside Norfolk. The information is not always available from GP practices. Having access to earlier HES years will provide information that is currently missing. Missing data can have serious impact on research, resulting in biased estimates, reduce statistical power and weaken findings that would be difficult to publish.

EPIC-Norfolk is an ongoing longitudinal study. The University of Cambridge received last HES update in 2016. The study continues to use outcome measures from HES data in publications and it is essential for the study to have up to date events for a number of reasons;

• Firstly, the statistical power of the analyses depends on the number of known events. Less common outcomes can only be studied with sufficiently long follow-up and event numbers.

• Secondly, EPIC-Norfolk has made multiple approaches to the cohort. Each approach is a new baseline and is necessary to have non-fatal events

• Thirdly, journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and their interpretation.

In this amendment. we have requested additionally, the Mental Health Services Data (MHSDS) and Mental Health and Learning Disabilities Data Set (MHLDDS) which we were unaware of at the time of the original application. This dataset contains the latest figures for dementia cases that are not held with the Mental Health Minimum Dataset (MHMDS). It is extremely important to maximise on numbers and have the longest follow-up time from the cognitive measures taken between 2004-2011 for accurate analysis of the data. Combining the figures from MHMDS, MHSDS and MHLDDS will give better and more accurate estimates of dementia numbers. We are also requesting additional HES years that have become available since the original application, again, this is to provide the most recent updates on health outcomes to allow accurate data analysis for publications for the reasons given above.

Any output shared outside the University of Cambridge will contain data only where it is aggregated with small numbers suppressed in line with the NHS Digital requirements.

Outputs for participants and the public:

Equally important is the dissemination of results outside the research community. The University of Cambridge communicate the results to the research participants newsletters. A list of recent newsletters can be found on the study website at http://www.srl.cam.ac.uk/epic/newsletter_archive.shtml.

Information is also disseminated to the general public via printed and digital media. Examples of research results communicated to the public can be found at http://www.srl.cam.ac.uk/epic/news.shtml

The University of Cambridge also actively promote participant involvement in this research. The University of Cambridge set up an advisory panel in 2010 to act as a consultation group to advise us on the research. The EPIC-Norfolk Participant Advisory Panel (EPAP) has been involved in all aspects of the research project from designing health questionnaires, writing of lay summaries, participant information, dissemination of results and providing a lay perspective on potential projects being considered for the future. Further information on EPAP can be found at http://www.srl.cam.ac.uk/epic/participant_panel.shtml

The University of Cambridge also shares results from this study via extensive public engagement activities including regular Science Festival events and lectures to the general public and charitable groups.

Outputs for the research/scientific community:

The University of Cambridge communicates research findings to members of the scientific community through publication in a broad range (both specialist and more general, scientific and medical based) national and international peer-reviewed journals and at national and international conferences.

There have been over 1400 peer reviewed scientific publications from this study, with a number of findings making it into news. There are too many publications to list, but can be found at the website at http://www.srl.cam.ac.uk/epic/publications.shtml with news articles found at http://www.srl.cam.ac.uk/epic/news.shtml.

Some specific recent publications using HES and mortality data as outputs:

- Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort (Luben R, Hayat S, Wareham N, et al, BMJ Open 2016)

- Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study (Basu etal., BMC Medicine2016)

- Accuracy of death certification and hospital record linkage for identification of incident stroke (Sinha, S., Myint, P.K., Luben, R.N. et al. BMC Med Res Methodol 2008)

Outputs for collaborating researchers:

As part of this collaboration, NHS Digital data (including mortality) may be shared with the other centres but data to be shared will contain data from NHS Digital only where it is aggregated with small numbers suppressed in line with the NHS Digital requirements.

The aggregated data are only shared by the University of Cambridge with other collaborators from recognised academic and research institutions on receiving a formal data request. Prior to the release of any data, the management committee of the EPIC-Norfolk study scrutinises the scientific rationale and extent of the data request, reducing it if necessary in order to provide the minimal dataset for release. No identifiable data is shared with collaborating researchers. Datasets are checked by the University of Cambridge EPIC-Norfolk research informatics team before release.

Understanding what the study can do to improve health and prevent disease and disability in ageing populations will have benefits for society and the general public nationally and internationally. Results have already and will continue to contribute to health and clinical policy. Clarification of the mechanisms underlying diseases will enable us to understand pathophysiological processes to support better prevention and treatment, understanding the risk profile for diseases will enable more targeted screening and prevention programmes and understanding and quantifying specific behaviours that influence functional health and healthy ageing will enable us to improve the health experience and quality of life in populations as they age.

University of Cambridge (EPIC-Norfolk Investigators) have contributed to national and international (e.g. WHO) clinical and public health guideline panels, Department of Health initiatives, and invited to provide evidence to Select Committees on health issues in the Houses of Parliament.

Results from this study have informed Department of Health public health initiatives, NICE and other clinical and public health policies and guidelines.

Examples include:

Research from EPIC-Norfolk quantifying the association between four health behaviours (not smoking, modest alcohol intake, physical activity and consumption of 5 servings of fruit and vegetable intake) were associated with a 14 year difference in life expectancy. This directly influenced the Department of Health "Small change big difference" national public health campaign launched from Downing Street, underpinned regional initiatives to promote health behaviour change and has been taken up in national guidance.

EPIC findings have been reported to meetings contributing European policies on ageing (invited presentations to the European Commission DG Health on Frailty in Old Age 2013) http://ec.europa.eu/dgs/health_consumer/dyna/enews/enews.cfm?al_id=1365

Results from EPIC have contributed to clinical guidelines on screening for osteoporosis using heel ultrasound measures, a low cost and safe feasible assessment ( Lewiecki EM et al, Official Positions for FRAX Bone Mineral Density and FRAX simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom. 2011 Jul-Sep;14(3):226-36).

Results from EPIC have also contributed to clinical guidelines on the use of glycated haemoglobin in the diagnosis of diabetes. (RydenL et al, ESC Guidelines on diabetes, prediabetes and cardiovascular diseases in collaboration with the EASD- Summary. Eur Heart J 2013;34: 3035; Anderson T et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidaemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167.

In addition general findings from EPIC-Norfolk have informed publications from charities (e.g. Cancer Research UK, British Heart Foundation, Stroke Association, AgeUK) on disease prevention and maintenance of health.

According to the Chief Executive of Public Health England (PHE), “Type 2 diabetes is one of the biggest health challenges of our time.” Data from EPIC-Norfolk was used in a large study to show the link between sugar-sweetened beverages and the risk of Type 2 Diabetes. Based on these results, University of Cambridge researchers have engaged with national and international policymakers and media to help shape the way that policy and decision-makers and the public understand and act upon these issues.Researchers have contributed to discussions on sugar reduction that were part of PHE’s Sugar Reduction: Responding to the Challenge document; and provided expert input and reviewed the Parliamentary Office on Science and Technology POSTNote on Sugar and Health.

This research was covered by the BBC's 'One Show' ( attracting an audience of over four million viewers), explaining the health impacts of sugary drinks.

The EPIC-Norfolk researchers recognise the importance of engagement with media, the general public and policymakers, tailoring the message according to the target audience.

The EPIC-Norfolk research team also recognises the value of public engagement and have made this an integral part of its research agenda. The primary objective is to raise awareness and inform the general public (all age ranges) on the high-quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at http://www.srl.cam.ac.uk/epic/publicevents.shtml.

The European Prospective Investigation into Cancer (EPIC) is a long-standing research project that was established to examine the relationship between lifestyle, in particular, diet and physical activity, biological factors and health outcomes. EPIC is an international ten country collaboration, coordinated by the International Agency for Research into Cancer in Lyon, which is part of World Health Organisation, such that collaborating partners agreed on a core protocol for the collection and standardisation of data throughout EPIC. However, each individual cohort has also developed specialist areas for investigation. This agreement relates to the Norfolk component of EPIC (EPIC-Norfolk) and the follow-up on approximately 30, 000 men and women aged 40-79 resident in Norfolk at the time of recruitment. Data provided by NHS Digital will not be shared with collaborating partners or any other organisation that is not listed in this agreement except as aggregated data with small numbers suppressed (in line with the HES analysis guide).

The scientific and public health strength of the population cohort is that through routine record linkage, the researchers of University of Cambridge are able to follow up the whole cohort who originally participated for health outcomes. Access to data only for the subset that, almost 25 years later are able to provide new signed informed consent will bias the follow up hugely, and make subsequent follow up and results impossible to interpret. The substantial investment of effort by participants over nearly 2.5 decades in contributing to this research and increasingly valuable information from long-term follow-up of the whole population will be lost. S.251 approval was therefore obtained because reconsenting would reduce participation rates. Also, non-fatal disease is an important area of the research and access to linked HES data is essential to analyse. Many diseases cannot be studied using mortality data alone as the diseases do not cause a death and may only occasionally appear on death certificates. These would include diabetes, eye diseases such as glaucoma, bone diseases such as osteoporosis, frailty and sarcopenia, inflammatory bowel diseases and dementia. Hospital usage is another important area for future research.

EPIC-Norfolk is a flagging study and data from NHS Digital is restricted to the 30,445 EPIC-Norfolk participants recruited at inception of the study. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, and cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow-up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes.

Linkage strengthens the study by allowing the follow-up of participants who drop out of the study due to health reasons or death. It also allows the validation of self-reported conditions such as Parkinson's disease, dementia and stroke. Access to death data provides information on mortality but is also used for administrative purposes to prevent inappropriately mailing to participants who have died and thus avoiding unnecessary distress to family members. Events identified through record linkage will be documented and linked with data collected from individuals on lifestyle so that the University of Cambridge can assess associations between lifestyle and subsequent health outcomes.

The University of Cambridge has combined mortality data and Hospital Episode Statistics data to define outcomes for fatal and non-fatal incident diseases. For example, the University of Cambridge can define an outcome of heart disease using the same range of ICD 10 codes applied to both fatal events from death certificates and non-fatal events from hospital admissions. Data from NHS Digital is processed by a restricted number of trained staff within the EPIC-Norfolk team, Cambridge School of Clinical Medicine, Cambridge. Data is not accessed outside the UK. On-going updates of data are necessary for the accurate follow-up of participants.

Over 600,000 people in the UK suffer from dementia, costing over £17 billion a year. Dementia is an extremely important health issue. Figures released by the Office of National Statistics showed dementia replacing ischaemic heart diseases as the leading cause of death registered in England and Wales in 2015. Several studies have shown the increased risk of mortality not only with dementia but also cognitive impairment. However, in an ageing population, understanding the influence of poor cognitive performance on mortality and health endpoints is also important in terms of advising on public health as this is likely to affect far more individuals than those with impaired cognition. With the data collected over the past 2.5 decades, EPIC will be able to examine associations of a range of lifestyle factors and dementia outcomes and mortality. EPIC-Norfolk study is a partner of Dementia Platform UK (DPUK) to further develop understanding of predictors of dementia outcomes. From the latest 2016 updates from NHS Digital, 2 manuscripts are currently in progress 1/ Investigating Cognitive Performance as a Predictor of Mortality in EPIC-Norfolk and 2/ Hospital use in the last year of life. The data analysis for both these papers were done by researchers with substantive contracts and approved users under the DSA. However even in these cases, the NHS Digital data used were in aggregated format, with small numbers supressed.

This agreement relates to data already held and additional HES year, the Mental Health Minimum Dataset (MHMDS), and Mental Health and Learning Disabilities Data Set (MHLDDS) that have not been requested previously. The MHMDS is extremely important for dementia case ascertainment as dementia diagnoses cannot be adequately captured from the HES data. Having the MHMDS will give better and more accurate estimates of dementia numbers. Currently, dementia diagnoses are significantly underestimated with the data available to this study. Having the accurate figures is necessary for current work examining predictors of dementia outcomes. Again data provided by NHS Digital will only be shared with collaborating partners (including DPUK), as aggregated data with small numbers supressed (in line with the relevant guidance).

There are a number of scientific reasons as to why the earlier HES data is important. This data will allow validation of the self-report from the earliest point of the study allowing the identification of pre-existing conditions. Information on existing disease can also be used in the analysis to account for reverse causality and confounding. Furthermore, HES data gives national coverage of health whereas previously, when the study obtained health outcomes locally, this was only from local healthcare providers. Thus participants receiving medical care or a diagnosis elsewhere would not always be included in available records. Currently, information is missing on individuals who may have had treatment or diagnoses in other hospitals outside Norfolk. The information is not always available from GP practices. Having access to earlier HES years will provide information that is currently missing. Missing data can have serious impact on research, resulting in biased estimates, reduce statistical power and weaken findings that would be difficult to publish.

EPIC-Norfolk is an ongoing longitudinal study. The University of Cambridge received last HES update in 2016. The study continues to use outcome measures from HES data in publications and it is essential for the study to have up to date events for a number of reasons;

• Firstly, the statistical power of the analyses depends on the number of known events. Less common outcomes can only be studied with sufficiently long follow-up and event numbers.

• Secondly, EPIC-Norfolk has made multiple approaches to the cohort. Each approach is a new baseline and is necessary to have non-fatal events

• Thirdly, journals are unwilling to accept publications where the outcomes presented are too old since the missing information may affect the results and their interpretation.

In this amendment. we have requested additionally, the Mental Health Services Data (MHSDS) and Mental Health and Learning Disabilities Data Set (MHLDDS) which we were unaware of at the time of the original application. This dataset contains the latest figures for dementia cases that are not held with the Mental Health Minimum Dataset (MHMDS). It is extremely important to maximise on numbers and have the longest follow-up time from the cognitive measures taken between 2004-2011 for accurate analysis of the data. Combining the figures from MHMDS, MHSDS and MHLDDS will give better and more accurate estimates of dementia numbers. We are also requesting additional HES years that have become available since the original application, again, this is to provide the most recent updates on health outcomes to allow accurate data analysis for publications for the reasons given above.

Any output shared outside the University of Cambridge will contain data only where it is aggregated with small numbers suppressed in line with the NHS Digital requirements.

Outputs for participants and the public:

Equally important is the dissemination of results outside the research community. The University of Cambridge communicate the results to the research participants newsletters. A list of recent newsletters can be found on the study website at http://www.srl.cam.ac.uk/epic/newsletter_archive.shtml.

Information is also disseminated to the general public via printed and digital media. Examples of research results communicated to the public can be found at http://www.srl.cam.ac.uk/epic/news.shtml

The University of Cambridge also actively promote participant involvement in this research. The University of Cambridge set up an advisory panel in 2010 to act as a consultation group to advise us on the research. The EPIC-Norfolk Participant Advisory Panel (EPAP) has been involved in all aspects of the research project from designing health questionnaires, writing of lay summaries, participant information, dissemination of results and providing a lay perspective on potential projects being considered for the future. Further information on EPAP can be found at http://www.srl.cam.ac.uk/epic/participant_panel.shtml

The University of Cambridge also shares results from this study via extensive public engagement activities including regular Science Festival events and lectures to the general public and charitable groups.

Outputs for the research/scientific community:

The University of Cambridge communicates research findings to members of the scientific community through publication in a broad range (both specialist and more general, scientific and medical based) national and international peer-reviewed journals and at national and international conferences.

There have been over 1400 peer reviewed scientific publications from this study, with a number of findings making it into news. There are too many publications to list, but can be found at the website at http://www.srl.cam.ac.uk/epic/publications.shtml with news articles found at http://www.srl.cam.ac.uk/epic/news.shtml.

Some specific recent publications using HES and mortality data as outputs:

- Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort (Luben R, Hayat S, Wareham N, et al, BMJ Open 2016)

- Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study (Basu etal., BMC Medicine2016)

- Accuracy of death certification and hospital record linkage for identification of incident stroke (Sinha, S., Myint, P.K., Luben, R.N. et al. BMC Med Res Methodol 2008)

Outputs for collaborating researchers:

As part of this collaboration, NHS Digital data (including mortality) may be shared with the other centres but data to be shared will contain data from NHS Digital only where it is aggregated with small numbers suppressed in line with the NHS Digital requirements.

The aggregated data are only shared by the University of Cambridge with other collaborators from recognised academic and research institutions on receiving a formal data request. Prior to the release of any data, the management committee of the EPIC-Norfolk study scrutinises the scientific rationale and extent of the data request, reducing it if necessary in order to provide the minimal dataset for release. No identifiable data is shared with collaborating researchers. Datasets are checked by the University of Cambridge EPIC-Norfolk research informatics team before release.

Understanding what the study can do to improve health and prevent disease and disability in ageing populations will have benefits for society and the general public nationally and internationally. Results have already and will continue to contribute to health and clinical policy. Clarification of the mechanisms underlying diseases will enable us to understand pathophysiological processes to support better prevention and treatment, understanding the risk profile for diseases will enable more targeted screening and prevention programmes and understanding and quantifying specific behaviours that influence functional health and healthy ageing will enable us to improve the health experience and quality of life in populations as they age.

University of Cambridge (EPIC-Norfolk Investigators) have contributed to national and international (e.g. WHO) clinical and public health guideline panels, Department of Health initiatives, and invited to provide evidence to Select Committees on health issues in the Houses of Parliament.

Results from this study have informed Department of Health public health initiatives, NICE and other clinical and public health policies and guidelines.

Examples include:

Research from EPIC-Norfolk quantifying the association between four health behaviours (not smoking, modest alcohol intake, physical activity and consumption of 5 servings of fruit and vegetable intake) were associated with a 14 year difference in life expectancy. This directly influenced the Department of Health "Small change big difference" national public health campaign launched from Downing Street, underpinned regional initiatives to promote health behaviour change and has been taken up in national guidance.

EPIC findings have been reported to meetings contributing European policies on ageing (invited presentations to the European Commission DG Health on Frailty in Old Age 2013) http://ec.europa.eu/dgs/health_consumer/dyna/enews/enews.cfm?al_id=1365

Results from EPIC have contributed to clinical guidelines on screening for osteoporosis using heel ultrasound measures, a low cost and safe feasible assessment ( Lewiecki EM et al, Official Positions for FRAX Bone Mineral Density and FRAX simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom. 2011 Jul-Sep;14(3):226-36).

Results from EPIC have also contributed to clinical guidelines on the use of glycated haemoglobin in the diagnosis of diabetes. (RydenL et al, ESC Guidelines on diabetes, prediabetes and cardiovascular diseases in collaboration with the EASD- Summary. Eur Heart J 2013;34: 3035; Anderson T et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidaemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167.

In addition general findings from EPIC-Norfolk have informed publications from charities (e.g. Cancer Research UK, British Heart Foundation, Stroke Association, AgeUK) on disease prevention and maintenance of health.

According to the Chief Executive of Public Health England (PHE), “Type 2 diabetes is one of the biggest health challenges of our time.” Data from EPIC-Norfolk was used in a large study to show the link between sugar-sweetened beverages and the risk of Type 2 Diabetes. Based on these results, University of Cambridge researchers have engaged with national and international policymakers and media to help shape the way that policy and decision-makers and the public understand and act upon these issues.Researchers have contributed to discussions on sugar reduction that were part of PHE’s Sugar Reduction: Responding to the Challenge document; and provided expert input and reviewed the Parliamentary Office on Science and Technology POSTNote on Sugar and Health.

This research was covered by the BBC's 'One Show' ( attracting an audience of over four million viewers), explaining the health impacts of sugary drinks.

The EPIC-Norfolk researchers recognise the importance of engagement with media, the general public and policymakers, tailoring the message according to the target audience.

The EPIC-Norfolk research team also recognises the value of public engagement and have made this an integral part of its research agenda. The primary objective is to raise awareness and inform the general public (all age ranges) on the high-quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at http://www.srl.cam.ac.uk/epic/publicevents.shtml.