Continuation of AVON LONGITUDINAL STUDY OF PARENTS AND CHILDREN (ALSPAC): consent

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 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).

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.

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.

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.

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 University of Bristol 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 the 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).

As described above, this study is of great public and scientific interest. This work therefore relies on Articles 6(1)e (processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller) and 9(2)j (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes) as the GDPR legal basis for processing the data disseminated under this Agreement.

The University of Bristol is the sole Data Controller under this Agreement; no other organisations have any involvement in determining the purpose for which the data supplied under this Agreement is used. ALSPAC make use of a secure research infrastructure developed to support the SAIL databank of Welsh routine health and administrative records 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 is the Data Processor working to instruction from the University of Bristol who is the 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). Therefore, the University of Swansea are listed as the sole Data Processor under this Agreement.

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 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 University of Bristol's press-release system (http://www.bristol.ac.uk/alspac/news/) and via 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)

The 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. University of Bristol will publish the findings in relevant academic journals (e.g., Epidemiology, Wellcome Open, Child & Family Social Work, British Journal of Social Work, Adoption and Fostering). University of Bristol will disseminate relevant project findings to charities (e.g., NSPCC) and the NHS England ‘National Looked After Children Safeguarding Sub Group’.

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.

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 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).

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.

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.

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.

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 University of Bristol 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 the 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).

As described above, this study is of great public and scientific interest. This work therefore relies on Articles 6(1)e (processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller) and 9(2)j (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes) as the GDPR legal basis for processing the data disseminated under this Agreement.

The University of Bristol is the sole Data Controller under this Agreement; no other organisations have any involvement in determining the purpose for which the data supplied under this Agreement is used. ALSPAC make use of a secure research infrastructure developed to support the SAIL databank of Welsh routine health and administrative records 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 is the Data Processor working to instruction from the University of Bristol who is the 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). Therefore, the University of Swansea are listed as the sole Data Processor under this Agreement.

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 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 University of Bristol's press-release system (http://www.bristol.ac.uk/alspac/news/) and via 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)

The 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. University of Bristol will publish the findings in relevant academic journals (e.g., Epidemiology, Wellcome Open, Child & Family Social Work, British Journal of Social Work, Adoption and Fostering). University of Bristol will disseminate relevant project findings to charities (e.g., NSPCC) and the NHS England ‘National Looked After Children Safeguarding Sub Group’.

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.

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 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).

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.

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.

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.

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 University of Bristol 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 the 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).

As described above, this study is of great public and scientific interest. This work therefore relies on Articles 6(1)e (processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller) and 9(2)j (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes) as the GDPR legal basis for processing the data disseminated under this Agreement.

The University of Bristol is the sole Data Controller under this Agreement; no other organisations have any involvement in determining the purpose for which the data supplied under this Agreement is used. ALSPAC make use of a secure research infrastructure developed to support the SAIL databank of Welsh routine health and administrative records 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 is the Data Processor working to instruction from the University of Bristol who is the 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). Therefore, the University of Swansea are listed as the sole Data Processor under this Agreement.

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 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 University of Bristol's press-release system (http://www.bristol.ac.uk/alspac/news/) and via 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)

The 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. University of Bristol will publish the findings in relevant academic journals (e.g., Epidemiology, Wellcome Open, Child & Family Social Work, British Journal of Social Work, Adoption and Fostering). University of Bristol will disseminate relevant project findings to charities (e.g., NSPCC) and the NHS England ‘National Looked After Children Safeguarding Sub Group’.

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.

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).

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)

The 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’.

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.