Andy Boyd

Cohort Profile: The ‘Children of the 90s’—the index offspring of the Avon Longitudinal Study of Parents and Children

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enrol pregnant women in the Bristol area of the UK during 1990–92; this was extended to include additional children eligible using the original enrolment definition up to the age of 18 years. The children from 14 541 pregnancies were recruited in 1990–92, increasing to 15 247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks–18 years of age) and 9 clinical assessment visits (7–17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11 343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.

Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort

Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Using linked educational attainment data to reduce bias due to missing outcome data in estimates of the association between the duration of breastfeeding and IQ at 15 years

Background: Most epidemiological studies have missing information, leading to reduced power and potential bias. Estimates of exposure-outcome associations will generally be biased if the outcome variable is missing not at random (MNAR). Linkage to administrative data containing a proxy for the missing study outcome allows assessment of whether this outcome is MNAR and the evaluation of bias. We examined this in relation to the association between infant breastfeeding and IQ at 15 years, where a proxy for IQ was available through linkage to school attainment data. Methods: Subjects were those who enrolled in the Avon Longitudinal Study of Parents and Children in 1990–91 (n = 13 795), of whom 5023 had IQ measured at age 15. For those with missing IQ, 7030 (79%) had information on educational attainment at age 16 obtained through linkage to the National Pupil Database. The association between duration of breastfeeding and IQ was estimated using a complete case analysis, multiple imputation and inverse probability-of-missingness weighting; these estimates were then compared with those derived from analyses informed by the linkage. Results: IQ at 15 was MNAR—individuals with higher attainment were less likely to have missing IQ data, even after adjusting for socio-demographic factors. All the approaches underestimated the association between breastfeeding and IQ compared with analyses informed by linkage. Conclusions: Linkage to administrative data containing a proxy for the outcome variable allows the MNAR assumption to be tested and more efficient analyses to be performed. Under certain circumstances, this may produce unbiased results.

Using Linkage to Electronic Primary Care Records to Evaluate Recruitment and Nonresponse Bias in The Avon Longitudinal Study of Parents and Children

Supplemental Digital Content is available in the text.

An evaluation of the impact of 'Lifeskills' training on road safety, substance use and hospital attendance in adolescence

Highlights • Lifeskills training is for 10–11 year olds and covers many safety domains.• Evaluated using longitudinal cohort data linked to hospital attendance data.• Attendance at A&E common but hospital admissions coded as due to an accident rare.• Lifeskills attendance associated with some reported safer behaviours in adolescence.• Use of cycle helmets and reflective/fluorescent clothing low overall.

Young people’s views about the purpose and composition of research ethics committees: findings from the PEARL qualitative study

BackgroundAvon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study within which the Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. PEARL incorporated qualitative research to seek the views of young people about data linkage, including their opinions about appropriate safeguards and research governance. In this paper we focus on views expressed about the purpose and composition of research ethics committees.MethodsDigitally recorded interviews were conducted with 48 participants aged 17–19 years. Participants were asked about whether medical research should be monitored and controlled, their knowledge of research ethics committees, who should sit on these committees and what their role should be. Interview recordings were fully transcribed and anonymised. Thematic analysis was undertaken, assisted by the Framework approach to data management.ResultsThe majority of interviewees had little or no specific knowledge of ethics committees. Once given basic information about research ethics committees, only three respondents suggested there was no need for such bodies to scrutinise research. The key tasks of ethics committees were identified as monitoring the research process and protecting research participants. The difficulty of balancing the potential to inhibit research against the need to protect research participants was acknowledged. The importance of relevant research and professional expertise was identified but it was also considered important to represent wider public opinion, and to counter the bias potentially associated with self-selection possibly through a selection process similar to ‘jury duty’.ConclusionsThere is a need for more education and public awareness about the role and composition of research ethics committees. Despite an initial lack of knowledge, interviewees were able to contribute their ideas and balance the rights of individuals with the wider benefits from research. The suggestion that public opinion should be represented through random selection similar to jury duty may be worth pursuing in the light of the need to ensure diversity of opinion and establish trust amongst the general public about the use of ‘big data’ for the wider public good.

Local- and regional-scale air pollution modelling (PM 10 ) and exposure assessment for pregnancy trimesters, infancy, and childhood to age 15 years: Avon Longitudinal Study of Parents And Children (ALSPAC)

We established air pollution modelling to study particle (PM10) exposures during pregnancy and infancy (1990–1993) through childhood and adolescence up to age ~15 years (1991–2008) for the Avon Longitudinal Study of Parents And Children (ALSPAC) birth cohort. For pregnancy trimesters and infancy (birth to 6 months; 7 to 12 months) we used local (ADMS-Urban) and regional/long-range (NAME-III) air pollution models, with a model constant for local, non-anthropogenic sources. For longer exposure periods (annually and the average of birth to age ~8 and to age ~15 years to coincide with relevant follow-up clinics) we assessed spatial contrasts in local sources of PM10 with a yearly-varying concentration for all background sources. We modelled PM10 (μg/m3) for 36,986 address locations over 19 years and then accounted for changes in address in calculating exposures for different periods: trimesters/infancy (n = 11,929); each year of life to age ~15 (n = 10,383). Intra-subject exposure contrasts were largest between pregnancy trimesters (5th to 95th centile: 24.4–37.3 μg/m3) and mostly related to temporal variability in regional/long-range PM10. PM10 exposures fell on average by 11.6 μg/m3 from first year of life (mean concentration = 31.2 μg/m3) to age ~15 (mean = 19.6 μg/m3), and 5.4 μg/m3 between follow-up clinics (age ~8 to age ~15). Spatial contrasts in 8-year average PM10 exposures (5th to 95th centile) were relatively low: 25.4–30.0 μg/m3 to age ~8 years and 20.7–23.9 μg/m3 from age ~8 to age ~15 years. The contribution of local sources to total PM10 was 18.5%–19.5% during pregnancy and infancy, and 14.4%–17.0% for periods leading up to follow-up clinics. Main roads within the study area contributed on average ~3.0% to total PM10 exposures in all periods; 9.5% of address locations were within 50 m of a main road. Exposure estimates will be used in a number of planned epidemiological studies.

Defining adolescent common mental disorders using electronic primary care data: a comparison with outcomes measured using the CIS-R

Objective To compare the prevalence of common mental disorders (CMDs) derived from data held in primary care records with that measured using the revised Clinical Interview Schedule (CIS-R) in order to assess the potential robustness of findings based only on routinely collected data. Design and setting Comparison study using linkage between the Avon Longitudinal Study of Parents and Children (ALSPAC) and electronic primary care records. Participants We studied 1562 adolescents who had completed the CIS-R in ALSPAC at age 17–18 years and had linkage established to their primary care records. Outcome measures Outcome measures from ALSPAC were whether or not an individual met International Classification of Diseases-10 criteria for a diagnosis of (1) a CMD or, specifically, (2) depression. Lists of Read codes corresponding to diagnoses, symptoms and treatments were used to create 12 definitions of CMD and depression alone using the primary care data. We calculated sensitivities and specificities of these, using CIS-R definitions as the reference standard. Results Sensitivities ranged from 5.2% to 24.3% for depression and from 3.8% to 19.2% for CMD. The specificities of all definitions were above 98% for depression and above 96% for CMD. For both outcomes, the definition that included current diagnosis, treatment or symptoms identified the highest proportion of CIS-R cases. Conclusions Most individuals meeting case definitions for CMD based on primary care data also met CIS-R case definitions. Conversely many individuals identified as cases using the CIS-R had no evidence of CMD in their clinical records. This suggests that clinical databases are likely to yield underestimates of the burden of CMD in the population. However, clinical records appear to yield valid diagnoses which may be useful for studying risk factors and consequences of CMD. The greatest epidemiological value may be obtained when information is available from survey and clinical records.

Young people’s views about consenting to data linkage: findings from the PEARL qualitative study

BackgroundElectronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants’ views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent.MethodsDigitally recorded interviews were conducted with 55 participants aged 17–19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach.ResultsParticipant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with ‘opt-in’ consent through which participants are ‘asked’ if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent.ConclusionsFindings from this study question the validity of ‘informed consent’ as a cornerstone of good governance, and the extent to which potential research participants understand different types of consent and what they are consenting, or not consenting, to. Pragmatic, imaginative and flexible approaches are needed if research using data linkage is to successfully realise its potential for public good without undermining public trust in the research process.

The destruction of the ‘Windrush’ disembarkation cards: a lost opportunity and the (re)emergence of Data Protection regulation as a threat to longitudinal research

Historical records and the research databases of completed studies have the potential either to establish new research studies or to inform follow-up studies assessing long-term health and social outcomes. Yet, such records are at risk of destruction resulting from misconceptions about data protection legislation and research ethics. The recent destruction of the Windrush disembarkation cards, which potentially could have formed the basis of a retrospective cohort study, illustrates this risk. As organisations across Europe transition to the EU General Data Protection Regulation (GDPR), this risk is being amplified due to uncertainty as to how to comply with complex new rules, and the requirement under GDPR that data owners catalogue their data and set data retention and destruction rules. The combination of these factors suggests there is a new meaningful risk that scientifically important historical records will be destroyed, despite the fact that GDPR provides a clear legal basis to hold historical records and to repurpose them for research for the public good. This letter describes this risk; details the legal basis enabling the retention and repurposing of these data; makes recommendations as to how to alleviate this risk; and finally encourages the research and research-active clinical community to contact their ‘Data Protection Officers’ to promote safe-keeping of historical records.