MR400 - Cohort Study of People with Insulin Treated Diabetes

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

Objective for processing

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The Institute of Cancer Research to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance). This Agreement permits the secure retention of the data only and no other processing. The Institute of Cancer Research (ICR) will store the data with the intention to run updated analyses in 2028. The following provides background information on the purpose of the original study: ICR holds Mortality, Cancer Registration and Demographics data for the purpose of a national cohort study of mortality and cancer incidence in patients with insulin-treated diabetes. The Institute of Cancer Research (ICR) requires mortality, cancer incidence and demographic data for the purpose of a national cohort study of mortality and cancer incidence in patients with insulin-treated diabetes. This study is being conducted by the ICR on a larger scale than elsewhere, to provide the best, most powerful, data available to patients and their doctors about long-term health risks. This will lead to better information for patients in general and their families; to improved prognostic data for patient advice, and to improved clinical follow-up, and where needed, screening. Diabetes mellitus is the most common metabolic abnormality in Western populations. The health care costs and implications are very large. It occurs through two different primary disease processes, type I (insulin-dependent) and type II (non-insulin dependent), with different patient characteristics. Type I diabetes largely starts in childhood, and is one of the major childhood chronic diseases, with serious consequences for life expectancy and disability. It has implications for risk of several major chronic diseases, especially cardiovascular diseases, but data on very long-term risks are limited. A cohort study is the methodologically most rigorous study design that can be undertaken of long-term cancer and mortality risks in such patients, and the ICR has the largest cohort worldwide with such long follow-up. The metabolic and hormonal antecedents and consequences of diabetes, and the treatments for it, might also affect the risk of cancer. Most studies of cancer risks in patients with diabetes have related to type II diabetes, but interpretation is uncertain because of potential confounding by obesity and alcohol consumption. Pancreatic cancer risk has been found raised, but there is uncertainty about the direction of causation, because pancreatic cancer can cause diabetes. The aetiology of type I diabetes is not related to obesity or alcohol use, and the diabetes generally occurs well before the ages at which pancreatic cancer is prevalent. Studies of cancer risk in patients with type I diabetes, however, have generally been relatively small. Because modern treatments have led to greatly improved survival of patients with diabetes, the issue of long-term side-effects of the disease has become an important one for advice to patients and (for children) to their parents. It is also important to clinicians deciding about treatment of diseases and the balance of benefit vs. side-effects and complications, and to the Health Service, because of the costs accruing for continued follow-up and care of these patients and the planning required to take account of long-term consequences and to plan strategies, where possible, for their prevention and early detection. The risks of cancer are also of major importance to patients and their families, and to clinical practice and health service planning, because cancer is one of the major causes of morbidity and death in the UK. Long follow-up is important because onset of type I diabetes is usually diagnosed in childhood, with lifetime continuing treatment and ill effects on morbidity and mortality risks. In the UK there is a unique potential to include patients diagnosed as far back as the 1930s, almost when insulin treatment first became available. Therefore at the instigation of and in collaboration with, the British Diabetic Association (the leading, patient-centred, diabetes research charity: now Diabetes UK), a long-term cohort study of mortality and cancer incidence in 29,500 patients in the UK with insulin-treated diabetes was inaugurated 25 years ago. A cohort study is the methodologically most rigorous study design that can be undertaken of long-term cancer and mortality risks in such patients, and the ICR has the largest cohort worldwide with such long follow-up. Long follow-up is important because onset of type I diabetes is usually in childhood, with lifetime continuing treatment and ill effects on morbidity and mortality risks. The study includes patients diagnosed as far back as the 1930s, almost when insulin treatment first became available. By conducting such a study, on a larger scale than elsewhere, the ICR will provide the best, most powerful, data available to patients and their doctors about the long-term hazards of this condition. This study has been running for over 20 years and has contributed unique data on several aspects of genetic and environmental/ prenatal aetiology of cancer. Several papers have been published from it (see section 5d(ii) for list or previous publications and number of times these publications have been cited in the scientific literature). The study needs to be maintained so that in 5 years time ICR can run updated analyses, to be updated in the future with additional follow-up, which would lead to future publications. The study needs to be maintained so that it may be updated in the future with additional follow-up, which would lead to future publications. ICR therefore inaugurated 25 years ago, at the instigation of and in collaboration with, the British Diabetic Association (the leading, patient-centred, diabetes research charity: now Diabetes UK) a long-term cohort study of mortality and cancer incidence in 29,500 patients in the UK with insulin-treated diabetes. It is much the largest cohort study of such patients in the world with such length of follow-up, and is providing unique information, currently with up to 35 years follow-up, but in the future with longer follow-up, on the long-term consequences of diabetes and the extent to which duration of diabetes and age at onset are risk factors for mortality and morbidity. The study is important to inform parents of children with diabetes, patients themselves, those treating the patients, and the health service, on the long-term consequences and prognosis of this chronic disease, which consumes considerable health service resources. 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. This will: The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The processing is record linkage to NHS-England deaths and cancer notifications for scientific analyses. The standard statistical analyses are those for cohort studies comparing rates in the cohort with published rates in the general population. Results are presented as summary measures or regression coefficients from statistical models. 1. Provide information on which to base advice to patients and their relatives about their life expectancy and risks of cancer and fatal chronic diseases. No identifiable level data would be published and results are reviewed for small number suppression to protect confidentiality. 2. Provide guidance on follow-up strategies of patients after initial treatment, by giving information on the likely long-term effects that may need prevention or early detection. BACKGROUND: 3. Provide information for health service planning, particularly because long survival gives rise to considerable costs to health services in provision of health care for these patients. 4. Improve understanding of disease aetiology and hence prevention by, for instance, illuminating the relation of cancer risks to duration of diabetes, and examining the relation of diabetes complications to age of onset of diabetes. [3 paragraphs unchanged] 2) A cohort study of 48,000 patients with cytogenetic disorders from across Britain diagnosed up to 40 years ago… ago [3 paragraphs unchanged] The cohort is fully flagged and no new patients will be identified or flagged. Therefore, ICR will not be sending direct identifiable data to NHS-England. ICR only received downloads from NHS-England for data items required for analysis. The direct identifiable data ICR hold for the study is retained to ensure Medical Research Council good practice guidelines have been met on data retention for veracity in research. These guidelines are an important ethical and scientific obligation on researchers because of the requirement to be able to respond, should the need arise, to queries regarding alleged fraud and scientific inveracity, and to prove that the results published from this study are indeed as they purport to be and data were correctly collected and analysed: this requirement could not currently be met in this study without the ability to go back to original records via their direct identifiers. ICR have reviewed this again during the year (2022), and it remains the case that the current NHS systems would not enable data files to be linked and paper records to be reliably found without identifiers. The Institute of Cancer Research is the sole data controller who will also (solely) process the data. No other organisations are involved in the project. The research was initially funded by the British Diabetic Association. Funding is no longer received from this organisation and the minimal maintenance costs for the study come from discretionary funds held by the Principal Investigator (at ICR).

Processing activities

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement. The cohort identifiers were supplied to ONS (then OPCS) many years ago and the participants’ entries were flagged on NHS England’s computer system (under the predecessor organisation at the time). A cohort study, by definition, follows people with exposure information already collected (in this instance diagnostic information) to ascertain their subsequent risks of morbidity and/or mortality. ICR already holds the exposure (diagnostic) data and follow-up data up to the present (sent by NHS England and predecessor organisations over the last >20 years). There is no requirement for new data under this agreement. At a later date, under a future iteration of the agreement, ICR would seek updated follow-up data on cancer incidence, mortality and other losses to follow-up to enable analyses of cancer incidence and cause-specific mortality risks over longer periods for the benefit of current and future patients, and their health care. The study data, including data provided by NHS Digital under previous agreements, are currently held by The Institute of Cancer Research. No new data will be shared with NHS England. NHS England routinely supplied data to the ICR and these data are stored and processed in the Epidemiology secure data safe haven, a part of the ICR network with additional security to meet Data Security and Protection (DSP) Toolkit requirements. These data are used only for analyses for the approved medical research project identified above. The data are not linked to datasets other than the clinical source data and the ONS/NHS England data. The following provides background on the processing activities undertaken prior to this Agreement: For historical purposes, after the data sent by NHS England have been linked, the analysis was conducted on pseudonymised files within the data safe haven. The data would be accessed and analysed by authorised researchers at ICR, in order to produce the analyses described above, which are the purpose of the study and the purpose of obtaining the data from NHS England. Data would only be accessed by individuals within the ICR who have authorisation from the Principal Investigator at the ICR. Access will only be authorised for the purposes described and for individuals who are substantive employees of the ICR. The cohort identifiers were supplied to ONS (then OPCS) many years ago and the participants’ entries were flagged on NHS Digital’s computer system. A cohort study, by definition, follows people with exposure information already collected (in this instance diagnostic information) to ascertain their subsequent risks of morbidity and/or mortality. ICR already holds the exposure (diagnostic) data and follow-up data up to the present (sent by NHS Digital and predecessor organisations over the last >20 years) and needs continuing follow-up data on cancer incidence, mortality and other losses to follow-up to enable analyses of cancer incidence and cause-specific mortality risks over longer periods for the benefit of current and future patients, and their health care. No new data will be shared with NHS digital. NHS Digital supplies quarterly data to the ICR. These data are used only for analyses for the approved medical research project identified above. The standard statistical analyses are those for cohort studies comparing rates in the cohort with published rates in the general population. Results are presented as summary measures or regression coefficients from statistical models. No identifiable level data would be published and results are reviewed for small number suppression to protect confidentiality. The data are not linked to other datasets other than the clinical source data and the ONS/NHS Digital data. Identifiable data are required to ensure accurate linkages of individual patients’ data. After the data sent by NHS Digital have been linked, the analysis is conducted on pseudo-anonymised files. The data will be accessed and analysed by the authorised Approved Researchers at ICR, in order to produce the analyses described above, which are the purpose of the study and the purpose of obtaining the data from NHS Digital. For clarity, Deepstore do not process the data. Deepstore are a secure off-site storage facility where ICR stores backup tapes. Any access by Deepstore Ltd to data held under this agreement would be considered a breach of the agreement. This includes granting of access to the database[s] containing the data. Data will only be accessed by individuals within the ICR who have authorisation from the Principal Investigator of the study, to access the data for the purpose(s) described, all of whom are substantive employees of the Institute of Cancer Research. 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

This Agreement permits the secure retention of the data only and no other processing. There is no intention to produce any new outputs under this Data Sharing Agreement. No new data is being requested under this agreement. ICR intend to acquire the latest available follow-up information in 2028 and will then evaluate if there was sufficient new results to justify new analyses and publication. No new outputs will be produced under this Data Sharing Agreement. A scientific paper with 30 years average of follow-up is currently in preparation using the previous outputs. In 2028, ICR intend to acquire the latest available follow-up information on the cohort. There should sufficient new events, and there will be longer follow-up, to allow new scientific analyses and publications would be expected by 2028. It is planned that future outputs will include published papers with longer follow-up over the next 20 years in high-profile peer-reviewed scientific journals on the risks of site-specific cancer incidence and cause-specific mortality in patients with type I diabetes, with analyses subdivided by age at onset of diabetes, duration since onset, and attained age (see below for examples). A scientific paper with 30 years average of follow-up is currently in preparation using the previous outputs. It is planned that future outputs will include published papers with longer follow-up over the next 20 years in high-profile peer-reviewed scientific journals on the risks of site-specific cancer incidence and cause-specific mortality in patients with type I diabetes, with analyses subdivided by age at onset of diabetes, duration since onset, and attained age (see below for examples). ICR will publicise the results to patients, their parents, and society more widely by press releases and blogs, to professional standard, from the Institute’s very active communications department, information sent to patient-centred charities (notably Diabetes UK) and help groups and put on the ICR’s website, and by talks given to patient and lay groups as well as to appropriate medical speciality (paediatric endocrinology and genetics) conferences, meetings and seminars. Results are to be presented as summary measures or regression coefficients from statistical models. No identifiable level data would be published, and results would be reviewed for small number suppression to protect confidentiality. The research was initially funded by the British Diabetic Association. It has produced several high-profile publications (references in section 5d. iii), so NHS Digital can be assured that it will do so again with longer follow-up and hence more valuable results. The extended follow-up will also enable analyses of less-common outcomes for which the ICR was unable to publish stable results in its previous round of analyses because of limited numbers of cancers and deaths, and for which there are currently no published analyses available for long durations, to inform patients, their parents and clinicians on risks. It will also enable far longer-term risks to be assessed (up to 45 years follow-up from study entry) than has previously been possible. Below are a list of publications, with the number of times the paper has been cited in square brackets (from Google Scholar). ICR will publicise the results to patients, their parents, and society more widely by press releases and blogs, to professional standard, from the Institute’s very active communications department, information sent to patient-centred charities (notably Diabetes UK) and help groups and put on the ICR’s website, and by talks given to patient and lay groups as well as to appropriate medical speciality (paediatric endocrinology and genetics) conferences, meetings and seminars. Swerdlow et al., Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005;92:2070-5 [195 citations], Previous outputs from this study have been widely used for care of the relevant patients, as evidenced by the exceptionally high citation rates of the papers (in square brackets below): Laing et al., Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003; 46:760-5 [978 citations], Swerdlow Laing et al., Cancer incidence and mortality Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005;92:2070-5 [151 diabetes. Stroke 2003;34:418-21 [194 citations], Laing et al., Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003; 46:760-5 [645 citations], dos Santos Silva et al., Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95. Diabet Med 2005;22:440-7 [43 citations], Laing et al., Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 2003;34:418-21 [152 citations], Laing et al., The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:459-65 [214 citations], dos Santos Silva et al., Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95. Diabet Med 2005;22:440-7 [38 citations], Laing et al., The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:466-71 [473 citations], Laing Swerdlow et al., The British Diabetic Association Cohort Study, II: cause-specific mortality in Mortality of South Asian patients with insulin-treated diabetes mellitus. mellitus in the United Kingdom: a cohort study. Diabet Med 1999;16:466-71 [387 2004;21:845-51 [36 citations], Laing et al., The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:459-65 [176 citations], Laing et al., Psychosocial and socioeconomic risk factors for premature death in young people with type 1 diabetes. Diabetes Care 2005;28:1618-23 [116 citations]. Swerdlow et al., Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study. Diabet Med 2004;21:845-51 [26 citations], Laing et al., Psychosocial and socioeconomic risk factors for premature death in young people with type 1 diabetes. Diabetes Care 2005;28:1618-23 [69 citations].

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. Diabetes mellitus is the most common metabolic abnormality in Western populations. The health care costs and implications are very large. It occurs through two different primary disease processes, type I (insulin-dependent) and type II (non-insulin dependent), with different patient characteristics. Type I diabetes largely starts in childhood, and is one of the major childhood chronic diseases. With the introduction of insulin treatment in 1922, survival beyond a year or two became possible, but this entailed serious long-term consequences for risks of several major chronic diseases, especially cardiovascular diseases. Because modern treatments have led to greatly improved survival of patients with diabetes, the issue of long-term side-effects of the disease has become an important one for information and advice to patients and (for children) to their parents. It is also important to clinicians deciding about treatment of diabetes and the balance of benefit vs. side-effects and complications, and to the Health Service, because of the costs accruing for continued follow-up and care of these patients and the planning required to take account of long-term consequences and to plan strategies, where possible, for their prevention and early detection. The risks of cancer are also of major importance to patients and their families, and to clinical practice and health service planning, because cancer is one of the major causes of morbidity and death in the UK and type I diabetes requires lifelong treatment and follow-up. However, data on very long term risks are limited. Diabetes mellitus is the most common metabolic abnormality in Western populations. The health care costs and implications are very large. It occurs through two different primary disease processes, type I (insulin-dependent) and type II (non-insulin dependent), with different patient characteristics. Type I diabetes largely starts in childhood, and is one of the major childhood chronic diseases. With the introduction of insulin treatment in 1922, survival beyond a year or two became possible, but this entailed serious long-term consequences for risks of several major chronic diseases, especially cardiovascular diseases. Because modern treatments have led to greatly improved survival of patients with diabetes, the issue of long-term side-effects of the disease has become an important one for information and advice to patients and (for children) to their parents. It is also important to clinicians deciding about treatment of diabetes and the balance of benefit vs. side-effects and complications, and to the Health Service, because of the costs accruing for continued follow-up and care of these patients and the planning required to take account of long-term consequences and to plan strategies, where possible, for their prevention and early detection. The risks of cancer are also of major importance to patients and their families, and to clinical practice and health service planning, because cancer is one of the major causes of morbidity and death in the UK and type I diabetes requires lifelong treatment and follow-up. Data on very long term risks are limited, however. [1 paragraph unchanged] ICR therefore inaugurated 25 years ago a long-term cohort study of mortality and cancer incidence in 29,500 patients in the UK with insulin-treated diabetes. It is much the largest cohort study of such patients in the world with such long follow-up, and is providing unique information, currently with up to 35 years follow-up, but in the future with longer follow-up, on the long-term consequences of diabetes and the extent to which duration of diabetes and age at onset are risk factors for mortality and morbidity. There is very limited published data available on these latter variables. The study is important to inform parents of children with diabetes, patients themselves, those treating the patients, and the health service, on the long-term consequences and prognosis of this chronic disease, which consumes considerable health service resources. Overall, the study will enable patients, their parents and clinicians to undertake more-informed discussion and decision-making about the patient’s risk of long-term morbidity and mortality, and therefore understand risks better and embark on a more personalised care pathway. In particular: - Overall the study will enable patients, their parents and clinicians to undertake more-informed discussion and decision-making about the patient’s risk of long-term morbidity and mortality, and therefore understand risks better and embark on a more personalised care pathway. In particular:- 1. The study will provide information on relative and absolute risks of the full spectrum of long-term site-specific cancer incidence and cause-specific mortality, and on life expectancy, for patients to be able to make fully informed decisions on their care and for clinical decisions on long-term care and will enable follow-up and screening schedules tailored to their personal risks and hence potentially to more patient-centred and effective follow-up, earlier diagnosis of adverse events, and improved outcomes. 1. The study will provide information on relative and absolute risks of the full spectrum of long-term site-specific cancer incidence and cause-specific mortality, and on life expectancy, which will provide a more informed knowledge base from which patients can ascertain their personal risks of developing a range of late effects through life than has previously been possible, and enable them to take into account the age at which they developed diabetes and the duration that has elapsed since. This is important for patients to be able to make fully informed decisions on their care and for clinical decisions on long-term care and will enable follow-up and screening schedules tailored to their personal risks and hence potentially to more patient-centred and effective follow-up, earlier diagnosis of adverse events, and improved outcomes. 2. By improving knowledge of risk complications, the results should contribute to consensus and guidelines for management of long-term hazards to improve outcomes, e.g., via screening tools and standardising of follow-up schedules. 2. By improving knowledge of risk complications, the results should contribute to consensus and guidelines for management of long-term hazards to improve outcomes, e.g. via screening tools and standardising of follow-up schedules. [1 paragraph unchanged] 4. Improve The study will improve understanding of disease aetiology and hence prevention by, for instance, illuminating the [9 words unchanged] examining the relation of diabetes complications to age of onset of diabetes. One measure of the success will be the number of times new scientific publications from the study are cited in the scientific or medical literature (as measured by Google Scholar). One previous publication from the study has over 300 citations and ICR expect future output to also have an impact. However, ICR do not plan further publications until the follow-up time in the cohort has increased by around another five years. Previous outputs from this study have been widely used for care of the relevant patients.

Benefits reported

A scientific paper with 30 years average of follow-up is currently in preparation using the previous outputs. The next set of publications are planned for 5 years from now when further follow-up has accrued. Yielded benefits include the use of scientific publications from this study in: • Guidelines for the management of dyslipidaemias by the European Society of Cardiology and European Atherosclerosis Society • Guidelines for the diagnosis and management of patients with stable ischemic heart disease in a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons • Clinical practice consensus guidelines on microvascular and macrovascular complications in children and adolescents by the International Society for Paediatric and Adolescent Diabetes • Guidelines for the management of dyslipidaemias by the European Society of Cardiology and European Atherosclerosis Society • Clinical practice consensus guidelines on microvascular and macrovascular complications in children and adolescents by the International Society for Paediatric and Adolescent Diabetes Online publications can be seen on the following web-links Cancer incidence and mortality in patients with insulin-treated diabetes: - https://www.nature.com/articles/6602611 Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.- https://link.springer.com/article/10.1007/s00125-003-1116-6 Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. - https://www.ahajournals.org/doi/10.1161/01.STR.0000053843.03997.35 Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus - https://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.2005.01434.x The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus - https://onlinelibrary.wiley.com/doi/full/10.1046/j.1464-5491.1999.00075.x The next set of publications are planned after 2028 when further follow-up has accrued. The extended follow-up will enable analyses of less-common outcomes for which the ICR was unable to publish stable results in its previous round of analyses because of limited numbers of cancers and deaths, and for which there are currently no published analyses available for long durations, to inform patients, their parents and clinicians on risks. It will also enable far longer-term risks to be assessed (up to 45 years follow-up from study entry) than has previously been possible.

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

Expected output

[2 paragraphs unchanged] The A scientific paper with 30 years average of follow-up is currently in preparation using the previous outputs. It is planned that future outputs will include several published papers in high-profile peer-reviewed scientific journals, submitted over the next 2-3 years, and subsequently further papers with longer follow-up over the next 20 years in high-profile peer-reviewed scientific journals on the risks of site-specific cancer incidence and cause-specific mortality in patients with type I diabetes, with [6 words unchanged] of diabetes, duration since onset, and attained age (see below for examples). [11 paragraphs unchanged]

Benefits reported

Not stated in the previous version; added here.

A scientific paper with 30 years average of follow-up is currently in preparation using the previous outputs. The next set of publications are planned for 5 years from now when further follow-up has accrued.

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

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

Datasets: + Cancer Registration Data; + Civil Registrations of Death; + Demographics

Objective for processing

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The Institute of Cancer Research to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance). The following provides background information on the purpose of the original study: [17 paragraphs unchanged]

Processing activities

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement. The study data, including data provided by NHS Digital under previous agreements, are currently held by The Institute of Cancer Research. The following provides background on the processing activities undertaken prior to this Agreement: [4 paragraphs unchanged]

Expected output

This Agreement permits the secure retention of the data only and no other processing. No new outputs will be produced under this Data Sharing Agreement. [3 paragraphs unchanged] Previous outputs from this study have been widely used for care of the relevant patients, as evidenced by the exceptionally high citation rates of the papers (in square brackets below): Swerdlow et al., Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005;92:2070-5 [151 citations], Laing et al., Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003; 46:760-5 [645 citations], Laing et al., Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 2003;34:418-21 [152 citations], dos Santos Silva et al., Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95. Diabet Med 2005;22:440-7 [38 citations], Laing et al., The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:466-71 [387 citations], Laing et al., The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:459-65 [176 citations], Swerdlow et al., Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study. Diabet Med 2004;21:845-51 [26 citations], Laing et al., Psychosocial and socioeconomic risk factors for premature death in young people with type 1 diabetes. Diabetes Care 2005;28:1618-23 [69 citations].

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. [2 paragraphs unchanged] ICR therefore inaugurated 25 years ago a long-term cohort study of mortality [61 words unchanged] diabetes and age at onset are risk factors for mortality and morbidity. The ICR There is not aware of other very limited published cohort studies with information data available on these latter variables. The study is important to inform parents of [17 words unchanged] and prognosis of this chronic disease, which consumes considerable health service resources. [5 paragraphs unchanged]

Benefits reported

Stated in the previous version and removed here.

Previous outputs from this study have been widely used for care of the relevant patients, as evidenced by the exceptionally high citation rates of the papers (in square brackets below):

Swerdlow et al., Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005;92:2070-5 [151 citations],

Laing et al., Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003; 46:760-5 [645 citations],

Laing et al., Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 2003;34:418-21 [152 citations],

dos Santos Silva et al., Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95. Diabet Med 2005;22:440-7 [38 citations],

Laing et al., The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:466-71 [387 citations],

Laing et al., The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:459-65 [176 citations],

Swerdlow et al., Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study. Diabet Med 2004;21:845-51 [26 citations],

Laing et al., Psychosocial and socioeconomic risk factors for premature death in young people with type 1 diabetes. Diabetes Care 2005;28:1618-23 [69 citations].