NHS Digital Data Release Register - reformatted

University of Cambridge

Project 1 — DARS-NIC-147034-XH3H2

Opt outs honoured: No - consent provided by participants of research study (Consent (Reasonable Expectation))

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2019/09.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Flagging Current Status Report

Yielded Benefits:

CFAS has over a period of 25+ years provided evidence to Governmental bodies including the House of Lords and David Cameron’s Dementia 2020 campaign. The study has provided pseudonymised data to local authorities – Cambridgeshire and Peterborough clinical commissioning group used CFAS data to look at Long Term Conditions across the life course for their Joint Strategic Needs Assessment (JSNA) in 2015. The Alzheimer’s Society used CFAS data for their Dementia UK reports and the University of Cambridge’s paper on Anticholinergic Medication use and Cognitive impairment in the older population raised awareness that use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality. Dementia Prevalence 7,635 people aged 65 years or older where interviewed in CFAS I in Cambridgeshire, Newcastle and Nottingham with 1,457 being diagnostically assessed. In the same geographic areas CFAS II interviewed 7796 individuals. Using CFAS I, age and sex specific estimates of prevalence in people over 65 years, standardised to the 2011 population, 8.3% (884,000) of this population would be expected to have dementia in 2011. However CFAS II showed the prevalence (1) was lower (6.5%; 670,000), a decrease of 1.8%. This paper received a Royal College of General Practitioners (RCGP) paper of the year award in 2013. Dementia Incidence Two years after completion of the baseline interviews, CFAS I re-interviewed 5,156 people (76% response) and CFAS II re-interviewed 5,288 (74% response). The study reported a 20% drop in incidence (2) (95% CI: 0-40%), driven by a reduction in dementia in men across all ages above 65 years. CFAS has supported NHS England (at their request) using the dementia prevalence and incidence data to allow more accurate estimates of dementia at a CCG level. CFAS II was a major contributor to a project modelling projections of multi-morbidity in the older population in England to 2035: Estimates from the Population Ageing and Care Simulation (PACSim) model. Age specific mortality reduction has been accompanied by a decrease in the prevalence of some diseases and increase in others. CFAS has provided evidence that the relationship between frailty and mortality did not significantly differ across CFAS I and CFAS II. Severe frailty as an indicator or mortality is shown to be a stable construct. Reference to the research 1. A two-decade comparison of prevalence of dementia in individuals aged 65 and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet 2013;382:1405-12 2. A two decade dementia incidence comparison from the Cognitive Function and Ageing studies I & II. NATURE COMMUNICATIONS | 7:11398 | DOI: 10.1038/ncomms11398 3. Wu, Y.T., Fratiglioni L., Matthews, F.E., Lobo, A., Breteler, M.M., Skoog, I., & Brayne, C (2016) Dementia in western Europe: epidemiological evidence and implications for policy making. The Lancet Neurology, 15(1), 116-124. 4. Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS). Kingston A, Wohland P, Wittenberg R, Robinson L, Brayne C, Matthews FE, Jagger C. 2017, The LancetAugust 15, 2017 http://dx.doi.org/10.1016/ S0140-6736(17)31575-1 5.Clare, L., Wu, Y.T., Teale, J.C., MacLeod, C., Matthews, F., Brayne, C. & Woods, B. on behalf of the CFAS-Wales study team. (2017). Potentially-modifiable Lifestyle Factors, Cognitive Reserve and Cognitive Function in Later Life: a Cross-sectional Study. PLOS Medicine. http://dx.doi.org/10.1371/journal.pmed.1002259 6. Yates, J.A., Clare, L., Woods, R.T., & Cognitive Function and Ageing Study Wales (2017) What is the Relationship between Health, Mood, and Mild Cognitive Impairment? Journal of Alzheimer's disease, 55(3), 1183-1193. 7. Burholt, V., Windle, G., & Morgan, D. J. (2016). A Social Model of Loneliness: The Roles of Disability, Social Resources, and Cognitive Impairment. The Gerontologist, gnw125. 8. Yates, J. A., Clare, L., & Woods, R. T. (2017). “You’ve got a friend in me”: can social networks mediate the relationship between mood and Mild Cognitive Impairment?. BMC Geriatrics, 17(1), 144. 9. Andrew Kingston, Louise Robinson, Heather Booth, Martin Knapp, Carol Jagger for the MODEM Project. (2018) Projections of multi-morbidity in the older population in England to 2035: estimates from the Population Ageing and Care Simulation (PACSim) model. Age and Ageing 2018; 0:1-7 doi: 10.1093/ageing/afx201. 10. Andria Mousa, George M Savva, Arnold Mitnitski, Kenneth Rockwood, Carol Jagger, Carol Brayne, Fiona E Matthews. Is frailty a stable predictor of mortality across time? Evidence from the Cognitive Function and Ageing Studies. Age and Ageing 2018; 0:1-7 doi: 10.1093/ageing/afy077.

Objectives:

MRC Cognitive Function and Ageing Study - CFAS II This study builds on the design and infrastructure of the MRC Cognitive Function and Ageing Study collaborative (CFAS). New cohorts in Cambridgeshire, Newcastle and Nottingham (N=7,500) are now to be included and will provide important base−line information on older people aged 65−84 in 2007−2008 who will reach the age of greatest frailty during the 2020's. The integration of a new cohort will provide the opportunity to address government policy of whether gains in active life expectancy have occurred between generations. By studying a recent cohort it will be possible to estimate the effect that changing mortality and incidence rates of specific diseases have had on active life expectancy The data from MRIS will be used to model life expectancy, differentials between different diseases and causes of death. The use of exact dates of death will ascertain the survival of individuals based on different conditions and then be used in population modelling and public health policy outcomes.

Expected Benefits:

The CFAS has been and will continue to be beneficial to health care in the following ways: Findings on dementia prevalence and incidence are extremely beneficial to the NHS. Services are planned based on estimates of prevalence and incidence but the CFAS study is providing evidence that reductions in numbers are possible through proactive interventions. Such information encourages such interventions and helps care providers to more accurately plan services ensuring patients’ needs are catered for while reducing risk of wasting resources. The benefits are achieved through use of the full data the CFAS studies collect from various sources. Mortality data comprises a small but important proportion of that data making it possible to ascertain the survival of individuals based on different conditions which can then be used in population modelling and public health outcomes. Specifically for example, the date of death will enable estimates of life expectancy for those who develop cognitive impairment between different waves of interviewing. Information is also required in relation to those leaving the NHS through emigration etc. in order to allow more accurate estimates of survival rates. Dramatic global increases in future numbers of people with dementia have been predicted. No multi-centre population based study powered to detect changes over time had previously reported dementia incidence. Dependency: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. The CFAS study aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011(4) and provided new projections of future demand for care. These recent findings will have considerable implications for families of older people, who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. CFAS Wales – The initial outputs using longitudinal data are expected to be published in 2018 (initial outputs using cross-sectional data from the wave 1 interviews have been published in 2015) In Wales, the approach to targets differs, but policy will be influenced by findings on the concordance of dementia registers and ascertained dementia in the community. Public Health Wales issues guidance on lifestyle changes to reduce the risk of developing dementia (5). The studies will contribute to revisions of this advice. The study will inform the Welsh government regarding aspects of social exclusion and the relationship between social exclusion and mortality (6,7,8) will be a key part of these findings. Service planning will benefit from more accurate estimates of morbidity and disability, and will allow resources to be targeted where they can be most effective.

Outputs:

The CFAS study (which comprises the original CFAS study (CFAS I) plus CFAS II and CFAS Wales) has produced over 250 peer reviewed papers in high profile publications including The Lancet, BMJ, New England Journal of Medicine, Age and Ageing and Mental Health. All study papers can be accessed via the study website: www.cfas.ac.uk. The study covers multiple areas including: population projections of risk, mortality, dementia prevalence and incidence, policy, healthy active life expectancy, social implications, pharmacology, mild cognitive impairment (MCI) and neuropathology. In the past four years the study has led to the publication of 33 academic papers and there are currently 14 papers in draft, awaiting submission or awaiting acceptance by publications. CFAS disseminates its findings widely in both the UK and abroad, recent activity includes: • Presentation to Participant Panel of European Prospective Investigation of Cancer (EPIC Norfolk), April 2017, Norwich. • Presentations at the Alzheimer’s Society annual conference, June 2017 in London. • Symposium at the Alzheimer’s Association International Conference (AAIC), July 2017 London. • Presentations at International Association of Gerontology and Geriatrics (IAGG) World Congress in San Francisco, July 2017 • Presentation at the British Society of Gerontology conference, July 2017 Swansea. The study is one of the core cohorts of the Dementias Platform UK (DPUK). CFAS data (non- identifiable) is available to researchers through the DPUK data application processes. Though the mortality data supplied by NHS Digital is not made available, it is used to calculate binary mortality outcomes (i.e. living or deceased) which are made available through the DPUK. Current CFAS work with the Newcastle DELIRIUM study is helping to prospectively elucidate the size of the effect of delirium upon cognitive decline and incident dementia. The results will be used to inform future dementia prevention trials that focus on delirium intervention. The study is expected to report in 2018. In the coming three years CFAS will be conducting a Dementia risk reduction pilot study funded by Alzheimer’s Research UK (ARUK) with CFAS II participants in Cambridgeshire, Newcastle and Nottingham to test feasibility, acceptability and adherence of the proposed intervention. The results will be available in 2020.

Processing:

The University of Cambridge is the administrative centre for all the CFAS studies. The University of Cambridge maintains an administrative database containing participants’ identifying details and a separate pseudonymised database containing self-reporting information and data from tests (e.g. hearing tests) and from analysing samples (e.g. saliva, blood, etc.). The University of Cambridge has previously supplied lists of identifiers for CFAS II participants to NHS Digital. This contained the name, date of birth, NHS number, postcode and a unique study identifier for each participant. NHS Digital linked that data and routinely reports details of participants’ deaths (date and cause) to the University of Cambridge. In addition, the University of Cambridge will securely transfer to NHS Digital a file of identifiers for each CFAS Wales participant. These will be added to the existing cohort held by NHS Digital. NHS Digital will continue to provide routine reports of participants’ deaths and/or exits from the NHS for the existing cohort plus the additional participants. The data supplied by NHS Digital is held as identifiable data within the Secure Data Hosting Service (SDHS) at the School of Clinical Medicine, University of Cambridge. Only the core CFAS team (4 persons) has access to the identifiable data held on the secure server. All are substantive employees of the University of Cambridge. Access to the SDHS is via a 15 character password and 2 factor authentication token. There is no internet access inside the SDHS. All data imported or exported to/from the SDHS is made via the secure transfer server. All transfers are audited. No identifiable data is ever released to collaborating researchers. No data set with mortality information from NHS Digital will be transferred, with all analyses on mortality information undertaken solely within the core study team at the University of Cambridge. All outputs produced will be aggregated and anonymised with small numbers suppressed, in line with HES governance guidelines. Mortality data is converted into binary indicators (i.e. deceased; not deceased) and those derivations are made more widely available along with other data collected by the CFAS II and CFAS Wales studies. The data from NHS Digital will be used to model life expectancy, differentials between different diseases and causes of death. The use of exact dates of death will ascertain the survival of individuals based on different conditions and then be used in population modelling and public health policy outcomes. The mortality data are linked with other data collected on the CFAS II and CFAS Wales cohorts and analyses of that data may be compared with equivalent analyses from the original CFAS study to assess changes in prevalence and incidence within the same geographical areas or variations across different areas.


Project 2 — DARS-NIC-147750-8GS7S

Opt outs honoured: N, Yes - patient objections upheld (Section 251, Section 251 NHS Act 2006)

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2019/09.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Yielded Benefits:

The ADDITION study has already provided useful information about screening for diabetes: • Screening for diabetes does not make people feel anxious, depressed or falsely reassured. • The health status of ADDITION participants was improved five years after diagnosis e.g. there were important reductions in levels of blood pressure, cholesterol and blood glucose over the five years of the study. • Earlier diagnosis and treatment of diabetes has contributed to lower than expected rates of heart attacks and premature death, which are now similar to those in the general population without diabetes. There have been more than 35 publications from the UK alone feeding into the academic discourse on the treatment of diabetes: the full list can be seen here, http://addition.au.dk/publications/, but some example papers are: Patient-centred care, health behaviours and cardiovascular risk factor levels in people with recently diagnosed type 2 diabetes: 5 year follow-up of the ADDITION-plus trial cohort. Dambha-Miller H, Cooper AJM, Simmons RK, Kinmonth AL, Griffin SJ. BMJ Open 2016;6(1):e008931. Medication burden in the first 5 years following diagnosis of type 2 diabetes: findings from the ADDITION-UK trial cohort. Black JA, Simmons RK. BMJ Open Diabetes Res Care. 2015 Oct 1;3(1):e000075. doi: 10.1136/bmjdrc-2014-000075. eCollection 2015 Cardiovascular risk reduction following diagnosis of diabetes by screening: one-year results from the ADDITION-Cambridge trial cohort. Charles M, Simmons RK, Williams KM, Roglic G, Sharp SJ, Kinmonth AL, Wareham NJ, Griffin SJ. Brit J Gen Pract 2012;62:294-295. Are people with negative screening tests falsely reassured? A parallel group cohort study embedded in the ADDITION (Cambridge) randomised controlled trial. Paddison CAM, Eborall HC, Sutton S, French DP, Vasconcelos J, Prevost AT, Kinmonth AL, Griffin SJ. BMJ 2009;339:b4535. Patients’ experiences of screening for type 2 diabetes: prospective qualitative study embedded in the ADDITION (Cambridge) randomised controlled trial. Eborall HC, Davies R, Kinmonth AL, Griffin S, Lawton J. BMJ 2007;335:490-493. Findings from the study have also been presented at GP forums, policy briefings and major international conferences.

Objectives:

To evaluate the effectiveness and cost (economic and psychological) of a program of screening and intensive multifactorial intervention for Type 2 diabetes in primary care.To measure the effect of a multifactorial intervention for people with screen-detected Type 2 diabetes aged 40 to 69 years on modelled mortality and cardiovascular risk.To assess the psychological and health service costs of screening for Type 2 diabetes.To determine whether an approach, based on theory and evidence from psychology, to increase and maintain health-promoting behaviours (physical activity, taking medication and dietary change) can achieve clinically important and measurable change in these behaviours when offered to people with screen-detected diabetes.To assess the added benefits and costs of facilitation of healthy behaviours among people aged 40 to 69 years with diabetes detected by screening and intensively treated.To provide the National Screening Committee with timely evidence to inform the decision on whether screening for Type 2 diabetes should become part of health policy in the UK

Expected Benefits:

a) Type 2 diabetes is frequently asymptomatic, with the true onset occurring several years before diagnosis. While detection of the condition may be improving, around 30-50% of people with diabetes remain undiagnosed, and when patients are diagnosed, around 20-30% have evidence of diabetic complications. Long-term follow-up of the ADDITION study will inform the management of newly diagnosed patients and to establish the size and nature of the benefits of detecting and treating diabetes earlier. NHS digital data will inform the long term follow up and allow study of mortality events in participants across the ADDITION cohort. This will add to the evidence of treatment and screening options for diabetes and will influence NHS policy makers and clinician decisions nationally on the best way to care for this population. The data will also be used to inform the cost-utility analysis. Completeness of information on the health outcomes, including death, is crucial to enable a true cost to the NHS to be determined and hence influence implementation decisions on the course of treatment for the population. This could lead to reductions in NHS spending on treatments without proven effectiveness or to invest in treatments that will generate savings in the future through reduced NHS service use. b) ADDITION-Cambridge has existing responsibility for organisation and delivery of diabetes care both locally and nationally (e.g. guideline development, managed care networks, expert review group for diabetes QOF indicators, National Screening Committee Advisory Group, UK Department of Health Vascular screening programme) and therefore have established mechanisms for influencing policy and practice in these and related fields. c) Results from this study will help inform care early in the course of the disease and will provide information on whether people in middle-age should be offered screening for diabetes in the UK and worldwide . d) It is estimated that 1 in 16 UK adults has (diagnosed or undiagnosed) type 2 diabetes, and this creates a substantial burden of suffering and health service use. Treatment of type 2 diabetes and related complications (cardiovascular disease, amputation, blindness, kidney failure) accounts for 10% of the NHS budget. This is expected to rise as the number of people in the UK who have type 2 diabetes is estimated to rise to 6.25 million by 2035. Type 2 diabetes is frequently asymptomatic, with the true onset occurring several years before diagnosis.

Outputs:

The following outputs have been produced: The ADDITION Europe study has so far led to the publication of 76 papers in peer-reviewed scientific journals, with a further 4 under review or in press. Data from ADDITION has also contributed to 12 PhD theses and 52 oral presentations or posters at international conferences. The primary analysis of 5 year outcomes was published in the Lancet (Griffin et al. (2011). Lancet, 378 (9786), 156167). Participant dissemination events have continued throughout the past 10 years, including public meetings and annual newsletters. The following outputs will be produced: The results of the 10 year analysis will be submitted to this or a similar leading medical journal by December 2018 (subject to the completion of the processing activities described above). Findings were presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September 2016. Throughout 2018, secondary analyses including cost-utility analysis and mechanistic analyses will be published in leading medical or disease-specific peer-reviewed journals such as the Lancet, BMJ, Diabetalogia, Diabetes Care, and International Journal of Obesity. All publications will be open access, in line with the University of Cambridge open-access policy, and can be accessed by clinicians, academics, policy makers and interested members of the public. A simplified version of the findings will be issued to participants and GP practices that took part as part of our annual newsletter. Lay-summary findings are also published on the organisation’s website. All outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. No personal identifiable data will be released or published.

Processing:

Data Flow & What data is provided a) NHS Digital already hold a file from the University of Cambridge containing identifiers of participants (less any that object to data linkage) recruited in Cambridge. This includes: STUDY_ID NHS number Date of Birth Sex Postcode The cohort will then be linked to mortality data and will be extracted for each participant. No additional filters will be applied to the data, nor any additional derived fields provided. b) The University of Cambridge will use the Study ID to link the data previously disseminated (i.e. data the University of Cambridge holds). By means of this re-identification, the mortality data to be disseminated is therefore considered Identifiable. c) The data will be downloaded at the University of Cambridge MRC Epidemiology Unit and transferred immediately to an independent, physically-separated network that is isolated from public network systems and can only be accessed locally, with a managed access system including both password and procedural controls. This other network is still on the Unit premises but is known as the private network where all of the Unit's patient data is stored. It is not connected to the internet and can only be accessed by being at the Unit. Access to this network must be approved by both local senior management and the ADDITION study CI and access will only be granted for the purpose described. All study team members accessing the data have a contract with the Unit. Pseudonymised data may be released from the Unit’s physically separate server onto the Unit's main network, and may be accessed on site or by remote access. The data will not be made available to any third parties. All outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. Mortality data sets are requested in this application. Previously received quarterly update of mortality data since 2006 (previously from ONS). Data is requested going forward for the duration of the Data Sharing Agreement. All mortality outcomes are of relevance, no filters will be applied. It is essential to be able to identify which participant data relates to, to enable the study to link mortality outcome data with measures that were taken as part of their screening for ADDITION. 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data).


Project 3 — DARS-NIC-147829-5K4QP

Opt outs honoured: Y, N, Yes - patient objections upheld (Mixed, Mixture of confidential data flow(s) with consent and flow(s) with support under section 251 NHS Act 2006)

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2019/09.

Repeats: Ongoing, One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012 – s261(2)(c)

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Flagging Current Status Report

Yielded Benefits:

The CFAS Study has a number of key findings to date which, as noted above, are used by policy makers, such as the dementia targets for GPs developed by NHS England, and in primary care settings in contributing to the planning of services for the ageing population, and particularly people with dementia: 1. A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I & II. This multi-centre population-based study powered to detect changes over time reported dementia incidence, estimating 209,600 new dementia cases per year. The study was uniquely designed to test for differences across geography and time. At 2 years CFAS I interviewed 5,156 (76% response) with 5,288 interviewed in CFAS II (74% response). The University reported a 20% drop in incidence (95% CI: 0-40%), driven by a reduction in men across all ages > 65 years developing dementia. 2. Prevalence of Dementia in England and Wales – a two decade comparison – Using CFAS I age and sex specific estimates of prevalence in individuals aged> 65 years, standardised to the 2011 population, 8.3% (884 000) of this population would be expected to have dementia in 2011. However, CFAS II shows that the prevalence is lower (6.5%; 670 000), a decrease of 1.8% (odds ratio for CFAS II vs CFAS I 0.7, 95% CI 0.6-0.9, p=0.003). Sensitivity analyses suggest that these estimates are robust to the change in response. This study provided further evidence that a cohort effect exists in dementia prevalence. Later-born populations have a lower risk of prevalent dementia than those born earlier in the past century. 3. Changing non-participation in epidemiological studies of older people: Evidence from the Cognitive function and Ageing Study I & II Non- participation was found to be higher in CFAS II (45.3% than in CFAS I (18.3%). After adjustments were made for confounders, in both CFAS I and CFAS II, women were more likely to decline to take part (CFAS I: odds ratio (OR) 1.3 95% confidence interval (CI) 1.3 to 1.4; CFAS II 1.1 95% CI 1.1 to 1.2) Deprivation was associated with non-participation in both studies (highest versus lowest Townsend deprivation quintile, CFAS I: OR 1.4 95% CI 1.2 to 1.6; CFAS II: 2.0 95% CI 1.8 to 2.2). Age was not associated with non-participation in either study (CFAS I, p=0.21; CFAS II, p=0.47). 4. Findings from the paper, Projections of multi-morbidity in the older population (2018) concludes between 2015-2035, numbers of older people with 4+ diseases will double and a third will have mental ill-health. Two thirds or more of the gain in years of life at age 65 will be years with 4+ long term conditions (complex multi-morbidity). These findings suggest the need to focus on prevention of and service provision for those with complex multi-mobidity addressing mid and later life risk factors. 5. The impact of dementia on service use by individuals with a comorbid health condition: a comparison of two cross sectional analyses conducted approximately 10 years apart. Holly Q Bennett, Sam Norton, Frances Bunn, Louise Robinson, Greta Rait, Claire Goodman, Carol Brayne and Fiona E Matthews. Bennett et al. BMC Medicine (2018) 16.114 https://doi.org/10.1186/s12916-018-1105-8. These findings show that less people are moving into care settings and more pressure is being put on unpaid carers. Future research is necessary to examine whether care is optimum and in line with national guidelines. 6. Is Frailty a stable predictor of mortality across time? Evidence from the Cognitive Function and Ageing Studies. Andria Mousa, George M Savva, Arnold Mitnitski, Kenneth Rockwood, Carol Jagger, Carol Brayne, Fiona E Matthews. Age and Ageing 2018; 0:1-7 doi:10.1093/ageing/afy077. The findings show the relationship between frailty and mortality did not significantly differ across the studies. Severe frailty as an indicator of mortality is shown to be a stable construct.

Objectives:

The data supplied will be used only for the approved medical research project MR480 - MRC Study of Cognitive Function and Ageing

Expected Benefits:

The CFAS has been and will continue to be beneficial to health care in the following ways: Findings on dementia prevalence and incidence are extremely beneficial to the NHS. Services are planned based on estimates of prevalence and incidence but the CFAS study is providing evidence that reductions in numbers are possible through proactive interventions. Such information encourages such interventions and helps care providers to more accurately plan services ensuring patients’ needs are catered for while reducing risk of wasting resources. The benefits are achieved through use of the full data the CFAS studies collect from various sources e.g. MRC CFAS, ALPHA, CFAS II and CFAS Wales. Mortality data comprises a small but important proportion of that data making it possible to ascertain the survival of individuals based on different conditions which can then be used in population modelling and public health outcomes. Specifically for example, the date of death will enable estimates of life expectancy for those who develop cognitive impairment between different waves of interviewing. Information is also required in relation to those leaving the NHS through emigration etc. in order to allow more accurate estimates of survival rates. The study is one of the core cohorts of the Dementias Platform UK (DPUK). CFAS data (non- identifiable) is available to researchers through the DPUK data application processes. Though the mortality data supplied by NHS Digital is not made available, it is used to calculate binary mortality outcomes (i.e. living or deceased) which are made available through the DPUK. The DPUK data portal brings together over 30 UK cohorts with records of over 2 million people in a free to access resource which will allow researchers across the world to apply for access to the data which can transform our understanding of dementias. By maintaining the data in an environment operating to the highest data protection standards, cohort participants and researchers can be reassured that the data are managed securely and responsibly; maintaining privacy whilst maximising scientific value. In addition, the large number of cohorts allows key research questions to be answered more rigorously and more rapidly than would otherwise be possible, with the aim of facilitating and accelerating the discovery of new ways to understand, diagnose, and treat dementia.

Outputs:

The CFAS studies (MRC CFAS, ALPHA, CFAS II and CFAS Wales) has published over 250 papers in high profile publications including the Lancet, BMJ, New England Journal of Medicine, Age and Ageing etc. All papers are available from our study website: www.cfas.ac.uk. The CFAS study have, in conjunction with the CFAS II study (2008-Present), produced generational differences in dementia prevalence and incidence. The studies dementia diagnosis rates are currently used by NHS England. Expected outputs: Paper: Changing prevalence and treatment of depression among the over 65s over two decades: findings from the Cognitive Function and Ageing Study – British Journal of Psychiatry – in press. Paper: Iba-1-/CD68+ microglia are a prominent feature of age-associated deep subcortical white matter lesions" PLOS ONE – in press Current CFAS work with the Newcastle DELIRIUM study is helping to prospectively elucidate the size of the effect of delirium upon cognitive decline and incident dementia. The results will be used to inform future dementia prevention trials that focus on delirium intervention. The study is expected to report in December 2018. The CFAS study continues to provide study data to other researchers following approval from the CFAS management committee: In the past year (2018) the study team have received 11 requests for anonymised study data including the following (this data is not NHS Digital data, but is derived from NHS Digital data): Data only: Exploring the role of survival bias in gender differences in cognitive decline, University of Cambridge 01/07/2018 – 31/12/2018 The influence of anti-depressants in older people with depression, Newcastle University 1/11/2018 – 31/03/2019 Identifying delirium in people in Parkinson’s disease (DETERMINE-PD) Newcastle University 1/12/18 – 1/12/19 Data/Brain tissue: Dysregulation of nitric oxide synthases (NOS) expression in the ageing brain. 01/10/2018 – 31/08/2019 Defining the effects of Type 2 Diabetes on the Brain, University of Sheffield June 2019 – June 2020 It is expected that all of the above research will result in papers within nine months of the project completion dates. In the past four years the study has led to the publication of 30 academic papers and there are currently papers on the following: Risk/frailty, projection of care costs, regional differences of life expectancy, Social isolation, education, mild cognitive impairment (MCI) and Neuropathology which are in draft, awaiting submission or awaiting acceptance by publications and expected in the next 4 months – 1 year. All outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide.

Processing:

This agreement covers the release of data for the main study cohort under section 251, and for a sub-cohort of 47 participants who have given informed consent for data linkage to take place. The University of Cambridge is the administrative centre for all the CFAS studies. The University of Cambridge maintains an administrative database containing participants’ identifying details and a separate pseudonymised database containing self-reporting information and data from tests (e.g. hearing tests) and from analysing samples (e.g. saliva, blood, brain tissue etc.). The University of Cambridge has previously supplied lists of identifiers for CFAS (MR480) and ALPHA (MR490) participants to NHS Digital separately. Data provided to NHS Digital have consisted of name, date of birth, NHS number, postcode and a unique study identifier for each participant. NHS Digital have linked that data and routinely provided reports containing details of participants’ deaths (date and cause of death) to the University of Cambridge. As the cohort is already flagged by NHS Digital, no new data will flow into NHS Digital under this agreement. The data supplied by NHS Digital is held as identifiable data within the Secure Data Hosting Service (SDHS) at the School of Clinical Medicine, University of Cambridge. Only the core CFAS team (4 employees) has access to the identifiable data held on the secure server. All are substantive employees of the University of Cambridge. Access to the SDHS is via a 15-character password and 2 factor authentication token. There is no internet access inside the SDHS. All data imported or exported to/from the SDHS is made via the secure transfer server. All transfers are audited. No identifiable data is ever released to collaborating researchers. The University sends record-level linked data with a study ID to collaborating researchers, but do not send identifiable data to them. This is not NHS Digital data, however, but it is derived from NHS Digital data. The information of whether people are dead or not is provided to these researchers based on the pseudonymised linked ID that is used throughout the entire study for sharing individual’s information to agreed researchers. This data relates both to the deceased and the living. There will be no attempt to re-identify by recipients of the derived data. No NHS Digital data will be transferred, with all analyses on mortality information undertaken solely within the core study team at the University of Cambridge. All outputs produced will be aggregated and anonymised with small numbers suppressed, in line with the HES Analysis Guide. Proposed Data Flows Going Forward A. University of Cambridge securely transferred a file of identifiers (NHS number, date of birth, and postcode plus unique study ID to NHS Digital for both ALPHA and MRC CFAS. These studies will be brought together by NHS Digital/MRIS team. B. NHS Digital will reflag the ALPHA study (MR490 cohort) before adding this cohort to the CFAS study (MR480 cohort) C. NHS Digital will then disseminate the same data that was disseminated for the two studies under the previous DSAs (NHS number, member ID, supplied identifiers, latest identifiers, fact of death, cause of death and date of death) to University of Cambridge. - Quarterly dissemination of data are being requested in June, Sep, Dec, March D. University of Cambridge will store, as it has previously, the data on a server in the secure data hosting service (SDHS) held at the Clinical School, University of Cambridge, which can only be accessed by the approved CFAS core team. E. The death data received from NHS Digital will be securely stored in a separate location to the participant identifiers F. University of Cambridge will extract subsets of the mortality data provided by NHS Digital and will convert it into binary indicators (i.e. deceased; not deceased) and those derivations are made more widely available along with other interview data, e.g. depression, anxiety, sleep, loneliness, cognition, health risk factors such as stroke, heart attack, transient ischaemic attacks (TIA's), diabetes, smoking, alcohol use, etc. which are collected during participant interviews by all CFAS studies - (www.cfas.ac.uk). The subsets are made available to other researchers for projects which have been approved by the CFAS management committee (CMC) and for those applications requiring a combination of tissue and data following approval from both the CMC and the CFAS Biological Resource Advisory Committee (BRAC). This is not NHS Digital data, but it is derived from NHS Digital data. Individuals who have taken part in the study (with consent) have agreed that their data is shared widely as is research council funding best practice. The information of whether people are dead or not is provided to these researchers based on the pseudoymised linked ID that is used throughout the entire study for sharing individual’s information to agreed researchers. This data relates both to the deceased and the living. There will be no attempt to re-identify by recipients of the derived data. The data from NHS Digital has been and will be used to model life expectancy, differentials between different diseases and causes of death. The use of exact dates of death will ascertain the survival of individuals based on different conditions and then be used in population modelling and public health policy outcomes. The mortality data are linked with other extensive variables (as above) collected on the CFAS and ALPHA cohorts from the study questionnaires and analyses of that data may be compared with equivalent analyses from CFAS II and CFAS Wales to assess changes in prevalence and incidence within the same geographical areas or variations across different areas. All outputs are aggregated with small numbers suppressed in line with the HES Analysis Guide. 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).


Project 4 — DARS-NIC-147874-HVBFB

Opt outs honoured: Y, N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2017/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

Are to estimate the incidence and mortality of Psychiatric and Mental Illnesses i.e Dementia, Neurosis,Alzheimer's Disease and Depression and to assess their relationships with various external factors.


Project 5 — DARS-NIC-148129-FK1JJ

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/09 — 2017/05.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

The data supplied to the University of Cambridge will be used for the approved Medical Research Project identified above.


Project 6 — DARS-NIC-156334-711SX

Opt outs honoured: Y, No - consent provided by participants of research study (Reasonable Expectation, Consent (Reasonable Expectation))

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2019/03.

Repeats: Ongoing, One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(2)(c), Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Flagging Current Status Report
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients

Yielded Benefits:

Results from the initial stage of INTERVAL and COMPARE are already shaping policy, nationally and internationally, and leading to improvements in the health of blood donors. For example, results from INTERVAL have shown that more frequent blood donations from donors, than is now standard care, can be done without causing harm to donor health, allowing better management of the supply of units of blood to the NHS (in particular supply of in-demand blood groups). These results have been published in a major international scientific journal (Di Angelantonio Lancet 2017) and have been disseminated to the public and donors through study website, newsletters, national and international press release and media interviews. Results from COMPARE have been disseminated within the NHSBT and will be published later in 2018. Results of the INTERVAL and COMPARE studies are already shaping policy, nationally and internationally, and leading to improvements in the health of about 1 million blood donors in England. Results from the INTERVAL trial have published in The Lancet (Di Angelantonio et al, 2017), are already shaping policy nationally and internationally, and leading to the improvements in the health of donors. In particular, results from INTERVAL have shown that more frequent blood donations from donors can be done without causing harm to donor health. It has provided policy-makers with evidence that more frequent collection from donors than is now standard can be done over two years without causing harm to donor health, allowing better management of the supply to the NHS of units of blood with in-demand blood groups. Furthermore, INTERVAL has led to NHSBT’s adoption of comprehensive multi-modal reminders (eg, SMS messages) to help donors make and keep appointments. The COMPARE study was designed to evaluate the optimum method to measure haemoglobin levels in ~30,000 potential whole blood donors in advance of each donation. Results from COMPARE have led to an evidence-based decision by NHSBT to replace the copper sulphate-based haemoglobin screening with finger-prick haemoglobin testing, thereby preventing ~350 female donors being inappropriately bled each day in England (ie, female donors with haemoglobin levels <12.5g/dL, the minimum threshold mandated by regulators).

Objectives:

This randomised study aims to determine: 1. What is the optimum interval between donations that maximises blood supply, maintains well-being, and avoids unacceptably increasing risk of iron deficiency/anaemia and its potential complications, for men and women? 2. If it is appropriate to tailor blood donation intervals to donors by their demographic, haematological, genetic and lifestyle factors? The benefits of this study are twofold. Firstly, identification of donors that are likely to become anaemic following blood donation would enable NHS Blood and Transplant to allow such donors a longer period to recover their iron stores post-donation. Currently, such donors often fail their anaemia screening test at their next donation appointment and are temporarily prevented (or deferred) from donating blood; this often results in donors withdrawing completely from donating. Secondly, the ability to decrease donation intervals would enable NHSBT to collect more blood from the same number of donors.

Expected Benefits:

As described above, these translational research studies have been designed to deliver a multi-purpose strategy, with an *initial purpose* related to blood donation research aiming to improve NHSBT’s core services (e.g. safety and efficiency of blood donation), and a *longer-term purpose* related to the creation of a comprehensive resource that will enable detailed studies of health-related questions. It is expected that the creation of these resources will help address NHSBT-relevant safety and efficiency questions which will shape future donation policies in the UK and elsewhere. For example, findings from this study will help: i) determine the optimum interval between donations that maximises blood supply and maintains long-term donor well-being. These results will be expected to benefit several millions of blood donors that are donating blood in worldwide and in the UK. Creation of these resources will also provide significant benefit for future health-related research in general. For example, linkage with the health records data listed in this application will allow the study of genetic, biological and lifestyle associations with long-term health outcomes which will be important to help: i) understand genetic, biochemical and lifestyle determinants of chronic diseases; and ii) inform the development of new medicines by prioritisation of targets and biological mechanisms implicated in chronic diseases such as cardiovascular disease and cancer. Findings from these resources will have specific implications for patients and the public in relation to risk prediction/screening and therapeutic target prioritisation for chronic diseases, potentially benefit several millions of patients worldwide. For the purposes of this application, only researchers from the University of Cambridge will access the data products requested in this application. Approval for access by third parties (bona fide researchers) may be considered as a future amendment to the data sharing agreement. Given that health outcomes will accrue over time and that we intend to track participants’ health over many years it is anticipated that the benefits of this research will be realised for a considerable time into the future.

Outputs:

Results from the studies have led to an evidence-based decision by NHSBT to replace the copper sulphate-based haemoglobin screening with finger-prick haemoglobin testing. As described, outputs from the initial stage if these studies have been disseminated to participants via regularly updates of websites, email communications, and newsletters. Subsequent stages of both the INTERVAL and COMPARE studies are related to the creation of a comprehensive resource that will enable detailed studies of health-related questions by linking health outcomes data to genetic, biological and lifestyle information. As such, it is expected that findings from this resource will extensively advance biomedical research and inform public health policy. Multiple high-impact publications are expected from these resources. Findings will be published and disseminated through publications in high impact journals, dissemination to academic, health service, and general public audiences. Publications arising from these studies will be available on the studies website at http://www.intervalstudy.org.uk/publications/ for INTERVAL and http://www.comparestudy.org.uk/publications/ for COMPARE. Given that health outcomes will accrue over time and that we intend to track participants’ health over many years, it is anticipated that the outputs of this research will be realised for a considerable time into the future. In addition to submissions of papers to scientific journals and academic conferences, the university will disseminate findings and study progression to donors, the blood service, and the wider public. The approach will be to build on – and to extend substantially – methods that have so far succeeded in INTERVAL and COMPARE. The INTERVAL study website and the COMPARE study website will be used throughout the project to disseminate research findings and study progression. Furthermore, information produced as a result of processing the data will be disseminated by regular newsletters, local and national newspapers and radio, and printed publications available to blood donors (eg, articles in “The Donor” e-Magazine). The university will also disseminate the results of the research widely (eg, through press releases) to a variety of target audiences through close liaison of communication departments from the University of Cambridge and NHSBT. The audiences will include the donor community and the general public as well as clinicians and/or scientists, health policy makers, the wider scientific community. The applicant has also used Patient and Public Involvement (PPI) panel (involving many blood donors and other lay representatives) to communicate results and discuss feedback on their involvement in the study. This approach supplements our existing study helpline for queries and feedback. When sharing research findings, results will be displayed as aggregate data only (with small numbers suppressed, in line with the HES analysis guide), therefore individual data cannot be recognised. For the purposes of this application, only researchers from the University of Cambridge will access the data products requested in this application.

Processing:

To minimise the amount of data being requested, the University of Cambridge is requesting only a carefully selected subgroup of variables necessary to address the overarching study aims listed in the ‘Objective for processing’ section. For HES data, the University of Cambridge is requesting both historical (going back up to 10 years from the recruitment of the first INTERVAL participant) and future (every 6 months) reports. Linkage to historical records will be used to enhance information already recorded at baseline in the INTERVAL and COMPARE studies about the donors’ prior medical history. Given the age of participants enrolled in these cohorts it is believed that 10 years will provide a reliable timeframe to capture pre-existing medical conditions. INTERVAL and COMPARE participant data are stored securely on the study database, held at the University of Cambridge. Datasets used by researchers are pseudonymous with each individual assigned a unique study identification number (study ID). A link table between a participants study ID and person-identifiable data (Donor Number and NHS number) is maintained for linking with health records. Access to the link table is restricted to the study data manager / senior investigators. NHS numbers for INTERVAL and COMPARE participants have principally been retrieved via NHSBT’s national database (approximately 70% of cohort). In INTERVAL, where NHS numbers were missing via this source, these data were retrieved via NHS Digital under an existing agreement (Study Ref: MR1292, NIC: DSAS0423) between the University of Cambridge and NHS Digital. In this current application the University of Cambridge is requesting that a similar approach be taken to retrieve missing NHS numbers for the COMPARE cohort (manual matching will be required). Once the retrieval process for missing NHS numbers for COMPARE is complete, it is proposed that the: a) INTERVAL/COMPARE data manager will be responsible for the secure transfer of NHS numbers to NHS Digital for the purpose of health records linkage. b) On receipt of information described in a) above, NHS Digital will retrieve requested hospital episode statistics and ONS data and return a file to the INTERVAL/COMPARE data manager including NHS number and requested health records data. c) On receipt of information described in b) above, the INTERVAL/COMPARE data manager will link the health records information to participants’ Study ID and update the anonymous research database with the retrieved health records data. For the purposes of this application, only researchers from the University of Cambridge will access the data products requested in this application. Approval for access by third parties (bona fide researchers) may be considered, by the study, as a future amendment to the data sharing agreement. Under this agreement no further access is permitted. All processing of ONS data will be in line with ONS standard conditions. All outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. There will be no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement. 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data).


Project 7 — DARS-NIC-199682-T1L7Z

Opt outs honoured: Yes - patient objections upheld (Section 251)

Sensitive: Sensitive

When: 2019/05 — 2019/05.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - List Cleaning Report

Objectives:

The University of Cambridge, MRC Epidemiology Unit (MRCEU) wishes to request access to data held by NHS Digital for the WRAP trial cohort. This is the first application relating to this cohort. In this submission the MRCEU would like to apply for current address details for the WRAP trial cohort, via MRIS - List Cleaning Report, with section 251 support from the Confidentiality Advisory Group. The List Clean Report data is being requested for the Weight Loss Referrals for Adults in Primary Care (WRAP) trial. This trial ran from 09/12 to 03/16, and assessed the effect of referral to a community based open-group programme (12 weeks or 52 weeks) vs standard care, on weight and glycaemia, at 12 and 24 months. Cost-effectiveness was demonstrated at 12 and 24 months for adults who are overweight or obese. The impact of the three programmes was modelled over the next 25 years and cost-effectiveness was demonstrated; 5-year follow-up of the cohort will help establish whether medium-term assumptions of weight loss were correct. WRAP participants are currently being invited to participate in a 5-year follow-up visit as part of the WRAP-Up study. WRAP-Up is the 5- and 10-year follow up of the WRAP trial. WRAP-Up will provide objective evidence of 5-year and 10-year outcomes for body weight, glycaemia, and incidence of diabetes and cardiovascular disease. These data will also allow the MRCEU to improve its modelling of longer-term outcomes. Approvals have been received for 5-year follow-up, a new application will be sought for 10-year follow-up. The MRIS List Cleaning Report will provide current address details for the cohort; a subsequent amendment to this application will request HES data, supported by the appropriate legal basis. The 5-year follow-up of the trial participants has been funded by the National Institute of Health Research to provide the NHS with vital evidence about the long-term impact of commonly commissioned weight management services on health and health resource use. It will be used to inform policy makers about which weight management services offer best value for money and will support commissioning decisions. The study team aims to complete 5- and 10-year follow-up of the WRAP participants with as high a follow-up rate as possible, in order to reduce uncertainties and provide a more precise estimate of longer-term impact of referral to community based open-group behavioural weight loss programmes on incidence of diabetes and other obesity-related conditions and associated resource use. Of the original WRAP cohort size of 1267, 225 participants did not complete the study visits and 2 declined access to medical records, and the remaining 1040 participants are recorded as maintaining their consent to remain in the cohort. The 1040 participants have provided consent to be contacted for further follow-up. Purpose: List Cleaning (MRIS) service is being requested now that Section 251 support has been granted from the Confidentiality Advisory Group for this purpose. Access to up-to-date address information is required to cross-reference our existing contacts database with details in the list clean provided by NHS Digital to ensure our participant records are up to date, to allow follow-up of participants who have moved since the last trial contact and to prevent the MRCEU from attempting to contact participants who have passed away since their previous contact with the MRCEU. The list clean data will not be linked to study questionnaires, HES, MINAP or SSNAP data. The WRAP contacts database with personal identifiable information is held separately to any outcome data and linked only by ID numbers.

Expected Benefits:

WRAP-Up is the 5 and 10 year follow up of the WRAP trial, which was one of the largest trials of publicly available based open-group weight management programmes for people with overweight and obesity. Overweight and obesity are a major risk factor for diabetes type 2. WRAP results demonstrated that referring people with overweight and obesity to publicly available open-group weight management programmes (such as Weight Watchers or Slimming World) can help people to lose weight and reduce glycaemia over 2 years. Modelled data suggests it is likely to be cost-effective in the long term because it reduces disease incidence and associated health care costs. The 5 and 10 year follow up of the WRAP trial (WRAP Up) will provide important data about weight regain, disease incidence, and health resource use. The objective data on 5-year and 10-year outcomes will enable more realistic estimations of long-term impacts on disease incidence and associated resource use. The overall results of this research will provide policy makers and commissioners with robust evidence regarding the effectiveness and value for money of scalable behavioural weight management programmes for the prevention and treatment of type 2 diabetes. This will help them to decide which programmes to fund.

Outputs:

The direct outputs from this application will be an up-to-date list of participant address records, to support initial contact to commence the WRAP-Up study. The initial 5-year WRAP Up results are planned to be published at the end of 2019. They will also be included in a grant report to the NIHR which is due in April 2022. The 10 year WRAP Up results are planned to be published at the end of 2024. Previous outputs of the WRAP trial include two papers in peer-reviewed scientific journals, including the Lancet (Lancet, v.389(10085), p2214–2225). Results from WRAP have also been presented at conferences and NHS Primary care meetings. Data has also contributed to MSc and PhD theses. All publications will be open access, in line with the University of Cambridge open-access policy, and can be accessed by clinicians, academics, policy makers and interested members of the public. Outputs presented and/or reported will contain aggregate level data with small numbers sup[ressed in line with the HES analysis guide. No personal identifiable data will be released or published. Findings will also be used to advise policy makers on the cost-effectiveness of referral to behavioural weight management programmes and the impact on incidence of diabetes and other risk factors for cardiovascular diseases. When the study is completed, meta-data will be added to the data dictionary on the meta-data access portal http://epi-meta.medschl.cam.ac.uk/. The trial team will also send all WRAP-Up participants a summary of the results in the form of a newsletter. NHS Digital reminds all organisations party to this agreement of the need to 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data)

Processing:

List clean data will be used to cross reference the MRCEU's existing contacts database with details in the list clean provided by NHS Digital to ensure participant address records are up to date, to allow follow-up of participants who have moved since the last trial contact and to prevent the MRCEU from attempting to contact participants have passed away since our previous contact. The list clean data will not be linked to study questionnaires, HES, MINAP or SSNAP data. The WRAP contacts database with personal identifiable information is held separately to any outcome data and linked only by ID numbers. The data will be downloaded at the University of Cambridge’s MRC Epidemiology Unit and transferred immediately to an independent, physically-separated network that is isolated from public network systems and can only be accessed locally, with a managed access system including both a password and procedural controls. This ‘other network’ is still on the Unit premises but is known as the ‘private network’ where all of the Unit's patient data is stored. It is not connected to the internet and can only be accessed by being at the Unit. Access to this network must be approved by both local senior management and the Chief Investigator for the WRAP-Up study. All study team members accessing the data have a contract with the Unit. The Unit’s data policies and governance are available at: http://epi-meta.medschl.cam.ac.uk/data_sharing_policy.html


Project 8 — DARS-NIC-24422-R3W3S

Opt outs honoured: No - consent provided by participants of research study (Reasonable Expectation, Consent (Reasonable Expectation))

Sensitive: Non Sensitive, and Sensitive

When: 2017/09 — 2019/07.

Repeats: Ongoing, One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(2)(c)

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Admitted Patient Care
  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Yielded Benefits:

As the trial has still been recruiting, no data analysis has been performed yet. Any benefits yielded will be reported on a later date.

Objectives:

The randomised controlled trial aims to assess the effect of colecalciferol (vitamin D) supplementation versus standard care on health outcomes in patients with kidney failure receiving dialysis and will involve approximately 4,200 patients over a 7-8 year period. This novel approach of capturing follow up will remove the need for additional study visits and will lessen the burden and cost of participating in research for both patients and sites. Vitamin D deficiency is highly prevalent in patients with kidney failure and is associated with increased mortality. Kidney failure patients are treated with “active” vitamin D compounds (VDRAs) based on the now disproven belief that activation can only occur in the kidneys. VDRAs induce hypercalcaemia, result in tissue deficiency of calcitriol, and may promote vascular calcification. Contemporary treatment guidelines now recommend administration of “native” vitamin D (colecalciferol). This guidance is not currently implemented given the lack of evidence from randomised trials. Colecalciferol has been used to treat vitamin D deficiency for more than 80 years. It is cheap and safe, even at high doses. In contrast, VDRAs are expensive and despite their wide use, their efficacy and safety have never been tested in interventional trials. There is an urgent unmet need for a trial to determine which approach is preferable. In this trial, the University of Cambridge will test the hypothesis that population-wide supplementation with high-dose colecalciferol (inactive vitamin D) in patients receiving dialysis will reduce mortality and improve quality of life.

Expected Benefits:

Supplementation with colecalciferol at high and infrequent doses in patients with renal failure on dialysis provides an effective, safe approach to addressing vitamin D deficiency. It is also cheaper than active vitamin D compounds which are in wide clinical use and have not been assessed in interventional trials. Current treatment guidelines recommend cholecalciferol or ergocalciferol in patients on dialysis, even when they are receiving treatment with VDRAs. The Kidney Disease Improving Global Outcomes (KDIGO) guideline group identified “native” vitamin D supplementation in dialysis as a key research priority, but nevertheless argues for its use on the basis that the intervention is safe and inexpensive. Caution is necessary, however, as epidemiological data similarly supported the use of anti-oxidant vitamins including vitamins C and E, which were found to be of no benefit or even harmful in adequately powered interventional trials. Widespread supplementation with cholecalciferol should therefore be rigorously tested in an adequately powered randomised trial. Further, most clinicians continue to preferentially prescribe 1-hydroxyated compounds on the basis of epidemiological data suggesting a survival benefit compared to no vitamin D; Despite guidleines to supplement “native” vitamin D being in force since 2007, clinical practice has not changed. It is therefore imperative to generate data from an adequately powered randomised comparison of colecalciferol versus standard care. The findings of the trial will be provided to NICE. Study findings will have the potential to influence the NICE guidelines and other guidelines regarding clinical practice in this areas.

Outputs:

The University of Cambridge will test the hypothesis that supplementation with high dose colecalciferol (inactive vitamin D) in patients receiving dialysis will reduce mortality and improve quality of life. The trial results will be published in peer-reviewed journals and presented at national and international conferences. These outputs are dependent upon the primary endpoint being achieved. With an average median survival of 5.5 years for patients on dialysis, the trial is likely to end in 2023, with the final study report being available in 2024. Prior to the final publication, the trial will have an interim analysis as described in the protocol. A feasibility assessment will be carried out between months 12 and 15 of the trial. Feasibility will be predicated on recruitment rate (target 887 patients recruited after 12 months), and separation between arms by plasma vitamin D concentration after 4 months of treatment of 20nmol/l. Publications will follow in 2025 although this target date is difficult to accurately predict at this early stage. The trial protocol will be submitted for publication in “Trials” (target date February 2017), and will include a section on data capture and handing. During the conduct of the trial, reports will be submitted to the NIHR as required. Findings from the trial will be presented at the British Renal Society annual UK Kidney Week (June 2025), the European Renal Association (May 2025) and the American Society of Nephrology annual meeting November 2025). The primary report from the trial will be submitted for publication in the New England Journal of Medicine or The Lancet during the course of 2025. The results will also be published on the EU Clinical Studies Register website, a central registry for all clinical trials conducted within the EU. Participating patients will be informed of the results and can request a copy of published papers. The final study report will be provided to NICE

Processing:

The University of Cambridge aim to harness the information routinely collected by NHS Digital (including HES and ONS Mortality data) for use as follow-up for those patients participating in their clinical trial. The University of Cambridge will also be collecting data from the UK Renal Registry and UKIACR for the same purposes. All datasets will be linked. The University of Cambridge will submit the following patient identifiers to NHS Digital on a quarterly basis: - NHS number, date of birth and initials. Using these minimal patient identifiers NHS Digital will correctly identify the clinical trial patients of their cohort and track their cohort, providing quarterly updates of cancer registrations, cause of death (ONS Mortality) and linked HES APC, A&E and CC. Data will be uploaded by NHS Digital to the secure DES (cancer registrations and cause of death) and SEFT (HES) accounts; available to download by the study team at the University of Cambridge. The study team will download the data onto a secure hosting environment and anonymised datasets generated . The team is made up of both University of Cambridge and Cambridge University Hospital NHS Trust employees. Data will be stored, processed and linked in a secure university data hosting server, which can be accessed on a permission basis via NHS computers. Only the database programmer, coordinator and data manager have access to data in the Secure Data Hosting Server (SDHS) provided by the university. Access to the SDHS may be done via NHS hardware however access will only ever be permitted subject to permissions which are controlled by the university of Cambridge. These permissions are also required where a university computer is used. Access to SDHS is only ever permitted via a secure encrypted remote desktop connection via the University network and the data will remain at all times within the SDHS. Access to the SDHS is protected by three factor authentication (username, password, PIN + Signify key fob code). All processing activities will take place in Cambridge University Hospitals (CUH). The data set will be kept and stored at the secure data hosting server at patient level. All reports/outputs will be aggregated with small numbers suppressed in line with the HES analysis guide. The only exception to this is safety events, which may be listed at an individual patient level as is standard practice for clinical trials study reports. In these circumstances data will be anonymised and un-linkable. An internal participant trial number will be used to keep the data anonymised at the stages of analysis, reporting and eventually publishing. The anonymised safety reports will initially be shared only by the DMEC committee members and CCTU Pharmacovigilance team. The anonymised datasets, in aggregated format with small numbers suppressed in line with the HES analysis guide will be used for statistical analysis and incorporated into the study report. Trial results will be submitted for publishing in peer-reviewed medical journals, presented at conferences and published on EU Clinical Studies Register Website. All processing and storage will take place at the University of Cambridge. All data collected will be stored on highly secure encrypted servers held within the University of Cambridge secure data hosting area, and will be accessible only to the team of researchers directly involved with the study. All individuals with access to the data are substantive employees of the University of Cambridge or Cambridge University Hospitals NHS Foundation Trust. The secure data hosting area for this study is subject to an existing data governance agreement between the University of Cambridge and the Cambridge University Hospitals NHS Foundation Trust. The use of personal identifiers is to correctly identify clinical trial subjects only. Anonymised datasets for analysis will be generated within the secure data hosting environment and transferred securely to the trial statistician within the Cambridge Trials Unit. These anonymised datasets will be used to determine the primary and secondary endpoints of the clinical trial, namely patient survival, quality of life, and secondary clinical outcomes including cardiovascular events, infections requiring admission, cancer incidence, and fractures requiring admission.


Project 9 — DARS-NIC-28744-S4F8H

Opt outs honoured: N, Yes - patient objections upheld (Section 251)

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2018/12.

Repeats: Ongoing, One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data, Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - List Cleaning Report
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Accident and Emergency

Yielded Benefits:

The primary benefits of using NHS Digital's List Cleaning service are that it has enabled ADDITION-Cambridge to continue to collect information about its participants fairly and transparently giving participants the option to withdraw should they wish. Furthermore, knowing which participants are deceased has enabled the study team to avoid attempting contact and potentially causing distress to living relatives.

Objectives:

ADDITION-Europe is a 4 centre (Cambridge, Leicester, Denmark and the Netherlands) trial of assessing the effectiveness & cost effectiveness of intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes. It has been supported by grants from the MRC, NIHR and the Wellcome Trust. This study aims to collect 10 year follow up information on cardiovascular events and risk factors, treatment and mortality for the cohort of 1,212 participants of the ADDITION study who enrolled in the UK. This will allow an assessment of the long term effects of the differences in intensity of treatment achieved during the first five years after diagnosis. The researchers plan to contact all ADDITION participants in the UK with a self-report questionnaire to assess health behaviour and patient-reported outcomes. Prior to sending any questionnaires, the participant list will be cross-checked with available records to minimise the risk of sending questionnaires to participants who are deceased. Section 251 support has been granted to permit the study to obtain up to date address details for all participants in order to inform them of the 10 year follow up (and if they wish, speak to the study team about the study); invite them to fill in questionnaires, and to update the study team of their current GP practice in order to complete the follow up. The University of Cambridge requires a List Cleaning service for a subset of the 867 participants recruited in Cambridge between 2001 & 2007. A separate application in respect of the participants recruited in Leicester will be made in the future. Personal identifiable data will only be accessed and used by those who have permission within the research team. Personal identifiable data cannot be used or given to any other third party. Results from this trial are needed in order to inform the management of newly diagnosed patients and to establish the size and nature of the benefits of detecting and treating diabetes earlier. Ten year follow-up of the trial participants will add to the existing research base concerning early treatment of type 2 diabetes and inform NHS policy decisions concerning whether population-based diabetes screening programmes should be established in Europe and worldwide.

Expected Benefits:

The primary benefits of using the HSCIC’s List Cleaning service are that it enables ADDITION-Cambridge to continue to collect information about its participants fairly and transparently giving participants the option to withdraw should they wish and mitigates the risk of attempting to contact deceased participants and potentially causing distress to living relatives. The benefits of collecting information about the participants are achieved through the wider study. It is estimated that 1 in 16 UK adults has (diagnosed or undiagnosed) type 2 diabetes, and this creates a substantial burden of suffering and health service use. Treatment of type 2 diabetes and related complications (cardiovascular disease, amputation, blindness, kidney failure) accounts for 10% of the NHS budget. This is expected to rise as the number of people in the UK who have type 2 diabetes is estimated to rise to 6.25 million by 2035. Type 2 diabetes is frequently asymptomatic, with the true onset occurring several years before diagnosis. While detection of the condition may be improving, around 30-50% of people with diabetes remain undiagnosed, and when patients are diagnosed, around 20-30% have evidence of diabetic complications. Long-term follow-up of the ADDITION-Europe trial will inform the management of newly diagnosed patients and to establish the size and nature of the benefits of detecting and treating diabetes earlier. Participation in the trial has facilitated earlier diagnosis and treatment of diabetes. The ADDITION trial has shown that this is not associated with adverse consequences in terms of anxiety and depression. Data from one year follow-up show that overall trial participants had lower levels of risk factors at one year than at the time of diagnosis. Furthermore, one year data suggest that, compared with routine care, intensive treatment is associated with reduced CVD risk, reduced anxiety, increased functional status and treatment satisfaction, with no detriment to quality of life. The intervention promoting target driven, intensive management of patients with screen-detected type 2 diabetes in ADDITION-Cambridge was associated with a non-significant relative reduction (17%) in the incidence of cardiovascular events and a reduction in all-cause mortality at 5 years. The lower than expected event rate during the trial suggests five years of follow up may have been insufficient to detect a potentially important difference. Furthermore, the apparent divergence of event rates from four years indicates that further follow up of this cohort is justified to establish whether early intensive multifactorial treatment reduces long term cardiovascular risk. Modelling work suggests that there might be a difference in cardiovascular risk over the long term. Significant reductions in myocardial infarction and all-cause mortality associated with glucose lowering were only observed after ten years of follow up in the UKPDS trial. Whether such a legacy effect might be seen in ADDITION Europe is unclear. Resolving this uncertainty is important in assessing the costs and benefits of screening for diabetes. No other trials of screening for diabetes or intensive treatment of screen detected cases have been reported and no others are underway in Europe. First line treatment for diabetes has changed following results from the UKPDS. While newly diagnosed individuals were previously offered lifestyle advice for six months and then prescribed metformin, metformin is increasingly being prescribed from diagnosis. Long term follow up of the ADDITION-Europe trial will allow examination of the potential legacy effect of a health service intervention that targeted practices and patients, and whether differences in the intensity of the intervention of the routine care and intensive treatment practices remain. Results will add evidence to decisions about treatment from diagnosis and the balance between treatment and disease burden. ADDITION-Cambridge has existing responsibility for organisation and delivery of diabetes care both locally and nationally (e.g. guideline development, managed care networks, expert review group for diabetes QOF indicators, National Screening Committee Advisory Group, UK Department of Health Vascular screening programme) and therefore have established mechanisms for influencing policy and practice in these and related fields. Results from this study will help inform care early in the course of the disease and will provide information on whether people in middle-age should be offered screening for diabetes in the UK and worldwide.

Outputs:

As described above, the outputs to be achieved from use of the List Cleaning service are: (1) Informing living participants of the 10-year follow-up process; reminding them of their right to withdraw from the study; providing them with an up to date study Participant Information Sheet, and inviting them to fill in study questionnaires; (2) Requests to participants’ GPs asking them to provide data from consenting participants’ medical notes; (3) Medical notes passed to the ADDITION Study Research Assistant who will review the notes to look for CVD endpoints and clinical measures (during surgery visits or remotely, with remote electronic access approved by the surgery). Knowing which participants are deceased will enable the study team to avoid attempting contact and potentially causing distress to living relatives. The aim of contacting participants is to enable the study to continue collecting information to be used in the ADDITION-Europe study. The ADDITION–Europe study has so far led to the publication of 76 papers in peer-reviewed scientific journals, with a further 4 under review or in press. Data from ADDITION has also contributed to 12 PhD theses and 52 oral presentations or posters at international conferences. The primary analysis of 5 year outcomes was published in the Lancet (Griffin et al. (2011). Lancet, 378 (9786), 156–167). The results of the 10 year analysis will be submitted to this or a similar leading medical journal by December 2016 (subject to the completion of the processing activities described above). Findings will also be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September 2016. Throughout 2017 and 2018, secondary analyses including cost-utility analysis and mechanistic analyses will be published in leading medical or disease-specific peer-reviewed journals such as the Lancet, BMJ, Diabetalogia, Diabetes Care, and International Journal of Obesity. All publications will be open access, in line with the University of Cambridge open-access policy, and can be accessed by clinicians, academics, policy makers and interested members of the public. Outputs presented and/or reported will contain aggregate level data with small numbers supressed in line with the HES analysis guide. No personal identifiable data will be released or published.

Processing:

The University of Cambridge will submit a file containing the identifiers of the 867 participants recruited in Cambridge to the HSCIC using its secure electronic file transfer system. The HSCIC will link the identifiers to its copy of Patient Demographic Service (PDS) data and produce an output file containing the latest name, NHS number, GP practice code, address and postcode, date of birth and, where applicable, date of death for each participant. The data will be downloaded at the University of Cambridge’s MRC Epidemiology Unit and transferred immediately to an independent, physically-separated network that is isolated from public network systems and can only be accessed locally, with a managed access system including both password and procedural controls. Access to this network must be approved by both local senior management and the ADDITION study CI. The address and GP data will be used to re-contact participants who were lost to follow up, and to contact their registered GP surgery to enable to collection of recent endpoint and clinical measures. Where HSCIC data identifies changed contact details for participants, the data will leave the MRC Epidemiology Unit in one of two ways: (1) Individual letters addressed to participants informing them of the 10-year follow-up process, reminding them of their right to withdraw from the study, providing them with an up to date study Participant Information Sheet, and inviting them to fill in study questionnaires. (2) Individual letters to GPs asking them to provide data from consenting participants' medical notes. The supplied address and GP data will never be released for analysis; it will only be used for locating participants and their GPs to enable them to be asked if they wish to take part in the 10-year follow-up.


Project 10 — DARS-NIC-302473-K6R0Z

Opt outs honoured: Yes - patient objections upheld (Section 251, Section 251 NHS Act 2006)

Sensitive: Sensitive

When: 2016/04 (or before) — 2019/09.

Repeats: Ongoing

Legal basis: Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Yielded Benefits:

Some of the publications that have arisen from the Embrace study are indicated above. The Embrace study is helping to provide the most reliable information on the cancer risks in BRCA1 and BRCA2 carriers, and the effects of both genetic and lifestyle factors on these risks. Some of these have been clearly established already, in part using EMBRACE study data. These include the effects of SNPs on cancer risk in carriers (Antoniou et al. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet. 2008 Apr;82(4):937-48, Kuchenbaecker KB et al. Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. JNCI 2017:109(7):djw302) and the effects of oral contraceptive use on ovarian cancer risk in carriers (Antoniou et al, Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study. CEBP 2009:18(2):601-10). As noted above, these results influence management guidelines such as the NICE guidelines, and clinical practice through the counselling offer to carriers. For many questions, however (for example providing reliable estimates on the risk of cancers other than breast and ovarian cancer, and the survival from cancer in carriers), much longer term follow-up of carriers to study incidence and mortality will be required. Individuals are identified and recruited at a relative young age but cancer cases and deaths accrue over many years, and it is only with long term follow-up that reliable estimates can be obtained.

Objectives:

Purpose The data supplied by the NHS IC to University of Cambridge will be used only for the approved Medical Research Project identified above.

Expected Benefits:

The results from this study underpin counselling and management of women with a family history of cancer. Management of individuals with a family history of cancer is a major part of the workload of NHS clinical genetics services. The results of the research will guide clinical geneticists and other health professionals in determining the appropriate provision of cancer screening (for example using mammography or MRI), prophylactic surgery or risk reducing medication. In the last 2 years, Embrace has made major contributions to five recently published or soon to be published, papers. The first is a JAMA paper (Kuchenbaecker KB et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA 2017:317(23):2402-2416) that provides the most reliable estimates on cancer risks to women with BRCA1/2 mutations to date. The second paper (in preparation) evaluates the effect of oophorectomy on breast cancer risk in carriers of BRCA1/2 mutations. This could change clinical practice by altering the advice to women on the uptake and timing of risk reducing oophorectomy. A parallel paper examines the effect of oral contraceptive use on breast cancer risk in carriers (Schrijver L et al. JNCI Cancer Spectrum). The fourth important piece of recent work looked at the effect of SNPS on the risk of cancer in BRCA1/2 carriers (Kuchenbaecker KB et al. Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. JNCI 2017:109(7):djw302). This may also influence clinical practice as clinicians incorporate SNP testing into genetic counselling. Clinical implementation studies to evaluate such testing are currently ongoing. This would allow risk reducing surgery or other interventions to be targeted more effectively at those women at the highest risk. Finally, in the largest study of its kind to date, Embrace examined breast and ovarian cancer risks for BRCA1/BRCA2 predictive test negatives (proven non-carriers of the BRCA mutation segregating in their family) and found that they are not at elevated risk of breast or ovarian cancer. There have been conflicting approaches in the clinical management of these women. The results suggest that risk reducing surgeries may not be appropriate in women who are relatives of BRCA1/BRCA2 mutation carriers. In some cases the effects on healthcare are likely to be rapid. In the case of the 2nd and 5th paper for example, dissemination of these findings to clinical practitioners will likely have an immediate effect on practice, though surveys would be required to monitor the extent of the change in behaviour. These findings are also likely to alter guidelines on risk management, namely NICE guidelines e.g. CG164 which form the basis of clinical management of familial cancer risk in the UK (and are also used by many other countries). CG164 is used to direct surveillance protocols in the UK. In the case of the 4th paper, further studies will be required to evaluate the acceptability and impact of SNP testing in carriers, so the impact on healthcare is likely to take longer. In other cases, for example considering the risks of other cancers, any impact is likely to be long term and will require consideration of data from multiple studies. Similarly, the effect of lifestyle or genetic factors on cancer, or non-cancer, mortality, in carriers, will take many years to evaluate. Examples of this are the long-term effects of risk-reducing oophorectomy and of risk reducing medication such as tamoxifen. The outcomes of these analyses could have major implications to health provision in this population. The Mortality data has also been vital to ensure the Embrace study team does not inadvertently contact deceased participants for follow up questionnaires.

Outputs:

Results from the Embrace study will be published in peer-reviewed journals. Multiple publications are expected over the next four years, and beyond subject to funding (the study is currently funded until 2022 but further funding will be sought to continue follow-up beyond that date). More than 70 publications to date have used Embrace data. Due to the continuous nature of the study there will be no “final” results paper: results will be published once sufficient data have been accrued to allow robust statistical analysis. In particular, multiple papers are planned over the next 1-3 years that examine the effects of different risk factors on cancer risk in carriers. Later analyses, however, will require a larger dataset with longer follow-up. Interim reports will be made to our main funding body (Cancer Research UK) on an annual basis. Cancer Research UK has a clear interest in the outputs of the study, and is able to assist in promoting key papers in the media. Important publications are also highlighted on social media. Results from the EMBRACE study are regularly presented at the UK Cancer Genetics Group (CGG) meetings, which is the national forum to assess and implement new findings of clinical relevance - http://www.ukcgg.org. These meetings have a membership of 350 made up of clinicians, counsellors and scientists, including all the clinics already involved in the study. New results and future plans are discussed. The purpose of the CGG is to improve the quality of care of patients and their families with any condition resulting in hereditary tumours. Having frontline clinicians involved in the study and discussing progress with them directly in this fashion helps ensure our findings are communicated to the relevant groups i.e. the genetic counsellors and by extension their patients. The University of Cambridge currently lists some publications on its Embrace study website and will produce simplified summaries of the findings for key papers. The University of Cambridge is committed to open access publications and our publications will be available free of charge. No restrictions are placed on publications and dissemination of results. All outputs will contain only data that are aggregated with small numbers suppressed in line with the HES Analysis Guide.

Processing:

Data are provided to NHS Digital for the purposes of correctly identifying study participants, which allows their incidence and mortality data to be sent to the Embrace study team at the University of Cambridge. Only participants belonging to the retrospective cohort as defined by the study’s section 251 support will be covered by this agreement, and as such no further participant details will need to flow to NHS Digital for this cohort. The University of Cambridge is responsible for ensuring that details of participants recruited subsequently who are not part of the retrospective cohort will not be shared with NHS Digital unless covered by a separate agreement. The data from NHS Digital is downloaded into the Secure Data Hosting System (SDHS) based at the clinical school at the University of Cambridge. This is a distinct area set up to ensure the security of personal identifiable data for studies like Embrace. Only the Embrace study team can access the Embrace data, and only when onsite, using their own two passwords and their physical ‘Signify’ key, which generates a unique third password every minute. Data will only be accessed by individuals within the Embrace study team who have authorisation from the Data Manager and Study Principal Investigator to access the data for the purpose(s) described, all of whom are substantive employees of the University of Cambridge. Internet traffic to and from the SDHS is severely limited, for example an exception had to be applied for to allow access to the NHS Digital site from within the SDHS. The downloaded data are linked to the study data using the artificial identifier supplied to NHS Digital. Cancer incidence data are compared to and stored alongside the information we already hold based on self-reporting, if present. Mortality data are stored separately, but require linking periodically to ensure deceased patients are not contacted by Embrace for follow up. The data are required for a long period as the project is monitoring cancers that may take many years to manifest. Additionally the study aims to analyse the long-term survival from cancer and other diseases, and requires continued access to mortality data. The study is UK wide. The genetic mutations in these genes are uncommon and it is therefore necessary to recruit patients from the whole country to provide an adequately powered study. In addition, without using national data, it would not be possible to guarantee that the dataset would be accurately representative of the mutation carriers and hence the results may not be broadly applicable. Although the main cancers of interest are breast and ovarian certain, analyses need to take account of other cancers (either prior to the start of the study or after recruitment). Other types of cancers have been shown to have a link with BRCA1/2, including prostate and pancreatic cancer. The increasing recruitment base combined with additional years of follow up may reveal more associations. As the project aims to evaluate the full spectrum of cancer risk in carriers, it is necessary to analyse the data on all cancers that occur in the cohort: a filter would remove this valuable information. No data covered under this Data Sharing Agreement will be shared with any third parties outside of the University of Cambridge except in the form of aggregated data with small numbers suppressed in line with the HES Analysis Guide. No data will be used for any purpose other than for the Embrace study as described here. 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data).


Project 11 — DARS-NIC-321968-S4Q6L

Opt outs honoured: Yes - patient objections upheld (Section 251, Section 251 NHS Act 2006)

Sensitive: Sensitive, and Non Sensitive

When: 2016/09 — 2019/09.

Repeats: Ongoing, One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data, Health and Social Care Act 2012 – s261(7), Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients
  • Mental Health Minimum Data Set
  • MRIS - Members and Postings Report
  • Mental Health and Learning Disabilities Data Set
  • Mental Health Services Data Set

Yielded Benefits:

Understanding what the study can do to improve health and prevent disease and disability in ageing populations will have benefits for society and the general public nationally and internationally. Results have already and will continue to contribute to health and clinical policy. Clarification of the mechanisms underlying diseases will enable us to understand pathophysiological processes to support better prevention and treatment, understanding the risk profile for diseases will enable more targeted screening and prevention programmes and understanding and quantifying specific behaviours that influence functional health and healthy ageing will enable us to improve the health experience and quality of life in populations as they age. University of Cambridge (EPIC-Norfolk Investigators) have contributed to national and international (e.g. WHO) clinical and public health guideline panels, Department of Health initiatives, and invited to provide evidence to Select Committees on health issues in the Houses of Parliament. Results from this study have informed Department of Health public health initiatives, NICE and other clinical and public health policies and guidelines. Examples include: Research from EPIC-Norfolk quantifying the association between four health behaviours (not smoking, modest alcohol intake, physical activity and consumption of 5 servings of fruit and vegetable intake) were associated with a 14 year difference in life expectancy. This directly influenced the Department of Health "Small change big difference" national public health campaign launched from Downing Street, underpinned regional initiatives to promote health behaviour change and has been taken up in national guidance. EPIC findings have been reported to meetings contributing European policies on ageing (invited presentations to the European Commission DG Health on Frailty in Old Age 2013) http://ec.europa.eu/dgs/health_consumer/dyna/enews/enews.cfm?al_id=1365 Results from EPIC have contributed to clinical guidelines on screening for osteoporosis using heel ultrasound measures, a low cost and safe feasible assessment ( Lewiecki EM et al, Official Positions for FRAX Bone Mineral Density and FRAX simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom. 2011 Jul-Sep;14(3):226-36). Results from EPIC have also contributed to clinical guidelines on the use of glycated haemoglobin in the diagnosis of diabetes. (RydenL et al, ESC Guidelines on diabetes, prediabetes and cardiovascular diseases in collaboration with the EASD- Summary. Eur Heart J 2013;34: 3035; Anderson T et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidaemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167. In addition general findings from EPIC-Norfolk have informed publications from charities (e.g. Cancer Research UK, British Heart Foundation, Stroke Association, AgeUK) on disease prevention and maintenance of health. According to the Chief Executive of Public Health England (PHE), “Type 2 diabetes is one of the biggest health challenges of our time.” Data from EPIC-Norfolk was used in a large study to show the link between sugar-sweetened beverages and the risk of Type 2 Diabetes. Based on these results, University of Cambridge researchers have engaged with national and international policymakers and media to help shape the way that policy and decision-makers and the public understand and act upon these issues.Researchers have contributed to discussions on sugar reduction that were part of PHE’s Sugar Reduction: Responding to the Challenge document; and provided expert input and reviewed the Parliamentary Office on Science and Technology POSTNote on Sugar and Health. This research was covered by the BBC's 'One Show' ( attracting an audience of over four million viewers), explaining the health impacts of sugary drinks. The EPIC-Norfolk researchers recognise the importance of engagement with media, the general public and policymakers, tailoring the message according to the target audience. The EPIC-Norfolk research team also recognises the value of public engagement and have made this an integral part of its research agenda. The primary objective is to raise awareness and inform the general public (all age ranges) on the high-quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at http://www.srl.cam.ac.uk/epic/publicevents.shtml.

Objectives:

The European Prospective Investigation into Cancer (EPIC) was established to examine the relationship between lifestyle, in particular, diet and physical activity, biological factors and health outcomes. Though EPIC is an international ten country collaboration, co-ordinated by the International Agency for Research into Cancer in Lyon, which is part of World Health Organisation, such that collaborating partners agreed a core protocol for the collection and standardisation of data throughout EPIC, each individual cohort is able to develop specialist areas for investigation. As part of this collaboration, data may be shared with the nine other centres but strictly in anonymised aggregated format. Anonymised data is also shared with other collaborators from recognised academic and research institutions. No identifiable data from HSCIC is processed or stored at any other site or location other than at the Department of Public Health and Primary Care University of Cambridge School of Clinical Medicine, Cambridge. This application relates to the Norfolk component of EPIC (EPIC-Norfolk) and the follow-up on approximately 25,000 men and women aged 40-79 resident in Norfolk at the time of recruitment. The scientific and public health strength of the population cohort is that through routine record linkage, the University of Cambridge are able to follow up the whole cohort who originally participated for health outcomes. Access to data only for the subset that, more than 20 years later are able to provide new signed informed consent will bias the follow up hugely, and make subsequent follow up and results impossible to interpret. The substantial investment of effort by participants over two decades in contributing to this research and increasingly valuable information from long term follow up of the whole population will be lost. Non-fatal disease is an important area of the research and access to linked HES data is essential to analyse this. Many diseases cannot be studied using mortality data alone as the diseases do not cause a death and may only occasionally appear on death certificates. These would include diabetes, eye diseases such as glaucoma, bone diseases such as osteoporosis, frailty and sarcopenia, inflammatory bowel diseases and dementia. Hospital usage is another important area for future research.

Expected Benefits:

The University of Cambridge has already contributed substantially to clinical and health policy guidelines as detailed above. The University of Cambridge anticipates adding to the knowledge to improvements in preventing chronic disease and maintaining good health in later life in the next 5 years. This is a long term study involving a huge amount of data and EPIC has a well-characterised cohort that has been shown to be comparable to the general UK population. EPIC hopes to continue to add to this rich database and further characterise the longitudinal trajectory of the population as it ages and examine determinants of healthy ageing as well as chronic disease. Prevention depends on understanding of causes. We need a much better understanding of the biological mechanisms underlying disease and health; how these are influenced by the environment and what the potential population impact might be. There is increasing evidence for common pathophysiological pathways including glucose metabolism, inflammation, hormonal profile (thyroid and sex hormones) for ageing related conditions. In addition to chronic disease, we need to have a much better understanding of outcomes relevant to older populations such as functional health and quality of life. EPIC-Norfolk is a large long term prospective study that allows this approach. Previous results from the EPIC study have informed Department of Health public health initiatives (2010 ‘Small Change, Big Difference’ campaign), NICE and other clinical and public health policies and guidelines. Findings are also shared through extensive public engagement activities including regular Science Festival events and lectures to general public and charitable groups.

Outputs:

There have been over 1300 peer reviewed scientific publications from this study, with a number of findings making it into news. There are too many publications to list, but can be found at the website at http://www.srl.cam.ac.uk/epic/publications.shtml with news articles found at http://www.srl.cam.ac.uk/epic/news.shtml. Results from this study have informed Department of Health public health initiatives (2010 ‘Small Change, Big Difference’ campaign), NICE and other clinical and public health policies and guidelines. The University of Cambridge also shares results from this study via extensive public engagement activities including regular Science Festival events and lectures to general public and charitable groups. As well as continuing to analyse the data collected so far and publish on the health outcomes covered to date, the University of Cambridge have more recently collected objective data on cognition and hope to gather data on Dementia outcomes. Over 600,000 people in the UK suffer from dementia, costing over £17 billion a year. Dementia is such an important health issue, that the Prime Minister, David Cameron launched a challenge on Dementia on 26 March 2012 in order to speed up the progress in prevention and treatment. The MRC Dementias Platform UK (DPUK), a multi-million pound initiative that was developed and led by the Medical Research Council as part of the activity to meet this challenge. The EPIC-Norfolk study is a partner of DPUK and with the data collected to date and in the follow up planned for 2015-2018, will make EPIC-Norfolk a hugely powerful study of Dementia. The University of Cambridge also plans to use the linkage data to investigate the healthier individuals in the cohort to be able to inform policies on healthy and successful ageing. EPIC-Norfolk is an ongoing longitudinal study. The University of Cambridge received last HES update in 2015. The study continues to use outcome measures from HES data in publications and it is essential for the study to have up to date events for a number of reasons; • Firstly, the statistical power of the analyses depend on the number of known events. Less common outcomes can only be studied with sufficiently long follow-up and event numbers. • Secondly, EPIC-Norfolk has made multiple approaches to the cohort. Each approach is a new baseline and is necessary to have non-fatal events • Thirdly, journals are unwilling to accept publications where the outcomes presented are too old since the missing information may effect the results and their interpretation. Outputs will contain only aggregate level data with small numbers suppressed in line with the HES analysis guide. The University of Cambridge communicate research findings to members of the scientific community through publication in a broad range (both specialist and more general, scientific and medical based) national and international peer-reviewed journals and at national and international conferences. Please find below selected conferences and a list of some the journals that EPIC-Norfolk (plus the international EPIC study or consortia using EPIC-Norfolk data) have published in. Equally important is the dissemination of results outside the research community. The University of Cambridge communicate the results to the research participants via an annual newsletter. A list of recent newsletters can be found on our website at http://www.srl.cam.ac.uk/epic/newsletter_archive.shtml. The EPIC-Norfolk research team also recognises the value and importance of public engagement and have made this an integral part of its research agenda. The primary objective is to inform the general public (all age ranges) on high quality research data collected by the EPIC-Norfolk researchers team relating to diet, lifestyle choices, ageing and health and also to promote awareness of healthy living. The secondary objective is to make science more accessible and better understood in society. A list of public events including activities designed for younger individuals presented at the Cambridge Science Festival for the past few years can be found at http://www.srl.cam.ac.uk/epic/publicevents.shtml. In 2015, the EPIC-Norfolk researchers developed (and continue to manage) a web based system where other researchers taking part in the Cambridge festival could contribute their activities to be catalogued that could then be borrowed by schools and local community group setting. Information on this ‘library’ can be found at http://www.sciencefestival.cam.ac.uk/resources The University of Cambridge also actively promote participant involvement in this research. The University of Cambridge set up an advisory panel in 2010 to act as a consultation group to advise us on the research. The EPIC-Norfolk Participant Advisory Panel (EPAP) has been involved in all aspects of the research project from designing health questionnaires, writing of lay summaries, participant information, dissemination of results and providing a lay perspective on potential projects being considered for the future. The panel met three times in 2015, details of the meetings can be found at http://www.srl.cam.ac.uk/epic/participant_panel_archive_2015.html. Further information on EPAP can be found at http://www.srl.cam.ac.uk/epic/participant_panel.html The University of Cambridge held a public meeting to celebrate 20 years of EPIC-Norfolk research in 2013 . Details of this meeting and the posters presentations can be found at http://www.srl.cam.ac.uk/epic/20yr_meeting.shtml Recent Selected Conferences where EPIC data has been presented 7-9 December 2015 nutrition society winter conference. Oral presentation: "Total (food and supplement) n-3 PUFA intake is associated with lower Coronary Heart Disease mortality, independently of fish intake". March 2015 American Heart Association Scientific sessions Lifestyle and Epidemiology Science Festival Cambridge Institute of Child Health London GP Forum Norfolk May 2015 International society for Atherosclerosis Scientific symposium August 2015 European Society of Cardiology September 2015 European Association for the Study of Diabetes Nordic Epidemiology Conference October 2015 Singapore/Cambridge Scientific symposium November 2015 Netherlands Symposium on dietary saturated fats Cambridge Denmark Symposium 2015 American Heart Association Scientific Sessions on Epidemiology and Lifestyle March 2015 Baltimore USA Plenary invited Lecture on Optimizing Cardiovascular Health: examples from the EPIC-Norfolk study 17th International Symposium on Atherosclerosis May 2015 Amsterdam Invited lectures on • Epidemiology and prevention of Cardiovascular disease • Cardiovascular disease risk prediction Both presenting EPIC-Norfolk data International Society of Cardiovascular Disease Epidemiology and Prevention, seminar Fiji June 2015 Cardiovascular disease Epidemiology and Prevention examples from EPIC-Norfolk Cancer Research UK Researchers Scientific sessions Leeds July 2015 Population Research on Cancer aetiology and prevention: examples from the EPIC Norfolk study Cambridge Science Festival March 12 2015 Cambridge Vitamin D and health –findings from EPIC-Norfolk University College London Institute of child Health March 2015 London Ageing and lifecourse - data from EPIC-Norfolk Poster presentation at the Nutrition Society's Summer Meeting in July 2015 2014 Oslo University Department of Medicine Obesity and genetics – EPIC Norfolk findings Karolinska Institute Stockholm April 2014 Is Ageing modifiable: findings from EPIC-Norfolk CambridgeScience and Policy June 2014 Work shop on ageing – data from EPIC-Norfolk ARVO – Association of Research into Vision and Ophthalmology (also presented 2011, 2012, 2013) American association of Ophthalmologists (also presented in 2012, and 2013) Nutrition Society meetings (also presented in 2007, 2011, 2013,) Cardiovascular Research Trust (2014) 2013 and before Royal College of Ophthalmologists 2013 Faculty of Public Health annual conference 2012 Vision 2020 UK in 2012 Oral presentation at ICDAM 2006 in Copenhagen International Conference of Dietary and Activity Methods (2012 and 2006) Hundreds of manuscripts on EPIC data have been published in journals. The most common journals in which manuscripts have been published are (number indicates number of manuscripts per journal): 109 Int J Cancer 80 Cancer Epidemiol Biomarkers Prev 72 Am J Clin Nutr 61 Eur J Clin Nutr 50 Public Health Nutr 36 Int J Epidemiol 36 Br J Nutr 36 Am J Epidemiol 30 PLoS One 29 Nat Genet 26 Diabetologia 24 Cancer Causes Control 23 Br J Cancer 21 Hum Mol Genet 21 Eur J Epidemiol 20 Carcinogenesis 19 J Natl Cancer Inst There have been many more publications in many other journals.

Processing:

With the permission of the GPs, all patients on their registers born between 01/01/1918 and 31/12/1957 were invited to join EPIC. Those who consented were asked to provide information via questionnaires and undertake health checks. All participants attending the baseline health examination provided signed informed consent at inception of the study agreeing to provide lifestyle and health data and biological samples for this study and access to medical records. Participants provided signed informed consent again for subsequent attendance at follow up examinations in 1997-2005, in 2006-2011 and 2012-present. At each point the University of Cambridge have updated the consent process to be in line with the current guidelines. This included permission for access to medical records. The study has also received approval from the Norfolk and Norwich Ethics committee of each phase as well as clarification of previous permissions to be in line with current standards. EPIC-Norfolk is a flagging study and data form HSCIC (and previously ONS) is restricted to the EPIC-Norfolk participants. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, and cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes. All participants in the study have to date been followed up through routine data linkage for mortality with death certification by cause, and cancer incidence through cancer registration and linkage with hospital records, GP records and other disease registers. This has allowed for the follow up for a large range of health outcomes that are relevant to an ageing population. The data has been subjected to ongoing analysis to determine links between dietary and lifestyle factors and health outcomes. Linkage strengthens the study by allowing the follow up of participants who drop out of the study due to health reasons or death. It also allows the validation of self-reported conditions such as Parkinson's disease, dementia or stroke. Access to death data provides information on mortality but is also used for administrative purposes to prevent inappropriately mailing to participants who have died. Events identified through record linkage will be documented and linked with data collected from individuals on lifestyle so that the University of Cambridge can assess associations between lifestyle and subsequent health outcomes. The University of Cambridge combines mortality data and Hospital Episode Statistics data to define outcomes for fatal and non-fatal incident diseases. For example, the University of Cambridge can define an outcome of heart disease using the same range of ICD 10 codes applied to both fatal events from death certificates and non-fatal events from hospital admissions. Data from HSCIC is processed by a EPIC-Norfolk team within the Department of Public Health and Primary Care University of Cambridge School of Clinical Medicine, Cambridge. Data is not accessed outside the UK. On-going updates of data are necessary for the accurate follow up of participants.


Project 12 — DARS-NIC-34907-D9R3N

Opt outs honoured: Yes - patient objections upheld (Section 251)

Sensitive: Sensitive

When: 2018/10 — 2018/12.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • MRIS - List Cleaning Report

Objectives:

The University of Cambridge, MRC Epidemiology Unit requires a List Cleaning (MRIS) service for the purpose of cross referencing and updating their contacts database with those in the list clean provided by NHS Digital (via MRIS) to ensure University of Cambridge participant records are up to date and to allow follow-up of participants who have moved since last follow-up. It is estimated that 1 in 16 UK adults has (diagnosed or undiagnosed) type 2 diabetes, and this creates a substantial burden of suffering and health service use. Treatment of type 2 diabetes and related complications (cardiovascular disease, amputation, blindness, kidney failure) accounts for 10% of the NHS budget. This is expected to rise as the number of people in the UK who have type 2 diabetes is estimated to rise to 6.25 million by 2035. For background; the ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care) Plus study is a randomised controlled trial (i.e. an equal chance of being selected in the control group or intervention group) to see if changes in behaviour (physical activity, diet, smoking and adherence to medication) can be achieved among individuals recently diagnosed with type 2 diabetes via an intervention delivered by facilitators trained in behaviour change theory and techniques, and whether behaviour change is associated with reductions in risk factors for cardiovascular disease. Approximately 36,000 people in or near Cambridge were invited to screening (the ADDITION-Cambridge screening cohort, NIC-147750-8GS7S/MR798). Of these, 867 were diagnosed with diabetes as a result of screening (the ADDITION-Cambridge main cohort, NIC-28744-S4F8/MR1406). 239 of the participants from the ADDITION-Cambridge main cohort were included in a sub-study called ADDITION-plus. These participants were list cleaned under NIC-28744-S4F8 (v1.2 approved 01/08/2016) 239 extra, new participants were also recruited for ADDITION-plus. This Data Sharing Agreement covers a list clean for the extra, new 239 participants. This study aims to collect 10 year follow up information on cardiovascular events (such as heart attacks and strokes) and cardiovascular risk factors, treatment and mortality for the cohort of 239 participants of the ADDITION Plus study who enrolled in the UK. This will allow an assessment of the long term effects of the differences in behaviours and intensity of treatment achieved during the first five years after diagnosis. This MRIS list clean is needed to complete 10-year follow-up of this cohort with as high a follow-up rate as possible, in order to inform the management of newly diagnosed patients and to establish the size and nature of the benefits of detecting and treating diabetes earlier, and of changes in behaviour following diagnosis. Ten year follow-up of the trial participants will add to the existing research base concerning early treatment of type 2 diabetes and inform NHS policy decisions. The data within the NHS Digital list clean will not be shared with any other entity and will only be used for the purpose stated above. Section 251 support has been granted to permit the study to obtain up to date address details for all participants in order to inform them of the 10 year follow up (and if they wish, speak to the study team about the study); invite them to fill in questionnaires, and to update the study team of their current GP practice in order to complete the follow up. Participants originally consented to take part in the ADDITION plus study, including access to medical records, at the point of enrolment and again at 5 year follow up. All participants who have not withdrawn to date will be written to to inform them of this wave of data collection and ask them to complete a self-report questionnaire. Information will also be provided on how participants can opt out. Prior to sending any questionnaires, the participant list will be cross-checked with the list clean update provided by NHS Digital to minimise the risk of sending questionnaires to participants who are deceased.

Expected Benefits:

The primary benefits of using NHS Digital’s List Cleaning service are that it enables ADDITION-Plus to continue to collect information about its participants fairly and transparently giving participants the option to withdraw should they wish and mitigates the risk of attempting to contact deceased participants and potentially causing distress to living relatives. It is estimated that 1 in 16 UK adults has (diagnosed or undiagnosed) type 2 diabetes, and this creates a substantial burden of suffering and health service use. Treatment of type 2 diabetes and related complications (cardiovascular disease, amputation, blindness, kidney failure) accounts for 10% of the NHS budget. This is expected to rise as the number of people in the UK who have type 2 diabetes is estimated to rise to 6.25 million by 2035. The ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care) Plus study is a randomised controlled trial (i.e. an equal chance of being selected in the control group or intervention group) to see if changes in behaviour (physical activity, diet, smoking and adherence to medication) can be achieved among individuals recently diagnosed with type 2 diabetes via an intervention delivered by facilitators trained in behaviour change theory and techniques, and whether behaviour change is associated with reductions in risk factors for cardiovascular disease. All participants were receiving intensive multifactorial treatment (i.e. treating several conditions all at once) as part of the parent trial (ADDITION) and half were randomised to also receive the behavioural intervention. The initial trial included follow-up at one and five years incorporating self-report and objective assessment of four behavioural outcomes (physical activity, diet, smoking and medication adherence) and cardiovascular risk factors. The lifestyle intervention did not improve modelled (i.e. predicted) cardiovascular risk, but it did improve functional status and health utility. These latter variables as well as acquired skills and knowledge relating to behaviour change could have implications for longer-term cost-effectiveness. Ten-year follow up of the ADDITION-Plus trial will establish the longer-term effectiveness and cost-effectiveness of delivering a behavioural intervention among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. It will also allow the University to evaluate the impact of this intervention on cardiovascular endpoints (such as heart attacks and strokes, as well as mortality) which were not previously captured. These data would also provide a unique opportunity to investigate the association between changes in objectively measured behaviours in the first five years after diagnosis and cardiovascular outcomes over ten years, and to estimate the amount of behavioural change that interventions need to achieve to have a significant impact on cardiovascular outcomes. ADDITION Plus investigators contribute to the organisation and delivery of diabetes care both locally and nationally (e.g. guideline development, managed care networks, expert review group for diabetes QOF indicators, National Screening Committee Advisory Group, NICE committees, NHS Health Checks advisory panel, Diabetes Prevention Programme advisory panel) and therefore have established mechanisms for influencing policy and practice in these and related fields. Results from this study will help inform care early in the course of the disease.

Outputs:

The primary output from the list clean will be that the University of Cambridge's contacts database will be updated to ensure that information regarding the study is sent to the correct address of participants and that information is not addressed to any individuals who have died, causing distress and upset to family members. Ultimately, this will facilitate contact with living participants to enable the data collection described which will then lead to the outputs detailed below. The ADDITION-Plus study has so far led to the publication of 10 papers in peer-reviewed scientific journals. Data from ADDITION-Plus has also contributed to 5 PhD theses. The primary analysis of 1-year outcomes was published in Diabetologia (Griffin et al. (2014) Diabetologia, 57, 1308-19). The results of the 5-year analysis have been submitted for publication. Analysis of the 10-year data will be submitted to a similar leading medical journal. Throughout 2017, secondary analyses and mechanistic analyses will be submitted for publication to leading medical or disease-specific peer-reviewed journals. All publications will be open access, in line with the University of Cambridge open-access policy, and can be accessed by clinicians, academics, policy makers and interested members of the public. Outputs presented and/or reported will contain aggregate level data with small numbers supressed in line with the HES analysis guide. No personal identifiable data will be released or published. Findings will also be used to advise policy makers on the cost-effectiveness of adding lifestyle intervention to treatment packages for people who are newly diagnosed with diabetes, and the level of behavioural change that is associated with reduction in risk of cardiovascular outcomes. When the study is completed, meta-data will be added to the online data dictionary http://epi meta.medschl.cam.ac.uk/includes/add/add.html. Bonafide researchers can then apply to access the anonymised data set to conduct their own secondary analyses subject to the terms of the MRC Data Sharing Policy http://epi-meta.medschl.cam.ac.uk/data_sharing_policy.html and appropriate collaborative/data sharing agreements. The University of Cambridge will also send all ADDITION Plus participants a summary of the results in the form of a newsletter.

Processing:

The University of Cambridge will submit a file containing the identifiers of the 239 participants recruited to NHS Digital using its secure electronic file transfer system. This will include: STUDY_ID NHS number Date of Birth Sex Postcode NHS Digital will link the identifiers to its copy of MRIS data and produce an output file containing the latest name, NHS number, GP practice code, address and postcode, date of birth and, where applicable, date of death for each participant. The data will be downloaded at the University of Cambridge’s MRC Epidemiology Unit and transferred immediately to an independent, physically-separated network that is isolated from public network systems and can only be accessed locally, with a managed access system including both password and procedural controls. Access to this network must be approved by both local senior management and the ADDITION Plus study CI. All study team members accessing the data have a contract with the Unit. The updated participant address and GP details will be used to re-contact participants who were lost to follow up, and to contact their registered GP surgery to enable collection of recent endpoint and clinical measures. Where NHS Digital data identifies changed contact details for participants, the data will leave the MRC Epidemiology Unit in one of two ways: (a) Individual letters addressed to participants informing them of the 10-year follow-up process, reminding them of their right to withdraw from the study, providing them with an up to date study Participant Information Sheet, and inviting them to fill in study questionnaires. Data shared in this way will necessarily involve sharing the participant’s name and address, but will not include any other data from NHS Digital, nor will the letters include linkage to any other study data. (b) Individual letters to GP's asking them to provide data from relevant consenting participants' medical notes. Data shared in this way must be sufficient to allow the GP surgery to identify the correct person, but will be limited to the participant’s name, date of birth, and NHS number. The letters will not include any other study data. Address and GP details will be linked to University of Cambridge's existing contact records via pseudonymised study identifier. The address and GP data supplied by NHS Digital will never be released for analysis; it will only be used for locating participants and their GP's to enable them to be asked if they wish to take part in the 10-year follow-up, or to opt out. Personal identifiable data provided for this purpose will be stored on a physically separate server in the Unit offices and can only be accessed and used on site by those who have permission within the research team. Other than this contact with individual participants who were previously lost to follow-up and their GP's, no personal identifiable data will be used by or given to any other third party, and no record-level data will be shared outside the Unit. NHS Digital reminds all organisations party to this agreement of the need to 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data)


Project 13 — DARS-NIC-38314-C3P0Z

Opt outs honoured: No - consent provided by participants of research study (Reasonable Expectation, Consent (Reasonable Expectation))

Sensitive: Non Sensitive

When: 2018/03 — 2019/01.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(2)(c)

Categories: Identifiable

Datasets:

  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

Cancer of the stomach or oesophagus (gullet) or at the junction between the oesophagus and the stomach (Oesophageal and junctional adenocarcinomas (OAC)) have a poor prognosis and survival rate and in contrast to other cancers, knowledge of the molecular pathogenesis of the disease has not yet been used to determine prognosis and therapy. Cambridge University and the Cambridge University Hospitals NHS Foundation Trust require ONS mortality data for use in the Oesophageal cancer clinical and molecular stratification (OCCAMS) research study. The study is funded by Cancer Research UK and has been running since 2010. It was instigated by Cambridge University in collaboration with Cambridge University Hospitals NHS Foundation Trust. OCCAMS is a large multisite observational study involving over 15 NHS hospital trusts in the UK and it has been adopted on the National Institute for Health Research’s portfolio of high-quality research studies. Recruitment to the study and data collection will be complete in 2020. The main focus of the OCCAMS study is to develop a model that can be used to better assess therapeutic options for future patients with this specific condition. A key aim is identifying markers that indicate the likely pathway and rate of progression of the condition in individuals so that care plans can be appropriately tailored. The aims of the OCCAMS study are to: Better characterise the clinico-demographic risk factors; Characterise the molecular genetic landscape (DNA, RNA, epigenome); Determine disease sub-types and develop new clinically relevant classification systems; Develop and validate improved clinical staging and prognostic algorithms; Ascertain new therapeutic targets for future research Mortality data is required in order to complete the clinical research records collected from the participating NHS hospital trusts. It gives a vital end point. Understanding how long a participant has lived with the disease and the particular nature of their condition will allow the research team to better understand the progression of the disease. With a poor prognosis, the patient group is likely to move into palliative pathway and die in the community including in hospices and at home. As such, the recording of death is less likely to be part of the original hospital record supplied by the participating hospital trusts. Full date of death is required as these patients' prognosis is measured in months. If only the month and year of death were provided, it would make survival data inaccurate (+/- 4 weeks is a very long period for these patients), rendering this dataset less valuable and rich for research purposes. This study aims to maximise specificity in order to achieve clear and robust outcomes. Where deaths are recorded in the hospital record, the study will have access to full date of death supplied by the NHS hospital trusts so receiving equivalent data from NHS Digital will enable consistency in analyses.

Expected Benefits:

The outcomes of this study are expected to directly benefit patients by improving the understanding of this poorly-understood disease to enable earlier detection and determination of the likely severity and rates of progression so that more appropriately personalised medicines and treatment plans can be prescribed. This will also improve awareness for patients so they can better understand their pathway so that their own expectations and those of their families can be appropriately managed. The current knowledge base for this cancer type is particularly small and patients’ outcomes not often analysed on an aggregate level. This study will perform one of the first analyses of prognosis and mortality on a cohort of this size. The release of mortality data will enhance the existing efforts to fully categorise Oesophageal cancer and understand the different prognosis and pathway of patients with particular clinical and genomic characteristics. One aim and potential benefit if successful is to understand how an individual’s genetic profile determines whether they will be respond to particular treatment or which sub-category of cancer type (and prognosis) they fall in to. The analysis and publication of the findings are expected to pave the way for more effective strategies including earlier detection of cancer or more targeted, personalised treatment approaches providing benefits to individuals, health care services and society in general. In future, alternative cancer treatments and diagnostics will benefit from the increased knowledge base that the research team expect to develop through the ONS dataset to allow further research teams to develop new treatment trials. One such treatment trial already linked in to OCCAMS is Neo-AEGIS, led by Plymouth which is trialling different approaches to chemotherapy in treatment. The findings of this study and associated clinical trials, which will include information on differentiating more aggressive cancers from less aggressive cancers as well as biomarkers for earlier detection will be widely disseminated on an international scale to maximise the impact and benefits to patients and patient care. The aim is also to feed into NICE guidelines via publications, recommendations from key advisory bodies, and stakeholder consultations. OCCAMS additionally convey information to current patients in follow up, meeting up with patients regularly at clinics and giving feedback about study progress and recruitment. This keeps the patients motivated and also lets them know how valuable their contribution is. New patients are also very keen to know details of how current samples and data are progressing the study towards improving knowledge and treatment options and developing new trials. At no point in this process would specific information about another patient be given to anyone else, and no information from NHS Digital be shared with anyone else. NHS Digital data will not be shared with associated clinical trials or any other third party, except in aggregate form with small numbers suppressed.

Outputs:

The OCCAMS research team regularly publish findings relating to their studies about oesophageal cancer in high profile journals such as ‘Nature Genetics’ and the ‘British Medical Journal’. The most recent publication was a paper on ‘Mutational signatures in oesophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance’ published in ‘Nature Genetics’ in September 2016. This paper proposed a framework to classify types of oesophageal cancer by genomic profile. To date, 5 papers have been published as a direct result of the study and over 20 from closely-linked research projects. Findings from the analyses of the ONS data will supplement existing data areas as well as allowing the team to test further certain correlations between what is affecting prognosis and length of time that a participant is living with the disease and clinical and genomic characteristics of the individual. A mortality-related paper will be submitted to journals such as ‘Nature Genetics’ and the ‘British Medical Journal’. This is expected by December 2021. This is beyond the end date of the OCCAMS research project as there is necessarily some time needed between the last patient enrolled and the final processing being finished. Please note that OCCAMS clinical trial is a single research project that will solely have access to data provided by NHS Digital. It is one of the largest cohort studies of its kind, and is invaluable for increasing/improving the knowledge base for oesophageal cancer. This project is not done in a vacuum, however: the OCCAMS research team have additional projects that will look at the end results of this work, but no data provided by NHS Digital will be shared with other studies. Any outputs from the OCCAMS trial will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. The OCCAMS dataset is being continually expanded as hospitals continue to enrol patients and submit findings. As more information is amassed, it enables re-examination of previous findings but also new depths of analysis. For example, increasing evidence makes it possible to identify groups of patients with common characteristics that can be studied. As a consequence, the exact subjects of future studies and publications is unknown from the outset. However, it is expected that papers will continue to be written and published and the study disseminates findings regularly through conferences presentations in the UK and internationally where experts in the field will meet to discuss the latest developments in classification of cancer through genomics and treatment/diagnosis innovations. The Principal Investigator is actively working to use evidence from the study to make recommendations on how treatments are planned and delivered based on specific indicators. Specifically: - Developing algorithms to reduce diagnostic delay - Developing trials to evaluate precision treatment based on the molecular make-up of the tumour matched with treatment response and outcome - Developing standardised reporting tools in oesophageal cancer for endoscopy, surgery and pathology through evaluation of geographical variation in data collected in this UK wide study The outcomes of the OCCAMS clinical trial will be used in corroborating findings and showing evidence of the benefits of new treatment pathways and early detection to evidence best practice; this will be shared directly with NICE. (No patient-level data will be shared with any other party, solely research result and generic findings.) The ultimate aim is to influence the NICE guidelines which determine best practice for GPs and doctors via publications, recommendations from key advisory bodies, and stakeholder consultations. Recruitment and data collection is expected to continue until 2020 and numerous outputs, in line with those described above, are expected over the course of the study. Findings will be fed back directly to collaborating hospitals. As is common in research, depending on findings, there may be appropriate media attention to this work. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Processing:

Data supplied by participating trusts The NHS hospital trusts identify and recruit eligible participants and provide details of the participants (including biological samples and person identifiable data) to the Cambridge University Hospitals NHS Foundation Trust. The samples are labelled with a unique patient ID, and Cambridge University performs laboratory tests on the anonymised samples. NHS Digital data Access and storage The Cambridge University Hospitals NHS Foundation Trust will provide to NHS Digital a list of participants’ identifiers (specifically name, sex, date of birth and NHS number plus unique OCCAMS ID). NHS Digital will provide quarterly cohort event notification and Cause of Death reports (including date of death) for all deceased participants. This data will only be stored at the Cambridge University Hospitals NHS Foundation Trust. The date and cause of death data will only be accessed by individuals within the Upper GI trials office at the Cambridge University Hospitals NHS Foundation Trust who have authorisation from the Clinical Study Coordinator to access the data for the purpose(s) described, all of whom are substantive employees of the Cambridge University Hospitals NHS Foundation Trust or Cambridge University. Processing Mortality data will be linked and analysed in conjunction with data acquired from the participating trusts and derived from analysing the samples. The mortality data will provide additional intelligence to analyses already being undertaken. This data provides the outcome and indicates effectiveness of treatment each patient received. Analysts at the Cambridge University Hospitals NHS Foundation Trust will have access to the minimum amount of personal data necessary to perform their analyses including full date of birth and date of death, as well as cause of death. OCCAMS is an independent clinical trial , although it is expected that findings from OCCAMS trial will pave the way for future research in this area. The data will not be made available to any third parties except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.


Project 14 — DARS-NIC-43771-N0W3Q

Opt outs honoured: Yes - patient objections upheld

Sensitive: Sensitive

When: 2017/09 — 2019/09.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, National Health Service Act 2006 - s251 - 'Control of patient information'.

Categories: Identifiable

Datasets:

  • MRIS - List Cleaning Report

Objectives:

The objective of the current data request is to obtain current address, GP information and mortality data for participants of the Fenland study to enable the University of Cambridge to invite appropriately to phase 2 of the study. Without up-to-date contact information from NHS Digital a significant proportion of participants will not be notified of the opportunity to take part in phase 2. Maintaining a high retention rate to the study will ensure the continued quality of the University of Cambridge research outputs in terms of completeness of follow up and ability to generalise to the wider population. Mortality data will enable the University of Cambridge to avoid attempting contact with deceased participants and therefore prevent unnecessary distress for relatives. The Fenland study began in 2005 and is funded by the Medical Research Council through its block grant to the University of Cambridge to support the MRC Epidemiology Unit. The study aims to investigate the interaction between genetic and lifestyle factors in determining obesity, diabetes and related metabolic disorders which present a considerable public health concern. The University of Cambridge recruited 12,435 participants from general practices across Cambridgeshire to phase 1 of the study. All attended a baseline visit and provided information on their health-related behaviours, past and current medical conditions and family history. They also participated in objective assessment of body composition, cardio-respiratory fitness and physical activity. They provided blood samples to determine blood glucose and blood fat (such as cholesterol) levels, and for further research aimed at understanding the cause of diabetes and related disorders. In phase 2 of the study the University of Cambridge will re-approach the same cohort of participants to invite them to re-attend for screening with the same battery of tests. This will provide information on the change in quantitative metabolic-related behaviours and health status over time and allow longitudinal investigation of the determinants of change. Finally, the assembly of information at the individual and collective level will permit investigations into the relative importance of different factors that drive key lifestyle behaviours.

Expected Benefits:

The Fenland study has a number of outputs that have significantly impacted on health policy and have provided important evidence for NHS commissioners in the priority area of type 2 diabetes. In March 2015 a Fenland study professor delivered an expert testimony on the impact of physical activity and diet on health at the House of Commons Select Committee inquiry looking at the most effective way of conveying healthy eating and drinking to the public in order to achieve a more healthy weight, and evidence of the impact of physical activity on health, including its impact independent of weight. A summary of the written evidence submitted, which used data from the Fenland study is available here: http://www.cedar.iph.cam.ac.uk/wp-content/uploads/2014/04/HoC-Health-Diet-and-PA-Dec14-PHYSICAL-ACTIVITY-from-MRC-Epid-CEDAR.pdf The Fenland cohort was also used to examine the association between density of takeaway food outlets at home, at work, as well as along commuting routes from home to work. We found that takeaway exposure was associated with increased takeaway consumption and was strongly associated with a greater Body Mass Index (BMI). This research has influenced the NICE diet recommendations, which has recommendations for strategy, policy and commissioning for local authorites: http://pathways.nice.org.uk/pathways/diet Continued longitudinal follow up of the Fenland study will provide information on the change in quantitative metabolic risk factors over time, an important aspect not covered by the single snapshot we have of participants at the moment. The Fenland team is committed to continue to influence health policy and have a significant benefit to public health.

Outputs:

The primary output form this application will be an updated cohort contact database, which will allow the Fenland study to invite participants appropriately to phase 2 of the study. This follow-up study will enable important aetiological investigations into the causes of common metabolic disease, including the interplay between genetic and environmental risk factors. By studying the determinants of lifestyle behaviour change in mid-life, it will also contribute to the translation of that aetiological understanding into preventive action. The University of Cambridge are also keen to ensure participants are updated of their findings and have recently run a second series of opening evenings in a number of local areas. In summer 2016 the University of Cambridge held a series of public meetings for Fenland Study volunteers, to provide an opportunity to hear about progress so far, key scientific findings and plans for future. More than 550 people attended the three meetings, which comprised of a short presentation from Fenland Chief Investigator, followed by a longer panel discussion with Fenland researchers, who answered questions from the audience about the study, its’ findings, and their implications for public health policy and practice. These panel discussions were very lively, with many excellent questions from audience members. Feedback from the meetings was collected on paper forms with free-text space available for attendees to add comments. Participant responses have been overwhelmingly positive, with most keen to return for a second visit as they benefit from a free comprehensive ‘health check’ of sorts and see the research we are producing is relevant and high impact. Completion of phase 2 is expected by 2019. Fenland data has already led to a number of publications in leading peer reviewed journals, as listed on the University of Cambridge webpage: http://www.mrc-epid.cam.ac.uk/research/studies/fenland/fenland-publications/ The MRC Epidemiology Unit is committed to building clinical and public health pathways for the application of their work. Examples of their outputs include: · Research regularly receives national and international press coverage. Many of our news stories have direct relevance to practice and policy: www.mrc-epid.cam.ac.uk/news · The majority of scientific publications are Open Access: www.mrc-epid.cam.ac.uk/research/research-papers. CEDAR publications can also be searched at www.cedar.iph.cam.ac.uk/publications/ · Evidence Briefs and data visualisations (http://www.cedar.iph.cam.ac.uk/resources/evidence/-) . Succinct summaries of research findings for policymakers and practitioners, developed in collaboration with our partners. · Evidence submissions (http://www.cedar.iph.cam.ac.uk/resources/evidence-submissions/ )to policy bodies and guidance producing organisations. The Fenland study cohort is a unique in the scale and depth of phenotyping and constitutes a significant resource to researchers investigating questions important to the management and prevention of diabetes. Follow up of this cohort (completion of phase 2) will collect longitudinal data on key risk factors and continuous metabolic traits, in order to define the temporal and dynamic relationships between these exposures and changes in metabolism, which are currently limited by the cross-sectional nature of Fenland 1.

Processing:

Data will be sent securely to NHS Digital using encryption software as instructed by NHS Digital. Data received from NHS Digital will be downloaded at the MRC Epidemiology Unit and transferred immediately to an independent, physically-separated network that is isolated from public network systems and can only be accessed locally, with a managed access system including both password and procedural controls. Access to this network must be approved by both local senior management and the Fenland study CI. MRC Epidemiology data security processes are compliant with the MRC Information Security Policy and are also aligned with ISO 27001. The Unit has a System Level Security Policy (SLSP) which applies to all studies and has been approved by the National Information Governance Board (NIGB, prior to its replacement). The standard that the Unit works to is also recognised as being equivalent to the University of Cambridge Clinical School Information Security Policy. All persons accessing the data are substantive employees of the University of Cambridge. NHS Digital address will be used to contact participants who were lost to follow up. Where NHS Digital data identifies changed contact details for participants, NHS Digital data will leave the MRC Epidemiology Unit through individual letters addressed to participants inviting them to participate in phase 2 of the Fenland study. GP practice code is required as participants were originally recruited through their GP practices and the University of Cambridge therefore keep GPs informed of their patient’s involvement in the study and feedback clinical results (such as blood pressure, blood test results) where participants have consented to this. The University of Cambridge also highlight abnormal results (for example a blood result indicating diabetes) with the participant’s GPs so it is important to have current information on where they are registered for their continued care. NHS Digital address and GP data will never be released for analysis; it will only be used for locating participants and their GPs to ask them to take part in follow-up. Fact of death will be used to cross reference with the University of Cambridge's mailing list to exclude participants who are deceased from further contact. Where NHS Digital are unable to find a positive data match to records from the cohort the study will remove these participants from the study and they will therefore not be re-contacted or invited to take part in the second phase of the study.