NHS Digital Data Release Register - reformatted

University of Bristol

Project 1 — DARS-NIC-119910-K6W9Q

Opt outs honoured: N

Sensitive: Non Sensitive, and Sensitive

When: 2017/09 — 2018/09. breached contract — audit report.

Repeats: One-Off, Ongoing

Legal basis: Health and Social Care Act 2012, 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: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Outpatients
  • Diagnostic Imaging Dataset
  • Bridge file: Hospital Episode Statistics to Diagnostic Imaging Dataset
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

Cluster randomised trial of testing for Prostate cancer (CAP) is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based Prostate Specific Antigen (PSA)-testing for prostate cancer (intervention arm) with standard NHS care (control arm) amongst men aged 50 to 69 years registered with GP practices in eight centres in England and Wales. Recruitment to the DH/CRUK-funded CAP trial was completed in 2009 and it is currently in the follow-up phase. Over 415,000 men are being followed-up for incident and fatal prostate cancer via NHS Digital. Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage to estimate the cost effectiveness of prostate cancer screening in the UK CAP are applying for permission to perform record linkage for all 415,000 men in the CAP trial with NHS Digital for the provision of resource use information.

Expected Benefits:

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources). The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer. Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the team’s randomised trials. This research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits, and saved the UK economy. The median 10 years follow-up will be reached in 2016 and it is anticipated that the first publication will report these results as soon as possible following this, the University would nevertheless wish to apply for additional funding for longer term follow–up. The dataset already held by SAIL has been used to develop the STATA do files, and confirmed the feasibility of extracting unbiased health-related costs for comparison across the two groups.

Outputs:

CAP plan to publish median 10 year results in The New England Journal of Medicine (NEJM) or The Journal of the American Medical Association (JAMA). A statistical analysis plan detailing the analyses that will be included in the publications has been uploaded onto the University of Bristol research information repository (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1). Statistics involved in these papers usually refer to measures such as rate ratios and 95% confidence intervals rather than actual numbers of cases. CAP will follow ONS non-disclosure rules for small numbers of cases and will not include any counts of less than 5 in a Table. As stated above the median 10 years follow-up will be reached in 2016, the applicant would nevertheless wish to apply for additional funding for longer term follow–up. As stated above the primary outcome is reached at a median 10 years follow up in 2016 there are however a number of recent publications directly related to the study, listed below: Williams NJ, Hill EM, Ng SY, Martin RM, Metcalfe C, Donovan JL, Evans S, Hughes LJ, Davies CF, Hamdy FC, Neal DE, Turner EL, for the CAP Cause of Death Committee. Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer). BMC Medical Research Methodology (2015) 15:6 (doi:10.1186/1471-2288-15-6) Turner EL, Metcalfe C, Donovan JL, Noble S, Sterne JAC, Lane A, Avery K, Down L, Walsh E, Davis M, Ben-Shlomo Y, Oliver S, Evans S, Brindle P, Williams N, Hughes LJ, Hill E, Davies C, Ng SY, Neal DE, Hamdy FC, Martin RM. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). British Journal of Cancer (2014) 110; 2829-36 (doi: 10.1038/bjc.2014.242) Lane JA, Donovan JL, Davis M, Walsh E, Dedman D, Down L, Turner EL, Mason MD, Metcalfe C, Peters TJ, Martin RM, Neal DE, Hamdy FC, for the ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncology (2014) 15: 1109-18 (http://dx.doi.org/10.1016/ S1470-2045(14)70361-4) Hill EM, Turner EL, Martin RM & Donovan JL. "Let's get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study. BMC Medical Research Methodology (2013) 13:72 (doi: 10.1186/1471-2288-13-72) Williams NJ, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, Martin RM, Metcalfe C. Prostate-specific antigen testing rates remain low in UK general practice: A cross-sectional study in six English cities. British Journal of Urology International (2011) 108:9; 1402-08 (doi:10.1111/j.1464-410X.2011.10163.x) Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies. European Journal of Cancer (2010) 46; 3095-3101 (doi:10.1016/j.ejca.2010.09.016) Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as NICE or the Cochrane Centre will also be informed. The papers will be available on the University of Bristol PURE pages https://research-information.bris.ac.uk/ - these publications are available to download with open access allowing anyone to access publications. We also publish with open access rights when submitting to journals, ensuring we maintain CRUKs publication ethos of ensuring research funded by them is available to all. Publications are also uploaded to 'researchfish' allowing the research community to clearly see what has been published.

Processing:

In this renewal request, the linked HES data would be accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data and can never be linked to it. Processing steps - 1.NHS Digital will utilise the identifier (unique study ID) for MR738A and link these data from the HES dataset held at NHS Digital. The HES data extract and unique study ID for the cohort will be sent to SAIL by NHS Digital. 2.The applicant will transfer a study ID and the following primary and secondary mortality outcome variables to SAIL: month and year of birth; date of prostate cancer diagnosis; prostate cancer stage and grade, if present; month and year of death, if deceased; prostate cancer attributed death, if deceased; date of censor, if no longer in follow up; month and year of censor. 3.SAIL will then link these data to the HES extract from NHS Digital. SAIL will also encrypt the unique study ID to create a unique pseudo anonymised ID number for each individual, area identifiers will also be pseudonymised HES data will be used to identify all inpatient and outpatient resources used by men in CAP. Costs will be assigned to the identified events and used alongside the linked outcome data to conduct the CAP cost-effectiveness analysis from the perspective of the UK NHS (secondary care). This dataset will be remotely accessed from Bristol for analysis and only aggregated results tables (verified by SAIL to be unidentifiable) would be extracted from the dataset. Only individuals substantively employed by the University of Bristol will have access to the data. All processing of ONS data will be in line with standard ONS terms and conditions. All outputs will be restricted to aggregate data with small numbers suppressed in line with the HES Analysis Guide. The funding organisation, CRUK, has confirmed in writing that it agrees that no NHS Digital data will be shared with it or with 3rd parties, and that in the unlikely event that they would wish to share the data they would direct any request through NHS Digital.


Project 2 — DARS-NIC-13133-B7B3K

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

Sensitive: Sensitive, and Non Sensitive

When: 2018/06 — 2018/12. breached contract — audit report.

Repeats: One-Off, Ongoing

Legal basis: Health and Social Care Act 2012 – s261(2)(c)

Categories: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Mental Health Minimum Data Set
  • Hospital Episode Statistics Accident and Emergency
  • Mental Health and Learning Disabilities Data Set
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Outpatients
  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Yielded Benefits:

There have been >2,000 articles published using ALSPAC data; details of these can be found on the ALSPAC study website. A lay summary of some of the key ALSPAC findings is available here: http://www.nature.com/news/children-of-the-90s-coming-of-age-1.10396 Notable examples of how ALSPAC findings have informed health and social policy include the following: (i) providing evidence to help persuade policy makers to support the ‘back to sleep’ policy change. This campaign started in the UK prior to ALSPAC's initiation, and initially advised parents not to place their babies to sleep in the prone position to reduce the risk of cot death. ALSPAC reassured sceptical health professionals and policy makers to proceed to recommending the supine position by demonstrating that this position was not associated with factors detrimental to child health.This finding also helped to persuade the US National Institutes of Health to carry out their own ‘Back to Sleep’ campaign that started in 2004. (ii) The finding that the application of skin creams containing peanut oil as a base ingredient to broken skin sensitized children to peanut allergy has led to some manufacturers altering the composition of the creams and the Committee on Safety in Medicines recommending that warning labels be included on all medicinal products containing peanut oil. (iii) ALSPAC has contributed to the debate on the consumption of fish during pregnancy. Established advice in the UK and USA was that on balance the risks of consuming toxins while eating more than two portions of fish per week outweighed the known benefits of eating fish. ALSPAC findings have influenced UK and US guidelines concerning fish consumption in pregnancy by demonstrating that benefits to child behaviour and verbal IQ, early development and visual stereoacuity outweigh potential harm of neurotoxicity from mercury and other sources of contamination. (iv) Evidence from ALSPAC including the influence of socio-economic position on life chances and aspirations were used to support the Independent Review on Poverty and Life Chances by Frank Field MP ‘The Foundation Years: Preventing Poor Children becoming Poor Adults’ and the Marmot Review Fair Society, Healthy Lives. Genetic investigations using the candidate approach to studying gene variation and phenotypic outcome have described the influence of the filaggrin gene (FLG) on child susceptibility to atopic eczema and asthma. ALSPAC was the largest follow-up sample in the discovery that variation at the FTO gene is associated with increased adiposity and predisposition to obesity; using DXA assessment measures ALSPAC showed that the association was only present for fat mass and not lean mass. ALSPAC holds DNA collected at multiple time points, allowing researchers to explore DNA methylation and epigenetics. To realize the full potential of the resource ALSPAC is involved in genetic consortium studies including UK10K and EGG (early growth genetics). Environmental studies have explored the antecedents of asthma where environmental exposures including prenatal maternal anxiety and paracetamol use, exposure to a range of cleaning products and excessive hygiene regimes have been found to influence the development of asthma in the child. Analysis of early life influences including maternal age, diet and smoking do not appear to influence blood pressure in the child although maternal weight gain in pregnancy is associated with increased risk of child adiposity and adverse cardiovascular risk factors. ALSPAC has also shown that fat mass contributes to higher bone mineral density. Full references available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600618/

Objectives:

Background The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective birth cohort study that recruited women during pregnancy in the early 1990s. ALSPAC is designed to investigate influences on health, wellbeing and development across the life course. To inform these investigations ALSPAC collects information on genetic, epigenetic, biological, psychological, social and environmental exposures and a similar range of health, social and developmental outcomes. ALSPACs primary objective is to manage a long-term relationship with the study families and through this to build a DataBank resource that can be used to inform the investigation of diverse health and social hypotheses across the life course. To achieve this objective, data are collected through postal questionnaires, study clinical assessments, the collection of biological samples and through linkage to routinely collected health and social administrative records (including those held by the NHS Digital). ALSPAC is part of the Population Health Science group within the Bristol Medical School at the University of Bristol. Over £100m has been invested into ALSPAC by UK funding councils, charities (e.g. Wellcome Trust, British Heart Foundation, Asthma UK, Cancer UK), the NHS NHIR and directly from UK Government Departments. ALSPACs primary funding comes from the Wellcome Trust, The Medical Research Council and the University of Bristol. The Study The study seeks approval to link to, extract and use NHS Digital data (Flagging and Tracing, Hospital Episode Statistics and Mental Health Services Data Set) to inform a set of specific research investigations (listed below). These are specific questions – that require linked data - that have arisen from existing work, are led by University of Bristol investigators and are tied to health service improvements (as described later in the application). Study Administration Data provided by NHS Digital will be used by ALSPAC staff to facilitate study administration. Within this, the study will use participant contact details to help trace participants lost to follow-up (NHS contact details will be kept separate from the primary administrative database which will only be updated in the event of a participant responding to a contact request). The database will also be updated with fact of death and date of death in order to stop inappropriate future contact attempts. Scope This data processing agreement (NHS Digital reference number: MR1048) relates to the records of the ALSPAC index children (i.e. those born in the early 1990s). Eligibility for ALSPAC is defined as all mothers who were pregnant and due to deliver between 01/04/1991 and 31/12/1992 while resident in certain health administrative areas within the County of Avon. There were 19,600 live born children resulting from these pregnancies. At the point where the index children had reached 18 years of age, ALSPAC had enrolled 14,775 live born children from 15,247 pregnancy events. Recruitment of the remaining eligible index children, and members of their extended family units, remains ongoing. The ‘children’ are all now adults (mean 26 years old). Detailed description of eligibility and enrolment into ALSPAC are provided in two ‘Cohort Profile’ publications (http://www.bristol.ac.uk/alspac/researchers/cohort-profile/). This agreement is for data relating to the ~5,000 (precise numbers vary over time as eligible children enrol or, conversely, if enrolled children withdraw) index children who are enrolled into ALSPAC and where consent is the legal basis for these uses of their health service data. The index children have moved across the UK over time, so the cohort is no longer geographically distinguishable and cannot be filtered by geographical area. Legal Basis All the projects detailed below are considered to be supported through explicit participant consent as a legal basis. The consent statements provide an explicit participant declaration for the linkage, extraction and research use of the records held by NHS digital. ALSPAC participants are free to object to the studies use of their health records at any time through contacting the study. Records of objections are stored in a central database. ALSPAC will ensure that objectors wishes are upheld and they will not be included in the list of MR1048 participants for whom we request records. Specific purposes Note: All specified researchers accessing NHS Digital data are University of Bristol contracted staff. Additional researchers and clinicians will advise the research team, but will not have access to individual personal information (i.e. only anonymous tabular information and statistical outputs that has been assessed for disclosure risk before consultation). 1. The effect of substance use in adolescence on mental health Project: The study will use HES and MHSDS data, along with linked ALSPAC, GP data and education data, to investigate the association between mental health outcomes in young people and substance use in adolescence. The study will consider the use of three of the most widely used substances (alcohol, cannabis and tobacco), and their association with a diagnosis of a mental or psychological disorder in general, and specifically a clinical diagnosis of mood disorder (e.g. depression), anxiety or psychotic disorder (e.g. schizophrenia). ALSPAC collected data will provide information on substance use exposure and NHS Digital and GP data will provide objective assessments of mental health outcomes. NHS Digital and GP data may be used (where possible) to assess reporting accuracy within the self-reported data and to inform strategies to deal with missing data. This research will improve understanding of the risks of substance use, and the patterns of health service use for young people with mental health problems. 2. Chlamydia testing, infection, and sequelae in young people Project: The study will use HES data, along with ALSPAC Data, GP records and linked National Chlamydia Screening records, to examine which factors influence Chlamydia testing, infection, and sequelae in young people. HES records will be used in the identification of pelvic inflammatory disease, ectopic pregnancy and reduced fertility amongst female ALSPAC participants with different evidence of exposure to Chlamydia (only negative tests, any positive tests, no evidence of testing). Reduced fertility will also be considered for male participants. 3. Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response Project: The study will investigate and describe 1) the reliability and validity of self-reported hospital admissions and those recorded in HES and MHSDS and 2) assess if individuals with adverse health status profiles are more likely to be missing from study follow-up assessments. Self-reported data suffers from participant reporting bias introduced by factors such as recall error (i.e. the ability to accurately remember and report information) or social desirability (i.e. where perceived social influences impact on the answers individuals give). This project will help inform researchers, public health officials and policy makers as to how to interpret findings generated using self-reported data. Separately, it is known that participants who respond to studies are different to those who do not, and there is potential for health effects to impact on individuals’ likelihood to take part. Findings from this study will improve the understanding of study error (e.g. errors in prevalence estimates introduced where the likelihood of follow-up is differentiated by social, demographic or health conditions). 4. Investigating the accuracy of current estimates of self-harm Project: The study will use the data to investigate a) the accuracy of current estimates of self-reported self-harm in the community (exploring the impact of non-response bias and misreporting) b) the long-term risk of hospital admission for self-harm in those self-harming in the community. This information is of critical importance to prevent over or under-estimation of the magnitude of self-harm, as policies based on inaccurate estimates may lead to the wrong policy decisions and incorrect prioritisation of particular health risk factors. Findings will also help to identify risk factors for future self-harm hospitalisation, and improve understanding regarding the relevance of findings from population-based studies using self report to clinical practice. 5. Early life causes of adolescent depression and anxiety Project: The main research objective is to obtain accurate estimates of the association between maternal smoking and binge drinking during pregnancy and depression and anxiety in late adolescence and to investigate how (a) non-response and (b) misreporting in questionnaires affects estimates of this association. GP data will be used to provide depression and anxiety data for those individuals for whom we do not have self-reported information (just over 65% of the cohort). The secondary objective is to obtain accurate estimates of the prevalence of depression and anxiety in late adolescence. 6. Investigating the association between IQ and self-harm Project: The main research objective is to obtain a more accurate estimate of the association between IQ and suicidal and non-suicidal Self-harm among adolescents and to investigate how (a) nonresponse and (b) underreporting in questionnaires affects estimates of this association. GP, hospital admissions and A&E data will be used to provide self-harm data for those for whom the study does not have self-reported information. ALSPAC self-reported data will provide information on IQ and linked education records will provide proxy information on educational attainment. The GP and hospital data will also be used to correct for any under-reporting. The secondary research objective is to examine the extent to which adolescents seek GP help for self-harm and suicidal feelings. 7. Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records Project: The study will use the data to investigate a) the accuracy of current estimates of self-reported asthma in the community (exploring the impact of non-response bias and misreporting) and b) to calculate the extent of asthma severity from recorded hospital attendance/admissions as well as primary care emergency visits and treatment steps. There is concern that asthma may be socially patterned and that it is known that key exposure and confounders collected through observational studies certainly are. Therefore the concern is that assumptions made about the associations and confounding structures of relationships between environmental exposures and asthma outcomes may not be valid. Insights into the accuracy of ALSPAC self-reported and study clinic assessed asthma and the severity of asthmas will support our investigations into the genetic and environmental influences of asthma and current work into the impact of traffic pollution on asthma. The study will investigate i) the natural history of early wheeze in relation to later asthma outcomes; 2) the relationships between early wheezing and later clinical records to determine if a severe asthma profile can be detected in early childhood; 3) compare the impact of smoking and biomarker data from ALSPAC and respiratory function; 4) investigate the relationships between childhood infections and wheezing phenotypes with asthma and lung function in later childhood; 5) compare exposure to traffic pollution and asthma incidences (included A&E and admitted care). These projects may help confirm an association (identified elsewhere between early respiratory infection and decreased lung-function during childhood that may be antecedent to adult respiratory morbidity and possibly mortality; and, 6) investigate the relationships between treatment for asthmas in primary care, adherence to treatment and outcomes of asthma and lung function in later childhood and early adulthood. 8. Antecedent factors predictive of later ear disease Project: Serious ear disease in later childhood and adulthood is distressing and burdensome on those effected and incurs treatment costs on the NHS. This project will investigate whether early signs of ear disease identified in ALSPAC at age 9 (categorised from photographs of the ear drum) are predictive of the development of serious ear disease requiring hospital treatment in later childhood and adulthood (as identified through HES). 9. Parental and child alcohol use and later criminality and injury outcomes Project: The number of children who are affected by parental alcohol misuse is largely unknown although estimates suggest a third of all UK children live with at least one parent who uses alcohol hazardously. How this impacts on their health, mental health and education is unclear. ALSPAC has multi informant measures of parental alcohol use reported by the mothers and partners during pregnancy and throughout childhood (allowing comparison of maternal and paternal effects) and child self-reported alcohol use. Self-reported and linked health and social outcome data will be assessed to help understand associations between parental alcohol use, child alcohol use and child cognitive, behavioural and emotional development. This research will study child engagement in criminal activities and injury. Linked HES records will contribute information on admission rates, accidents and injuries. 10. Understanding drug use pathways and resulting accident and injury Project: When reaching their early twenties, almost 60% of ALSPAC participants have reported cannabis use at some point in their life, one in five has used ecstasy, and around one in ten young adults has used amphetamines, cocaine, or magic mushrooms. Given the adverse effects of adolescent drug use on adult outcomes, these numbers are alarming. This project will seek answers to the following questions: • Why do so many young people experiment with drugs? • How many of them are regular users? • Is the use of illicit drugs systematically linked to alcohol and tobacco use? • How are temporary and chronic use reflected in psychosocial adjustment and accomplishment of normative development milestones? • Can protective factors be identified that increase the likelihood for youngsters to abstain and users to desist from using drugs before they can leave lasting damage? HES data will be used in combination with ALSPAC self-reported data and data from linked GP and Education records. The linked HES data will contribute outcome data on A&E admissions patterns and injury outcomes. 11. Understanding drug use pathways and resulting mental health outcomes. Project: When reaching their early twenties, almost 60% of ALSPAC participants have reported cannabis use at some point in their life, one in five has used ecstasy, and around one in ten young adults has used amphetamines, cocaine, or magic mushrooms. Given the adverse effects of adolescent drug use on adult outcomes, these numbers are alarming. This project will seek answers to the following questions: • Why do so many young people experiment with drugs? • How many of them are regular users? • Is the use of illicit drugs systematically linked to alcohol and tobacco use? • How are temporary and chronic use reflected in psychosocial adjustment and accomplishment of normative development milestones? • Can protective factors be identified that increase the likelihood for youngsters to abstain and users to desist from using drugs before they can leave lasting damage? HES and MHSDS data will be used in combination with ALSPAC self-reported data and data from linked GP and Education records. The linked HES and MHSDS data will contribute outcome data on mental health (cognitive function, depressive symptoms, psychotic symptoms). 12. Parental and child alcohol use and later mental health and development outcomes Project: The study will use the data to investigate the associations between maternal substance use in pregnancy (where 'substance use' is defined as alcohol, tobacco, medicinal and recreational drug use and other stimulants (e.g. caffeine)) on child physiological, developmental and mental health outcomes. This component of ELASTIC will extend our research into child health and social outcomes of parents with differing alcohol consumption patterns by using linked HES and MHSDS records to study mental health outcomes including self-harm, suicide, addiction, anxiety, depression and psychosis. Linked education records will allow assessment of impacts on educational attainment and attendance. 13. Investigating the incidence and aetiology of psychosis. Project: Psychotic experiences (PEs) are reported by around 5-10% of the general population. Although usually transient, they are associated with increased risk of schizophrenia over time, but the natural progression of PEs and transition to schizophrenia in adulthood has not been examined in detail previously. This study will: i) Examine the proportion of children and adolescents with PEs who transition to clinical disorder in adulthood, and estimate the extent to which these individuals are identified by primary/secondary care services (i.e. highlighting potential unmet needs) ii) Use detailed data on ALSPAC participants to identify those at highest risk of transition to psychotic disorder and inform tools for prediction iii) Examine the extent to which associations observed between risk factors (e.g. cannabis use) and psychosis outcomes in ALSPAC and other cohort studies are likely to be over- or under-estimated due to selective loss to follow-up. Linkage to primary and secondary care (HES and MHSDS) records is necessary to accurately identify individuals who have sought help for psychotic psychopathology, estimate the unmet public health needs of non help-seeking individuals with PEs, and examine the extent of potential biases in identifying risk factors. Access to full mental health data within primary care records will enable us to identify early (prodromal) symptoms in individuals who have not yet transitioned into a full-blown illness, to inform identification of those at highest risk of developing psychosis, and where closer medical supervision might therefore be appropriate. 14. Antecedents and health outcomes of intellectual disabilities and autism. Project: The overarching aim of this project is to make use of HES and MHSDS data in conjunction with GP data, education records and ALSPAC parent and self-reported and clinic measures, to understand the i) prenatal and early life antecedents and ii) later life outcomes children with intellectual (learning) disabilities and autism. ALSPAC data will be used to identify prenatal and early life antecedents including maternal stress, anxiety and depression, substance use (including smoking, alcohol, cannabis and other drugs). The linked data will be used to cross validate individuals with intellectual disability and autism identified through questionnaire/clinic data and school records and identify further cases which may have been missed. Later life outcomes will include questionnaire and clinic measures of mental health as well as health service usage and diagnoses recorded in the linked data. The study will use the wealth of socioeconomic and lifestyle data collected in ALSPAC as potential confounders or mediators as appropriate. This research will further the understanding of the causes and adolescent and early adulthood outcomes including health needs and health inequalities of children with intellectual disabilities and autism. 15. Patterns of engagement with health and education services as predictors of child looked-after or in-need status. Project: We will use HES and MHSDS data, along with ALSPAC self-reported data and extracted general practice data, to examine whether patterns of health service engagement (e.g. missed routine appointments, regular attendance at A&E or out-of-hours services, receipt of care for real or alleged ‘accidental’ injuries) are useful predictors of a child becoming in need or looked-after. The study will also use HES and MHSDS data to investigate health outcomes and health service usage in ALSPAC participants who were in need or looked-after as children. Both mental and physical health will be considered. ALSPAC are engaged with the nascent National Child Looked After Observatory and local (Bristol) safeguarding teams in order to effectively disseminate the findings. Findings will also be published in appropriate academic journals and through conferences and local workshops (in partnership with the South West BRC, NHS CLHARC West and Bristol Health Partners). 16. Comparison of proposed HES extract with ALSPACs historical HES extract. Project: ALSPAC has previously extracted HES records on ~3,000 consenting participants. This extract has informed published scientific investigations (e.g. Mars et al 2016: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841016/). In line with established scientific method it is necessary for ALSPAC to retain data supporting these investigations to support scientific challenges or replication studies. NHS Digital have expressed their preference that this historical extract is now securely destroyed. This project will compare – for the subset of consenting participants – if the initial extract is fully replicated in the proposed extract (bar change introduced through participants withdrawing consent) and if the data within these records are exact matches. If it is found that the historic extract is fully represented in the proposed extract then ALSPAC commit to securely destroying the historic extract (following the methodology provided in the security documentation). If it is found that the historic extract differs from the proposed extract then ALSPAC will securely archive the historic extract within the ‘safe haven’ and only make it available for scientific challenge/replication with prior consultation and approval of NHS Digital. It is not the intention to publish findings of this evaluation as it is for internal data management purposes.

Expected Benefits:

The described investigations have defined primary objectives to improve the understanding amongst some of the most concerning and prevalent areas of adolescent health; i.e. those relating to depression, psychosis, self-harm and suicide and substance use. Through this innovative use of a cohort study of adolescents linked to health records we can study exposure/outcome associations in marginalised groups (i.e. those in need/in care and those suffering from mental health conditions). Secondary objectives relate to a better understanding of self-reported measurement error which will be used to inform interpretation of evidence emerging from longitudinal research studies and therefore improve the accuracy of evidence informing health and social care policy development. The project level anticipated benefits include: Project 1 (The effect of substance use in adolescence on mental health):Based on study findings being disseminated in public health academic journals and conferences outlined in the Outputs for Project 1 This research will lead to a better understanding of the risks associated with substance use in adolescence, and the aetiology of mental health difficulties. It therefore has the potential to impact on public health policy. Project 2 (Chlamydia testing, infection, and sequelae in young people): Effective reduction of adverse sexual health outcomes depends in part on an understanding of the factors and processes that predispose an individual to experience these outcomes. Such understanding depends on the ability to consider the influence of exposures acting across the life course from early childhood. Based on study findings being disseminated in public health academic journals and conferences outlined in the Outputs for Project 2 this research will lead to a better understanding of sexual health and testing behaviours in young adults. It therefore has the potential to impact on public health policy and General Practice administration of testing and testing guidance. The Deputy Chair of the NICE Public Health Advisory Committee ((PHAC-F) - a committee responsible for the development of NICE public health guidance), will lead professional dissemination Project 3 (Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response): This methodological work that will support interpretation of ALSPAC data in other research projects (including the studies listed in this application). The work also has potential to support wider understanding and interpretation of bias in self reported health status (e.g. in the NHS Survey of Mental Health and Wellbeing). This is increasingly important as ‘Big Data’ approaches in contemporary Data Science are being used to inform health policy development through the analysis of combined study data and routine records. Study findings are to be disseminated via the appropriate academic journals and conferences outlined in the Outputs for Project 3 The potential benefits of Project 3 are illustrated by Project 4 and 5. While Project 3 will look at this in broad terms, Projects 4 and 5 will study some of the same issues at more depth within the context of specific health status. Project 4 (Investigating the accuracy of current estimates of self-harm): Outputs from this project are of critical importance to prevent over or under-estimation of the magnitude of self-harm, as policies based on inaccurate estimates may lead to the wrong policy decisions and incorrect prioritisation of particular health risk factors. Findings will also help to identify risk factors for future self-harm hospitalisation, and improve understanding regarding the relevance of findings from population-based studies using self-report to clinical practice. . Study findings are to be disseminated via the appropriate academic journals and conferences outlined in the Outputs for Project 4. Preliminary work (based on those participants who provided consent to link their data with medical records) has been published in Archives of Suicide Research (http://dx.doi.org/10.1080/13811118.2015.1033121), and has been selected as a case study by the understanding patient data taskforce that is developing mechanisms to communicate recommendations from the third Caldicott Review to the public Project 5 (Early life causes of adolescent depression and anxiety): Rates of anxiety and depression among children and adolescents in the UK have increased markedly in recent decades. Maternal smoking and alcohol consumption during pregnancy have been shown to be associated with many adverse psychological and behavioural outcomes among children, including in ALSPAC. The study would like to find out if these are risk factors for adolescent depression/anxiety. It is possible that the predictors of depression/anxiety may be different among individuals for whom self-reported data is held, compared to those who are no longer participating in the study. Study findings are to be disseminated via the appropriate academic journal outlined in the Outputs for Project 5 and will inform the methodological understanding of self-reported depression and anxiety and public policy development. Project 6 (Investigating the association between IQ and self-harm): Findings from our research will add value to epidemiological research on self-harm and have wider benefit for the scientific community as it will increase our knowledge of how best to combine self-harm data from different sources. With the inclusion of GP data, it will build on work being undertaken by colleagues and allow researchers to make appropriate decisions regarding missing self-reported data in their analyses. This research also has the potential to impact on public health policy as it will lead to a better understanding of who is at greatest risk of self-harm. This is important in terms of the appropriate design and targeting of interventions. Project 7 (Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records): Findings will improve the understanding of asthma research based on the ALSPAC study and other studies using similar methodologies. Specifically, longitudinal approaches will allow greater understanding on precursor GP reporting (e.g. presenting with wheeze) prior to diagnosis of asthma status. Accurate asthma status informed by objective assessment and therapeutic data will enable more accurate assessment of the environmental and genetic development influences of asthma and other respiratory conditions and be disseminated through the network of Clinical Respiratory Paediatricians. Project 8 (investigating early signs of ear disease): Information about the prognosis of these early signs and their likely development into serious disease will inform clinical decision making about the need for early preventative surgical intervention, which is currently not known. Study findings will be published in appropriate journals and presented locally and nationally through specialist Networks. Project 9 (parental and child alcohol use and later criminality and injury outcomes): In part, this research will address the evidence gap on in utero substance use exposure on child outcomes. The importance of this work has recently been highlighted in a systematic review of the effects of maternal alcohol consumption in pregnancy on later child outcomes (see http://www.bris.ac.uk/news/2017/september/drinking-during-pregnancy.html for more details), and the confusion this generates with conflicting press reporting of 'safe' levels of substance use public health guidance for pregnant women. The research will also consider childhood exposure to parental alcohol consumption and later child/adolescent/young adult alcohol consumption and resulting patterns of criminality and personal injury. Evidence of complex health and social associations is lacking due to the challenge of building sufficiently rich and diverse data to inform these investigations. Our aim is that linked ALSPAC-HES-General Practice-Education records will inform understanding in this area and allow dissemination via relevant journals, press releases and appropriate networks as outlined in Outputs for Project 9. Project 10 (Understanding drug use pathways on accident and injury) Answering questions addressed in this research programme is crucial to understand drug use pathways and their antecedents and outcomes, through the life course. Contemporary and robust evidence drawn from large population samples is challenging given the complex and illicit subject matter. The aim is through linking a large scale population cohort (ALSPAC) with rich information on drug use with routine medical records (HES), we will be able to improve the understanding of the impact of drug use on accident and injury. The intention is that this evidence will help inform effective policy development and to help understand the resource burden on A&E and other injury treatment services resulting from drug use. Project 11 (Understanding drug use pathways on mental health outcomes) Answering questions addressed in this research programme is crucial to understand drug use pathways and their antecedents and outcomes, through the life course. Contemporary and robust evidence drawn from large population samples is challenging given the complex and illicit subject matter. The aim is through linking a large scale population cohort (ALSPAC) with rich information on drug use with routine medical records (HES and MHSDS), we will be able to improve the understanding of the impact of drug use on mental health and inform effective policy development. Project 12 (parental and child alcohol use and later mental health and development outcomes): In part, this research will aim to address the evidence gap on in utero substance use exposure on child outcomes. The importance of this work has recently been highlighted in a systematic review of the effects of maternal alcohol consumption in pregnancy on later child outcomes (see http://www.bris.ac.uk/news/2017/september/drinking-during-pregnancy.html for more details), and the confusion this generates with conflicting press reporting of 'safe' levels of substance use public health guidance for pregnant women. The research will also consider childhood exposure to parental alcohol consumption and later child/adolescent/young adult alcohol consumption and resulting patterns of mental health and development outcomes. Evidence of complex health and social associations is lacking due to the challenge of building sufficiently rich and diverse data to inform these investigations. Via dissemination of study findings through the appropriate academic journals, press releases and local networks outlined in the Outputs for Project 12, the aim is that linked ALSPAC-HES-MHSDS-General Practice-Education records will inform understanding in this area. Project 13 (aetiology of psychosis) The main research objective is to obtain accurate estimates of how common psychosis-related outcomes are in the general population at the age of 24 years, and to use data from primary and secondary care to test whether the Psychosis-like Symptoms (PLIKS) interview used in the ALSPAC cohort is a valid measurement of psychosis. This will inform the interpretation of evidence from other studies using the PLIKS assessment. The secondary research objectives of this study are: i) to use the data from primary and secondary care to examine whether individuals lost to follow-up in the ALSPAC cohort are more or less likely to have a psychotic disorder, to help us understand to what extent research into psychosis in the ALSPAC cohort may be subject to bias; and ii) to identify early symptoms (prodromes) that occur in individuals who subsequently develop a psychotic disorder. The identification of prodromes may inform future initiatives to develop predictive algorithms and other tools to aid early identification of individuals with psychotic tendencies and study findings will support this via dissemination in relevant academic publications’ as detailed in the outputs for Project 13. Project 14 (antecedents and health outcomes of intellectual disabilities and autism): Despite being disabling long term conditions, there is still very little research done on the causes or later life consequences of intellectual disabilities using unselected samples. Much of the research comes from clinical populations without control groups and thus liable to selection bias and confounding. This research will enhance the understanding of the antecedents and outcomes of these neurodevelopmental conditions including health inequalities. The project will improve the evidence base, and highlight issues that will be important for public health, service planning and commissioning. Dissemination routes detailed in outputs for Project 14 Project 15 (Patterns of engagement with health and education services as predictors of child looked-after or in-need status. It is known that children in care have poorer health and education outcomes than those not in care. Early identification of children at risk of care status will aid early intervention. If the project identifies strong predictors it will investigate the potential for them being incorporated into a predictive tool to be used by health or social care professionals. Such a tool could be embedded in clinical software and improve the early identification of risk, a key challenge in the safe-guarding of children.

Outputs:

All investigations are due to be conducted between 2018 and 2020. Timings of the dissemination via journal articles will be constrained by the nature of the peer-review system. ALSPAC employ dedicated communications experts to assist with dissemination and engagement. Public and professional publicity (e.g. press releases, twitter posts, newsletter and facebook articles) will be coordinated with the publication of findings. Dissemination via conferences and workshops will occur throughout the project period using interim results. For all the investigations, we are committed to feeding back findings to our participants. Participants will be informed through the ALSPAC print and social media newsletters. ALSPAC have a strong track record of running study engagement events which are designed with input from participants. In recent years we have held ‘data linkage’ themed evening lectures (e.g. http://www.bristol.ac.uk/alspac/external/presentations/how-we-are-using-your-records.pdf) and ‘ResearchFest’ (http://www.bristol.ac.uk/alspac/events/researchfest2012/), a day-long event with a wide series of public lectures in Bristol. Periodically the study produces a book (e.g. http://www.bristol.ac.uk/alspac/go/21st-book/) or YouTube videos (https://www.youtube.com/user/children90s) that describe findings and how we use participant data. We work with national and local media to disseminate findings, along with local attractions such as the MSHED museum of Bristol Life. Study findings from the applications described in this application will be incorporated into future activities. Our specific project level dissemination plans are: Project 1 (The effect of substance use in adolescence on mental health): The findings will be disseminated through appropriate epidemiological and public health academic journals (e.g. Addiction, International Journal of Epidemiology, Epidemiology, Wellcome Open) and findings (including interim results) at conferences (e.g. Society Academic Primary Care, MRC Farr Institute). The study will also work with members of the NHS Bristol Health Impact Team – Directed by the Professor in Public Health and Epidemiology & Head of Population Health Sciences - to feed findings to local service providers. Project 2 (Chlamydia testing, infection, and sequelae in young people): This research will lead to a better understanding of sexual health and testing behaviours in young adults. It therefore has the potential to impact on public health policy. Findings will be published in an appropriate epidemiology journal(s) or those dedicated to sexual health findings (e.g. International Journal of Sexual Health) and presented at conference (e.g. Society of Academic Primary Care). The Deputy Chair of the NICE Public Health Advisory Committee ((PHAC-F) - a committee responsible for the development of NICE public health guidance) - who is also the Director of the NHS Bristol Health Partners sexual health for population and patients health integration team, will lead professional dissemination. Project 3 (Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response): Insights from this work will be published in an appropriate epidemiology/survey methods journal (e.g. Society of Longitudinal and Life Course Studies, BMC Medical Research Methodology, Survey Research Methods), at similar conferences and via ALSPAC study website and the CLOSER longitudinal research consortium website. To ensure this information is fed back to the NHS we will send our project findings to the Care Quality Commission Survey Coordination Centre who facilitate NHS Surveys. Project 4 (Investigating the accuracy of current estimates of self-harm): Results from the study will be published in a suitable epidemiology/psychiatry journal and via the ALSPAC study website. Preliminary work (based on those participants who provided consent to link their data with medical records) has been published in Archives of Suicide Research (http://dx.doi.org/10.1080/13811118.2015.1033121), and has been selected as a case study by the understanding patient data taskforce that is developing mechanisms to communicate recommendations from the third Caldicott Review to the public (https://understandingpatientdata.org.uk/case-study/investigating-self-harm-young- To ensure this information is fed back to the NHS we will communicate our project findings to the Bristol Health Partners Improving Care in Self-Harm ‘STITCH’ Health Integration Team. The Professor of Epidemiology is the academic lead for STITCH and also a member of both England’s and Bristol’s Suicide Prevention Advisory Groups and works closely with Public Health England, and will feed back relevant findings into NHS and Public health strategy. Project 5 (Early life causes of adolescent depression and anxiety): Outputs will be published in academic journals (e.g. BMJ Open, International Journal of Epidemiology) and will inform methodological understanding of self-reported and public policy development. The Investigators will work with the Professor in Public Health and Psychiatry (University of Swansea, who will not have access to the data) to disseminate findings. Project 6 (Investigating the association between IQ and self-harm): Findings will be published in academic publications topical to the condition and/or epidemiological methods (e.g. BMC Medical Research Methodology). The researchers will work with the Professor of Epidemiology and the Professor in Public Health and Psychiatry to ensure wide dissemination of study findings within relevant NHS community (see Projects 4 and 5). Project 7 (Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records): Findings will improve the understanding of asthma research based on the ALSPAC study and other studies using similar methodologies. Understanding will be disseminated via the Medical Research Council and Asthma UK funded STELAR asthma research consortium. Findings will help support research by the Medical Research Council and Natural Environment Research Council ERICA study that will assess associations between traffic pollution exposure and asthma outcomes in ALSPAC index children. The findings will support the Professor of Paediatric Respiratory Medicine’s programme of work, as a part of which he was a lead contributor to the Royal College of Physicians Every Breath We Take report into the lifelong impacts of air pollution (https://www.rcplondon.ac.uk/file/2914/download?token=qjVXtDGo). Study findings will be disseminated through the network of clinical respiratory paediatricians. Project 8 (Antecedent factors predictive of later ear disease): The Senior Research Associate in Medical Statistics and the Professor of Community Child Health will use the data to conduct the research evaluation. Clinical expertise will be provided by a Research Fellow in Social and Community Medicine and a Lecturer/NHS ENT surgeon, neither of whom will be provided with access to the data. Academic findings will be published in journals (e.g. International Journal of Audiology, BMJ Open, PLoS ONE). Study findings will be disseminated via the ENT liaison with the local CCGs Clinical Policy Review Groups. On a national level the ENT Specialty Lead for the NIHR Clinical Research Network: West of England will disseminate via the ENT National specialty group. Project 9 (parental and child alcohol use and later criminality and injury outcomes): This work has been funded by the UK Medical Research Council and findings will be disseminated through academic routes (i.e. public health and health practitioner journals such as the BMJ as well as conferences such as the Society of Academic Primary Care), press releases and feedback to Department of Health policy makers. The Director of the NHS Bristol Health Partners ‘Drug and Alcohol’ Health Impact Team and will feed findings through into local care providers via this network. Project 10 (Understanding drug use pathways on accident and injury) We will publish in academic journals (e.g. Injury, Injury Prevention) and present at conferences (e.g. Society Academic Primary Care). The Director of the NHS Bristol Health Partners ‘Drug and Alcohol’ Health Impact Team and will feed findings through into local care providers via this network. Project 11 (Understanding drug use pathways on mental health outcomes) We will publish in focused academic journals (e.g. Drug and Alcohol Review) and present at similarly focused conferences (e.g. Managing Drug & Alcohol Problems in Primary Care Conference). The Director of the NHS Bristol Health Partners ‘Drug and Alcohol’ Health Impact Team and will feed findings through into local care providers via this network. Project 12 (parental and child alcohol use and later mental health and development outcomes): Findings will be disseminated through academic routes (i.e. public health and health practitioner journals such as the BMJ as well as conferences such as the Society of Academic Primary Care), press releases and feedback to Department of Health policy makers. The Director of the NHS Bristol Health Partners ‘Drug and Alcohol’ Health Impact Team and will feed findings through into local care providers via this network. Findings relating to self-harm and suicide will be disseminated via the Professor of Epidemiology and the Professor in Public Health and Psychiatry. Project 13 (Investigating the incidence and aetiology of psychosis). The Professor of Psychiatry and the co-director of the NHS Bristol Health Partners Psychosis Health Impact Team will use their clinical networks to disseminate findings. In addition to these clinical routes, the team will disseminate findings via academic publication (e.g. Psychological Medicine, Social Psychiatry and Psychiatric Epidemiology, European Psychiatry, Journal of Affective Disorders, Biological Psychiatry) and conferences (e.g. RCPsych International congress, IMFAR, Society for Epidemiological Research, The International Society for Developmental Origins of Health and Disease). Project 14 Antecedents and health outcomes of intellectual disabilities and autism) Research findings will be disseminated via appropriate academic journals in the field of medicine, psychiatry, epidemiology and public health (e.g. BMJ, British Journal of Psychiatry, International Journal of Epidemiology, Wellcome Open) with findings and preliminary results being presented at conferences (e.g. RCPsych International congress, IMFAR, Society for Epidemiological Research, The International Society for Developmental Origins of Health and Disease). We will also engage clinicians and service users through a variety of routes including ALDERN (Avon Learning Disability Education and research network- a network of clinicians, researchers and people with learning disabilities and their families. The lead investigator is an NHS consultant psychiatrist with extensive NHS roles. Project 15 (Patterns of engagement with health and education services as predictors of child looked-after or in-need status. Research findings will be disseminated by the emerging National Family Justice Observatory and the Children Looked After and In Need strands of the Administrative Data Research Network. We will publish our findings in relevant academic journals (e.g. Epidemiology, Wellcome Open, Child & Family Social Work, British Journal of Social Work, Adoption and Fostering). We will disseminate relevant project findings to charities (e.g. NSPCC) and the NHS England ‘National Looked After Children Safeguarding Sub Group’. Project 16 (Comparison of proposed HES extract with ALSPACs historical HES extract). The findings will not be disseminated but will be used internally to determine further data management options.

Processing:

Process Stage 1: Linking ALSPAC participants to the NHS/NHS Digital demographic database (this stage has already taken place and further linkage will only be applicable for those cohort participants not originally linked) ALSPAC have provided the NHS Digital (then NHS IC) with the personal identifiers of its study participants. NHS Digital commissioned linkage of the ALSPAC identifiers to the NHS central demographic register (now the NHS Spine). The product of this linkage (a link between ALSPAC MR1048 ID to NHS ID for each participant) is stored by NHS Digital and can be used to identify ALSPAC participants amongst NHS Digital records. Additional linkage may be required for newly enrolled cohort participants (approximately 15,000 of 20,000 eligible families are enrolled, but small numbers of the remaining 5,000 continue to enrol). A new Study ID will be allocated to these records. ALSPAC will securely provide NHS Digital with separate lists identifying (by Study ID) the MR1048:consent participants. The lists will be filtered for up-to-date consent/dissent/withdrawal from ALSPAC status prior to sending. Process Stage 2: NHS Digital Extraction of Records HES and MHSDS records of ALSPAC participants will be identified using the existing MR1048 link and NHS Digital will extract copies of participants records where found (with the same processing for ‘new’ cohort participants). MR1048 extracts will be sent to the ALSPAC Data Safe Haven. The extracts will be identified by Study ID and a check identifier (Date of Birth) to allow validation of the linkage. The extract will be sent to ALSPAC via the NHS Digital secure methodology (e.g. secure download site in an encrypted file). As ALSPAC are able to map MR1048 ID back to the ALSPAC administrative database these data extracts should be considered as being identifiable (even if pseudonymised). The extracts will be received into the ALSPAC Data Safe Haven; which is managed by a small, specialist, team of ALSPAC health informatics experts (employed by the University of Bristol). The data will be stored on a secure encapsulated virtual machine located at the University of Bristol. The safe haven is kept separately from the ALSPAC administrative database (which contains participant identifiers). The Data Safe Haven design has been adopted to restrict access to identifiable data used for secondary purposes and to support the de-identification of the data prior to the bulk of the data uses. The Data Safe Haven governance arrangements have been reviewed and approved by an NHS Research Ethics Committee (REC) and the Health Research Authorities Confidentiality Advisory Group (HRA CAG). The Data Safe Havens security arrangements have been independently audited and certified to the NHS IG Toolkit and ISO27001 security standards (described below). Process Stage 3: Data processing in the ALSPAC Data Safe Haven The ALSPAC Data Safe Haven was designed in accordance with NHS policy [3]. Incoming, identifiable, data is stored in an encrypted format on encrypted and firewalled demarcated server space. Access to this server space is restricted to the Data Safe Haven team (by user access controls and access is only permitted from a small number of desktop computers based in secure offices at the University of Bristol). On entry to the Data Safe Haven a copy of the data is archived. The data are processed for the following purposes: i. Assess Data & Data Linkage Quality: The data extract is compared against the agreed extract specification to ensure the content (both in terms of variables supplied and patients included) is correct. The linkage between ALSPAC participant and NHS record is quality checked using check variables (e.g. NHS ID to ALSPAC ID link is checked using date of birth and gender). The data values will be subject to logical error checks to assess if the value is consistent with the expected values (as defined in the source documentation). Inconsistent values will be recoded to missing (i.e. ALSPAC will not attempt to infer a correct value); ii. Derivation: Derived data are created in order to assist in the de-identification of the data (e.g. Age in days at the time of a health event will be derived from Date of Birth and the event date) and to distil records extracted from multiple sources into a cohort longitudinal record (e.g. age in days will allow accurate sequences of events to be created when combining NHS Digital data with other data), and to assist the research process (e.g. 1) a range of read codes, hospital admissions and prescription data are used to derive an indicator to whether an individual has had any interaction with the NHS relating to/or being coded as asthma, and 2) routine records are used to inform statistical techniques, such as multiple imputation, which can address missing self-reported data). All derivation routines are applied through computer syntax, which is stored along with a documented record of the derivations; iii. Linkage: The extract is linked to the internal ALSPAC individual ID numbers. The quality of the match is checked (see above). Linkage success or failure is assessed and documented within the data set (e.g. we attempt to distinguish between failure to link due to a patient not seeking consultation, with failure to link due to insufficient identifiers and failure to link as the individual is resident outside of the catchment area of the data extract in question). The extract is processed to ensure it is harmonised with the ALSPAC longitudinal data set; iv. De-Identification: The Safe Haven de-identification processes are designed to minimise the risks of disclosure through either: direct identification of an individual from a dataset (either accidentally or maliciously); through inference or through the potential of variables in combination to identify individuals; or the potential of inappropriately described outputs to identify individuals. The data are pseudonymised through removing NHS ID, name and address (where present). The extract is stored, within the Data Safe Haven, until information from it is requested for a research investigation. v. Consent status checks: To account for changes in consent status over time the data extract is compared against a master consent list before being de-identified and made available for research (where further consent check stages are used, see Process Stage 6); vi. Collation, Storage & Archiving: Copies of the data shared with researchers will be held securely within the Data Safe Haven. These will be used for audit purposes, to keep a record of research project sample selection (in order to allow follow-up assessments) and to fulfil the requirements that peer-reviewed findings are reproducible. The identifiable data are only used for these data processing purposes, i.e. to facilitate and support research. The Identifiable data are not used in research investigations. Process Stage 4: Participant Tracing Data Where the data extracted from the NHS Digital relates to participant contact details and status (e.g. left England and Wales, fact of death) the members of Data Safe Haven staff will swap the ID used to extract the data for ALSPACs internal system ID and will then pass the information to the ALSPAC team whose role it is to maintain communications and relationships with participants. Neither NHS IDs or clinical data (beyond ‘alive/deceased’ status) will be provided to this team. The details are then used to update ALSPACs administrative database. These details are not provided to researchers, although address information is used to derive spatial identifiers and other values which are used in some research projects in a non-disclosive form. ALSPAC will use a MRC Farr Institute ‘UK Secure eResearch Platform (UKSeRP) as a ‘secure research environment’ to combine records from different sources and to manage access to effectively anonymous sub-sets of combined records to specific researchers at a project level. UKSeRP is the technological infrastructure which supports the SAIL databank of Welsh routine health and administrative records. UKSeRP was developed by the Welsh MRC Farr Institute and is operated by two organisations: The NHS Wales Informatics Service (NWIS) and the University of Swansea Health Informatics Research Unit (HIRU). HIRU, through the MRC Farr Institute are making the UKSeRP infrastructure available to other research organisations. This means ALSPAC can make use of the full advantages of the secure research infrastructure developed to support SAIL by contracting the University of Swansea to provide a copy of the infrastructure to host ALSPAC data and data linked to ALSPAC. In this contractual arrangement, the University of Swansea will be Data Processor working to instruction from the University of Bristol who will be Data Controller (the contract will bind the University of Swansea to the same conditions (where relevant) as the University of Bristol have agreed to in their contract with the NHS Digital). UKSeRP has ISO27001 certification. This principle has been previously agreed as suitable for hosting linked NHS Digital records. Process Stage 5: Linking ALSPAC participants to the UKSeRP (this stage has already taken place and will not need repeating). UKSeRP operates on a ‘split file’ approach to handling data; where identifiers are handled separately from clinical or individual attribute data. Identifiers are processed by NWIS (within the confines of the NHS); where they are processed by an algorithm which consistently converts incoming identifiers (e.g. NHS ID, name, date of birth) into an encrypted ‘Anonymous Linkage Field’ (ALF). In this way identifiers relating to the same person coming from multiple sources can be linked to the same ALF. ALSPAC have already sent the identifiers to NWIS along with an externally meaningless ID number (KEY ID). NWIS have used the identifiers to create ALF IDs for ALSPAC participants. This is managed in such a way that 1) neither ALSPAC nor HIRU (who manage clinical data) are able to trace back ALF to a person’s identity and 2) ALSPAC are able to send clinical and other attribute data linked to KEY ID into the system which can then be automatically replaced with ALF in a ‘black box’ process. Process Stage 6a & 6b: Sending NHS Digital and ALSPAC data from ALSPAC into the UKSeRP ALSPAC research staff will replace the IDS on the de-identified data from the ALSPAC resource with the Key ID. We will then securely (using AES-256bit encryption) send the data into the ALSPAC UKSeRP via the automated ‘gateway’ upload appliance. ALSPAC data safe haven staff will also conduct the same process on the de-identified (see Stage 3) HES and MHSDS data. We will then securely (using AES-256bit encryption) send the HES and MHSDS data with Key ID into the ALSPAC UKSeRP via the automated ‘gateway’ upload appliance. Process stage 7: The UKSeRP automated gateway system automatically replaces Key ID on incoming data with ALF ID (yet the system has no access to identifiers of the individuals used to produce ALF as these never leave the NWIS trusted third party). The data are then deposited in the ALSPAC UKSeRP. Meaning the ALSPAC staff have no means of linking ALF back to the ALSPAC databases, yet can use ALF to join records coming in from different sources or at different times (e.g. longitudinal updates). Process Stage 8: Sub-setting and further anonymization of data prior to analysis The researchers with approval to access the ALSPAC HES and MHSDS data will be created project specific ‘containers’ in UKSeRP that they can access. ALSPAC Data Safe Haven staff will sub-set the extracted data to minimise it to only the information needed to conduct the project investigation. Each project data set will be given its own unique ID. The researchers will not have access to the ALSPAC administrative database and therefore – given the technological, contractual, training and data management steps involved – the data can be considered to meet the Information Commissioner’s Office ‘effectively anonymous’ requirements (as defined in the ICO Anonymisation Code Of Practice – we include a separate document describing how our process meets the ICO requirements). Information about these hypotheses – and the use of NHS data sourced from the NHS Digital – will be posted on the study website: - www.bristol.ac.uk/alspac/participants/young-people/. Participants have been notified about this information, and each study newsletter includes updates and reminders (e.g. page 2 of: - www.bris.ac.uk/alspac/external/newsletters/Childrenofthe90s_familynewsletter_2015.pdf ) Participants are able to opt-out of each individual study (before the study starts). This mechanism for providing on going fair processing information was developed with the HRA CAG with input from the Information Commissioners Office. Project specific datasets are risk assessed and disclosure control is applied as deemed appropriate. Further disclosure control ranges from suppression of rare values and outliers to a state where the possibility of disclosure is rendered so challenging that the data can be considered as being effectively anonymised in line with the HSCIC Anonymisation Standard for the publication of Health and social Care Data [4]. Case selections will be assessed for risks of disclosure through inference (e.g. where a sample selection is made on the basis of a health condition), where this is a risk the Safe Haven staff will add control or masking cases. The ALF used in the hypothesis specific dataset will undergo secondary encryption (reversible by ALSPAC) using an algorithm specific to each project. This means that a researcher with multiple project will not be able to join data across the different datasets using ALF. Participant consent status is checked as a final stage before making the data available to researchers. Process Stage 9: Researcher access to data Researchers are all contracted to University of Bristol (as described below). They will only be able to access the sub-partition(s) of the ALSPAC UKSeRP where their project specific data set is located. The UKSeRP technology restricts the actions that researchers can take, for example, it is not possible to plug in a USB stick, or to copy and paste or to connect from within UKSeRP to the internet. These restrictions – in conjunction with the training and binding agreements the researchers enter into – ensure good governance is maintained. Furthermore, the anonymization processes undertake (stages 3 and 6) are sufficient to reduce the risks of participant identifiably to a point that they are so remote that the data can be appropriately treated as effectively anonymous. Researchers are allowed to remove data outputs (e.g. statistical findings, graphs, tables of aggregated findings) from UKSeRP through a controlled process where each output is reviewed and assessed for disclosure risk by ALSPAC Data Safe Haven staff prior to being released. ALSPACs Data Access policies require that researchers submit all publications, prior to submission for publication, to the ALSPAC Executive. The Executive Committee assess the publications for issues including checks for potential disclosure risks (e.g. tables summarising statistical outputs containing small cell counts). Disclosure checks will ensure compliance with the small number suppression rules contained within the HES Analysis Guide. Data Specification: ALSPAC require life-course data from birth (i.e. maternity HES from 1990-1993) to the most recent finalised datasets (we appreciate that the records contained within different HES domains start at different points in time). This will allow the assessment of changing health status over time, changing severity of health status and the precursor health events leading up to health outcomes. ALSPAC require detailed information about these in order to build event sequence records comprising study collected information, linked health and social care records from NHS Digital and linked records from other providers (e.g. national pupil database records). The data request is limited to the cohort participants, but not limited geographically (given that our participants have moved away from the original cohort catchment area). Information Security: ALSPAC are committed to maintain high standards of information security and recognise that this is a key component of our trust relationship with participants and data owners alike. To achieve these standards ALSPAC have developed an Information Security Management System and associated management and governance structure that has been certified as meeting the ISO/IEC 27001:2013 Information Security standard. ALSAPC have submitted an NHS IG Toolkit assessment (edition 14: 2016/2017) which scored 97% in our last assessment. Participant Consent: ALSPAC have provided fair processing materials to all participants via a postal campaign (those we failed to contact will be excluded from the data extract request). The fair processing materials included a form through which participants could provide an explicit decision as to how they wanted their records to be used (returning this form was optional and the materials clearly described how ALSPAC would proceed with data sharing in the event of non-response). While the ‘fair processing’ campaign has concluded (having completed our REC approved protocol) ALSPAC continue to provide fair processing information via newsletters, the website and social media. Where we meet participants (e.g. at a study data collection clinic), we ask them to complete a form outlining their explicit preferences. In the event the participant changes their mind, then ALSPAC have a defined ‘withdrawal of consent’ protocol, which is available to participants via the study website: - http://www.bristol.ac.uk/alspac/participants/ The policy allows participants to tailor their involvement in the study; either by altering permissions for the use of their health records in a specific project, the use of their health records in general, or their continued involvement in the study. Research Purposes: Observational epidemiology aims to build a body of evidence related to any given topic. The investigations detailed below are designed to add to the relevant evidence base within that field. In themselves, these will typically not directly change NHS process. However, if replicated elsewhere and found to be important through systematic review then this could lead to policy change (e.g. NICE guidelines are frequently developed using systematic reviews of evidence). This is in contrast to other types of research (e.g. randomised controlled trial interventions or drug trials) that may provide stronger evidence of causation and can hence can lead to more immediate impact. To ensure full potential for impact on health and social care system, we will ensure that the findings of our investigations are well placed to feed into this process through ensuring publication in peer-reviewed journals that are fully indexed (e.g. pubmed, medline) and contain strong descriptive keywords (i.e. the findings will be discoverable by those conducting systematic reviews). This is the standard pathway to impact for observational research. Where possible, we will also directly feed findings into national or local health care initiatives, and we describe this where relevant (see below). The ALSPAC Data Safe Haven team who will process the data are University of Bristol contracted staff. The Safe Haven team will prepare the data extracts and also give ‘Data Science’ input into the research process (i.e. through offering expert guidance on ALSPAC, data linkage processes, and on the interpretation and statistical processing of linked records within an epidemiological context). As such they will undertake processing which from data management to research analysis. Previous data extracts ALSPAC received flagging and tracing extracts for many years. The study also, in 2013, received an extract of HES records for ~3,000 consenting index children. This extract was envisaged to be a technical pilot and to investigate exemplar hypotheses. While successful (see https://understandingpatientdata.org.uk/case-study/investigating-self-harm-young-people) this extract had restricted potential due to its small sample size. The overlap between the data extract requested in this application and this past application will be evaluated. If the data are found to be exact duplicates then the previous extract will be securely destroyed. If they are not equivalents, then the previous extract will be encrypted and archived. It will not be made available for new research, but may be used if our previously published work is challenged. Once the recommended period for retaining data is complete, it will then be securely destroyed.


Project 3 — DARS-NIC-147773-9G6ZN

Opt outs honoured: Y, N

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/11. breached contract — audit report.

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

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Members and Postings Report
  • MRIS - Flagging Current Status Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Bespoke
  • MRIS - Personal Demographics Service

Objectives:

The purpose of the proposed research is to evaluate the effectiveness and cost-effectiveness of population-based screening for prostate cancer. This study will allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide policy relevant data for one of the most controversial issues in health care: the potential impact on the UK population of screening for prostate cancer


Project 4 — DARS-NIC-147806-M11MB

Opt outs honoured: Y, N

Sensitive: Sensitive

When: 2016/04 (or before) — 2018/09. breached contract — audit report.

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 - Bespoke
  • MRIS - Scottish NHS / Registration

Objectives:

This study is part of an evaluation of the Integrated Drug Treatment System (IDTS), which has recently been introduced to prisons in England. The primary purpose of the study is to assess whether differences occur in relation to short-term mortality rates, engagement with treatment services, and offending behaviour between 10,000 IDTS clients released from prison while still receiving Opiate Substitution Treatment (OST) (e.g. methadone or buprenorphine) and 10,000 IDTS clients released after detoxification from opiate dependence.

Expected Benefits:

Research in the UK and elsewhere has repeatedly shown that drug users have an increased risk of death immediately following release from prison, most commonly due to overdose after loss of a previous tolerance to opiates. The IDTS aims to provide a more integrated and comprehensive system of treatment for drug users. A significant aspect of this has been the increased use of OST in prisons, the aims of which are to lessen the likelihood of illegal drug use in prison, opiate related overdose upon release, and disengagement from community services upon release. We have been funded by the English Department of Health and the Ministry of Justice to evaluate the effectiveness of this aspect of the IDTS.

Outputs:

Data will be collected from various databases one year after recruitment and again at ten years, and linked to the participant identifying information. Mortality data provided by the MRIS is crucial, a comparison of short-term mortality rates between cases and control participants being our primary outcome. This mortality data will be modelled using multivariable regressions, adjusting for baseline covariates available to us from the Drug Intervention Record (DIR), completed on entry to prison. In addition, we will examine the prevalence of different causes of death within prison or in the first year after prison release. As such, we also require information on causes of deaths from the MRIS. Our other analyses will rely on data from other sources, including the Police National Computer (PNC) and National Drug Treatment Monitoring System (NDTMS). Of particular interest in addition to mortality is a comparison of re-conviction rates / time to re-conviction between cases and controls and also of rates of engagement with community drug services.

Processing:

We aim to recruit a total of 20,000 adult opiate dependent participants from 42 prisons in England, over a period of 13 months: 10,000 cases released from prison opiate tolerant due to Opiate Substitution Therapy (OST) and 10,000 controls released from prison detoxified. Each prisoner entering a participating prison who is triaged as being opiate dependent will be invited to participate in the study by a member of the prison’s Health Care or Psychosocial team. Once a prisoner signs the study consent form or refuses to participate, that is the end of his / her active participation. The consent will allow information to be collected about a participant from a number of national databases. An individual’s participation in the study will be confirmed upon his / her release from prison, at which time his / her opiate tolerance status (detoxified / still in receipt of OST and therefore opiate tolerant) will be recorded, based on the prison’s OST dispensing data. These data will be collected and conveyed to the researchers using either encrypted data disks or sealed hard copy transferred using a secure parcel service. Participant prison release dates will be confirmed from dispensing data and the Local Inmate Database System (LIDS).


Project 5 — DARS-NIC-147901-2XMLG

Opt outs honoured: No - consent provided by participants of research study

Sensitive: Sensitive

When: 2016/04 (or before) — 2019/04. breached contract — audit report.

Repeats: Ongoing, One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Informed Patient consent to permit the receipt, processing and release of data by NHS Digital

Categories: Identifiable

Datasets:

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

Objectives:

The overall aim of the programme is evaluate and disseminate the outcome of centralization in Head and Neck cancer (H&N). In order to accomplish this we will create a clinical cohort of 5,000 people with H&N and follow up this cohort. This study will be large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with H&N as part of an ongoing National Head and neck cancer audit. The proposed studies will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes. We will collect data on people with H&N that would include age, sex, diagnosis and treatment. Additional data will be collected on socioeconomic status (including occupation, education and housing): lifestyle (including smoking and alcohol intake); questions on psychological status and general and cancer specific quality of life questions. We will collect a venous blood, saliva and tissue sample for use in future translational studies. The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with H&N.

Expected Benefits:

Head and neck cancer (H&N) is one of the commoner cancers with around 7,000 cases per year in England and Wales. The incidence appears to be increasing. The two year all cause mortality is around 35%. A person with H&N requires care from a range of disciplines. These include surgical teams to resect the tumour, dissect the neck and reconstruct the defect; radiotherapists and oncologists to provide radiotherapy and chemotherapy; clinical nurse specialists to offer pre and postoperative support; nutritionists to help with postoperative feeding and nutrition; speech therapists to assist with speech and swallowing; restorative dentists to fit and maintain prostheses and treat dental caries; palliative care physicians to support patients in the terminal stages of H&N and psychologists to provide psychological support. In an attempt to move beyond clinical outcomes, such as the surgical result or survival, quality of life scores have been developed for people with H&N and are being used to guide and monitor response to treatment. Despite their importance there is limited evidence on the modifiable psychological and social determinants of coping for people with H&N. There is thus a need to assess a broad range of patient centred outcomes in studies of H&N.

Outputs:

We will continue the follow up through flagging so participants that survive remain in the study for 10+ years. The MRIS will enable us to trace and identify those that have died to ensure that we do not send out further questionnaires. Furthermore, the flagging will provide ongoing notifications about our participants and will allow the study to compare morbidity and mortality outcomes across different centres. We will also be able to analyze the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

Processing:

The overall objective of the study is to recruit a clinical cohort of 5,000 people with H&N and then follow up this cohort for two years. This study will be large enough to compare groups by age, site and stage. Specifically, the objectives are to: 1. Compare morbidity and mortality outcomes across different centres. 2. Compare quality of life outcomes across different centres. 3. Describe the individual economic cost of head and neck cancer care. 4. Identify prognostic indicators for head and neck cancer. 5. Create a resource for translational and applied research in head and neck cancer. Research nurses at each participating H&N cancer centre together with the research team will recruit and collect data: • Obtain consent • Baseline collection - Collect blood, saliva and tissue sample accordance with the established biological sample protocol - Administer the base line questionnaire at the clinic - Provide the additional baseline questionnaire pack to be completed at home which should be sent back to the research team in the provided prepaid envelope. • The patients will be flagged with the NHS Information Centre (NHSIC) and followed for two years. • At 4 months, the research team will send out the 4 month questionnaire pack to the participants enrolled for self completion at their home together with a prepaid envelope to return the questionnaire pack. • At 12 months, the research team will send out the 12 month questionnaire pack to the participants enrolled for self completion at their home together with a prepaid envelope to return the questionnaire pack.


Project 6 — DARS-NIC-148033-FMST7

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/08. breached contract — audit report.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

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

Objectives:

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective birth Cohort study with detailed biological and behavioral data from before birth through till late adolescence and is organised as a resource for the whole scientific community (www.alspac.bris.ac.uk). Past assessments of ALSPAC participants have substantially been based on postal questionnaires, study clinics and increasingly through information obtained through linkage to routinely collected data. The data collected via this arrangement will be processed and provided in a suitably secure and non-disclosive form to our research collaborators. The ALSPAC resource is used extensively to investigate a wide range of research questions. To date there have been over 450 publications (http://www.bristol.ac.uk/alspac/sci-com/pubs/) with many more topics being actively investigated. Additionally these data will be used in an administrative function to help prevent causing distress to our study families through contacting them if there has been a bereavement. Embarkation and health authority data are used in our cohort tracking and tracing initiatives. ALSPAC conduct many data extraction and linkage projects in order to answer our research questions. The use of NHS ID number allows for greater efficiency and accuracy. ALSPAC will provide full information and seek prior approval from NHS IC before commencing any research projects using the NHS ID number.


Project 7 — DARS-NIC-148336-V4SL1

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/08. breached contract — audit report.

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

Objectives:

To examine behavioural, social,physiological and clinical factors determine healthy,ageing and disease risk. The Caerphilly Prospective Study (CaPS) is one of the oldest epidemiological cohort studies in the UK. It was set up by Prof. Peter Elwood, Director of the MRC Epidemiological Unit South Wales in 1979 and the male subjects who have been followed up ever since having been seen on five occasions and we are currently planning to do one final clinical assessment. The original cohort was established to examine risk factors for cardiovascular disease. However over the years the scope and breadth of interest has expanded so it is now focussing on cognitive decline, dementia and ageing. It has an extensive breadth of phenotypic dat including specialised clotting tests as we well as DNA and a range of biochemical results. The cohort is actively engaged in research particulary the Halcyon collaboration (http://www.halcyon.ac.uk/) which is a multicohort collaboration studying healthy ageing across the life course. It also contributes to large international genetic consortia as part of the validation set which have identified new genetic variants for disease and traits such as obsesity.


Project 8 — DARS-NIC-152414-W3P6Q

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

Sensitive: Non Sensitive, and Sensitive

When: 2018/06 — 2019/04. breached contract — audit report.

Repeats: One-Off, 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'. , Health and Social Care Act 2012 – s261(7)

Categories: Identifiable

Datasets:

  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Admitted Patient Care
  • Mental Health Minimum Data Set
  • Mental Health and Learning Disabilities Data Set
  • MRIS - Flagging Current Status Report
  • MRIS - Cohort Event Notification Report

Yielded Benefits:

University of Bristol received the data in late August 18 and are still processing and documenting it. Applied analysis is due to start in early 2019. There have been data quality issues with the HES data received - a full resupply will be given, so that correct analysis can be taken. Therefore no yielded benefits have been realised.

Objectives:

Background ALSPAC is a transgenerational prospective birth cohort study that recruited women during pregnancy in the early 1990s. ALSPAC is designed to investigate influences on health, wellbeing and development across the life course. To inform these investigations ALSPAC collects information on genetic, epigenetic, biological, psychological, social and environmental exposures and a similar range of health, social and developmental outcomes. ALSPACs primary objective is to manage a long-term relationship with the study families and through this to build a DataBank resource that can be used to inform the investigation of diverse health and social hypotheses across the life course. To achieve this objective, data are collected through postal questionnaires, study clinical assessments, the collection of biological samples and through linkage to routinely collected health and social administrative records (including those held by the NHS Digital). ALSPAC is part of the Population Health Science group within the Bristol Medical School at the University of Bristol. Over £100m has been invested into ALSPAC by UK funding councils, charities (e.g. Wellcome Trust, British Heart Foundation, Asthma UK, Cancer UK), the NHS NHIR and directly from UK Government Departments. ALSPACs primary funding comes from the Wellcome Trust, The Medical Research Council and the University of Bristol. The Study The study seeks approval to link to, extract and use NHS Digital data (Flagging and Tracing, HES and MHSDS) to inform a set of specific research investigations (listed below). These are specific questions – that require linked data - that have arisen from existing work, are led by University of Bristol investigators and are tied to health service improvements (as described later in the application). Scope/Cohort The Avon Longitudinal Study of Parents And their Children (ALSPAC), popularly known as “Children of the 90s”,  enrolled pregnant women in the early 1990s into a study which has followed the health and development of the  resulting children and their parents/carers for nearly twenty years. These children are now adults.  ALSPAC will work to continue to collect data from the young people and their parents, as well as seeking to extend enrollment to the offspring of the study children: the third generation of the ALSPAC cohort.  Legal Basis This DSA is supported by Section 251 (s251) support for other participants. When reviewing the application for s251 the Health Research Authority’s Confidentiality Advisory Committee (CAG) recommended that the conditions attached to the support should differ depending on the sensitivity of the data in question. Health data (which are all considered sensitive within the Data Protection Act) were considered to be either ‘sensitive’ or having ‘particular sensitivity’. It was considered that health records relating to Mental Health, Sexual Health and termination of pregnancy should all be considered as being particularly sensitive. This means the s251 legal basis differs between records of standard sensitivity (e.g. A&E admission for a broken bone) and those with particular sensitivity (e.g. admission for psychiatric disorder). The ‘primary application’ provides support to access and use all records with a standard sensitivity. Primary application reference: ECC 1-05(b)/2012 – ALSPAC Study Young Adults: Enrolment and Consent for Record Linkage (Lead: Macleod); The s251 support from this primary application is conditional on the particularly sensitive records being excluded from the extraction (e.g. those relating to mental or sexual health conditions cannot be extracted). However, this condition can be overridden by subsequent supporting applications, which justify at a project level the case for ALSPAC to access particularly sensitive records. Within each of these applications the researchers request support to extract and use a range of particularly sensitive records. ALSPAC have received s251 support for five of these supporting applications. Supporting applications: CAG 7-06(a)/2013 – Accuracy of estimates for selfharm 14/CAG/1032 – Association between IQ and selfharm 15/CAG/0175 – Early life causes of depression and anxiety 15/CAG/0176 – Predictors, prevalence and impact of chlamydia 15/CAG/0177 – Substance use and mental health To accommodate the filtering needed for s251 cases (both to remove certain particularly sensitive records and national patient objectors) the ‘pipelines’ have been split in the flow diagram and narrative description between MR1048a: consent (applied for under a separate agreement), and, MR1048b: s251. ALSPAC participants are free to object to the studies use of their records in this way at any time. Records of objections are stored in the central ALSPAC database. ALSPAC will ensure that objectors wishes are upheld and they will not be included in the list of MR1048b participants for whom records are requested. Previous data extracts ALSPAC received flagging and tracing extracts for many years. Also, in 2013, ALSPAC received an extract of HES records for ~3,000 consented index children . This extract was envisaged to be a technical pilot and to investigate exemplar hypotheses. Impact on Health and Social care ALSPAC work with NHS clinicians and advisors in a range of disciplines. Current projects include work conducted with: Director of the National Chlamydia Screening Programme, NHS ‘Bristol Health Partners’ Director of the Sexual Health Improvement for Population and Patients Health Integration Team, National Suicide Prevention Strategy Advisory Group member, NHS ‘Bristol Health Partners’ Director of the Addictions Health Integration Team and Chair of the National Advisory Group to Welsh Government on Suicide and Self Harm prevention. In this way it is ensured that the improved understanding of health and social care generated by the use of ALSPAC-NHS Digital data are flowing back into the NHS, through: academic routes (publication and conferences such as the Society for Academic Primary Care and Farr Institute Conferences); through clinical groups (e.g. the Bristol Health partners HITs) and advisory boards (e.g. National Suicide Advisory Group); direct feedback into improving service provision (e.g. National Chlamydia Screening Programme); and feedback into Government policy (e.g. ALSPACs contributions to the Marmott Review ‘Fair Society, Healthy Lives’). A past example of this is the role ALSPAC played in the ‘back to sleep’ intervention that aimed to reduce rates of sudden infant death syndrome (aka ‘Cot Death’). ALSPACs used its early life information to research the long-term development pathways of children put to sleep on their back. ALSPAC's findings reassured sceptical health professionals (concerned that putting children to sleep on their backs impacted on child motor development) and contributed to policy change in the UK and overseas; a policy change which has subsequently been credited with substantially cutting rates of sudden infant death. Specific purposes Linked health record extracts are requested to inform investigations into the following 10 questions: 1. The effect of substance use in adolescence on mental health (see HRA CAG 15/CAG/0177) Investigators: Senior Research Associate for PEARL, Professor in Clinical Epidemiology and Primary Care (all University of Bristol contracted staff). HES and MHSDS data will be used, along with GP data, to investigate the association between mental health outcomes in young people and substance use in adolescence. ALSPAC will consider the use of three of the most widely used substances (alcohol, cannabis and tobacco), and their association with a diagnosis of a mental or psychological disorder in general, and specifically a clinical diagnosis of mood disorder (e.g. depression), anxiety or psychotic disorder (e.g. schizophrenia). ALSPAC collected data will provide information on substance use exposure and NHS Digital and GP data will provide objective assessments of mental health outcomes. NHS Digital and GP data may be used (where possible) to assess reporting accuracy within the self-reported data and to inform strategies to deal with missing data. This research will improve understanding of the risks of substance use, and the patterns of health service use for young people with mental health problems. 2. Chlamydia testing, infection, and sequelae in young people (see HRA CAG 15/CAG/0176) Investigators: Senior Research Associate for PEARL, Professor in Clinical Epidemiology and Primary Care. ALSPAC will use HES data, along with GP records, to examine which factors influence Chlamydia testing, infection, and sequelae in young people. HES records will be used in the identification of pelvic inflammatory disease, ectopic pregnancy and reduced fertility amongst female ALSPAC participants with different evidence of exposure to Chlamydia (only negative tests, any positive tests, no evidence of testing). Reduced fertility will also be considered for male participants. 3. Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response (covered by CAG ECC 1-05(b)/2012) Investigators: Data Linkage and Information Security Manager, Senior Research Associate, Research Associate in Statistics/Epidemiology and Data Manager (PEARL) (all full University of Bristol employees) ALSPAC will investigate and describe 1) the reliability and validity of self-reported hospital admissions and those recorded in HES and MHSDS and 2) assess if individuals with adverse health status profiles are more likely to be missing from study follow-up assessments. This is methodological work which will support interpretation of ALSPAC data in other research projects (including the studies listed in this application) and also to support wider understanding and interpretation of bias in self-reported health status (e.g. in the NHS Survey of Mental Health and Wellbeing). This is increasingly important as ‘Big Data’ approaches in contemporary Data Science are being used to inform health policy development through the analysis of combined study data and routine records. 4. Investigating the accuracy of current estimates of self-harm (See HRA CAG 7-06(a)/2013) Investigators: Professor of Epidemiology, Research Fellow, Senior Research Fellow (all full University of Bristol employees) ALSPAC will use the data to investigate a) the accuracy of current estimates of self-reported self-harm in the community (exploring the impact of non-response bias and mis-reporting) b) the long-term risk of hospital admission for self-harm in those self-harming in the community. This information is of critical importance to prevent over or under-estimation of the magnitude of self-harm, as policies based on inaccurate estimates may lead to the wrong policy decisions and incorrect prioritisation of particular health risk factors. Findings will also help to identify risk factors for future self-harm hospitalisation, and improve understanding regarding the relevance of findings from population-based studies using self-report to clinical practice. 5. Early life causes of adolescent depression and anxiety (See HRA CAG 15/CAG/0175) Investigators: Senior Research Associate, Professor in Clinical Epidemiology and Primary Care (all University of Bristol contracted staff) The main research objective is to obtain accurate estimates of the association between maternal smoking and binge drinking during pregnancy and depression and anxiety in late adolescence and to investigate how (a) nonresponse and (b) misreporting in questionnaires affects estimates of this association. GP data will be used to provide depression and anxiety data for those individuals for whom we do not have self-reported information (just over 65% of the cohort). The secondary objective is to obtain accurate estimates of the prevalence of depression and anxiety in late adolescence. 6. Investigating the association between IQ and self-harm (see HRA CAG 14/CAG/1032). Investigators: Senior Research Associate, Professor in Clinical Epidemiology and Primary Care (all University of Bristol contracted staff) The main research objective is to obtain a more accurate estimate of the association between IQ and suicidal and non-suicidal Self-harm among adolescents and to investigate how (a) nonresponse and (b) underreporting in questionnaires affects estimates of this association. GP, hospital admissions and A&E data will be used to provide self-harm data for those for whom self-reported information is unavailable. The GP and hospital data will also be used to correct for any underreporting. The secondary research objective is to examine the extent to which adolescents seek GP help for self-harm and suicidal feelings. 7. Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records (supported by ECC 1-05(b)/2012) Investigators: Senior Research Associate, Data Linkage and Information Security Manager, Professor in Clinical Epidemiology and Primary Care, Professor of Paediatric Respiratory Medicine, Research Fellow (all University of Bristol contracted staff). ALSPAC will use the data to investigate a) the accuracy of current estimates of self-reported asthma in the community (exploring the impact of non-response bias and mis-reporting) and b) to calculate the extent of asthma severity from recorded hospital attendance/admissions as well as primary care emergency visits and treatment steps. There is concern that asthma may be socially patterned and that it is known that key exposure and confounders collected through observational studies certainly are. Therefore the concern is that assumptions made about the associations and confounding structures of relationships between environmental exposures and asthma outcomes may not be valid. Insights into the accuracy of ALSPAC self-reported and study clinic assessed asthma and the severity of asthmas will support our investigations into the genetic and environmental influences of asthma and current work into the impact of traffic pollution on asthma. ALSPAC will investigate i) the natural history of early wheeze in relation to later asthma outcomes; 2) the relationships between early wheezing and later clinical records to determine if a ‘severe asthma’ profile can be detected in early childhood; 3) compare the impact of smoking and biomarker data from ALSPAC and respiratory function; 4) investigate the relationships between childhood infections and wheezing phenotypes with asthma and lung function in later childhood. This may help confirm an association (identified elsewhere between early respiratory infection and decreased lung-function during childhood that may be antecedent to adult respiratory morbidity and possibly mortality; and, 5) investigate the relationships between treatment for asthmas in primary care, adherence to treatment and outcomes of asthma and lung function in later childhood and early adulthood. 8. Antecedent factors predictive of later ear disease (covered by CAG ECC 1-05(b)/2012) Project: Serious ear disease in later childhood and adulthood is distressing and burdensome on those effected and incurs treatment costs on the NHS. This project will investigate whether early signs of ear disease identified in ALSPAC at age 9 (categorised from photographs of the ear drum) are predictive of the development of serious ear disease requiring hospital treatment in later childhood and adulthood (as identified through HES). 9. Parental and child alcohol use and later child criminality and injury outcomes (covered by CAG ECC 1-05(b)/2012) The impact of parental and child alcohol use on child health and education is unclear, and have possible societal and service provider costs. ALSPAC has multi informant measures of parental alcohol use reported by the mothers and partners during pregnancy and throughout childhood (allowing comparison of maternal and paternal effects). ALSPAC have also collected child self-reported alcohol use and family-reported measures of child criminal and anti-social behaviour. These self-reported measures will be used to help understand associations between alcohol use and child outcomes including child alcohol use, criminal and antisocial behaviour and injury. As part of this investigation linked HES records will be used to contribute information on hospital admission (with codes related to injury linked to external causes of morbidity, i.e. alcohol) and attendance at A&E due to accidents and injuries. 10. Patterns of engagement with health and education services as predictors of child looked-after or in-need status (covered by CAG ECC 1-05(b)/2012). HES data will be used, along with ALSPAC self-reported data and education records (e.g. attendance rates) and extracted general practice data, to examine whether patterns of health service engagement (e.g. missed routine appointments, regular attendance at A&E or out-of-hours services, receipt of care for accidental injuries) are useful predictors of a child becoming in need or looked-after. ALSPAC are engaged with the nascent National Child Looked After Observatory and local (Bristol) safeguarding teams in order to effectively disseminate the findings. Findings will also be published in appropriate academic journals and through conferences and local workshops (in partnership with the South West BRC, NHS CLHARC West and Bristol Health Partners).

Expected Benefits:

The described investigations have defined primary objectives to improve the understanding amongst some of the most concerning and prevalent areas of adolescent health; i.e. those relating to depression, psychosis, self-harm and suicide and substance use. Through this innovative use of a cohort study of adolescents linked to health records ALSPAC can study exposure/outcome associations in marginalised groups (i.e. those in need/in care and those suffering from mental health conditions). Secondary objectives relate to a better understanding of self-reported measurement error which will be used to inform interpretation of evidence emerging from longitudinal research studies and therefore improve the accuracy of evidence informing health and social care policy development. The project level anticipated benefits include: Project 1 (The effect of substance use in adolescence on mental health): This research will lead to a better understanding of the risks associated with substance use in adolescence, and the aetiology of mental health difficulties. It therefore has the potential to impact on public health policy. here is unlikely to be any major direct benefit to study participants, although the study involves a wider public health benefit. Study participants experiencing mental health problems may benefit from improved understanding of the cause of these, but such benefit is difficult to quantify. Project 2 (Chlamydia testing, infection, and sequelae in young people): Effective reduction of adverse sexual health outcomes depends in part on an understanding of the factors and processes that predispose an individual to experience these outcomes. Such understanding depends on the ability to consider the influence of exposures acting across the life course from early childhood. This research will lead to a better understanding of sexual health and testing behaviours in young adults. It therefore has the potential to impact on public health policy. Project 3 (Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response): Self-reported data suffers from participant reporting bias introduced by factors such as recall error (i.e. the ability to accurately remember and report information) or social desirability (i.e. where perceived social influences impact on the answers individuals give). This project will help inform researchers, public health officials and policy makers as to how to interpret findings generated using self-reported data. Separately, it is known that participants who respond to studies are different to those who do not, and there is potential for health effects to impact on individual’s likelihood to take part. Findings from this study will improve the understanding of study error (e.g. error’s in prevalence estimates introduced where the likelihood of follow-up is differentiated by social, demographic or health conditions). The potential benefits of Project 3 are illustrated by Project 4 and 5. While Project 3 will look at this in broad terms, Project’s 4 and 5 will study some of the same issues at more depth within the context of specific health status’s. Project 4 (Investigating the accuracy of current estimates of self-harm): Outputs from this project are of critical importance to prevent over or under-estimation of the magnitude of self-harm, as policies based on inaccurate estimates may lead to the wrong policy decisions and incorrect prioritisation of particular health risk factors. Findings will also help to identify risk factors for future self-harm hospitalisation, and improve understanding regarding the relevance of findings from population-based studies using self-report to clinical practice. Project 5 (Early life causes of adolescent depression and anxiety): Rates of anxiety and depression among children and adolescents in the UK have increased markedly in recent decades. Maternal smoking and alcohol consumption during pregnancy have been shown to be associated with many adverse psychological and behavioural outcomes among children, including in ALSPAC. ALSPAC would like to find out if these are risk factors for adolescent depression/anxiety. It is possible that the predictors of depression/anxiety may be different among individuals for whom self reported data is available, compared to those who are no longer participating in the study. Outputs will inform the methodological understanding of self-reported depression and anxiety and public policy development. Project 6 (Investigating the association between IQ and self-harm): Findings from the research will add value to epidemiological research on self harm and have wider benefit for the scientific community as it will increase ALSPACs knowledge of how best to combine self harm data from different sources. With the inclusion of GP data, it will build on work being undertaken by colleagues and allow researchers to make appropriate decisions regarding missing self reported data in their analyses. This research also has the potential to impact on public health policy as it will lead to a better understanding of who is at greatest risk of self harm. This is important in terms of the appropriate design and targeting of interventions. Project 7 (Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records): Findings will improve the understanding of asthma research based on the ALSPAC study and other studies using similar methodologies. Specifically, longitudinal approaches will allow greater understanding on precursor GP reporting (e.g. presenting with wheeze) prior to diagnosis of asthma status. Accurate asthma status informed by objective assessment and therapeutic data will enable more accurate assessment of the environmental and genetic development influences of asthma and other respiratory conditions. Project 8 (investigating early signs of ear disease): Information about the prognosis of these early signs and their likely development into serious disease will inform clinical decision making about the need for early preventative surgical intervention, which is currently not known. Study findings will be published in appropriate journals and presented locally and nationally through specialist Networks. Project 9 (parental and child alcohol use and later criminality and injury outcomes): In part, this research will address the evidence gap on in utero substance use exposure on child outcomes. The importance of this work has recently been highlighted in a systematic review of the effects of maternal alcohol consumption in pregnancy on later child outcomes (see http://www.bris.ac.uk/news/2017/september/drinking-during-pregnancy.html for more details), and the confusion this generates with conflicting press reporting of 'safe' levels of substance use public health guidance for pregnant women. The research will also consider childhood exposure to parental alcohol consumption and later child/adolescent/young adult alcohol consumption and resulting patterns of criminality and personal injury. Evidence of complex health and social associations is lacking due to the challenge of building sufficiently rich and diverse data to inform these investigations. Our aim is that linked ALSPAC-HES-General Practice-Education records will inform understanding in this area and allow dissemination via relevant journals, press releases and appropriate networks as outlined in Outputs for Project 9. Project 10 (Patterns of engagement with health and education services as predictors of child looked-after or in-need status. It is known that children in care have poorer health and education outcomes than those not in care. Early identification of children at risk of care status will aid early intervention. If the project identifies strong predictors it will investigate the potential for them being incorporated into a predictive tool to be used by health or social care professionals. Such a tool could be embedded in clinical software and improve the early identification of risk, a key challenge in the safe-guarding of children.

Outputs:

All investigations are due to be conducted between 2018 and 2020. Timings of the dissemination via journal articles will be constrained by the nature of the peer-review system. ALSPAC employ dedicated communications experts to assist with dissemination and engagement. Public and professional publicity (e.g. press releases, twitter posts, newsletter and facebook articles) will be coordinated with the publication of findings. Dissemination via conferences and workshops will occur throughout the project period using interim results. For all the investigations, ALSPAC are committed to feeding back findings to our participants. Participants will be informed through the ALSPAC print and social media newsletters. ALSPAC have a strong track record of running study engagement events which are designed with input from participants. In recent years ALSPAC have held ‘data linkage’ themed evening lectures (e.g. http://www.bristol.ac.uk/alspac/external/presentations/how-we-are-using-your-records.pdf) and ‘ResearchFest’ (http://www.bristol.ac.uk/alspac/events/researchfest2012/), a day-long event with a wide series of public lectures in Bristol. Periodically the study produces a book (e.g. http://www.bristol.ac.uk/alspac/go/21st-book/) or YouTube videos (https://www.youtube.com/user/children90s) that describe findings and how participant data is used. ALSPAC works with national and local media to disseminate findings, along with local attractions such as the MSHED museum of Bristol Life. Study findings from the applications described in this application will be incorporated into future activities. ALSPAC will work with the University of Bristol press office and the team at Understanding Patient Data to promote the findings from these investigations (e.g. https://understandingpatientdata.org.uk/case-study/investigating-self-harm-young-people). The participants will be informed of the outputs through our press-release system (http://www.bristol.ac.uk/alspac/news/) and via our newsletters (http://www.bristol.ac.uk/alspac/participants/newsletters-leaflets/) and social media (https://en-gb.facebook.com/childrenofthe90s/ or https://www.youtube.com/user/children90s) Our specific project level dissemination plans are: Project 1 (The effect of substance use in adolescence on mental health):(See HRA CAG-15/CAG/0177) The findings will be disseminated through appropriate epidemiological and public health academic journals (e.g. Addiction, International Journal of Epidemiology, Epidemiology, Wellcome Open) and findings (including interim results) at conferences (e.g. Society Academic Primary Care, MRC Farr Institute). ALSPAC will also work with members of the NHS Bristol Health Impact Team to feed findings to local service providers. Project 2 (Chlamydia testing, infection, and sequelae in young people): (see HRA CAG 15/CAG/0176) This research will lead to a better understanding of sexual health and testing behaviours in young adults. It therefore has the potential to impact on public health policy. Findings will be published in an appropriate epidemiology journals or those dedicated to sexual health fgindings (e.g. International Journal of Sexual Health). The Senior Research Associate will lead professional dissemination based on understandings gained from his role as the Deputy Chair of the NICE Public Health Advisory Committee (PHAC-F), a committee responsible for the development of NICE public health guidance and is the Director of the NHS Bristol Health Partners sexual health for population and patients’ health integration team. Project 3 (Assessing the Validity of Self-Reported Hospital Admissions and the Implications of study non-response):(see ECC1/05(b)/2012) Insights from this work will be published in an appropriate epidemiology/survey methods journal (e.g. Society of Longitudinal and Life Course Studies, BMC Medical Research Methodology, Survey Research Methods), at similar conferences and via ALSPAC study website and the CLOSER longitudinal research consortium website. To ensure this information is fedback to the NHS ALSPAC will send the project findings to the Care Quality Commission ‘Survey Coordination Centre’ who facilitate NHS Surveys. Project 4 (Investigating the accuracy of current estimates of self-harm):(see HRA CAG 7-06(a)/2013 ) Results from the study will be published in a suitable epidemiology/psychiatry journal and via the ALSPAC study website. Preliminary work (based on those participants who provided consent to link their data with medical records) has been published in Archives of Suicide Research (http://dx.doi.org/10.1080/13811118.2015.1033121), and has been selected as a case study by the Wellcome Trust ‘understanding patient data’ taskforce (https://understandingpatientdata.org.uk/case-study/investigating-self-harm-young-people). To ensure this information is fed back to the NHS ALSPAC will communicate the project findings to the Bristol Health Partners ‘Improving Care in Self-Harm’ STITCH Health Integration Team. Professor David Gunnell (The project PI) is the academic lead for STITCH. DG is also a member of both England’s and Bristol’s Suicide Prevention Advisory Groups and works closely with Public Health England, and will feed back relevant findings into NHS and Public health strategy. Project 5 (Early life causes of adolescent depression and anxiety): (see HRA CAG 15/CAG/0175) Outputs will be published in academic journals (e.g. BMJOpen, International Journal of Epidemiology) and will inform methodological understanding of self-reported and public policy development. The Investigators will work with Prof. Ann John (University of Swansea, who will not have access to the data) to disseminate findings; Prof. John chairs the National Advisory Group to Welsh Government on Suicide and Self harm prevention and is honorary Consultant in Public Health Medicine with Public Health Wales. Project 6 (Investigating the association between IQ and self-harm):(see HRA CAG 14/CAG/1032) Findings will be published in academic publications topical to the condition and/or epidemiological methods (e.g. BMC Medical Research Methodology). The researchers will work with Professor Gunnell to ensure wide dissemination of study findings within relevant NHS community (see Project 4). Project 7 (Enabling the cross validation of asthma diagnosis using combinations of symptom and physiological data with GP and Hospital records):(supported by ECC1/05(b)/2012) Findings will improve the understanding of asthma research based on the ALSPAC study and other studies using similar methodologies. Understanding will be disseminated via the Medical Research Council and Asthma UK funded STELAR asthma research consortium. Findings will help support research by the Medical Research Council and Natural Environment Research Council ERICA study that will assess associations between traffic pollution exposure and asthma outcomes in ALSPAC index children. The findings will support Prof. Henderson’s programme of work, as a part of which he was a lead contributor to the Royal College of Physicians ‘Every Breath We Take’ report into the lifelong impacts of air pollution (https://www.rcplondon.ac.uk/file/2914/download?token=qjVXtDGo). Project 8 (Antecedent factors predictive of later ear disease): (supported by ECC1/05(b)/2012) The Senior Research Associate in Medical Statistics and the Professor of Community Child Health will use the data to conduct the research evaluation. Clinical expertise will be provided by a Research Fellow in Social and Community Medicine and a Lecturer/NHS ENT surgeon, neither of whom will be provided with access to the data. Academic findings will be published in journals (e.g. International Journal of Audiology, BMJ Open, PLoS ONE). Study findings will be disseminated via the ENT liaison with the local CCGs Clinical Policy Review Groups. On a national level the ENT Specialty Lead for the NIHR Clinical Research Network: West of England will disseminate via the ENT National specialty group. Project 9 (parental and child alcohol use and later criminality and injury outcomes): (supported by ECC1/05(b)/2012) This work has been funded by the UK Medical Research Council and findings will be disseminated through academic routes (i.e. public health and health practitioner journals such as the BMJ as well as conferences such as the Society of Academic Primary Care), press releases and feedback to Department of Health policy makers. The Director of the NHS Bristol Health Partners ‘Drug and Alcohol’ Health Impact Team and will feed findings through into local care providers via this network. Project 10 (Patterns of engagement with health and education services as predictors of child looked-after or in-need status): (supported by ECC1/05(b)/2012) Research findings will be disseminated by the emerging National Family Justice Observatory and the Children Looked After and In Need strands of the Administrative Data Research Network. We will publish our findings in relevant academic journals (e.g. Epidemiology, Wellcome Open, Child & Family Social Work, British Journal of Social Work, Adoption and Fostering). We will disseminate relevant project findings to charities (e.g. NSPCC) and the NHS England ‘National Looked After Children Safeguarding Sub Group’.

Processing:

Filtering based on Legal Basis: The CAG committee (in ECC 1-05(b)/2012) requested that ALSPAC distinguish between health records with normal sensitivity (e.g. relating to a broken leg or having asthma) and those that are particularly sensitive (including all mental health and sexual health records). ALSPAC have listed (using health codes) all the particularly sensitive types of records in existence. This list will be used to ‘filter’ out the particularly sensitive records for which there is not s251 support and must therefore be excluded from the extract. This filter list has been altered to include the particularly sensitive records needed for the research investigations included in this project and which are allowed under ALSPACs further s251 approvals. This has resulted in an ‘inclusion list’ of all the codes that have s251 support, and are to be extracted and provided by NHS Digital to ALSPAC. The technical feasibility of applying this inclusion list within the ALSPAC extract has been considered and agreed by NHS Digital staff. Steps are taken when generating the extract to ensure that particularly sensitive records which are not in the inclusion list neither appear in the extract, nor their presence can be inferred by ALSPAC when they receive the data. This is little difference in principle than a typical minimised data request based around a specific event (e.g. to extract coronary heart disease records only), only in this instance, there is a very wide range of specific events. Process Stage 1: Linking ALSPAC participants to the NHS/NHS Digital demographic database (this stage has already taken place and further linkage will only be applicable for those cohort participants not originally linked) ALSPAC have provided the NHS Digital (then NHS IC) with the personal identifiers of its study participants. NHS Digital commissioned linkage of the ALSPAC identifiers to the NHS central demographic register (now the NHS Spine). The product of this linkage (a link between ALSPAC MR1048 ID to NHS ID for each participant) is stored by NHS Digital and can be used to identify ALSPAC participants amongst NHS Digital records. Additional linkage may be required for newly enrolled cohort participants (approximately 15,000 of 20,000 eligible families are enrolled, but small numbers of the remaining 5,000 continue to enrol). A new Study ID will be allocated to these records. ALSPAC will securely provide NHS Digital with separate lists identifying (by Study ID) our MR1048b:s251 participants. The lists will be filtered for up-to-date consent/dissent/withdrawal from ALSPAC status prior to sending. Process Stage 2: NHS Digital Extraction of Records HES and MHSDS records of ALSPAC participants will be identified using the existing MR1048 link and NHS Digital will extract copies of participants records where found (with the same processing for ‘new’ cohort participants). The extract for MR1048b: s251 will be filtered (as described above) to erase the existence of the ‘sensitive’ records (in such a way that it cannot be determined that they previously existed) and to exclude any participants who have registered a national patient data sharing objection. The MR1048b:s251 extracts will be sent to the ALSPAC Data Safe Haven. The extracts will be identified by Study ID and a check identifier (Date of Birth) to allow validation of the linkage. The extract will be sent to ALSPAC via the NHS Digital secure methodology (e.g. secure download site in an encrypted file). As ALSPAC are able to map MR1048 ID back to the ALSPAC administrative database these data extracts should be considered as being identifiable (even if pseudonymised). The extracts will be received into the ALSPAC Data Safe Haven; which is managed by a small, specialist, team of ALSPAC health informatics experts (employed by the University of Bristol). The data will be stored on a secure encapsulated virtual machine located at the University of Bristol. The safe haven is kept separately from the ALSPAC administrative database (which contains participant identifiers). The Data Safe Haven design has been adopted to restrict access to identifiable data used for secondary purposes and to support the de-identification of the data prior to the bulk of the data uses. The Data Safe Haven governance arrangements have been reviewed and approved by an NHS Research Ethics Committee (REC) and the Health Research Authorities Confidentiality Advisory Group (HRA CAG). The Data Safe Havens security arrangements have been independently audited and certified to the NHS IG Toolkit and ISO27001 security standards (described below). Process Stage 3: Data processing in the ALSPAC Data Safe Haven The ALSPAC Data Safe Haven was designed in accordance with NHS policy [3]. Incoming, identifiable, data is stored in an encrypted format on encrypted and firewalled demarcated server space. Access to this server space is restricted to the Data Safe Haven team (by user access controls and access is only permitted from a small number of desktop computers based in secure offices at the University of Bristol). On entry to the Data Safe Haven a copy of the data is archived. The data are processed for the following purposes: i. Assess Data & Data Linkage Quality: The data extract is compared against the agreed extract specification to ensure the content (both in terms of variables supplied and patients included) is correct. The linkage between ALSPAC participant and NHS record is quality checked using check variables (e.g. NHS ID to ALSPAC ID link is checked using date of birth and gender). The data values will be subject to logical error checks to assess if the value is consistent with the expected values (as defined in the source documentation). Inconsistent values will be recoded to missing (i.e. ALSPAC will not attempt to infer a correct value); ii. Derivation: Derived data are created in order to assist in the de-identification of the data (e.g. Age in days at the time of a health event will be derived from Date of Birth and the event date) and to distil records extracted from multiple sources into a cohort longitudinal record (e.g. age in days will allow accurate sequences of events to be created when combining NHS Digital data with other data), and to assist the research process (e.g. 1) a range of read codes, hospital admissions and prescription data are used to derive an indicator to whether an individual has had any interaction with the NHS relating to/or being coded as asthma, and 2) routine records are used to inform statistical techniques, such as multiple imputation, which can address missing self-reported data). All derivation routines are applied through computer syntax, which is stored along with a documented record of the derivations; iii. Linkage: The extract is linked to the internal ALSPAC individual ID numbers. The quality of the match is checked (see above). Linkage success or failure is assessed and documented within the data set (e.g. ALSPAC attempts to distinguish between failure to link due to a patient not seeking consultation, with failure to link due to insufficient identifiers and failure to link as the individual is resident outside of the catchment area of the data extract in question). The extract is processed to ensure it is harmonised with the ALSPAC longitudinal data set; iv. De-Identification: The Safe Haven de-identification processes are designed to minimise the risks of disclosure through either: direct identification of an individual from a dataset (either accidentally or maliciously); through inference or through the potential of variables in combination to identify individuals; or the potential of inappropriately described outputs to identify individuals. The data are pseudonymised through removing NHS ID, name and address (where present). The extract is stored, within the Data Safe Haven, until information from it is requested for a research investigation. v. Collation, Storage & Archiving: Copies of the data shared with researchers will be held securely within the Data Safe Haven. These will be used for audit purposes, to keep a record of research project sample selection (in order to allow follow-up assessments) and to fulfil the requirements that peer-reviewed findings are reproducible. The identifiable data are only used for these data processing purposes, i.e. to facilitate and support research. The Identifiable data are not used in research investigations. Process Stage 4: Participant Tracing Data Where the data extracted from the NHS Digital relates to participant contact details and status (e.g. left England and Wales, fact of death) the members of Data Safe Haven staff will swap the ID used to extract the data for ALSPACs internal system ID and will then pass the information to the ALSPAC team whose role it is to maintain communications and relationships with participants. Neither NHS IDs or clinical data (beyond ‘alive/deceased’ status) will be provided to this team. The details are then used to update ALSPACs administrative database. These details are not provided to researchers, although address information is used to derive spatial identifiers and other values which are used in some research projects in a non-disclosive form. ALSPAC will use a MRC Farr Institute ‘UK Secure eResearch Platform (UKSeRP) as a ‘secure research environment’ to combine records from different sources and to manage access to effectively anonymous sub-sets of combined records to specific researchers at a project level. UKSeRP is the technological infrastructure which supports the SAIL databank of Welsh routine health and administrative records. UKSeRP was developed by the Welsh MRC Farr Institute and is operated by two organisations: The NHS Wales Informatics Service (NWIS) and the University of Swansea Health Informatics Research Unit (HIRU). HIRU, through the MRC Farr Institute are making the UKSeRP infrastructure available to other research organisations. This means ALSPAC can make use of the full advantages of the secure research infrastructure developed to support SAIL by contracting the University of Swansea to provide a copy of the infrastructure to host ALSPAC data and data linked to ALSPAC. In this contractual arrangement, the University of Swansea will be Data Processor working to instruction from the University of Bristol who will be Data Controller (the contract will bind the University of Swansea to the same conditions (where relevant) as the University of Bristol have agreed to in their contract with the NHS Digital). UKSeRP has ISO27001 certification. This principle has been previously agreed as suitable for hosting linked NHS Digital records. Process Stage 5: Linking ALSPAC participants to the UKSeRP (this stage has already taken place and will not need repeating). UKSeRP operates on a ‘split file’ approach to handling data; where identifiers are handled separately from clinical or individual attribute data. Identifiers are processed by NWIS (within the confines of the NHS); where they are processed by an algorithm which consistently converts incoming identifiers (e.g. NHS ID, name, date of birth) into an encrypted ‘Anonymous Linkage Field’ (ALF). In this way identifiers relating to the same person coming from multiple sources can be linked to the same ALF. ALSPAC have already sent the identifiers to NWIS along with an externally meaningless ID number (KEY ID). NWIS have used the identifiers to create ALF IDs for ALSPAC participants. This is managed in such a way that 1) neither ALSPAC nor HIRU (who manage clinical data) are able to trace back ALF to a person’s identity and 2) ALSPAC are able to send clinical and other attribute data linked to KEY ID into the system which can then be automatically replaced with ALF in a ‘black box’ process. Process Stage 6a & 6b: Sending NHS Digital and ALSPAC data from ALSPAC into the UKSeRP ALSPAC research staff will replace the IDS on the de-identified data from the ALSPAC resource with the Key ID. The data will then be securely sent (using AES-256bit encryption) into the ALSPAC UKSeRP via the automated ‘gateway’ upload appliance. ALSPAC data safe haven staff will also conduct the same process on the de-identified (see Stage 3) HES and MHSDS data. The HES and MHSDS data will then be securely sent (using AES-256bit encryption) with Key ID into the ALSPAC UKSeRP via the automated ‘gateway’ upload appliance. Process stage 7: The UKSeRP automated gateway system automatically replaces Key ID on incoming data with ALF ID (yet the system has no access to identifiers of the individuals used to produce ALF as these never leave the NWIS trusted third party). The data are then deposited in the ALSPAC UKSeRP. Meaning the ALSPAC staff have no means of linking ALF back to the ALSPAC databases, yet can use ALF to join records coming in from different sources or at different times (e.g. longitudinal updates). Process Stage 8: Sub-setting and further anonymization of data prior to analysis The researchers with approval to access the ALSPAC HES and MHSDS data will be created project specific ‘containers’ in UKSeRP that they can access. ALSPAC Data Safe Haven staff will sub-set the extracted data to minimise it to only the information needed to conduct the project investigation. Each project data set will be given its own unique ID. The researchers will not have access to the ALSPAC administrative database and therefore – given the technological, contractual, training and data management steps involved – the data can be considered to meet the Information Commissioner’s Office ‘effectively anonymous’ requirements (as defined in the ICO Anonymisation Code Of Practice – a separate document is included describing how our process meets the ICO requirements). Information about these hypotheses – and the use of NHS data sourced from the NHS Digital – will be posted on the study website: www.bristol.ac.uk/alspac/participants/young-people/. Participants have been notified about this information, and each study newsletter includes updates and reminders (e.g. page 2 of: www.bris.ac.uk/alspac/external/newsletters/Childrenofthe90s_familynewsletter_2015.pdf ) Participants are able to opt-out of each individual study (before the study starts). This mechanism for providing on going fair processing information was developed with the HRA CAG with input from the Information Commissioners Office. Project specific datasets are risk assessed and disclosure control is applied as deemed appropriate. Further disclosure control ranges from suppression of rare values and outliers to a state where the possibility of disclosure is rendered so challenging that the data can be considered as being effectively anonymised in line with the HSCIC Anonymisation Standard for the publication of Health and social Care Data [4]. Case selections will be assessed for risks of disclosure through inference (e.g. where a sample selection is made on the basis of a health condition), where this is a risk the Safe Haven staff will add control or masking cases. The ALF used in the hypothesis specific dataset will undergo secondary encryption (reversible by ALSPAC) using an algorithm specific to each project. This means that a researcher with multiple project will not be able to join data across the different datasets using ALF. Process Stage 9: Researcher access to data Researchers are all contracted to University of Bristol (as described below). They will only be able to access the sub-partition(s) of the ALSPAC UKSeRP where their project specific data set is located. The UKSeRP technology restricts the actions that researchers can take, for example, it is not possible to plug in a USB stick, or to copy and paste or to connect from within UKSeRP to the internet. These restrictions – in conjunction with the training and binding agreements the researchers enter into – ensure good governance is maintained. Furthermore, the anonymization processes undertake (stages 3 and 6) are sufficient to reduce the risks of participant identifiably to a point that they are so remote that the data can be appropriately treated as effectively anonymous. Researchers are allowed to remove data outputs (e.g. statistical findings, graphs, tables of aggregated findings) from UKSeRP through a controlled process where each output is reviewed and assessed for disclosure risk by ALSPAC Data Safe Haven staff prior to being released. ALSPACs Data Access policies require that researchers submit all publications, prior to submission for publication, to the ALSPAC Executive. The Executive Committee assess the publications for issues including checks for potential disclosure risks (e.g. tables summarising statistical outputs containing small cell counts). Disclosure checks will ensure compliance with the small number suppression rules contained within the HES Analysis Guide. Data Specification: ALSPAC require life-course data from birth (i.e. maternity HES from 1990-1993) to the most recent finalised datasets (it is appreciated that the records contained within different HES domains start at different points in time). This will allow the assessment of changing health status over time, changing severity of health status and the precursor health events leading up to health outcomes. ALSPAC require detailed information about these in order to build event sequence records comprising study collected information, linked health and social care records from NHS Digital and linked records from other providers (e.g. national pupil database records). The data request is limited to the cohort participants, but not limited geographically (given that our participants have moved away from the original cohort catchment area). ALSPAC is requesting that the extract is filtered to remove some particularly sensitive fields (to comply with the s251 approval conditions), but are not filtered for any other reason (i.e. a full range of health event information is needed in order to establish health status sequences for our diverse projects). Information Security: ALSPAC are committed to maintain high standards of information security and recognise that this is a key component of the trust relationship with participants and data owners alike. To achieve these standards ALSPAC have developed an Information Security Management System and associated management and governance structure that has been certified as meeting the ISO/IEC 27001:2013 Information Security standard. ALSAPC have submitted an NHS IG Toolkit assessment (edition 14: 2016/2017) which scored 97% in our last assessment. In the event the participant changes their mind, then ALSPAC have a defined ‘withdrawal of consent’ protocol, which is available to participants via the study website: - http://www.bristol.ac.uk/alspac/participants/ The policy allows participants to tailor their involvement in the study; either by altering permissions for the use of their health records in a specific project, the use of their health records in general, or their continued involvement in the study. Research Purposes: Observational epidemiology aims to build a body of evidence related to any given topic. The investigations detailed below are designed to add to the relevant evidence base within that field. In themselves, these will typically not directly change NHS process. However, if replicated elsewhere and found to be important through systematic review then this could lead to policy change (e.g. NICE guidelines are frequently developed using systematic reviews of evidence). This is in contrast to other types of research (e.g. randomised controlled trial interventions or drug trials) that may provide stronger evidence of causation and can hence can lead to more immediate impact. To ensure full potential for impact on health and social care system, ALSPAC will ensure that the findings of the investigations are well placed to feed into this process through ensuring publication in peer-reviewed journals that are fully indexed (e.g. pubmed, medline) and contain strong descriptive keywords (i.e. the findings will be discoverable by those conducting systematic reviews). This is the standard pathway to impact for observational research. Where possible, ALSPAC will also directly feed findings into national or local health care initiatives, and this is described where relevant (see below). The ALSPAC Data Safe Haven team who will process the data are:Data Linkage and Information Security Manager, Data Manager (PEARL), Research Associate in Statistics/Epidemiolog and the Senior Research Associate. All are University of Bristol contracted staff. The Safe Haven team will prepare the data extracts and also give ‘Data Science’ input into the research process (i.e. through offering expert guidance on ALSPAC, data linkage processes, and on the interpretation and statistical processing of linked records within an epidemiological context). As such they will undertake processing which from data management to research analysis. None of the data requested will be linked with any other data, apart from the linkages permitted in the DSA. Additionally there will be no attempt made to re-identify individuals from the the previous extract of consenting index children


Project 9 — DARS-NIC-17875-X7K1V

Opt outs honoured: N

Sensitive: Non Sensitive

When: 2016/04 (or before) — 2017/11. breached contract — audit report.

Repeats: Ongoing

Legal basis: Health and Social Care Act 2012

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients

Objectives:

University of Bristol (UOB) School of Social and Community Medicine (SSCM) will use the data for a programme of work based around identifying the magnitude and causes of variations in outpatient care, unplanned admission rates and procedure use. The work is funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West) (see: http://clahrc-west.nihr.ac.uk/). The CLAHRC West brings together a collaboration of the local providers of NHS services and NHS commissioners, universities (including UOB-SSCM), patients and members of the public. It conducts applied health research and implements research evidence, to improve health and healthcare across the West of England. The purpose of this programme of work is threefold: 1. Estimating the magnitude of variation UOB-SSCM aims to identify the clinical areas where outpatient care, unplanned admission rates and procedure use differ substantially across England. High variation is likely to be the result of clinical uncertainty in the optimal pathway of care including: when to refer patients for a specialist opinion; when to admit patients, and which procedures they should receive once admitted. Identifying high variations in care allows research funders and NHS managers to prioritise research towards the areas where additional evidence has the greatest potential to improve and standardise healthcare. For example, UOB-SSCM have previously demonstrated that admissions for hip fracture, where the diagnosis and need for admission are clear cut, vary much less than admissions for senility/dementia where making a diagnosis and judging the need for admission is more difficult. As the aim of this analysis is to identify new areas of exploration, rather than simply confirm that variation is present in clinical areas where it is already known to exist (e.g. mental health care, tonsillectomy), it is essential that it starts from a broad base. UOB-SSCM previously used the HES data from 200708-2011/12 to identify the most geographically variable therapeutic procedures. This study considered the 154 most common procedures which were recorded in 17.8 million finished consultant episodes. UOB-SSCM’s proposed analysis of the latest data will be at least as large and will require an unfiltered dataset. UOB-SSCM requires data on patients admitted in the previous ten years to investigate how geographic variation has evolved over time. Ref: www.ncbi.nlm.nih.gov/pubmed/25879119 2. Investigating the causes of variation UOB-SSCM aims to explore the causes of variation in hospital outpatient care, admission rates and procedure use. UOB-SSCM will use other freely available datasets (e.g. quality and outcomes framework, GP patient survey) to better understand how the characteristics of an area (e.g. age-sex composition, deprivation) or an organisation (e.g. availability and continuity of primary care) are related to hospital admission rates / procedure use. Understanding the causes of geographic variation will help inform the design of interventions that may be most successful in standardising care around best practice. UOB-SSCM has previously used HES data to demonstrate the associations between unplanned hospital admissions, GP proximity to A&E departments and hospital bed availability. This type of observational evidence has played a crucial role in current initiatives to co-locate GP services with A&E departments to triage and prevent unnecessary admissions. Refs: http://www.ncbi.nlm.nih.gov/pubmed/21719477; http://www.ncbi.nlm.nih.gov/pubmed/21183192 3. Identifying opportunities for disinvestment UOB-SSCM will work with the seven partner CCGs of the CLAHRC West to identify clinical areas where there may be an over-use of care locally. Identifying and reducing over-utilisation to free up resources for other, more productive activities is commonly termed ‘disinvestment’. For example, in previous work UOB-SSCM worked with a local CCG to explore why local rates of laser capsulotomy (to improve 'cloudy' vision after initial cataract surgery) were apparently much higher than the national average. Analysis revealed that locally procedures were performed as (more expensive) day cases, whereas elsewhere the procedure was done in the (cheaper) outpatient setting, therefore identifying an opportunity for CCG savings. Part of these investigations will include a time trend analysis to identify if local high utilisation is a recent phenomenon or if differences are more entrenched over time which will require multiple years of inpatient and outpatient data. UOB-SSCM’s plans for this programme of work have been strongly supported by local NHS organisations through the Bristol Health Partners (a strategic collaboration between the city's three NHS trusts, three clinical commissioning groups, two universities and its local authority) and the West of England Academic Health Science Network (a collaboration of healthcare organisations, industry, universities, research bodies and patients). Ref: www.ncbi.nlm.nih.gov/pubmed/25879119 UOB-SSCM require multiple years of data to investigate if geographic variation has increased over time. Having previously received only inpatient data, UOB-SSCM requires outpatient data because many minor procedures may be performed in the outpatient clinic or as day cases. In accordance with the Data Protection Act, UOB-SSCM are minimising the data held by requesting a smaller amount of outpatient data, excluding earlier years when data were considered experimental. UOB-SSCM will be requesting their HES extracts to be updated annually. With each update, UOB-SSCM will destroy the oldest year of data on its server meaning that only ten years of data will be held on the server and be available for active data analysis at any time. UOB-SSCM will follow established best practice by archiving the dataset underpinning work published in medical journals for five years after publication to ensure that queries or disputes can be appropriately addressed.

Expected Benefits:

Estimating the magnitude of variation UOB-SSCM will disseminate lists of the most variable conditions / procedures using journal articles. These articles will be aimed at research funders, commissioners and clinicians. The output will help research funders identify where the most important treatment uncertainties exists and prioritise research to these clinical areas. For example, in previous work high variation in transluminal and combined varicose vein procedures flagged up the clinical uncertainty about the use of minimally invasive techniques and the criteria for when each procedure is appropriate. This research has the potential to reduce treatment uncertainties and lead to more standardised and better quality care, and improved patient outcomes. Although the immediate impact of this research will be difficult to measure, UOB-SSCM would expect benefits from 2017 onwards. Ref: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0081522/ Investigating the causes of variation Work exploring the causes of geographic variation will be aimed at NHS commissioners. The output will help NHS commissioners by providing insight into the influence of population and organisational factors on admission rates / procedure use. For example, in current work UOB-SSCM identified continuity of GP care, rather than accessibility of GP care, as a key factor in reducing unplanned hospital admission rates. UOB-SSCM has previously used HES data to investigate how demographic, geographic and NHS institutional factors affect emergency hospital admissions which has added to the debate around the most appropriate structure of English general practice. This type of observational evidence has played a crucial role in the design of the NHS and has directly influenced recent government-led initiatives to provide 7-day primary care access and increase hospital staffing levels at weekends. UOB-SSCM expects the analysis to have an effect on NHS policy and, although the effect will be difficult to evaluate, UOB-SSCM would expect benefits from 2017 onwards. Identifying opportunities for disinvestment Work identifying opportunities for disinvestment will be aimed at commissioners in the seven partner CCGs of the CLAHRC West. UOB-SSCM will collaborate with individual partner CCGs to better understand the causes of high admission rates or procedure use and, where appropriate, help design interventions to reduce utilisation to more appropriate levels. Helping commissioners appropriately disinvest from poor-value healthcare will free up resources for more cost-effective treatments and will result in patient benefit. In a previous project UOB-SSCM undertook a benchmarking process with Suffolk PCT to identify clinical areas where disinvestment was necessary. UOB-SSCM identified high utilisation of carpal-tunnel surgery, which was centered on one of the two hospitals in the area, leading to the PCT to change the provider of these services which reduced costs and released funds for other healthcare activity.

Outputs:

Estimating the magnitude of variation 1) Publish national-level analysis of variations in procedure rates in peer-reviewed medical journal by December 2017. 2) Publish national-level analysis of variations in unplanned admissions and outpatient care in peer-reviewed medical journal by December 2017. Investigating the causes of variation 1) Explore temporal and geographic variations in specific procedures and medical admissions in a series of peer-reviewed medical journals by December 2018. Identifying opportunities for disinvestment 1) Benchmark local CCG unplanned admission and procedure rates against the national average. Provide report to each local CCG by December 2016. All outputs will include only aggregate data with small numbers suppressed in line with the HES analysis guide. No record level data will be shared with third parties including the partner CCGs.

Processing:

The data will be processed in the following way: Data preparation Upon receiving the data from the HSCIC, UOB-SSCM will store it on its secure server located Canynge Hall, Bristol. The data can only be accessed by authorized personnel with user accounts on UOB-networked computers. The network can be accessed remotely but all processing is logically on the server based at Canynge Hall and no data is removed from that server and the authorised personnel are all employees of UOB. UOB-SSCM will take following steps to create analysis datasets for the programme of research. 1. Analysis datasets will be created using an SQL query. UOB-SSCM will use filters (e.g. procedure codes, diagnosis codes), and restrict the data fields to those that are strictly required, to ensure the size of the analysis dataset is minimised. 2. Identify the finished consultant episodes to be included in the analysis based on diagnosis or procedure codes. 3. Count the number of unplanned hospital admissions / procedures within each CCG and GP practice. 4. Use appropriate methods (e.g. indirect standardisation, Poisson regression) to adjust for differences in need (e.g. age, deprivation) between CCGs and practices. Descriptive analysis This analysis will use the data produced from the ‘Data Preparation’ phase. Descriptive analysis will involve all ten years of data, to understand how the characteristics of patients has changed over time. 1. Describe the characteristics of patients admitted for each condition / procedure including demographics (e.g. age), admission details (e.g. source, method) and discharge details (e.g. source, method). Estimating the magnitude and understanding the causes of variation This analysis will use the data produced from the ‘Data Preparation’ phase. UOB-SSCM will calculate estimates of variation for each of the ten years of data. 1. Use appropriate methods (e.g. hierarchical models) to quantify variation in unplanned admission rates / procedure use between CCGs. 2. Rank conditions / procedures from the most to least variable. 3. Use appropriate methods (e.g. regression) to calculate trends in variability over time. 4. Use appropriate methods (e.g. Poisson regression) to investigate how demographic, geographic and NHS institutional factors affect unplanned hospital admissions and procedure use. Identifying opportunities for disinvestment This analysis will use the data produced from the ‘Data Preparation’ phase. UOB-SSCM will use the most recent year’s data to identify opportunities for disinvestment and will supplement this with a time trend analysis describing how local and national have differed over the previous ten years. 1. Rank conditions / procedures based on the difference between the local and national rate for each partner CCG. This will provide a starting point for conversations around potential opportunities for disinvestment. 2. Calculate time trends in the difference between national and local rates to understand if local high utilisation is a recent phenomenon or if differences are more entrenched.


Project 10 — DARS-NIC-207953-Q9H2M

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2016/11. breached contract — audit report.

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

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Flagging Current Status Report
  • MRIS - Personal Demographics Service

Objectives:

The Cleft Collective project's aim is to create the infrastructure, capacity and resources necessary to gain important new knowledge that will advance our understanding of the causes of cleft lip and/or palate, inform treatment and ultimately improve the lives of children, adolescents and adults with the condition through the creation of a Birth cohort study and a Five-Year cohort study.   We are conscious of the fact that a member of our cohort may die while we are out of contact with the study family and we wish to minimise the risk of upsetting them by attempting to make contact without knowing the circumstances. We also believe that learning of an individual's cancer registration will provide vital health information for this research project. Through continued notification of these data, The Cleft Collective will accumulate data that will enable studies to be undertaken on the environmental and genetic factors related to cleft. To clarify, we would like to receive the full range of data provided by the IC Flagging and Tracing service. Statistical analysis will take place at such times as the numbers in any particular group suggest that this would be feasible. Statisticians and researchers do not have access to the personal details of the study participants. Disclosure control mechanisms will be employed to limit the risk of disclosure through small cell counts.


Project 11 — DARS-NIC-30560-W4V1T

Opt outs honoured: N

Sensitive: Non Sensitive

When: 2016/04 (or before) — 2016/08. breached contract — audit report.

Repeats: One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care

Objectives:

Between 2003 and 2006 the DRIFT study recruited premature infants with post-haemorrhagic ventricular dilatation. Infants were randomised to receive a novel treatment (drainage, irrigation and fibrinolytic therapy [DRIFT]) or standard therapy which consisted of lumbar punctures and if needed a ventricular reservoir to drain cerebrospinal fluid. Initial results (at age 2) were promising. In 2014, the NIHR Health Technology Assessment programme funded the DRIFT research team (based at University Hospitals Bristol and the University of Bristol) to conduct long term follow up of children at school age (i.e. 9 to 11 years). The aims of this long term follow up were to: 1) To compare cognitive function, visual function, sensorimotor ability and emotional wellbeing, between the two treatment groups in the DRIFT trial at school age. 2) To quantify functional status and use of community and specialist health and educational services. 3) To estimate the economic cost and outcomes of the DRIFT intervention by age 11, and model long-term costs and outcomes. 4) To quantify degree of ventricular dilatation and neurosurgical sequelae in the two treatment groups by clinical neuroimaging. As part of aim 3, the University of Bristol requests data from HSCIC on hospital care received by DRIFT participants since birth. The specific requirement is for Hospital Episode Statistics (HES) data on the subset of DRIFT participants who were born in England and whose parents have provided consent for us to access routinely collected health data. The analysis of HES data is taking place solely at the University of Bristol. The data will not be made available to any third party. Without these data from the HSCIC it would not be possible to judge whether the initial cost of the DRIFT procedure results in subsequent savings to the NHS through reduced hospital care during the first 11 years of life. If the initial costs of DRIFT are justified by NHS savings and improved health outcomes for children, this procedure will become used widely across the NHS.

Expected Benefits:

Infants born prematurely are at high risk of brain injury and major disabilities/neurodevelopmental impairments later in life. Bleeding into the ventricles of the brain is one of the most common consequences of being born very early and has a very high rate of serious disability such as cerebral palsy and learning difficulties. Drainage, irrigation and fibrinolytic therapy (DRIFT) was developed as a method of washing out the ventricles to clear the effects of the bleeding. The DRIFT randomised trial was conducted in 2003-2006 among 74 premature babies (with parental consent) with bleeding into the ventricles. Babies were randomly allocated to get either DRIFT or standard therapy. When neurodevelopment was assessed by “blinded” observers at 2 years, severe disability or death was significantly reduced in the DRIFT group. There was a large reduction in severe learning difficulties from 59% to 31% in the DRIFT group compared to the control group. However longer term follow up at school age is needed as cognitive testing at 2 years is limited and can be difficult in children with motor impairment. In its current guidance to the NHS, NICE currently does not recommend drainage, irrigation and fibrinolytic therapy (DRIFT) because there is insufficient evidence. If the DRIFT school age follow up study demonstrates that DRIFT is effective for children and cost-effective for the NHS, NICE will update its recommendations. If so, measurable health benefits among thousands of premature infants with bleeding into the ventricles of the brain treated with DRIFT would be expected from 2017 onwards. Expected benefits range from saving babies' lives to improving lives (e.g. by enabling children to attend ordinary schools rather than specialised schools). Results will also be relayed to the patient group via newsletters and will be shared with relevant charities such as Bliss.

Outputs:

1) Final report to the NIHR HTA which will contain a chapter including a comparison of the use and cost of hospital care among participants in the DRIFT trial. It is anticipated that the final report based on the HES data will be submitted in Autumn 2016. 2) Peer reviewed article reporting on the cost effectiveness of the DRIFT procedure in a high impact medical journal. Target date late 2016. 3) Results of the DRIFT school age trial will be presented at the European Academy of Paediatric Societies, Geneva October 2016. 4) The University of Bristol will notify the NICE interventional procedure advisory committee of its findings so that they can update the NICE guidance, should the evidence support this. All outputs will include only aggregate data with small numbers suppressed in line with the HES Analysis Guide. No record level data will be shared with any third parties.

Processing:

1. The DRIFT project team at University Hospitals Bristol (UHB) will prepare a file containing the DRIFT study participant ID and patient identifiers (NHS number, date of birth and postcode at birth) to allow linkage to HSCIC data. Parents have provided informed consent for hospital episode statistics to be used in this research project. This file will be securely transferred to the HSCIC. 2. The HSCIC will use the identifiers to link to non-sensitive HES data on hospital admissions since birth. The HSCIC will prepare a file containing the DRIFT study participant ID linked to HES Pseudo ID (where a match has been found) and HES data. This file will be securely transferred to the DRIFT project team at the University of Bristol under the provisions of the Health & Social Care Act 2012. 3. All data analysis will be performed by the DRIFT project team at the School of Social Medicine, University of Bristol (UOB-SSCM) according to its System Level Security Policy (SLSP) for HES data. 4. Upon receiving the data from the HSCIC, UOB-SSCM will store it on its secure server located at Canynge Hall, Bristol. The data can only be accessed by authorized personnel with user accounts on UOB-networked computers. The network can be accessed remotely but all processing is logically on the server based at Canynge Hall and no data is removed from that server. Data will only be accessed by substantive employees of University of Bristol. 5. The data will be used to compare the use of hospital care between children who received the DRIFT procedure and those who received standard care. The pseudonymised data supplied by the HSCIC will not be reidentified nor linked with the UHB’s identifiable data or any other data.


Project 12 — DARS-NIC-30645-Z2Z2K

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2017/06 — 2017/11. breached contract — audit report.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012, 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

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data

Objectives:

This request is necessary to enable a new study which will determine how much social deprivation affects outcomes after hip fracture in terms of death, recovery, institutionalisation, and readmission. The study will identify areas in the UK where hip fracture patients receive inequitable health care which is below the expected standard. The findings are designed to drive equal access to high quality services for all hip fracture patients across the country by influencing policy and the commissioning of services. This 3 year program aims to establish: 1. Variation in the incidence of hip fractures across the different regional healthcare economies in England and Wales, and how deprivation relates to incident hip fractures within these regions. 2. After sustaining a hip fracture, the effect of individual social deprivation on; (i) Day 7, Day 14, Day 21, Day 30, Day 60, Day 90, Day 120, Day 182, Day 274, Day 365 mortality, (ii) length of hospital stay, (iii) walking ability (iv) return home (vs. need for institutionalised care), (v) 30-day readmissions and (vi) days spent in hospital over the next 12 months. 3. Whether the effect of social deprivation on the outcomes in Aim 2 varies across different regional healthcare economies in England and Wales; identifying healthcare providers/CCGs with suboptimal outcomes necessitating revision to commissioned services. 4. The financial cost to the NHS, by healthcare provider/CCG and deprivation, of readmissions (all and fracture-related) over the 12 months after hip fracture, or until death; generating valuable intelligence for NHS commissioners, supported by a systematic review of readmission avoidance post hip fracture. Reducing health inequalities is a fundamental health care goal. This proposal is important as it will address the lack of information on the extent of regional variation on hip fracture incidence, or the impact of social deprivation across the different regional healthcare economies on fundamental health outcomes after hip fracture such as a death, mobility, institutionalization, and readmissions which carry such a high financial burden. Results are intended to influence national commissioning of hip fracture services and thus reduce health inequalities.

Expected Benefits:

Reducing health inequalities is a fundamental health care goal. This proposal is important as currently the extent of regional variation on hip fracture incidence is not known, nor the impact of social deprivation across the different regional healthcare economies on fundamental health outcomes after hip fracture such as a death, mobility, institutionalization, and readmissions which carry such a high financial burden. Benefits to patients and the health system: Around 60,000 older adults fracture a hip each year in England. As our population ages, fracture numbers are predicted to rise. Fractures represent a major trauma for individuals and a significant societal burden, both through direct medical costs (UK predicted £2.2 billion by 2025), and important social sequelae. Details regarding 95% of hip fractures are now routinely recorded through the National Hip Fracture Database (NHFD); after adjusting for case-mix, by 30-days between 3 and 17% of patients will have died and 5 to 75% will have returned home; percentages vary across the 186 NHS hospitals. Mean acute hospital length of stay varies from 9 to 32 days. Health and healthcare inequalities still persist. Previous research has established lower socioeconomic status is a predictor of poorer health outcomes, associated with increased rates of incident hip fracture in Nottingham, whilst regional variation across the country is unknown. Previous research also shows that nationally there are identified geographic and socioeconomic variation in the provision of elective hip replacement , found that socioeconomic deprivation predicts poorer post-operative outcomes, and showed socioeconomic deprivation reduces the chance of returning to one’s own home following a hospital admission with a fall. Recent results suggest patients from deprived areas in southwest England, despite being younger, are more likely to be transferred to community rehabilitation hospitals following hip fracture, than be discharged directly home, with consequently longer lengths of stay in the NHS. A third of hospital expenditure is spent on those in the last year of life, with 58% of UK citizens dying in hospital. Hip fracture is the commonest cause of injury related death. One-year mortality following hip fracture is approximately 30%. Lower socioeconomic status predicts higher inpatient mortality after hip fracture in England; however, the relationship with 30-day and one year mortality has not been defined nationally. This research will investigate and quantify the true impact of deprivation on hip fracture outcomes and to identify deprived healthcare regions, with potentially the poorest outcomes, where peri-operative inpatient care may not be optimal. Emergency 30-day readmissions following hip fracture have risen progressively over 10 years in England from 8.3% to 12.0%. The extent to which survival, co-morbidity, geographic and socioeconomic factors influence this trend has not been assessed. Given the high financial burden of readmissions, such data will have high utility to policy makers (e.g. Public Health England) and those commissioning local hip fracture services (e.g. Clinical Commissioning Groups (CCGs) in England). Understanding the effects of deprivation on the incidence of hip fracture, the outcomes after hip fracture and the cost implications, and how this all varies across different parts of the country, will identify those health systems with greatest need, in greatest need of reform, and potentially those to be high-lighted as ‘gold-standards’. This research will ensure these patterns can be understood in order to design and implement change, to drive down the current health inequalities, improve patient health outcomes and reduce the economic burden on the health system.

Outputs:

The intention is for each of the 4 aims to produce at least one peer-reviewed published paper (target journals include: The BMJ, Osteoporosis International, Journal of Bone and Mineral Research) and at least one conference abstract for national/international presentation (target conferences: The National Osteoporosis Society conference, the European Fragility Fracture Network conference, The Bone Research Society, the American Society of Bone and Mineral Research). These will be delivered sequentially over the course of the 3-year programme with the first publication targeted for submission by the end of 2016. The types of journals to be targeted will depend on the nature of the findings. All outputs will contain only aggregated data, with small number suppressed in line with the HES analysis guide. As part of this programme, a systematic review assessing the effects of deprivation on hip fracture incidence will also be completed and published. In preparing this proposal advice was obtained from a Commissioner at NHS England, advisor to the National Osteoporosis Society (NOS) and RCP Fracture Liaison Service Database committee representative. He is well positioned, and with a vested interest, to help to disseminate our research findings in the interests of improving models of hip fracture care. He has a voice amongst NHS commissioners which will permit this research a direct path so that the findings directly influence national commissioning and hence lead to improved patient care. The rates at which patients need to move to care homes and the costs incurred through hospital readmissions are of crucial importance to commissioners. This research is funded by the NOS and hence we will work with the NOS’ publicity office to disseminate our research findings. The data produced by this study will inform Public Health England (PHE), for whom elimination of health inequalities is a priority target: PHE direct local organisations towards appropriately commissioned services. Given current political priorities, it is also planned that findings will be disseminated directly to Westminster MPs. Furthermore, the Welsh Assembly clearly prioritized the tackling of health inequalities in its publication ‘Fairer Health Outcomes for All: Reducing Health Inequalities in Health Strategic Action Plan’; stating that currently there is little evidence of differential impacts on different socio-economic groups. One of the leaders of the study is well placed as National Hip Fracture Database (NHFD) clinical lead to feedback the findings to key stakeholders, such as the Royal College of Physicians. . Findings will further be disseminated by the NHFD Publications and Scientific Committee which the applicant takes over as chair of this committee in May 2017.

Processing:

Only substantive employees of Bristol University will access the disseminated data and only for the purposes described in this document . Under this application/Agreement, a pseudonymised extract of linked NHFD and HES/ONS data will supplied by NHS Digital to University of Bristol. The data will be exclusively stored on University of Bristol’s servers and will not be accessible to any third parties. Data flow: 1. The cohort will be provided for linkage from Crown Informatics (who are the DP for the NHFD but play no other role in this application and receive no linked data) who will supply NHS number, DOB and postcode. 2. NHS Digital will link HES and ONS data to the cohort and patients with related ICD/diagnosis codes. 3. NHS Digital will supply the linked pseudonymised data to Bristol (replacing date of death with death status at various stages in one year). Over the course of a 3-year programme, the data will be analysed to produce research outputs in relation to the four aims listed above. The processing activities for each aim will take place in sequential order but there will be overlaps between the processing activities for different aims. The analyses and statistical programmes written will differ for each aim and different variables will be used. For the 4 study aims, the respective processing activities are as follows: 1. Three years of data will be analysed to calculate rates of different types of hip fracture for different age groups amongst men and women across 11 geographical regions in England and Wales. Then the study will look at how these rates vary according to levels of social deprivation. Social deprivation will be measured using the Index of Multiple Deprivation (IMD). 2. The study will determine how levels of social deprivation relate to a range of outcomes after hip fracture, including: a. A patient’s ability to walk indoors and outdoors 30 days after sustaining a hip fracture b. Rates of death 2 days, 14 days, 21 days, 30 days, 60 days, 90 days, 120 days, 182 days, 274 days and 365 days after sustaining a hip fracture c. How long patients stay in hospital, and afterwards in rehabilitation hospitals, after sustaining a hip fracture d. How often patients are able to return to their own home, or whether they need to move to live in a care home, after a hip fracture How often patients need to be readmitted to hospital having been discharged after an admission with hip fracture; calculating the total number of days spent in hospital in the year following a hip fracture. 3. The study will investigate how the relationships established in Aim 2, between social deprivation and hip fracture outcomes, vary across 11 different geographical regions (and smaller subgroups within these regions) in England and Wales. It will be determined whether these relationships vary according to whether patients live in rural or urban environments, or whether they are treated in larger teaching hospitals or smaller district general hospitals). The study will determine to what extent hospital characteristics explain difference in patient outcomes after hip fracture, such as delays in operating, access to medical assessment, specialist geriatricians, a full multidisciplinary team, fracture liaison services 4. The study will calculate the total costs associated with hospital readmissions following a hip fracture for each region and clinical commissioning group. The study will also perform a detailed review of the scientific literature to assess measures to avoid hospital readmission after hip fracture so that both the financial impact and the current evidence based can be presented to commissioners and policy makers.


Project 13 — DARS-NIC-319171-G7H8K

Opt outs honoured: N, Y

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2018/09. breached contract — audit report.

Repeats: One-Off, Ongoing

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

Categories: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Outpatients
  • Diagnostic Imaging Dataset
  • Bridge file: Hospital Episode Statistics to Diagnostic Imaging Dataset
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

Cluster randomised trial of testing for Prostate cancer (CAP) is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based Prostate Specific Antigen (PSA)-testing for prostate cancer (intervention arm) with standard NHS care (control arm) amongst men aged 50 to 69 years registered with GP practices in eight centres in England and Wales. Recruitment to the DH/CRUK-funded CAP trial was completed in 2009 and it is currently in the follow-up phase. Over 415,000 men are being followed-up for incident and fatal prostate cancer via the Health and Social Care Information Centre (HSCIC). Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage to estimate the cost effectiveness of prostate cancer screening in the UK CAP are applying for permission to perform record linkage for all 415,000 men in the CAP trial with the HSCIC for the provision of resource use information.

Expected Benefits:

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources). The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer. Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the team’s randomised trials. This research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits, and saved the UK economy. The median 10 years follow-up will be reached in 2016 and it is anticipated that the first publication will report these results, the University would nevertheless wish to apply for additional funding for longer term follow–up.

Outputs:

CAP plan to publish median 10 year results in The New England Journal of Medicine (NEJM) or The Journal of the American Medical Association (JAMA) in 2016. A statistical analysis plan detailing the analyses that will be included in the publications has been uploaded onto the University of Bristol research information repository (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1). Statistics involved in these papers usually refer to measures such as rate ratios and 95% confidence intervals rather than actual numbers of cases. CAP will follow ONS non-disclosure rules for small numbers of cases and will not include any counts of less than 5 in a Table. As stated above the median 10 years follow-up will be reached in 2016, the applicant would nevertheless wish to apply for additional funding for longer term follow–up. As stated above the primary outcome is reached at a median 10 years follow up in 2016 there are however a number of recent publications directly related to the study, listed below: Williams NJ, Hill EM, Ng SY, Martin RM, Metcalfe C, Donovan JL, Evans S, Hughes LJ, Davies CF, Hamdy FC, Neal DE, Turner EL, for the CAP Cause of Death Committee. Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer). BMC Medical Research Methodology (2015) 15:6 (doi:10.1186/1471-2288-15-6) Turner EL, Metcalfe C, Donovan JL, Noble S, Sterne JAC, Lane A, Avery K, Down L, Walsh E, Davis M, Ben-Shlomo Y, Oliver S, Evans S, Brindle P, Williams N, Hughes LJ, Hill E, Davies C, Ng SY, Neal DE, Hamdy FC, Martin RM. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). British Journal of Cancer (2014) 110; 2829-36 (doi: 10.1038/bjc.2014.242) Lane JA, Donovan JL, Davis M, Walsh E, Dedman D, Down L, Turner EL, Mason MD, Metcalfe C, Peters TJ, Martin RM, Neal DE, Hamdy FC, for the ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncology (2014) 15: 1109-18 (http://dx.doi.org/10.1016/ S1470-2045(14)70361-4) Hill EM, Turner EL, Martin RM & Donovan JL. "Let's get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study. BMC Medical Research Methodology (2013) 13:72 (doi: 10.1186/1471-2288-13-72) Williams NJ, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, Martin RM, Metcalfe C. Prostate-specific antigen testing rates remain low in UK general practice: A cross-sectional study in six English cities. British Journal of Urology International (2011) 108:9; 1402-08 (doi:10.1111/j.1464-410X.2011.10163.x) Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies. European Journal of Cancer (2010) 46; 3095-3101 (doi:10.1016/j.ejca.2010.09.016) Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as NICE or the Cochrane Centre will also be informed. The papers will be available on the University of Bristol PURE pages https://research-information.bris.ac.uk/ - these publications are available to download with open access allowing anyone to access publications. We also publish with open access rights when submitting to journals, ensuring we maintain CRUKs publication ethos of ensuring research funded by them is available to all. Publications are also uploaded to 'researchfish' allowing the research community to clearly see what has been published.

Processing:

In this amendment request, the linked HES data would be accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data and can never be linked to it. Processing steps - 1.HSCIC will utilise the identifier (unique study ID) for MR783 and MR738A and link these data from the HES dataset held at the HSCIC. The HES data extract and unique study ID for the cohort will be sent to SAIL by the HSCIC. 2.The applicant will transfer a study ID and the following primary and secondary mortality outcome variables to SAIL: month and year of birth; date of prostate cancer diagnosis; prostate cancer stage and grade, if present; month and year of death, if deceased; prostate cancer attributed death, if deceased; date of censor, if no longer in follow up; month and year of censor. 3.SAIL will then link these data to the HES extract from the HSCIC. SAIL will also encrypt the unique study ID to create a unique pseudo anonymised ID number for each individual, area identifiers will also be pseudonymised HES data will be used to identify all inpatient and outpatient resources used by men in CAP. Costs will be assigned to the identified events and used alongside the linked outcome data to conduct the CAP cost-effectiveness analysis from the perspective of the UK NHS (secondary care). This dataset will be remotely accessed from Bristol for analysis and only aggregated results tables (verified by SAIL to be unidentifiable) would be extracted from the dataset.