Study of Cancer in Vegetarians

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Objective for processing

The University of Oxford requires ongoing access to data supplied by NHS England (and predecessor organization's) for the purpose of a research study known as The Oxford Vegetarian Study (OVS). OVS, also known as the Study of Cancer in Vegetarians, was designed in 1980, with 11,040 participants recruited through the Vegetarian Society, media and by word of mouth between 1980 and 1984. Participants implicitly consented to the study by voluntarily completing and returning the questionnaire. The University of Oxford requires access to NHS England data for the purpose of the following research project: The aim of the study is to investigate the long-term health of vegetarians and comparable non-vegetarians, examining cancer risk and mortality. The design is an observational cohort, based on recruiting healthy volunteer participants and following their long-term health through linkage to NHS information on incident cancers and causes of death. All participants have been recruited and all follow up data has been collected. The application is to allow the University of Oxford to retain data until the end date of this DSA for longer analysis. Study of Cancer in Vegetarians. To support this research the Cancer Epidemiology Unit at the Nuffield Department of Population Health in University of Oxford have received MRIS data. The data received to date includes deaths and cancer from ONS MRIS data from 1980 through to 2017. The data supplied initially included directly identifying data items (e.g., names, NHS numbers, dates of birth, etc.) but from 2017 onwards, the data released by NHS England was pseudonymised, and this data will not be linked to the identifying data held in any way. The pseudonymised and identifiable data will also be stored separately. The data held cannot be minimized any further as all cancers and causes of death are required to analyse the data and remove any confounding factors. The following is a summary of the aims of the research project provided by University of Oxford: To address the GDPR Principle of Data Minimisation the data requested is limited to the 10626 cohort members residing in England and Wales. The University of Oxford only hold information that is deemed necessary for achieving the aims described within this agreement. The Oxford Vegetarian Study (OVS), also known as the Study of Cancer in Vegetarians, is a landmark observational cohort study initiated in 1980 by the University of Oxford. Between 1980 and 1984, the study recruited 11,040 participants through the Vegetarian Society, media campaigns, and word of mouth. Participants implicitly consented by voluntarily completing and returning a detailed dietary questionnaire. The cohort included vegetarians and comparable non-vegetarians, enabling long-term comparisons of health outcomes. All recruitment and follow-up data collection have been completed, and the current application seeks permission to retain data until the end of the Data Sharing Agreement for extended analysis. The lawful basis of this processing falls under GDPR Article’s 6(1)(e) ‘public interest’ and 9(2)(j). The processing can be deemed to be in the public interest because diet and health are of interest to health professionals and the public to establish how diet is a cause of many health-related problems in the general population. This will in turn help policy makers to make an informed decision regarding dietary risk factors in the general population. The project aims to investigate the long-term health effects of vegetarian diets, focusing on cancer risk and mortality. Participants were flagged for cancer and death notifications via Office for National Statistics (ONS) record linkage, and data from ONS MRIS has been received from 1980 through 2017. Initially, data included identifiable items (e.g., names, NHS numbers), but since 2017, NHS England has supplied pseudonymised data, stored separately from the identifiers. Participants in the study were immediately flagged for cancers and deaths with the Office for National Statistics (ONS) record linkage for supplying information for the Study of Cancer in Vegetarians (Ref: MR126). Deaths and cancer information was approved via ONS to supply this information from 1980 to 2013. The aim of the research project is: In November/ December 2015 the study received Ethics (NHS REC) approval, together with CAG Section 251 approval in 2015. The study has received continued support from REC and CAG. - To investigate the long-term health effects of vegetarian and non-vegetarian diets, with a particular focus on cancer incidence and mortality. The study completed follow-up in 2019 and funding for analysis is in place until 2023. As outlined in the specific outputs analysis of the data will continue into 2023 and the research findings will be presented in 2022-2024. The research objectives are: The University of Oxford is the sole data controller who also processes the data for the purposes described within this Agreement. - Assess cancer risk among vegetarians compared to non-vegetarians using linked cancer registry data. The OVS is supported by grants from the Medical Research Council (MRC) (“Health of Vegetarians”) and the World Cancer Research Fund. Neither of these organization's have access to NHS England, and do not play a role in determining how this data will be processed. - Evaluate mortality patterns for major causes of death, including cancer, cardiovascular disease, and other chronic conditions. - Analyse dietary factors such as meat, fish, and plant-based food consumption and their association with disease outcomes. The following NHS England Data will be accessed: - MRIS - Cohort Event Notification Report - MRIS - Cause of Death Report - MRIS - Members and Postings Report The MRIS data was requested because it contains official, longitudinal records of cancer incidence and mortality for the Study cohort. This information is essential to achieve the study’s aim of examining the long-term health of vegetarians and comparable non-vegetarians. By linking participants’ dietary data to verified NHS and ONS records, researchers can accurately analyse cancer risk and causes of death over several decades. The level of the Data will be: - Identifiable - Necessary because identifiable data is required to accurately link historical study records with NHS cancer and death registrations before pseudonymisation for analysis. Without the identifiers, linkage would be unreliable and compromise research validity. The Data will be minimised as follows: - Limited to a study cohort of 10,626 participants residing in England and Wales who were originally recruited for the Oxford Vegetarian Study. University of Oxford is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. The funding comes from multiple sources. Current funders include: - Medical Research Council - World Cancer Research Fund (WCRF) The funding is specifically for the research project described. The funders will have no ability to suppress or otherwise limit the publication of findings. The study was designed in 1980 as an observational cohort to investigate the long-term health of vegetarians and comparable non-vegetarians, focusing on cancer risk and mortality. Recruitment was through the Vegetarian Society of the UK, publicity in local and national media, and word of mouth between 1980 and 1984. Participants joined by voluntarily completing and returning a diet and lifestyle questionnaire. Public benefit was considered in the rationale: the study aimed to provide evidence for health professionals and policymakers on dietary risk factors for chronic diseases. Later engagement occurred when participants were informed of findings and invited to join EPIC-Oxford in 1994.

Processing activities

Under a previous iteration of this agreement The University of Oxford sent the details of their cohort to NHS England, in turn the University received MRIS data relating to these individuals. No new data is required under this Agreement. University of Oxford will transfer data to NHS England. The data will consist of identifying details (specifically Names, NHS Number, Date of Birth and a unique person ID) for the cohort to be linked with NHS England data. NHS England provided regular updates on participant events including removals and re-entries to NHS registration, cancer registrations and deaths. This data contained details of month, year and causes of deaths and month, year and diagnosis of cancer and a unique study ID. NHS England will provide the relevant records from the MRIS datasets to University of Oxford. The Senior Statistician within the Cancer Epidemiology Unit (CEU) at the University of Oxford linked the data, using Study ID, with study participants’ pseudonymised questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. The Data will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient. Various types of analyses are undertaken on an on-going basis for the overarching purpose of assessing cancer incidence and overall mortality. The data will be held only at the Cancer Epidemiology Unit within the Nuffield Department of Population Health at the University of Oxford. Current analyses are examining the risks of various types of cancer in fish-eaters, vegetarians and vegans compared to meat-eaters, using Cox proportional hazards models with adjustment for age, sex and other non-dietary risk factors such as smoking. Future work will look at heart disease death from stroke and risk of prostate cancer, as well as the protective impact of vegetarian diets in preventing the development of obesity. The Data will not be transferred to any other location. In the planned new analyses of ischaemic heart disease and stroke, the study will use their data on diet to estimate the impacts on health of replacing energy (calories) from red and processed meat with energy from plant foods which can be used to replace these foods, such as legumes (beans, peas and lentils) and nuts. The Data will be stored on servers at University of Oxford. The data is processed only by one named statistician, who is a substantive employee within the Cancer Epidemiology Unit (CEU). The analysis files are prepared by the statistician who manages the data, using only the variables required to answer the research question. The Data will be accessed onsite at the premises of University of Oxford only. The study will not share any data supplied by NHS England with any other institution or individual outside of the study team at Oxford University. The Data will not leave England and Wales at any time. Data supplied by NHS England and data generated by OVS will be kept in separate electronic files linked by a numerical, anonymous subject identifier. Lifestyle/dietary data required for analysis will be extracted from the relevant data files (which do not contain subject names, NHS numbers or full dates of birth) and merged with the data supplied by NHS England using the subject identifier, without having recourse to any identifiable data. Access is restricted to employees or agents of University of Oxford who have authorisation from the Principal Investigator. There will be no attempt to re-identify individuals from the pseudonymised data. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The Data will be linked at person record level with study participants’ pseudonymised questionnaire records held by University of Oxford using the unique person ID. All subsequent analyses use only subsets of the pseudonymised data. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. Analysts and researchers from the University of Oxford will process the Data for the purposes described above.

Expected output

Publications are produced on an ongoing basis, all outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. Examples of publications are: The expected outputs of the processing will be: Key TJ, Bradbury KE, Perez-Cornago A, Sinha R, Tsilidis KK, Tsugane S. Diet, nutrition, and cancer risk: what do we know and what is the way forward? BMJ 2020;368:m511. - Reports of findings to funders and stakeholders: Key TJ, Papier K, Tong TYN. Plant-based diets and long-term health: findings from the EPIC-Oxford study. Proc Nutr Soc 2022;81:190-198. Medical Research Council (MRC) and World Cancer Research Fund (WCRF) as part of grant deliverables. Results are disseminated in peer-reviewed open-access papers in research journals, and related presentations to national and international colleagues, including clinicians. - Submissions to peer-reviewed journals: First paper: Characteristics of vegetarians across cohorts will be submitted to American Journal of Clinical Nutrition in 2024 This study currently has funding to retain the identifiable data until the end of 2024. Second paper: Cancer risk by site will be submitted to British Medical Journal also in 2024 The data is processed only by one named researcher within the Cancer Epidemiology Unit (CEU). For all of these outputs, data is aggregated with small numbers suppressed in line with the HES analysis guidance. - Presentations to national and international colleagues, including clinicians Future anticipated work using ONS mortality and cancer registry data during 2020-2024: - Dissemination of findings through academic and clinical networks The World Cancer Research Fund Grant 2019/1953 “Vegetarian diets and cancer risk” specifies a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of cancer. - Presentations at specific conferences: In 2023-2024 the study will analyse the relationships of vegetarian diets with risk of cancer. In analyses combining the results from analyses of data from the Oxford Vegetarian Study, EPIC-Oxford and other large cohorts which include a substantial number of vegetarians, the cancer risk in vegetarians will be examined compared to non-vegetarians. The first paper will report in the characteristics of vegetarians in all the cohorts, the second will focus on cancers of the gastro-intestinal tract, the reproductive organs and other sites. The aim is to submit the first paper to the American Journal of Clinical Nutrition in 2024 and the second to the BMJ in 2024. - 2023: 14th European Nutrition Conference (FENS) Conferences - 2024: Nutrition Society UK Symposium University of Oxford plan to present research findings at the following conferences: - 2025: 8th International Congress on Vegetarian Nutrition (Loma Linda, California) • 2023 - 14th European Nutrition Conference FENS - Publication of aggregated results in open-access journals • 2024 – Nutrition Society UK Symposium 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. • 2025 – 8th International Congress on Vegetarian Nutrition, Loma Linda, California The outputs will be communicated to relevant recipients through the following dissemination channels: - Journals - Presentations at conferences - Direct engagement with academic and clinical colleagues - Public promotion of the research - Briefing documents provided to funders The target dates for production and dissemination are concentrated in the current funding period, ending in 2024. Two major journal submissions are planned for 2024: one on the characteristics of vegetarians across cohorts (targeting the American Journal of Clinical Nutrition) and another on cancer risk by site (targeting BMJ). Conference presentations will occur at the 14th European Nutrition Conference in 2023, the Nutrition Society UK Symposium in 2024, and the 8th International Congress on Vegetarian Nutrition in 2025. Aggregated results will continue to be published in open-access journals throughout this period, and briefing documents will be provided to funders as part of grant milestones.

Expected measurable benefits

The aim of the study is to improve information on diet in relation to the risk of cancer and cardiovascular disease and offers potential for improvements in public health in the UK. The results are published in peer-reviewed publications and presented at conferences, and are also reported through national media. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. University of Oxford research relates directly to the health of 1.2 million people in the UK who follow vegetarian diets (NHS 2014). The long-term effects on cancer of a vegetarian diet are not well understood, and little is known about the health effects of a vegan diet. Our previous research has demonstrated lower risks of obesity (50%), heart disease (30%), stomach cancer (60%) and haematological cancers (36%) in vegetarians compared with non-vegetarians Tong et al 2019, Key et al 2014), and further study is likely to reveal other associations between diet and cancer risk (Key et al 2019, 2022). As well as peer-reviewed scientific publications, where appropriate, University of Oxford will also communicate with the NHS and other organisations such as the National Cancer Intelligence Network within Public Health England and other health providers in the UK, where the outputs from the study will provide information to underpin their health advice to the public. The use of the data could: For example: The PI of this study sits on the Scientific Advisory Committee on Nutrition (SACN) which reports to UK government organisations. working group on plant-based drinks, which reports to the Office for Health Improvement and Disparities (OHID) and other UK government organisations. Conclusions from this committee are used to formulate government and NHS policy on diet and thus reduce the risk of disease and the burden on the NHS. In a current SACN update, the fortification of the UK food supply for folic acid to prevent neural tube defects included a key piece of evidence including data from the Oxford Vegetarian Study, related to the safety of folic acid with respect to cancer risk. (https://www.gov.uk/government/consultations/consultation-on-draft-sacn-update-on-folic-acid). - Help the system to better understand the health and care needs of populations by providing robust evidence on the long-term health outcomes of vegetarians and vegans compared to non-vegetarians. Future work will look at heart disease (further analyses with more data), death from stroke and risk of prostate cancer, as well as the protective impact of vegetarian diets in preventing the development of obesity. - Advance understanding of the need for, or effectiveness of, preventative health and care measures by assessing how plant-based diets influence cancer and cardiovascular disease risk, supporting strategies to reduce disease burden. In the planned new analyses of ischaemic heart disease and stroke, the study will use their data on diet to estimate the impacts on health of replacing energy (calories) from red and processed meat with energy from plant foods which can be used to replace these foods, such as legumes (beans, peas and lentils) and nuts. - Inform planning of health services and programmes by enabling policy-makers and commissioners to design dietary guidance and interventions that improve equity of access, experience, and outcomes for diverse populations. The NHS Choices website (http://www.nhs.uk/Livewell/Vegetarianhealth/Pages/Vegetarianhealthqanda.aspx#what) states that “a vegetarian diet can be very healthy” and reports on an NHS patient who comments “I feel much healthier on a vegan diet', but includes few specific statements about the benefits. The research will provide the robust information needed to include more specific facts and advice on the NHS website and thus enable the public to improve their health and reduce the burden on the NHS. - Lead to the identification or improvement of interventions by clarifying which dietary patterns are associated with reduced risk of chronic conditions, informing NHS dietary advice and public health campaigns. As well as peer-reviewed scientific publications, where appropriate, University of Oxford will also communicate with the NHS and other organisations such as the National Cancer Intelligence Network within Public Health England where the outputs from the study will provide information to underpin their health advice to the public. - Advance understanding of regional and national trends in health and social care needs through analysis of large cohorts and linkage to NHS data, supporting evidence-based decision-making at scale. This study will directly benefit health care through the NHS by providing clinicians and other NHS health care professionals with up-to-date evidence-based guidance on the effects of diet on cancer and the risk of death. This will improve clinical health care and inform planners and policy makers to address demands on health and social care in the present and future. - Support knowledge creation and exploratory research that underpins innovations in nutrition science and informs future preventive health strategies. The robust, reliable knowledge on vegetarian diets and risk of chronic disease will provide the evidence to underpin the judgements made by decision-makers on the future direction of NHS policy in relation to dietary advice, thus acting as an enabler. For example, the NHS reported in 2013 that a vegetarian diet brings a range of health benefits and is linked to longer lifespan (12% in risk of death from any cause, see http://www.nhs.uk/news/2013/06June/Pages/Vegetarian-diet-linked-to-longer-lifespan.aspx). This NHS assessment noted that the study concerned had a relatively short follow-up of six years, this is quite short to address how dietary patterns might affect the risk of death. The findings of this research are expected to deliver direct benefits to patients by providing accurate, evidence-based dietary guidance that supports informed choices about vegetarian and plant-based diets. This will help reduce the risk of cancer and cardiovascular disease through improved prevention strategies and updated NHS dietary advice. Patients will experience better health outcomes and care quality as clinicians use these findings to guide treatment and lifestyle recommendations. Ultimately, the research empowers patients with reliable information for self-care, contributing to healthier lifestyles and a reduction in diet-related conditions. In University of Oxford analyses, there is a follow-up of over thirty years which will provide the NHS with much more reliable information on the long-term health of people following a vegetarian diet. This reliable evidence will be available in publications in late 2017 and 2018, enabling updating of NHS sources during 2018. This reliable evidence will be available in publications in late 2024 and 2025, enabling updating of NHS sources during 2026. It is hoped that through publication of findings in peer-reviewed journals and presentations at major conferences, the research will add to the body of evidence considered by policy-making bodies such as the Scientific Advisory Committee on Nutrition (SACN), the Office for Health Improvement and Disparities (OHID), and individual clinicians when making treatment decisions. These outputs will inform updates to NHS dietary guidance and public health recommendations, enabling commissioners and practitioners to implement preventive strategies that reduce cancer and cardiovascular risk. In the link http://www.nhs.uk/news/2013/01january/pages/does-a-veggie-diet-lead-to-a-healthier-heart.aspx Clients and stakeholders will need to take action based on the evidence provided to realise these benefits. For example, NHS England and SACN may update national dietary guidelines to encourage plant-based eating patterns, which could lead to improved population health outcomes and reduced disease burden on the NHS. The researchers concluded that vegetarians had a 32% lower risk of IHD than non-vegetarians, and that this is likely due to “reduced levels of well-established risk factors for IHD, such as non-HDL cholesterol concentrations and systolic blood pressure”. This large and impressive prospective cohort study suggests that a vegetarian diet may benefit your heart; reducing the risk of IHD. This was a well-conducted, large long-term study that suggests there are heart healthy benefits to a vegetarian diet. The NHS will be able to continue to use University of Oxford data to update their websites accessible to the general public. To optimise the potential public benefits, the research team will publish findings in peer-reviewed open-access journals and present them at major national and international conferences to reach academic and clinical audiences. They will engage directly with policy-making bodies such as SACN and OHID to inform updates to NHS dietary guidance and public health recommendations. Where findings warrant wider attention, media engagement and public promotion will be undertaken, including press releases and updates to NHS Choices. Briefing documents will be shared with funders and relevant stakeholders, and collaboration with charities and professional societies in nutrition and cancer research will help ensure the findings are disseminated broadly and applied effectively. This NHS provided advice, based on OVS data, to their stakeholders. This will enable commissioners to implement appropriate policies in relation to diet, thus reducing the financial burden of dietary related diseases. More recently one of the named researchers attended the inaugural workshop of the Cancer and Nutrition NIHR infrastructure collaboration http://cancerandnutrition.nihr.ac.uk/wp-content/uploads/2016/06/Cancer-Nutrition-Full-Report-FINAL_03-06-16.pdf . OVS and EPIC will be part of this initiative. The Cancer and Nutrition NIHR infrastructure collaboration will improve cancer prevention and care for clinicians and patients.

Unchanged: Benefits reported.

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Benefits reported

[6 paragraphs unchanged] Work is ongoing on two manuscripts - one methods paper and one [23 words unchanged] first paper has been circulated to all collaborating authors and first results will be were presented by Dr Yashvee Dunneram at the 14th European Nutrition Conference FENS2023 in Belgrade, Serbia, 14th-17th November 2023.

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

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

Objective for processing

The University of Oxford requires ongoing access to data supplied by NHS Digital England (and predecessor organisations) organization's) for the purpose of a research study known as The Oxford Vegetarian [35 words unchanged] implicitly consented to the study by voluntarily completing and returning the questionnaire. [1 paragraph unchanged] To support this research the Cancer Epidemiology Unit at the Nuffield Department [43 words unchanged] of birth, etc.) but from 2017 onwards, the data released by NHS Digital England was pseudonymised, and this data will not be linked to the identifying data held in any way. The pseudonymised and identifiable data will also be stored separately. The data held cannot be minimised minimized any further as all cancers and causes of death are required to analyse the data and remove any confounding factors. [6 paragraphs unchanged] The OVS is supported by grants from the Medical Research Council (MRC) (“Health of Vegetarians”) and the World Cancer Research Fund. Neither of these organisations organization's have access to NHS Digital, England, and do not play a role in determining how this data will be processed.

Processing activities

Under a previous iteration of this agreement The University of Oxford sent the details of their cohort to NHS Digital, England, in turn the University received MRIS data relating to these individuals. No new data is required under this Agreement. NHS Digital England provided regular updates on participant events including removals and re-entries to NHS [16 words unchanged] and month, year and diagnosis of cancer and a unique study ID. [4 paragraphs unchanged] The study will not share any data supplied by NHS Digital England with any other institution or individual outside of the study team at Oxford University. Data supplied by NHS Digital England and data generated by OVS will be kept in separate electronic files [29 words unchanged] full dates of birth) and merged with the data supplied by NHS Digital England using the subject identifier, without having recourse to any identifiable data. [1 paragraph unchanged]

Expected output

[1 paragraph unchanged] Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain. Key TJ, Bradbury KE, Perez-Cornago A, Sinha R, Tsilidis KK, Tsugane S. Diet, nutrition, and cancer risk: what do we know and what is the way forward? BMJ 2020;368:m511. Thorogood M, Carter R, Benfield L, McPherson K, Mann JI. Key TJ, Papier K, Tong TYN. Plant-based diets and long-term health: findings from the EPIC-Oxford study. Proc Nutr Soc 2022;81:190-198. British Medical Journal 1987;295:351-353. Relationship of body mass index, weight and height to plasma lipid levels in people with different diets in Britain. Thorogood M, McPherson K, Mann J. Community Medicine 1989;11:230-233. Dietary intake and plasma lipid levels: lessons from a study of the diet of health conscious groups. Thorogood M, Roe L, McPherson K, Mann J, British Medical Journal 1990;300:1297-1301. (h:\docs\ovs\dietary_intake_and_plasma_lipid_levels.pdf) Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores. Key TJA, Roe L, Thorogood M, Moore JW, Clark GG, Wang DY. British Journal of Nutrition 1990;64:111-119. Asymptomatic hypothyroidism and hypercholesterolaemia. Ball MJ, Griffiths D, Thorogood M. Journal of the Royal Society of Medicine 1991;84:527-529. Risk of death from cancer and ischaemic heart disease in meat and non-meat eaters. Thorogood M, Mann J, Appleby P, McPherson K. British Medical Journal 1994;308:1667-1671. (h:\docs\ovs\risk_of_death_BMJ1994.html) Emergency appendicectomy and meat consumption in the UK. Appleby P, Thorogood M, McPherson K, Mann J. Journal of Epidemiology and Community Health 1995;49:594-596. Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr 2016;103:218-30. Key TJ, Appleby PN, Crowe FL, Bradbury KE, Schmidt JA, Travis RC. Cancer in British vegetarians: updated analyses of 4998 incident cancers in a cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246 vegans. Am J Clin Nutr 2014;100 Suppl 1:378S-85S. San Joaquin MA, Appleby PN, Key TJ. Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10998 vegetarians and non-vegetarians in the United Kingdom. Br J Cancer 2004;90:118-21. [1 paragraph unchanged] This study currently has funding to follow up patients retain the identifiable data until the end of 2024. [1 paragraph unchanged] Future anticipated work using ONS mortality and cancer registry data: data during 2020-2024: The Medical World Cancer Research Council Fund Grant MR/M012190/1 "Health of vegetarians" 2019/1953 “Vegetarian diets and cancer risk” specifies a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of common diseases. cancer. Future anticipated work using ONS mortality and cancer registry data during 2020-2023: In 2023-2024 the study will analyse the relationships of vegetarian diets with risk of cancer. In analyses combining the results from analyses of data from the Oxford Vegetarian Study, EPIC-Oxford and other large cohorts which include a substantial number of vegetarians, the cancer risk in vegetarians will be examined compared to non-vegetarians. The first paper will report in the characteristics of vegetarians in all the cohorts, the second will focus on cancers of the gastro-intestinal tract, the reproductive organs and other sites. The aim is to submit the first paper to the American Journal of Clinical Nutrition in 2024 and the second to the BMJ in 2024. The Medical Research Council Grant MR/M012190/1 "Health of vegetarians", the Wellcome Trust Grant 205212/Z/16/Z “Livestock, Environment and People” and the World Cancer Research Fund Grant 2019/1953 “Vegetarian diets and cancer risk” specify a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of cancer and risk of mortality for other common diseases. In 2021 to 2024 the study will analyse the relationships of vegetarian diets with risk of cancer. In analyses combining the results from analyses of data from the Oxford Vegetarian Study, EPIC-Oxford and other large cohorts which include a substantial number of vegetarians, we will examine cancer risk in vegetarians compared to non-vegetarians. The first paper will report in the characteristics of vegetarians in all the cohorts, the second will focus on cancers of the gastro-intestinal tract, and the third on cancers of the reproductive organs and other sites. We aim to submit the first paper to the American Journal of Clinical Nutrition in 2022, the second to the BMJ in 2023, and the third to Cancer Research in 2024. [2 paragraphs unchanged] • 2022 – Nutritional Society UK Symposium • 2023 - 14th European Nutrition Conference FENS • 2023 – 8th International Congress on Vegetarian Nutrition, Loma Linda, California • 2024 – Nutrition Society UK Symposium • 2024 – UK National Cancer Research Institute Conference • 2025 – 8th International Congress on Vegetarian Nutrition, Loma Linda, California

Expected measurable benefits

[1 paragraph unchanged] University of Oxford research relates directly to the health of 1.2 million [48 words unchanged] stomach cancer (60%) and haematological cancers (36%) in vegetarians compared with non-vegetarians (Key and Davey 1996, Crowe Tong et al 2013, 2019, Key et al 2009, 2014), and further study is likely to reveal other associations between diet and cancer risk. risk (Key et al 2019, 2022). As well as peer-reviewed scientific publications, where appropriate, University of Oxford will [31 words unchanged] study will provide information to underpin their health advice to the public. For example: The PI of this study sits on the Scientific Advisory Committee on Nutrition (SACN) which reports to Public UK government organisations. working group on plant-based drinks, which reports to the Office for Health England Improvement and Disparities (OHID) and other UK government organisations. Conclusions from this committee are used to [54 words unchanged] to the safety of folic acid with respect to cancer risk. (https://www.gov.uk/government/consultations/consultation-on-draft-sacn-update-on-folic-acid). [6 paragraphs unchanged] In University of Oxford analyses, there is a follow-up of over thirty [29 words unchanged] in late 2017 and 2018, enabling updating of NHS sources during 2018. This reliable evidence will be available in publications in late 2024 and 2025, enabling updating of NHS sources during 2026. [4 paragraphs unchanged]

Benefits reported

[6 paragraphs unchanged] Work is ongoing on two manuscripts - one methods paper and one results paper for the WCRF-funded vegetarians and cancer consortium and it is anticipated these will be submitted within the next six months. The first paper has been circulated to all collaborating authors and first results will be presented by Dr Yashvee Dunneram at the 14th European Nutrition Conference FENS2023 in Belgrade, Serbia, 14th-17th November 2023.

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

Objective for processing

The University of Oxford requires ongoing access to data supplied by NHS [20 words unchanged] known as the Study of Cancer in Vegetarians, was designed in 1980, and the with 11,040 participants were recruited through the Vegetarian Society, media and by word of mouth between 1980 and 1984. Participants implicitly consented to the study by voluntarily completing and returning the questionnaire. The aim of the study is to investigate the long-term health of [26 words unchanged] through linkage to NHS information on incident cancers and causes of death. All participants have been recruited and all follow up data has been collected. The application is to allow the University of Oxford to retain data until the end date of this DSA for longer analysis. To support this research the Cancer Epidemiology Unit at the Nuffield Department of Population Health in University of Oxford have received MRIS data. The data received to date includes deaths and cancer from ONS MRIS data from 1980 through to 2017. The data supplied initially included directly identifying data items (e.g., names, NHS numbers, dates of birth, etc.) but from 2017 onwards, the data released by NHS Digital was pseudonymised, and this data will not be linked to the identifying data held in any way. The data held cannot be minimised any further as all cancers and causes of death are required to analyse the data and remove any confounding factors. To address the GDPR Principle of Data Minimisation the data requested is limited to the 10626 cohort members residing in England and Wales. The University of Oxford only hold information that is deemed necessary for achieving the aims described within this agreement. The lawful basis of this processing falls under GDPR Article’s 6(1)(e) ‘public interest’ and 9(2)(j). The processing can be deemed to be in the public interest because diet and health are of interest to health professionals and the public to establish how diet is a cause of many health-related problems in the general population. This will in turn help policy makers to make an informed decision regarding dietary risk factors in the general population. [1 paragraph unchanged] In November/ December 2015 the study received Ethics (NHS REC) and approval, together with CAG Section 251 (CAG) approval. approval in 2015. The study has received continued support from REC and CAG. There have been 1108 incident cancers (to 31/12/2012) and 1955 deaths (to 31/3/2014) in the cohort. Analysis of the cohort has led to many publications, as recently as 2014, in peer reviewed journals such as the British Medical Journal and British Journal of Cancer. The study completed follow-up in 2019 and funding for analysis is in place until 2023. As outlined in the specific outputs analysis of the data will continue into 2023 and the research findings will be presented in 2022-2024. Data was initially collected by questionnaires on diet and lifestyle, returned by post in 1980-1984. The OVS is supported by a grant from the Medical Research Council (MRC) (“Health of Vegetarians”). The University of Oxford is the sole data controller who also processes the data for the purposes described within this Agreement. The study is needed to improve understanding of the effects of diet on health and thus inform advice to governments, health professionals and the public about dietary choices to maximise the potential for long-term good health. The OVS is supported by grants from the Medical Research Council (MRC) (“Health of Vegetarians”) and the World Cancer Research Fund. Neither of these organisations have access to NHS Digital, and do not play a role in determining how this data will be processed. The study is on-going and funding is in place until 2020. As outlined in the specific outputs analysis of the data will continue into 2018 and the research findings will be presented in 2019.

Processing activities

Under a previous iteration of this agreement The participants University of Oxford sent the details of their cohort to NHS Digital, in turn the study are already flagged on the NHS Digital system, therefore the customer does not need University received MRIS data relating to send in the cohort again. these individuals. No new data is required under this Agreement. Under previous iterations of this Agreement, NHS Digital provided regular updates on participant events including removals and re-entries to NHS registration, cancer registrations and deaths, including cause deaths. This data contained details of death details. The data supplied initially included directly identifying data items (e.g. names, NHS numbers, dates month, year and causes of birth, etc.) but from 2017 onwards, the data released by NHS Digital was pseudonymised deaths and this will not be linked to the identifying data held in any way. month, year and diagnosis of cancer and a unique study ID. NHS Digital provided the University of Oxford with month and year and causes of deaths and month and year and diagnosis of cancer and a unique study ID. The Senior Statistician within the Cancer Epidemiology Unit (CEU) at the University of Oxford linked the data, using Study ID, with study participants’ pseudonymised questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. The Senior Statistician within the Cancer Epidemiology Unit (CEU) at the University of Oxford linked the data, using Study ID, with study participants’ pseudonymised questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. All such subsets are customised according to the characteristics relevant to the specific analysis containing only the minimum data required for the specific purpose. Various types of analyses are undertaken on an on-going basis for the overarching purpose of assessing cancer incidence and overall mortality. The data will be held only at the Cancer Epidemiology Unit within the Nuffield Department of Population Health at the University of Oxford. Current analyses are examining the risks of various types of cancer in fish-eaters, vegetarians and vegans compared to meat-eaters, using Cox proportional hazards models with adjustment for age, sex and other non-dietary risk factors such as smoking. Future work will look at heart disease death from stroke and risk of prostate cancer, as well as the protective impact of vegetarian diets in preventing the development of obesity. Various types of analyses are undertaken on an on-going basis for the overarching purpose of assessing cancer incidence and overall mortality. The data will be held only at the Cancer Epidemiology Unit at the University of Oxford. The datasets will be pseudonymised as described above before statistical analyses are undertaken. In the planned new analyses of ischaemic heart disease and stroke, the study will use their data on diet to estimate the impacts on health of replacing energy (calories) from red and processed meat with energy from plant foods which can be used to replace these foods, such as legumes (beans, peas and lentils) and nuts. The data is processed only by one named statistician, who is a substantive employee within the Cancer Epidemiology Unit (CEU). The analysis files are prepared by the statistician who manages the data, using only the variables required to answer the research question. [1 paragraph unchanged] All users of the data are substantive employees of the University of Oxford. Data supplied by NHS Digital and data generated by OVS will be kept in separate electronic files linked by a numerical, anonymous subject identifier. Lifestyle/dietary data required for analysis will be extracted from the relevant data files (which do not contain subject names, NHS numbers or full dates of birth) and merged with the data supplied by NHS Digital using the subject identifier, without having recourse to any identifiable data. Data supplied by NHS Digital and existing data will be kept in separate electronic files linked by a numerical, anonymous subject identifier. Lifestyle/dietary data required for analysis will be extracted from the relevant data files (which do not contain subject names, NHS numbers or full dates of birth) and merged with the data supplied by NHS Digital using the subject identifier, without having recourse to any identifiable data. There will be no attempt to re-identify individuals from the pseudonymised data.

Expected output

[24 paragraphs unchanged] Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr 2016;103:218-30. Key TJ, Appleby PN, Crowe FL, Bradbury KE, Schmidt JA, Travis RC. Cancer in British vegetarians: updated analyses of 4998 incident cancers in a cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246 vegans. Am J Clin Nutr 2014;100 Suppl 1:378S-85S. San Joaquin MA, Appleby PN, Key TJ. Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10998 vegetarians and non-vegetarians in the United Kingdom. Br J Cancer 2004;90:118-21. [1 paragraph unchanged] This study currently has funding to follow up patients until 2020. 2024. [3 paragraphs unchanged] In 2017 and 2018 the study will analyse: Future anticipated work using ONS mortality and cancer registry data during 2020-2023: • the relationships of vegetarian diets with the risk for death from ischaemic heart disease, extending previous published research on this topic with larger numbers of cases and examining the extent to which the effects of a vegetarian diet may be explained by the consumption of saturated and polyunsaturated fatty acids, fruit and vegetables and dietary fibre; the intent is to complete this manuscript in late 2017 and to submit it to the BMJ. The Medical Research Council Grant MR/M012190/1 "Health of vegetarians", the Wellcome Trust Grant 205212/Z/16/Z “Livestock, Environment and People” and the World Cancer Research Fund Grant 2019/1953 “Vegetarian diets and cancer risk” specify a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of cancer and risk of mortality for other common diseases. • In parallel, analyses commencing later in 2017 will examine the associations of vegetarian diets with risk of death from stroke, it was suggested that vegetarians had a somewhat higher risk of stroke than meat-eaters, but the number of cases was too small for robust analyses; with the new current linkage combined with data from EPIC – Oxford, it is expected that approximately 2000 cases of stroke which will provide sufficient power to conduct reliable analyses, and to explore the possible roles of protein and vitamin B12 in determining stroke risk in vegetarians. The intent is to submit this manuscript in 2018 to the journal Circulation. In 2021 to 2024 the study will analyse the relationships of vegetarian diets with risk of cancer. In analyses combining the results from analyses of data from the Oxford Vegetarian Study, EPIC-Oxford and other large cohorts which include a substantial number of vegetarians, we will examine cancer risk in vegetarians compared to non-vegetarians. The first paper will report in the characteristics of vegetarians in all the cohorts, the second will focus on cancers of the gastro-intestinal tract, and the third on cancers of the reproductive organs and other sites. We aim to submit the first paper to the American Journal of Clinical Nutrition in 2022, the second to the BMJ in 2023, and the third to Cancer Research in 2024. • In analyses of prostate cancer, the study will report on the risk in relation to vegetarian diets and submit to the British Journal of Cancer, and present the results at the conference of Urologists stated below. [2 paragraphs unchanged] • 2017 2022 – Nutritional Society UK Symposium • 2017 – European Association of Urologists • 2023 – 8th International Congress on Vegetarian Nutrition, Loma Linda, California • 2018 – 7th International Congress on Vegetarian Nutrition, Loma Linda, California • 2024 – UK National Cancer Research Institute Conference • 2018 – NCIN Conference • 2019 – NCIN Conference

Expected measurable benefits

[5 paragraphs unchanged] The NHS Choices website (http://www.nhs.uk/Livewell/Vegetarianhealth/Pages/Vegetarianhealthqanda.aspx#what) states that “a vegetarian diet can be [5 words unchanged] an NHS patient who comments “I feel much healthier on a vegan diet”, diet', but includes few specific statements about the benefits. The research will provide [19 words unchanged] public to improve their health and reduce the burden on the NHS. [8 paragraphs unchanged] Selected publications: Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr 2016;103:218-30. Key TJ, Appleby PN, Crowe FL, Bradbury KE, Schmidt JA, Travis RC. Cancer in British vegetarians: updated analyses of 4998 incident cancers in a cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246 vegans. Am J Clin Nutr 2014;100 Suppl 1:378S-85S. San Joaquin MA, Appleby PN, Key TJ. Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10998 vegetarians and non-vegetarians in the United Kingdom. Br J Cancer 2004;90:118-21.

Benefits reported

As this is a long term longitudinal cohort study it will take many years to reach the final endpoints (death and cancer incidence). OVS was the first large-scale cohort study in the world with both detailed information and blood samples for a large number of vegetarians and otherwise comparable meat-eaters. Major findings from the study are lower cholesterol and body mass index in vegetarians, and a lower risk of several types of chronic disease including cancers. OVS has now been running for 40 years. Early results from the study showed robustly for the first time that vegetarians have lower LDL cholesterol than meat-eaters due to a lower intake of saturated fat, underpinning more recent work on diet and risk factors for coronary heart disease, and the UK Government's current recommendations on saturated fat intake https://www.gov.uk/government/publications/saturated-fats-and-health-sacn-report OVS was one of only eleven cohort studies worldwide used by the UK Government's Scientific Advisory Committee on Nutrition to conclude that there is adequate evidence that high intakes of dietary fibre have a beneficial impact on health by reducing the risk of coronary heart disease, and leading to the recent increase in the recommended intake of dietary fibre in the UK from 18 g/d of NSP fibre to 30 g/d of AOAC fibre https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/445503/SACN_Carbohydrates_and_Health.pdf The use of evidence from OVS in the reports of the UK Government's Scientific Advisory Committee on Nutrition has enabled the production of authoritative advice on diet to the NHS and the public, leading to large benefits in the health of the nation and reduction of the burden on the NHS.