Epidemiological studies of the Porton Down veterans: an update of mortality and cancer incidence

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

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Objective for processing

The legal basis for processing this data comes under GDPR Article 6(1)(e) of the General Data Protection Regulation (GDPR): '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'. King’s College London and the University of Lancaster require access to NHS England data for the purpose of the following research project: Epidemiological studies of the Porton Down veterans: an update of mortality and cancer incidence. Public Task: Section 8 of the Data Protection Act 2018 clarifies that “In Article 6(1) of the GDPR (lawfulness of processing), the reference in point (e) to processing of personal data that is necessary for the performance of a task carried out in the public interest or in the exercise of the controller’s official authority includes processing of personal data that is necessary for… (d) the exercise of a function of the Crown, a Minister of the Crown or a government department”. King's College London and Lancaster University both fall into this category as they have a Royal Charter: The following is a summary of the aims of the research project provided by King’s College London and University of Lancaster: (https://www.kcl.ac.uk/governancezone/governancelegal/charter-and-statutes, original Charter of 1829 The study aims to examine whether Porton Down veterans exposed to chemical warfare agents have unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans. https://www.lancaster.ac.uk/media/lancaster-university/content-assets/documents/strategic-planning--governance/governance/council-key-documents/Charter-Statutes-Ordinances.pdf To examine whether Porton Down veterans had unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans, their records were linked to routine cancer registration and mortality data held by the Office for National Statistics up to 2004, namely, cause and date of death, type and date of cancer registration. The study established that, although there was a small (6%) excess of all-cause mortality in Porton Down veterans, this could not be attributed to any specific chemical exposure and might have been related to unmeasured factors such as smoking. There was no excess of cancers. King's College London are satisfied that this request is appropriate, necessary and proportionate for the performance of the task described in the Purpose statement and that there is no other reasonable means for the data processor to achieve their purpose that is less intrusive to the data subjects. As part of the application process, the requirement for the data requested has been assessed and NHS Digital is content that it is appropriate, necessary and proportionate for the performance of the task described in the Purpose statement. This study aims to replicate the original analysis but with at least ten years of updated cancer registration and mortality data. This NHS England data will allow the study team to repeat the analyses carried out previously, but with increased statistical power so that the impact of rare exposures and outcomes can be examined more fully, at a level of detail not possible in the original study. The special condition category is article 9(2)(j) of the General Data Protection Regulation (GDPR): New research questions of relevance to public health were posed after the original papers were published. For example, Barth et al. (2009) reported that US Gulf War veterans with potential exposure to nerve agents had an increased risk of central nervous system cancers and other neurological mortality. Updating this cohort will give an opportunity to confirm or refute Barth’s et al. study, and to add to the evidence base on nerve agents. 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. Likewise, it should be possible to look in more detail at riot control agents (CS gas) for which the original study noted a two-fold excess of oesophageal cancer (currently CS is not a known carcinogen), and also the relationship between pralidoxime, a nerve agent antidote, and increased risk of all-cause mortality (there has been repeated suggestion that nerve agent antidotes might be implicated in Gulf War syndrome (Abou Donia et al. 1996, Zakirova et al. 2015). These research questions cannot be easily examined in the absence of well-documented cohort data. The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data. The specific objectives therefore are: In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include: i. The data will only be used in identifiable form for the specific purpose of data linkage and quality assurance of that linkage – for which purpose use of identifiable data is necessary – and measures are taken to ensure subsequent uses of the data will involve only data that has been appropriately pseudonymised. ii. The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details); iii. The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details); iv. Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection (see sections 5a, 5b and 8a of this application for further details); v. Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights to withdraw consent and/or have their data erased or rectified, etc. (further information on fair processing is provided within this Abstract below and in section 4 of this application). Common Law Duty of Confidentiality is met by the section 251 for NHS Digital data (England and Wales), but not for the linkages via NHS Scotland and Northern Ireland. The ethics, authorisations and permissions (section 251 equivalent) for NHS Scotland data will be covered when applying to the Public Benefit and Privacy Panel https://www.informationgovernance.scot.nhs.uk/pbpphsc/who-are-the-public-benefit-and-privacy-panel-and-what-do-they-do/. Northern Irish data will not be linked until equivalent ethics approvals and authorisations are in place. The study was originally set-up in 2003 by the University of Oxford to explore the long-term health of former servicemen who were exposed to chemical warfare agents as part of the ‘human volunteer programme’ at the UK government research establishment, Porton Down. Using historical records, the researchers assembled a cohort of 18441 veterans who attended Porton Down, and a comparison cohort of 18103 who did not. The cohort of veterans are UK service personnel from across the UK, plus 1.5% Rep. Ireland, and 2.5% overseas. To examine whether Porton Down veterans had unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans, their records were linked to routine cancer registration and mortality data held by the Office for National Statistics up to 2004, namely, cause and date of death, type, and date of cancer registration. The study established that, although there was a small (6%) excess of all-cause mortality in Porton Down veterans, this could not be attributed to any specific chemical exposure and might have been related to unmeasured factors such as smoking. There was no excess of cancers. The new study aims to replicate the original analysis but with at least ten years of updated cancer registration and mortality data. This new data will allow the study team to repeat the analyses carried out previously, but with increased statistical power so that the impact of rare exposures and outcomes can be examined more fully, at a level of detail not possible in the original study (see Expected Measurable Benefits, ‘Ability to address new questions relevant to public health using unique cohort data’ for further detail). The aim of this study is to examine whether Porton Down veterans exposed to chemical warfare agent have unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans. Study Objectives: [2 paragraphs unchanged] The new study will be undertaken by researchers at King’s College London (study lead) and the University of Lancaster. Researchers who worked on the original study at the University of Oxford will act as advisors due to their historical knowledge; for example, on how data was originally collected, study file structure and documentation, and suggestions for stakeholder engagement, but will not determine the manner in which data are to be processed. The following NHS England data will be accessed: King’s College London and Lancaster Universities are joint data controllers as both are involved in determining the purposes and means of processing the data; however the updated data will only be processed, stored, and analysed by King’s College London. MRIS- Cause of Death Report The study update has been awarded funding by the MRC (MR/R002932/1) to update cancer registration and death data to the latest available date; this data will be obtained from NHS Digital, NHS Scotland, and Northern Ireland and Statistics (for English/Welsh, Scottish, and Northern Irish data, respectively). MRIS- Flagging Current Status Report The study will not involve working with organisations outside the UK. MRIS – Member and Postings Report The data required is limited to members of the Porton Down veterans study; this also includes the study cohort. Record-level data is essential in order to link deaths and cancer registrations to the correct military veteran and chemical exposure at Porton Down. Cause of death and type of cancer are required in order to investigative investigate the wide variety of possible harms which might be attributed to chemical warfare agents. The identifiable cause and date of death, death and type and date of cancer registration data is are required to create time-to-event data so that the original analyses (which covered 1941 to 2004) can be updated. Access to date of birth data is required in order to i) calculate person-years as per the original analysis, and ii) validate linkage between the original and updated outcome data. Once time-to-event and person-years have been derived, date of birth and dates of death and cancer registration will be removed from the analysis file and stored separately. CAG approval has been granted to process this data. Date of embarkation/emigration is required to derive person-years of follow-up. Emigrants are estimated to account for approximately 5% of the Porton Down data. If they are not identified, this will bias results as their cancer and death status is effectively unknown. For example, a cohort member who embarked in 2004 would appear in Porton Down data as ‘alive’ up to 2020 but could have died in 2005. Date of emigration will allow KCL to include and account for emigration in the analysis. The date of embarkation/emigration is required to derive person-years of follow-up and account for emigration in the analysis. For the original study, Oxford had a 2003 agreement with ONS for the supply of data to Oxford under ONS reference 107/053/02 and MR reference 758. A previous request was for the same data fields as were supplied under the 2003 agreement. The level of the data will be identifiable – necessary to validate linkage between the original and NHS England data and derive required analysis fields. The data will only be used to investigate the relationship between exposure to chemical warfare agents at Porton Down and patterns of cancer incidence, and mortality. The data will be minimised as follows: •Limited to a study cohort provided by King's College London- 18441 veterans who attended Porton Down, and a comparison cohort of 18103 who did not. The cohort of veterans are UK service personnel from across the UK, plus 1.5% Rep. Ireland, and 2.5% overseas. •Limited to data between 1941 to at least 2014. King’s College London and the University of Lancaster are joint data controllers as the organisations responsible for ensuring that the data will only be processed for the purpose described above. The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This processing is in public interest because there is a plausible and ongoing risk of exposure to chemical warfare agents in civilian, military and emergency service populations in the UK and internationally, yet the long-term health effects of low-dose exposure to these agents are largely unknown. Concerns that these agents, or their antidotes, might cause delayed effects on health are likely to remain long into the future and it is in the public interest to accumulate research evidence to confirm, or refute, these concerns. The funding is provided by Medical Research Council and King's College London. The MRC funding is specifically for the study described. Funding is in place until 31/10/2021. King's College London funding is available within the department on an ongoing basis. The NHS England data will only be processed, stored, and analysed by King’s College London. Researchers who worked on the original study at the University of Oxford will act as advisors due to their historical knowledge; for example, on how data was originally collected, study file structure and documentation, and suggestions for stakeholder engagement, but will not determine the manner in which data are to be processed. In the original study, there had been extensive consultations with the Porton Down Veterans Support Group and with other stakeholders. It was concluded that it was not practicable to seek individual consent because it was a historical study; addresses in military personnel records were outdated, and due to the advanced age of the cohort by the end of 2004, approximately 40% had already died; using national age-specific mortality rates, it is estimated that by mid-2019 approximately 60% will have died. This was recognised by the Patient Information Advisory Group who gave ethics approval on the grounds that the public interest in completing the research outweighed the usual requirement for individual consent. The same arguments hold for not seeking consent for the NHS England data, especially as, with the passage of time, more cohort members have died and addresses in the military personnel records are further out-of-date. References: Abou-Donia, M. B. (1996). Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: implications of Gulf War chemical exposures. Journal of Toxicology and Environmental Health Part A, 48(1), 35-56. https://doi.org/10.1080/009841096161456 Zakirova, Z., Tweed, M., Crynen, G., Reed, J., Abdullah, L., Nissanka, N., ... & Ait-Ghezala, G. (2015). Gulf War agent exposure causes impairment of long-term memory formation and neuropathological changes in a mouse model of Gulf War Illness. PloS one, 10(3), e0119579. https://doi.org/10.1371/journal.pone.0119579

Processing activities

The Porton Down cohort is already assembled and no new participants will be sought. The original data was obtained from three sources: King's Centre for Military Health Research (KCMHR) will transfer data to NHS England. The data will consist of identifying details (specifically unique study ID, name, initials, sex, NHS number, date of birth, and postcode (district level)) for the cohort to be linked with NHS England data. 1) Porton down records: Chemical exposure data for the Porton Down veterans was collected in the original study from records held at Porton Down. This data was used to generate the ‘exposure’ database, which includes data on name, military service number, and chemical exposure information (e.g., date of test, type of exposure). NHS England data will provide the relevant records from the MRIS datasets to KCMHR. The data will contain directly identifying data items including Date of Birth which is required to validate linkage and derive person-years variables. 2) Military personnel files: The list of veterans assembled from the Porton Down records (n=18441) was sent to military personnel archives for verification of military personnel data, e.g., military service number, branch of service, military rank. A comparison group (n=18103) was generated within military personnel archives by choosing veterans with adjacent military service numbers who had not attended Porton Down. This data was used to create the ‘personnel’ database, which includes data on sex, date of birth, military rank, date of enlistment, date of discharge, and date and cause of death (if recorded). Once person-years have been derived, the date of birth will be removed from the outcome database and stored separately on encrypted external hard drives in the KCMHR study safe. 3) National registry data (outcome data): Study members were originally flagged by ONS and mortality and cancer registration data provided to the researchers up to 31/12/2004. This was the ‘outcome’ database, and includes sensitive personal data including cause of death, type of cancer, and date of death and cancer. The data will not be transferred to any other location. In the original study, there had been extensive consultations with the Porton Down Veterans Support Group and with other stakeholders. It was concluded that it was not practicable to seek individual consent because it was a historical study; addresses in military personnel records were outdated, and due to the advanced age of the cohort by the end of 2004, approximately 40% had already died; using national age-specific mortality rates, it is estimated that by mid-2019 approximately 60% will have died. This was recognised by the Patient Information Advisory Group who gave ethics approval on the grounds that the public interest in completing the research outweighed the usual requirement for individual consent. The same arguments hold for not seeking consent now, especially as, with the passage of time, more cohort members have died and addresses in the military personnel records are further out-of-date. The data is stored at the KCMHR offices. KCL network drives are backed up at JISC datacentre in Slough; however, the study data will be stored on encrypted external drives at the KCMHR offices. No data will be saved to university servers. Conditional support from the Confidentiality Advisory Group (CAG) and the Health Research Authority (HRA) for Section 251 approval under the National Health Service Act 2006, to process identifiable data without consent, has been granted and continually reviewed. The data will be analysed on a networked University managed PC; data will not be saved to a computer or any other electronic device. The flow of data is as follows: The data will not leave England at any time. 1) Transfer of original study data from Oxford to King's College Military Health Research: (complete) Only the KCMHR Data Manager and study Research Associate will have access to the data, both of which have undertaken training in data protection, i.e., MRC Research, GDPR and confidentiality training. Under a legal Data Transfer Agreement, all physical and electronic data was transferred from Oxford to KCMHR, King’s College London using a secure courier service. The chemical ‘exposure’, military ‘personnel’, and ‘outcome’ (cancer and death) data are classified as identifiable. Paper files are stored securely at KCMHR offices and in an off-site archive, and electronic databases are stored on an encrypted external hard drive. The data will be linked with chemical exposure data; military personnel files containing e.g., military service number, branch of service, military rank, date of enlistment, date of discharge; and mortality and cancer data received for the cohort from the Office for National Statistics. It will be held in the same database as the equivalent records for the Scottish members of the cohort. 2) KCMHR separate personal identifiers and de-identify databases: (complete) The identifying details will be stored in a separate database to the linked dataset used for analysis. This includes dates of death and dates of cancer registration and embarkation information. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. KCMHR stored personal identifiers from the electronic data securely in the KCMHR main office safe. Data files used for analysis will contain a unique study ID number only. Researchers from the KCMHR will analyse the data for the purposes described above. 3) Transfer of data from KCMHR to NHS Digital and NHS Scotland: (complete) After the necessary permissions were obtained, KCMHR sent NHS Digital/NHS Scotland the minimum personal information necessary to re-flag the cohort for deaths and cancers to the latest available date, namely, unique study ID, name, initials, sex, NHS number, date of birth, postcode (district level). The same identifiers were sent to NHS Digital and NHS Scotland. These identifiers were identical to those used in the original study and necessary to re-flag and validate matches. Note: data was not sent to NISRA (as stated in the previous version of this application) as no formal procedures were identified for mortality and cancer registry linkage with Northern Irish data. 4) NHS Digital and NHS Scotland transferred updated outcome data to KCMHR: (complete) The updated mortality and cancer data was sent securely from NHS Digital and NHS Scotland to KCMHR, which included cause and date of death, and type and date of cancer registration. The unique study ID number and date of birth was also requested back. 5) KCMHR linked the updated and original outcome data: (complete) The updated and original outcome data have been linked using a unique study ID number, and linkage has been validated using date of birth. Date of birth is needed to derive person-years variables, and dates of death cancer registration, and embarkation information will be needed to create time-to-event variables, as per the original analysis. 6) KCMHR separate personal identifiers and de-identify the analytical database: (in progress) Once time-to-event and person-years have been derived, date of birth, and dates of death, cancer registration and embarkation information will be removed from the outcome database and stored separately on encrypted external hard-drives in the KCMHR study safe. 7) Data analysis at KCMHR (linkage of the ‘exposure’, ‘personnel’ and ‘outcome’ data): (in progress) KCMHR will create an analysis file by linking the exposure, personnel, and outcome databases using the unique study ID. Due to the combination of variables, data will treated as identifiable, and stored on an encrypted external hard drive in a locked filing cabinet in the study office. The data will be analysed on a networked University managed PC; data will not be saved to a computer or any other electronic device. The data from NHS Digital and NHS Scotland will not be shared with third parties and will not be used for benchmarking against peer groups. There will be no requirement nor attempt to re-identify individuals from the data. The data is stored at the King's Centre for Military Health Research (KCMHR) offices. These offices have a higher level of physical security than standard as they store sensitive military data. The offices are situated within a building which is manned by a security team on a 24-hour basis. To enter the KCMHR building, an individual must have a swipe card ID and must present this on the ground floor to security guards and at a card reader to enter the main building. The study office at King’s Centre for Military Health Research at King’s College London is alarmed, and the door is secured with both a key lock and a digital coded lock, and there is CCTV in the corridor. Paper-based files will be stored in a locked cabinet in the study office, and in King’s secure archive at Guy's campus. De-identified electronic data will be stored on an encrypted external hard-drive in a locked drawer in the study office. Personal identifiers will be stored separately on an encrypted external hard-drive in a Ministry of Defence approved safe in the KCMHR main office. Only the KCMHR Data Manager and study Research Associate will have access to the data, both of which have undertaken training in data protection, i.e., MRC Research, GDPR and confidentiality training. KCL network drives are backed up at JISC datacentre in Slough; however the study data will be stored on encrypted external drives at the KCMHR offices. No data will be saved to university servers. Medical Research Council (MRC) guidelines on the holding and archiving of data in relation to cohort studies will be abided by. As recommended by the MRC, if no update of the study is forthcoming, the data will be electronically and physically destroyed. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

[1 paragraph unchanged] Subject to acceptance, research articles will are planned to be published in open-access, high impact, high-impact, peer-reviewed scientific journals, such as the British Medical Journal (BMJ). journals. 1) Mortality and cancer incidence in British military participants in human experimental research into chemical warfare agents at Porton Down: A 15-year update (planned submission (currently under second review - 2021) International Journal of Epidemiology) 2) Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: A 15-year update (planned submission 2021) 2) Cohort Profile: The Porton Down veterans’ cohort (published 2022): 3) Cohort Profile: The Porton Down veterans’ cohort (planned submission 2021) Gemma Archer, Thomas J Keegan, Katherine M Venables, Lucy M Carpenter, Nicola T Fear, Cohort Profile: The Porton Down Veterans cohort study, International Journal of Epidemiology, Volume 51, Issue 4, August 2022, Pages e200–e205, https://doi.org/10.1093/ije/dyac006 4) 3) Mortality and cancer morbidity in military participants exposed to Sarin as part of human experimental research at Porton Down (planned (in draft: planned submission 2022) April 2023) 6) An epidemiological review of chemical warfare agent exposure and long-term health (planned submission 2022) 4) Mortality and cancer morbidity in military participants exposed to sulfur mustard and riot control agents as part of human experimental research at Porton Down: (Planned submission July 2023) These above outputs were delayed slightly due to a delay in data receipt as well as other factors such as Covid-19 mitigation, and part-time working for post-doctoral Research Associate (Sept 19 to Feb 20). The expected dates for these outputs have been updated to reflect this. Several of the updated study’s findings have been presented at relevant academic conferences in 2022 (e.g., the Canadian Institute for Military and Veteran Health Research, Halifax, Canada, 2022, and the Occupational Health conference, Edinburgh, 2022). Anticipated findings from forthcoming analysis may be presented again here, or at other relevant conferences including the Occupational and Environmental Epidemiology conference and the International Symposium on Epidemiology in Occupational Health (EPICOH). The updated study’s findings will also be presented at relevant academic conferences in 2022 (e.g., the Canadian Institute for Military and Veteran Health Research, the International Symposium on Epidemiology in Occupational Health, Society for Longitudinal and Life course Studies conference. Reports of findings in lay language have and will continue to be disseminated to veterans by means of a specially-convened meeting and via the newsletters of veterans’ organisations and relevant websites, e.g., of veterans’ organisations and of the collaborating universities. The findings are also reported in a blog: https://kcmhr.org/the-porton-down-veterans-cohort-study-an-update/. Reports of findings in lay language will be disseminated to veterans by means of a specially-convened meeting and via the newsletters of veterans’ organisations and relevant websites, e.g., of veterans’ organisations and of the collaborating universities. Policy-relevant findings will be presented to official bodies e.g., the Ministry of Defence veterans’ section and Public UK Health England. Security Agency (UKHSA), with a meeting with Cabinet Office ministers arranged for February 2023. Future outputs will be shared with the Office for Veterans' Affairs (OVA) and the veteran community. It is intended that the recognition of veterans exposed to chemical warfare agents and their possible health needs will lead to new initiatives from the OVA and NHS. [1 paragraph unchanged] Any future data processing not covered in this application will be preceded by an amendment application to NHS Digital. England. [2 paragraphs unchanged] Allender S, Maconochie N, Keegan T, Brooks C, Fletcher T, Nieuwenhuijsen MJ, [11 words unchanged] life in a support group of Porton Down veterans. Occup Med 2006;56:329-137. doi: 10.1093/occmed/kql059 Keegan TJ, Nieuwenhuijsen MJ, Fletcher T, Brooks C, Doyle P, Maconochie NES, [6 words unchanged] from the UK chemical warfare human research programme. Ann Occup Hyg 2007;51:441-450. doi: 10.1093/annhyg/mem017 Keegan TJ, Walker SAS, Brooks C, Langdon T, Linsell L, Maconochie NES, [16 words unchanged] UK chemical warfare agent human research programme, 1941-89. Ann Occup Hyg 2009;53:83-97. doi: 10.1093/annhyg/men040 [4 paragraphs unchanged]

Expected measurable benefits

The original study was born out of concerns raised by veterans that their long-term health may have been affected by their exposure to chemical agents (e.g., vesicants, riot control agents, nerve agents, and their antidotes) as part of the ‘human volunteer programme’ at Porton Down. The study found that Porton Down veterans had no overall excess of cancer compared to non-Porton Down veterans, and a small excess (6%) of overall mortality, but this could not be attributed to any specific exposure. The main benefit to this study is to further understand long-term health risk of low-dose exposure to chemical warfare agents or their antidotes. Chemical warfare agents are easily manufactured and continue to be deployed. Most recently, a nerve agent developed in the former Soviet Union was used in Salisbury. Five people were exposed, and one died. These findings were published in the BMJ (Carpenter et al., 2009; Venables et al,. 2009), an international peer reviewed medical journal, and helped to clarify the health status of Porton Down veterans and other former service personnel exposed to chemical warfare agents, which was believed to be reassuring to many veterans and their families. The main benefit to this study is to further understand long-term health risk of low-dose exposure to chemical warfare agents or their antidotes. Chemical warfare agents are easily manufactured and continue to be deployed by rogue states, e.g., Syria and Iraq (United Nations 2013), and by terrorists, e.g., on the Tokyo subway (Coleman 2005, Okumura et al. 2005). Most recently, a nerve agent developed in the former Soviet Union was used in Salisbury (BBC News 19 July 2018, OPCW 13 March 2018). Five people were exposed, and one died. [1 paragraph unchanged] The Porton Down cohort study is the largest and best-documented cohort with exposure to chemical warfare agents in the world. It is the only cohort with accurate, quantitative information on exposure, thus allowing the study of exposure-response relationships. As well as its large size, the exposure data is of exceptionally high quality compared to other sources; for example, information gathered after warfare or terrorist scenarios has many attendant biases, i.e., the precise nature of the exposures may be unclear; mixtures of chemicals may have been used; and the dose and duration of exposure are unknown. In the original analysis, over 7,000 Porton Down veterans had died in the period 1941-2004. The study update will increase this to about 12,000 deaths, and a proportional increase in cancer registrations. The increased number of outcome events increases statistical power which will enable to gain a greater understanding of the relationship between specific chemical agents and health outcomes (e.g., rarer forms of cancer) at a level of detail not possible in the original study. If an association is found between exposure to chemical agents (e.g., vesicants, riot control agents, nerve agents, or their antidotes) and an increased risk of certain cancers, or cause of death, this could lead to raised awareness among health care providers, leading to improved diagnosis and quality of care. Likewise, if particular chemical warfare or riot control agents are associated with poor long-term health, the Ministry of Defence (MoD) and other public health organisations could act to protect individuals from exposure in the future. Conversely, if there appears to be no long-term health risk, then this will reassure veterans and their families, and any other exposed groups, leading to a reduction in anxiety about their exposure. New research questions of relevance to public health were posed after the original papers were published. For example, Barth et al. (2009) reported that US Gulf War veterans with potential exposure to nerve agents had an increased risk of central nervous system cancers and other neurological mortality. Updating this cohort will give an opportunity to confirm or refute Barth’s et al. study, and to add to the evidence base on nerve agents. The engagement with the MoD and the NHS Armed Forces Team will be sought to put in place any additional support needed for the veterans and their families prior to the publication of the results. The findings will be helpful to organisations concerned with the health and welfare of the Porton Down veterans, e.g. the Legacy section of the MoD, the Help Line at Porton Down, and the Medical Assessment Programme for the Porton Down veterans. Likewise, it will be possible to look in more detail at riot control agents (CS gas) for which the original study noted a two-fold excess of oesophageal cancer (currently CS is not a known carcinogen), and also the relationship between pralidoxime, a nerve agent antidote, and increased risk of all-cause mortality (there has been repeated suggestion that nerve agent antidotes might be implicated in Gulf War syndrome (Abou Donia et al. 1996, Zakirova et al. 2015). These research questions cannot be easily examined in the absence of well-documented cohort data. The findings should also be helpful for other groups exposed to chemical warfare or riot control agents including other military service personnel, emergency services, and the general population (e.g., police or demonstrators exposed to CS gas, and Salisbury residents following the Novichok incident). If an association is found between exposure to chemical agents (e.g., vesicants, riot control agents, nerve agents, or their antidotes) and an increased risk of certain cancers, or cause of death, this could lead to raised awareness among health care providers, leading to improved diagnosis and quality of care. Likewise, if particular chemical warfare or riot control agents are associated with poor long-term health, the Ministry of Defence and other public health organisations could act to protect individuals from exposure in the future. Conversely, if there appears to be no long-term health risk, then this will reassure veterans and their families, and any other exposed groups, leading to a reduction in anxiety about their exposure. The results will be useful to organisations responsible for public health and those concerned with the military response or emergency service response in the event of a release of a chemical warfare agent by a hostile country, individual, or agency, e.g., the MoD, ambulance, police forces and fire brigades, and organisations concerned with civilian emergency preparedness, e.g.,UK Health Security Agency (UKHSA). The findings of the study will be submitted to high-profile medical journals and should now be published between 2021-2023 due to the delay in data analysis detailed previously. The updated findings are also expected to offer a unique contribution to the academic literature, which could be of benefit to other researchers investigating the relationship between chemical warfare agents and long-term health. The engagement with the MoD and the NHS Armed Forces Team will be sought to put in place any additional support needed for the veterans and their families prior to publication of the results. The findings will be helpful to organisations concerned with the health and welfare of the Porton Down veterans, e.g. the Legacy section of the Ministry of Defence, the Help Line at Porton Down, and the Medical Assessment Programme for the Porton Down veterans. The findings will also be helpful for other groups exposed to chemical warfare or riot control agents including other military service personnel, emergency services, and the general population (e.g., police or demonstrators exposed to CS gas, and Salisbury residents following the Novichok incident). The results will be useful to organisations responsible for public health and those concerned with the military response or emergency service response in the event of a release of a chemical warfare agent by a hostile country, individual, or agency, e.g., the Ministry of Defence, ambulance, police forces and fire brigades, and organisations concerned with civilian emergency preparedness, e.g., Public Health England. The updated findings will also offer a unique contribution to the academic literature, which will be of benefit to other researchers investigating the relationship chemical warfare agents and long-term health. [2 paragraphs unchanged] References: Abou-Donia MB, Wilmarth KR, Jensen KF, Oehme FW, Kurt TL. Neurotoxicity resulting from coexposure to pralidoxime bromide, deet, and permethrin: implications of Gulf War chemical exposures. J Toxicol Environ Health. 1996;48:35-56. Barth SK, Kang HK, Bullman TA, Wallin MT. Neurological mortality among U.S. veterans of the Persian Gulf War: 13-year follow-up. Am J Ind Med. 2009;52:663-70. doi: 10.1002/ajim.20718. BBC News. Amesbury Novichok poisoning: What we know so far. 19 July 2018. (https://www.bbc.co.uk/news/uk-44721558). Carpenter, L. M., Linsell, L., Brooks, C., Keegan, T. J., Langdon, T., Doyle, P., ... & Venables, K. M. Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: cohort study. Bmj, 338, b655. 2009 (https://www.bmj.com/content/338/bmj.b655.full.pdf+html) Coleman K. A history of chemical warfare. Basingstoke: Palgrave, 2005. Venables, K. M., Brooks, C., Linsell, L., Keegan, T. J., Langdon, T., Fletcher, T., ... & Carpenter, L. M. Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: cohort study. Bmj, 338, b613. 2009. (https://www.bmj.com/content/338/bmj.b613.short) Okumura T, Hisaoka T, Yamada A, Naito T, Isonuma H, Okumura S, Miura K, Sakurada M, Maekawa H, Ishimatsu S, Takasu N, Suzuki K. The Tokyo subway sarin attack--lessons learned. Toxicol Appl Pharmacol. 2005;207:471-76. Office for the Prohibition of Chemical Weapons. EC-87/NAT.5 13 March 2018. Statement by H.E. Ambassador Peter Wilson Permanent Representative of the United Kingdom of Great Britain and Northern Ireland to the OPCW at the Eighty-Seventh Session of the Executive Council. (https://www.opcw.org/fileadmin/OPCW/EC/87/en/ec87nat05_e_.pdf).

Benefits reported

King’s College London received complete data from NHS Digital in September 2020 (and complete data from National Records Scotland in Jan 2021). Data cleaning and preparation has been completed but analysis is only at the early stages due to delays in obtaining the data. Outputs are still being generated. Publication of the cohort profile in a high quality journal (International Journal of Epidemiology (IJE)) and in the KCMHR blog has made the cohort and its potential value visible to a global academic and lay audience. The publication of the cohort profile paper resulted in contact from several veterans and their families, with whom the intention is to share planned and future work as part of an advisory group, increasing patient and public involvement and engagement.

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

Objective for processing

Study background: The legal basis for processing this data comes under GDPR Article 6(1)(e) of the General Data Protection Regulation (GDPR): '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'. Public Task: Section 8 of the Data Protection Act 2018 clarifies that “In Article 6(1) of the GDPR (lawfulness of processing), the reference in point (e) to processing of personal data that is necessary for the performance of a task carried out in the public interest or in the exercise of the controller’s official authority includes processing of personal data that is necessary for… (d) the exercise of a function of the Crown, a Minister of the Crown or a government department”. King's College London and Lancaster University both fall into this category as they have a Royal Charter: (https://www.kcl.ac.uk/governancezone/governancelegal/charter-and-statutes, original Charter of 1829 https://www.lancaster.ac.uk/media/lancaster-university/content-assets/documents/strategic-planning--governance/governance/council-key-documents/Charter-Statutes-Ordinances.pdf King's College London are satisfied that this request is appropriate, necessary and proportionate for the performance of the task described in the Purpose statement and that there is no other reasonable means for the data processor to achieve their purpose that is less intrusive to the data subjects. As part of the application process, the requirement for the data requested has been assessed and NHS Digital is content that it is appropriate, necessary and proportionate for the performance of the task described in the Purpose statement. The special condition category is article 9(2)(j) of the General Data Protection Regulation (GDPR): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data. In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include: i. The data will only be used in identifiable form for the specific purpose of data linkage and quality assurance of that linkage – for which purpose use of identifiable data is necessary – and measures are taken to ensure subsequent uses of the data will involve only data that has been appropriately pseudonymised. ii. The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details); iii. The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details); iv. Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection (see sections 5a, 5b and 8a of this application for further details); v. Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights to withdraw consent and/or have their data erased or rectified, etc. (further information on fair processing is provided within this Abstract below and in section 4 of this application). Common Law Duty of Confidentiality is met by the section 251 for NHS Digital data (England and Wales), but not for the linkages via NHS Scotland and Northern Ireland. The ethics, authorisations and permissions (section 251 equivalent) for NHS Scotland data will be covered when applying to the Public Benefit and Privacy Panel https://www.informationgovernance.scot.nhs.uk/pbpphsc/who-are-the-public-benefit-and-privacy-panel-and-what-do-they-do/. Northern Irish data will not be linked until equivalent ethics approvals and authorisations are in place. [1 paragraph unchanged] Using historical records, the researchers assembled a cohort of 18441 veterans who attended Porton Down, and a comparison cohort of 18103 who did not. The cohort of veterans are UK service personnel from across the UK, plus 1.5% Rep. Ireland, and 2.5% overseas. To examine whether Porton Down veterans had unusual patterns of cancer incidence [22 words unchanged] for National Statistics up to 2004, namely, cause and date of death, type type, and date of cancer registration. The study established that, although there was [26 words unchanged] to unmeasured factors such as smoking. There was no excess of cancers. [1 paragraph unchanged] Study aim: The aim of this study is to examine whether Porton Down veterans exposed to chemical warfare agent have unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans. To examine whether Porton Down veterans exposed to chemical warfare agent have unusual patterns of cancer incidence or mortality compared to non-Porton Down veterans [1 paragraph unchanged] 1. Describe cause-specific mortality from 1941 to at least 2014 for the [27 words unchanged] ‘other’ exposure, and (c) sub-cohorts exposed to specific chemicals of prior interest, e.g. e.g., sarin, pralidoxime; and examine dose-response relationships where data is available. 2. Describe cancer incidence from 1971 to at least 2014 for the [27 words unchanged] ‘other’ exposure, and (c) sub-cohorts exposed to specific chemicals of prior interest, e.g. e.g., sarin, pralidoxime; and examine dose-response relationships where data is available. What organisations are involved? [4 paragraphs unchanged] Reasons for data requested: The data required is limited to members of the Porton Down veterans study; this also includes the study cohort. Record-level data is essential in order to link deaths and cancer registrations to the correct military veteran and chemical exposure at Porton Down. Cause of death and type of cancer are required in order to investigative the wide variety of possible harms which might be attributed to chemical warfare agents. The updated data requested from NHS Digital is essential to enable the original analyses (which covered the period 1941-2004) can be updated. The identifiable cause and date of death, and type and date of cancer registration data is required to create time-to-event data so that the original analyses (which covered 1941 to 2004) can be updated. Access to date of birth data is required in order to i) calculate person-years as per the original analysis, and ii) validate linkage between the original and updated outcome data. Once time-to-event and person-years have been derived, date of birth and dates of death and cancer registration will be removed from the analysis file and stored separately. CAG approval has been granted to process this data. The data required is limited to members of the Porton Down veterans study, this also includes the study cohort. Record-level data is essential in order to link deaths and cancer registrations to the correct military veteran and chemical exposure at Porton Down. Cause of death and type of cancer are required in order to investigative the wide variety of possible harms which might be attributed to chemical warfare agents. [1 paragraph unchanged] For the original study, Oxford had a 2003 agreement with ONS for the supply of data to Oxford under ONS reference 107/053/02 and MR reference 758. The new A previous request is was for the same data fields as were supplied under the 2003 agreement. [1 paragraph unchanged]

Processing activities

Original sources of data: [1 paragraph unchanged] 1) Porton down records: Chemical exposure data for the Porton Down veterans [21 words unchanged] which includes data on name, military service number, and chemical exposure information (e.g. (e.g., date of test, type of exposure). 2) Military personnel files: The list of veterans assembled from the Porton Down records (n=18441) was sent to military personnel archives for verification of military personnel data, e.g. e.g., military service number, branch of service, military rank. A comparison group (n=18103) [41 words unchanged] enlistment, date of discharge, and date and cause of death (if recorded). [1 paragraph unchanged] Consent: In the original study, there had been extensive consultations with the Porton Down Veterans Support Group and with other stakeholders. It was concluded that it was not practicable to seek individual consent because it was a historical study; addresses in military personnel records were outdated, and due to the advanced age of the cohort by the end of 2004, approximately 40% had already died; using national age-specific mortality rates, it is estimated that by mid-2019 approximately 60% will have died. This was recognised by the Patient Information Advisory Group who gave ethics approval on the grounds that the public interest in completing the research outweighed the usual requirement for individual consent. The same arguments hold for not seeking consent now, especially as, with the passage of time, more cohort members have died and addresses in the military personnel records are further out-of-date. In the original study there have been extensive consultations with the Porton Down Veterans Support Group and with other stakeholders. It was concluded that it was not practicable to seek individual consent because it was a historical study; addresses in military personnel records were outdated, and due to the advanced age of the cohort by the end of 2004 approximately 40% had already died; using national age-specific mortality rates, it is estimated that by mid-2019 approximately 60% will have died. . This was recognised by the Patient Information Advisory Group who gave ethics approval on the grounds that the public interest in completing the research outweighed the usual requirement for individual consent. The same arguments hold for not seeking consent now, especially as, with the passage of time, more cohort members have died and addresses in the military personnel records are further out-of-date. Conditional support from the Confidentiality Advisory Group (CAG) and the Health Research Authority (HRA) for Section 251 approval under the National Health Service Act 2006, to process identifiable data without consent, has been granted and continually reviewed. Conditional support from the Confidentiality Advisory Group (CAG) and the Health Research Authority (HRA) for Section 251 approval under the National Health Service Act 2006, to process identifiable data without consent, has been granted. The flow of data is as follows: Data flow: 1) Transfer of original study data from Oxford to King's College Military Health Research: (complete) 1) Transfer of original study data from Oxford to King's College Military Health Research (complete): Under a legal Data Transfer Agreement, all physical and electronic data was transferred from Oxford to KCMHR, King’s College London using a secure courier service. The chemical ‘exposure’, military ‘personnel’, and ‘outcome’ (cancer and death) data are classified as identifiable. Paper files are stored securely at KCMHR offices and in an off-site archive, and electronic databases are stored on an encrypted external hard drive. Under a legal Data Transfer Agreement, all physical and electronic data was transferred from Oxford to KCMHR, King’s College London using a secure courier service. The chemical ‘exposure’, military ‘personnel’, and ‘outcome’ (cancer and death) data is classified as identifiable. Paper files are stored securely at KCMHR offices and in an off-site archive, and electronic databases are stored on an encrypted external hard drive. 2) KCMHR separate personal identifiers and de-identify databases: (complete) 2) KCMHR separate personal identifiers and de-identify databases (in progress): KCMHR stored personal identifiers from the electronic data securely in the KCMHR main office safe. Data files used for analysis will contain a unique study ID number only. KCMHR will remove personal identifiers from the electronic data and store these securely in the KCMHR main office safe. Electronic ‘exposure’, ‘personnel’, and ‘outcome’ databases will contain a unique study ID number. 3) Transfer of data from KCMHR to NHS Digital and NHS Scotland: (complete) 3) Transfer of data from KCMHR to NHS Digital/NHS Scotland/NISRA: After the necessary permissions were obtained, KCMHR sent NHS Digital/NHS Scotland the minimum personal information necessary to re-flag the cohort for deaths and cancers to the latest available date, namely, unique study ID, name, initials, sex, NHS number, date of birth, postcode (district level). The same identifiers were sent to NHS Digital and NHS Scotland. These identifiers were identical to those used in the original study and necessary to re-flag and validate matches. Note: data was not sent to NISRA (as stated in the previous version of this application) as no formal procedures were identified for mortality and cancer registry linkage with Northern Irish data. After the necessary permissions are obtained, KCMHR send NHS Digital/NHS Scotland/NISRA the minimum personal information necessary to re-flag the cohort for deaths and cancers to the latest available date, namely, unique study ID, name, initials, sex, NHS number, date of birth, postcode (district level). The same identifiers will be sent to NHS Digital, NHS Scotland, and Northern Ireland. These identifiers are identical to those used in the original study, and necessary to re-flag and validate matches. 4) NHS Digital and NHS Scotland transferred updated outcome data to KCMHR: (complete) 4) NHS Digital/NHS Scotland/NISRA transfer updated outcome data to KCMHR: The updated mortality and cancer data was sent securely from NHS Digital and NHS Scotland to KCMHR, which included cause and date of death, and type and date of cancer registration. The unique study ID number and date of birth was also requested back. The updated mortality and cancer data is sent securely from NHS Digital/NHS Scotland/NISRA to KCMHR, which will include cause and date of death, and type and date of cancer registration. We will also request back the unique study ID number and date of birth. 5) KCMHR linked the updated and original outcome data: (complete) 5) KCMHR link the updated and original outcome data: The updated and original outcome data have been linked using a unique study ID number, and linkage has been validated using date of birth. Date of birth is needed to derive person-years variables, and dates of death cancer registration, and embarkation information will be needed to create time-to-event variables, as per the original analysis. The updated and original outcome data will be linked using a unique study ID number, and linkage will be validated using date of birth. Date of birth will be used to derive a person-years variable, and dates of death cancer registration, and embarkation information will be used to create time-to-event variables, as per the original analysis. 6) KCMHR separate personal identifiers and de-identify the analytical database: (in progress) 6) KCMHR separate personal identifiers and de-identify the outcome database: [1 paragraph unchanged] 7) Data analysis at KCMHR (linkage of the ‘exposure’, ‘personnel’ and ‘outcome’ data): (in progress) [1 paragraph unchanged] The data from NHS Digital/NHS Scotland/NISRA Digital and NHS Scotland will not be shared with third-parties, third parties and will not be used for benchmarking against peer groups. There will be no requirement nor attempt to re-identify individuals from the data. Justification for processing identifiable data (CAG approval obtained): The data is stored at the King's Centre for Military Health Research (KCMHR) offices. These offices have a higher level of physical security than standard as they store sensitive military data. The offices are situated within a building which is manned by a security team on a 24-hour basis. To enter the KCMHR building, an individual must have a swipe card ID and must present this on the ground floor to security guards and at a card reader to enter the main building. Cause and date of death, and type and date of cancer registration is required to create time-to-event data so that the original analyses (which covered 1941 to 2004) can be updated. Access to date of birth data is required in order to i) calculate person-years as per the original analysis, and ii) validate linkage between the original and updated outcome data. Once time-to-event and person-years have been derived, date of birth and dates of death and cancer registration will be removed from the analysis file and stored separately. The study office at King’s Centre for Military Health Research at King’s College London is alarmed, and the door is secured with both a key lock and a digital coded lock, and there is CCTV in the corridor. Paper-based files will be stored in a locked cabinet in the study office, and in King’s secure archive at Guy's campus. De-identified electronic data will be stored on an encrypted external hard-drive in a locked drawer in the study office. Personal identifiers will be stored separately on an encrypted external hard-drive in a Ministry of Defence approved safe in the KCMHR main office. Only the KCMHR Data Manager and study Research Associate will have access to the data, both of which have undertaken training in data protection, i.e., MRC Research, GDPR and confidentiality training. Physical security arrangements at KCMHR: The KCMHR offices have a higher level of physical security than standard as they store sensitive military data. The offices are situated within a building which is manned by a security team on a 24-hour basis. To enter the KCMHR building an individual must have a swipe card ID and must present this on the ground floor to security guards and at a card reader to enter the main building. The study office at King’s Centre for Military Health Research at King’s College London is alarmed, and the door is secured with both a key lock and a digital coded lock, and there is CCTV in the corridor. Paper-based files will be stored in a locked cabinet in the study office, and in King’s secure archive at Guy's campus. De-identified electronic data will be stored on an encrypted external hard-drive in a locked drawer in the study office. Personal identifiers will be stored separately on an encrypted external hard-drive in a Ministry of Defence approved safe in the KCMHR main office. Only the KCMHR Data Manager and study Research Associate study will have access to the data. [1 paragraph unchanged] MRC Medical Research Council (MRC) guidelines on the holding and archiving of data in relation to cohort [14 words unchanged] the study is forthcoming, the data will be electronically and physically destroyed. All organisations party to this agreement must comply with the Data Sharing [11 words unchanged] that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

[1 paragraph unchanged] Planned outputs: Academic research articles: [1 paragraph unchanged] 1) Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: A 15-year update (planned submission 2019) - 2021) 2) Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: A 15-year update (planned submission 2021) A 15-year update (planned submission 2019) 3) Cohort Profile: The Porton Down veterans’ cohort (planned submission 2021) 3) Cohort Profile: The Porton Down veterans cohort (planned submission 2019) 4) Mortality and cancer morbidity in military participants exposed to Sarin as part of human experimental research at Porton Down (planned submission 2022) 4) A 6) An epidemiological review of epidemiological studies of chemical warfare agent exposed populations exposure and long-term health (planned submission 2019) 2022) Links to published scientific papers will appear on the websites of the collaborating universities. These above outputs were delayed slightly due to a delay in data receipt as well as other factors such as Covid-19 mitigation, and part-time working for post-doctoral Research Associate (Sept 19 to Feb 20). The expected dates for these outputs have been updated to reflect this. The update updated study’s findings will also be presented at relevant academic conferences (e.g. in 2022 (e.g., the Canadian Institute for Military and Veteran Health Research, the International Symposium on Epidemiology in Occupational Health, Society for Longitudinal and Life course Studies conference, 2019-2021). conference. Stakeholder engagement: Reports of findings in lay language will be disseminated to veterans by means of a specially-convened meeting and via the newsletters of veterans’ organisations and relevant websites, e.g., of veterans’ organisations and of the collaborating universities. Policy-relevant findings will be presented to official bodies e.g., the Ministry of Defence veterans’ section and Public Health England. Reports of findings in lay language will be disseminated to veterans by means of a specially-convened meeting and via the newsletters of veterans’ organisations and relevant websites, e.g. of veterans’ organisations and of the collaborating universities. Policy-relevant findings will be presented to official bodies e.g. the Ministry of Defence veterans’ section and Public Health England. Project report for funder: [11 paragraphs unchanged]

Expected measurable benefits

The original study: The original study was born out of concerns raised by veterans that their long-term health may have been affected by their exposure to chemical agents (e.g., vesicants, riot control agents, nerve agents, and their antidotes) as part of the ‘human volunteer programme’ at Porton Down. The study found that Porton Down veterans had no overall excess of cancer compared to non-Porton Down veterans, and a small excess (6%) of overall mortality, but this could not be attributed to any specific exposure. The original study was born out of concerns raised by veterans that their long-term health may have been affected by their exposure to chemical agents (e.g. vesicants, riot control agents, nerve agents, and their antidotes) as part of the ‘human volunteer programme’ at Porton Down. The study found that Porton Down veterans had no overall excess of cancer compared to non-Porton Down veterans, and a small excess (6%) of overall mortality, but this could not be attributed to any specific exposure. These findings were published in the BMJ (Carpenter et al., 2009; Venables et al,. 2009), an international peer reviewed medical journal, and helped to clarify the health status of Porton Down veterans and other former service personnel exposed to chemical warfare agents, which was believed to be reassuring to many veterans and their families. These findings were published in the BMJ (Carpenter et al., 2009; Venables et al,. 2009), an international peer reviewed medical journal, and helped to clarify the health status of Porton Down veterans, and other former service personnel exposed to chemical warfare agents, which was believed to be reassuring to many veterans and their families. The main benefit to this study is to further understand long-term health risk of low-dose exposure to chemical warfare agents or their antidotes. Chemical warfare agents are easily manufactured and continue to be deployed by rogue states, e.g., Syria and Iraq (United Nations 2013), and by terrorists, e.g., on the Tokyo subway (Coleman 2005, Okumura et al. 2005). Most recently, a nerve agent developed in the former Soviet Union was used in Salisbury (BBC News 19 July 2018, OPCW 13 March 2018). Five people were exposed, and one died. What are the benefits of the new study? Understanding long-term health risk of low-dose exposure to chemical warfare agents or their antidotes. Chemical warfare agents are easily manufactured and continue to be deployed by rogue states, e.g. Syria and Iraq (United Nations 2013), and by terrorists, e.g. on the Tokyo subway (Coleman 2005, Okumura et al. 2005). Most recently, a nerve agent developed in the former Soviet Union was used in Salisbury (BBC News 19 July 2018, OPCW 13 March 2018). Five people were exposed, and one died. [1 paragraph unchanged] Ability to address new questions relevant to public health using unique cohort data: The Porton Down cohort study is the largest and best-documented cohort with exposure to chemical warfare agents in the world. It is the only cohort with accurate, quantitative information on exposure, thus allowing the study of exposure-response relationships. As well as its large size, the exposure data is of exceptionally high quality compared to other sources; for example, information gathered after warfare or terrorist scenarios has many attendant biases, i.e., the precise nature of the exposures may be unclear; mixtures of chemicals may have been used; and the dose and duration of exposure are unknown. In the original analysis, over 7,000 Porton Down veterans had died in the period 1941-2004. The study update will increase this to about 12,000 deaths, and a proportional increase in cancer registrations. The increased number of outcome events increases statistical power which will enable to gain a greater understanding of the relationship between specific chemical agents and health outcomes (e.g., rarer forms of cancer) at a level of detail not possible in the original study. The Porton Down cohort study is the largest and best-documented cohort with exposure to chemical warfare agents in the world. It is the only cohort with accurate, quantitative information on exposure, thus allowing the study of exposure-response relationships. As well as its large size, the exposure data is of exceptionally high quality compared to other sources; for example, information gathered after warfare or terrorist scenarios has many attendant biases, i.e. the precise nature of the exposures may be unclear; mixtures of chemicals may have been used; and the dose and duration of exposure are unknown. In the original analysis, over 7,000 Porton Down veterans had died in the period 1941-2004. The study update will increase this to about 12,000 deaths, and a proportional increase in cancer registrations. The increased number of outcome events increases statistical power which will enable to gain a greater understanding of the relationship between specific chemical agents and health outcomes (e.g. rarer forms of cancer) at a level of detail not possible in the original study. [2 paragraphs unchanged] How will the findings be used? If an association is found between exposure to chemical agents (e.g., vesicants, riot control agents, nerve agents, or their antidotes) and an increased risk of certain cancers, or cause of death, this could lead to raised awareness among health care providers, leading to improved diagnosis and quality of care. Likewise, if particular chemical warfare or riot control agents are associated with poor long-term health, the Ministry of Defence and other public health organisations could act to protect individuals from exposure in the future. Conversely, if there appears to be no long-term health risk, then this will reassure veterans and their families, and any other exposed groups, leading to a reduction in anxiety about their exposure. If an association is found between exposure to chemical agents (e.g. vesicants, riot control agents, nerve agents, or their antidotes) and an increased risk of certain cancers, or cause of death, this could lead to raised awareness among health care providers, leading to improved diagnosis and quality of care. Likewise, if particular chemical warfare or riot control agents are associated with poor long-term health, the Ministry of Defence and other public health organisations could act to protect individuals from exposure in the future. Conversely, if there appears to be no long-term health risk, then this will reassure veterans and their families, and any other exposed groups, leading to a reduction in anxiety about their exposure. The findings of the study will be submitted to high-profile medical journals and should now be published between 2021-2023 due to the delay in data analysis detailed previously. Dissemination of findings: The findings of the study will be submitted to high-profile medical journals and should be published between 2019-21. [1 paragraph unchanged] The findings will also be helpful for other groups exposed to chemical warfare or riot control agents including other military service personnel, emergency services, and the general population (e.g. (e.g., police or demonstrators exposed to CS gas, and Salisbury residents following the Novichok incident). The results will be useful to organisations responsible for public health and [16 words unchanged] of a chemical warfare agent by a hostile country, individual, or agency, e.g. e.g., the Ministry of Defence, ambulance, police forces and fire brigades, and organisations concerned with civilian emergency preparedness, e.g. e.g., Public Health England. [1 paragraph unchanged] Summary: Very little is known about whether exposure to low-dose chemical agents (e.g., vesicants, riot control agents, nerve agents, and their antidotes) impact long-term health. The Porton Down cohort is uniquely placed to examine this question as it is the only dataset in the world with accurate, quantitative information on chemical agent exposure. Very little is known about whether exposure to low-dose chemical agents (e.g. vesicants, riot control agents, nerve agents, and their antidotes) impact long-term health. The Porton Down cohort is uniquely placed to examine this question as it is the only dataset in the world with accurate, quantitative information on chemical agent exposure. The findings of study are not only relevant to Porton Down veterans but all those who have been, or are at risk of, low-dose exposure to chemical warfare and riot control agents, including other military service personnel, emergency services, and the general population (e.g., those involved in warfare, public demonstrations, or caught in terrorist incidents). Greater understanding of the long-term risks associated with exposure to chemical agents could lead to improved diagnosis and quality of care, and help shape health policy to protect individuals from future exposure. The findings of study are not only relevant to Porton Down veterans but all those who have been, or are at risk of, low-dose exposure to chemical warfare and riot control agents, including other military service personnel, emergency services, and the general population (e.g. those involved in warfare, public demonstrations, or caught in terrorist incidents). Greater understanding of the long-term risks associated with exposure to chemical agents could lead to improved diagnosis and quality of care, and help shape health policy to protect individuals from future exposure. [11 paragraphs unchanged]

Benefits reported

Not stated in the previous version; added here.

King’s College London received complete data from NHS Digital in September 2020 (and complete data from National Records Scotland in Jan 2021). Data cleaning and preparation has been completed but analysis is only at the early stages due to delays in obtaining the data.

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

Datasets: + MRIS - Members and Postings Report

Objective for processing

[17 paragraphs unchanged] Date of embarkation/emigration is required to derive person-years of follow-up. Emigrants are estimated to account for approximately 5% of the Porton Down data. If they are not identified, this will bias results as their cancer and death status is effectively unknown. For example, a cohort member who embarked in 2004 would appear in Porton Down data as ‘alive’ up to 2020 but could have died in 2005. Date of emigration will allow KCL to include and account for emigration in the analysis. [2 paragraphs unchanged]

Processing activities

[18 paragraphs unchanged] The updated and original outcome data will be linked using a unique [15 words unchanged] will be used to derive a person-years variable, and dates of death cancer registration, and cancer registration embarkation information will be used to create time-to-event variables, as per the original analysis. [1 paragraph unchanged] Once time-to-event and person-years have been derived, date of birth, and dates of death and death, cancer registration and embarkation information will be removed from the outcome database and stored separately on encrypted external hard-drives in the KCMHR study safe. [11 paragraphs unchanged]

Unchanged: Expected output, Expected measurable benefits.

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

Datasets: − MRIS - Personal Demographics Service

Benefits reported

Stated in the previous version and removed here.

Yielded Benefits is not a requirement for new applications.

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