Long-term health outcomes in Christs Hospital School Cohort

Mortality and Cancer data were supplied to the University of Bristol by the Office for National Statistics (ONS) and subsequently the Health and Social Care Information Centre (which has since become NHS Digital and then NHS England) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital School (CHS) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long-term effect on chronic diseases such as cancer and heart disease. With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enables the University of Bristol to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease, diabetes and cancer. In particular, data provided by NHS Engalnd are essential for the ascertainment of key outcomes of interest for the whole cohort which include cardiovascular disease (from mortality data) as well as cancer incidence and case fatality (from mortality data and cancer registrations). These are the key outcomes which may be influenced by growth and development from childhood and adolescence.

The University of Bristol have previously demonstrated that participants who had an earlier pubertal growth spurt, as determined by the age of peak height velocity, had higher levels of a hormone called insulin-like growth factor I (IGF-I). This is a risk factor for certain types of cancer. To be able to further the research, it is essential that NHS England data are provided at an individual level so they can be linked to University of Bristol research data. There are no alternative, less intrusive ways of achieving the purpose.

The University of Bristol, who is the sole data controller who also processes the data for this study, currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above. No other organisations process the data for this purpose. There are no funders or commissioners involved with the use of these data. The study was originally undertaken by a research grant from Cancer Research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, Bristol Medical School, University of Bristol through staff time and support and infra-structure.

In line with past advice from IGARD and NHS England, the University of Bristol has applied and received new research ethics approval so that the project is now covered by a research database application. It has also applied for a new de novo CAG approval having previously been covered by a joint approval (CR20/2014) that covered three different studies (CaPS, Speedwell, CHS). These three studies now have their own independent CAG approvals in place.

Researchers at the University of Bristol are currently also exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval).

The University of Bristol require data on cause-specific mortality and cancer incidence so they can test whether pubertal growth patterns predict future diseases. By linking the existing detailed anthropometry (measurements and proportions of the human body) with these health outcomes, novel insights can be gained into disease aetiology (the cause, set of causes, or manner of causation of a disease or condition) which may help identify higher risk groups for stratification and potentially highlight interventions to prevent disease.

The data is minimised by:

-Limiting to a study cohort of ~2,700 former male students of CHS

-Destroying any identifiable information which is not required for analysis or linkage purposes

Processing of these data is in the public interest under UK GDPR Articles 6(1)(e) and 9(2)(j) as the processing may contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns, and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors.

The processing meets the conditions of Schedule 1 Part 1 paragraph 4 of the Data Protection Act 2018 as the processing:

(a) is necessary for archiving purposes, scientific or historical research purposes or statistical purposes,

(b) is carried out in accordance with Article 89(1) of the GDPR (as supplemented by section 19), and

(c) is in the public interest.

There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them.

CHS aims to examine whether timing of puberty is or is not associated with specific outcomes e.g. colorectal or prostate cancer, cardiovascular disease. This has been examined with the existing data held, but because of the limited small number of events, it was decided that it was premature at this stage to interpret these results due to lack of statistical power and therefore the University of Bristol have not attempted to publish these data.

Subject to receiving further data under a new data sharing agreement, the Department of Population Health Sciences, University of Bristol hopes to undertake and complete further analyses in the following 2-3 years modelling the participants' growth and weight trajectories with future cancer and mortality events as well as enhancing the value of the research by adding new genetic or other biomarker data to look at analyses of risk scores on outcomes. With this data, it is anticipated that the University of Bristol could undertake more substantive analyses to enable the below listed outputs. It is possible that for some events, there will still be too few events to enable valid analysis in which case further event updates would be requested over a longer period.

The University of Bristol have however been able to add to the scientific evidence base by showing how an earlier onset of puberty is associated with a raised hormone called IGF-I that may also increase future cancer risk. In addition, children who were heavier before puberty were more likely to have an earlier puberty with greater obesity in later adulthood as well as being shorter. These observations are important as they suggest the increasing rise of childhood obesity will in turn lead to greater adult obesity, diabetes and cardiovascular risk.

The University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification.

Abstracts will be submitted to relevant National and International conferences for oral presentation. If there is relevance to lay audiences then the University of Bristol would record podcasts or vlogs for dissemination through social media. Academic papers will be submitted to leading epidemiological and Public Health journals. If the findings have more specific policy relevance then the University of Bristol would aim to submit the evidence to the relevant bodies e.g. Royal Colleges.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest.

To advertise study findings to a wider audience where relevant, the University of Bristol would make use of the press release function of some academic journals which is sometimes picked up by newspapers and social media. In addition, if appropriate, the University of Bristol would aim to target the key charities, in this case Cancer Research UK to publicise the findings through their own website and newsletters.

The study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years.

This is the first study to document an association between timing of puberty and adult IGF-I levels. Higher levels of IGF-I has been implicated in an increased risk of certain cancers such as breast and prostate. A better understanding of the life course impact of obesity in childhood, adolescence and mid life on later life disease risk may provide new insights into disease aetiology and primary or secondary prevention. The University of Bristol anticipate future research outputs will be forthcoming over the next 5 to 10 years.

The University of Bristol believes that the knowledge gained from the analyses of this dataset will add to epidemiological understanding on life course influences on adult chronic diseases in relation to growth and development in childhood and adolescence. This is one of a few such cohorts in the world that have detailed data on childhood growth between the ages of 9 to 20. This has allowed the researchers to derive valuable measures such as peak height velocity and age at peak height velocity and relate this to risk markers of chronic disease risk such as IGF-I, a growth hormone associated with cancer risk.

Mortality and Cancer data were supplied to the University of Bristol by the Office for National Statistics (ONS) and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital School (CHS) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long-term effect on chronic diseases such as cancer and heart disease. With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enables the University of Bristol to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease, diabetes and cancer. In particular, data provided by NHS Digital are essential for the ascertainment of key outcomes of interest for the whole cohort which include cardiovascular disease (from mortality data) as well as cancer incidence and case fatality (from mortality data and cancer registrations). These are the key outcomes which may be influenced by growth and development from childhood and adolescence.

The University of Bristol have previously demonstrated that participants who had an earlier pubertal growth spurt, as determined by the age of peak height velocity, had higher levels of a hormone called insulin-like growth factor I (IGF-I). This is a risk factor for certain types of cancer. It is essential that NHS Digital data are provided at an individual level so they can be linked to University of Bristol research data. There are no alternative, less intrusive ways of achieving the purpose.

The University of Bristol, who is the sole data controller who also processes the data for this study, currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above. No other organisations process the data for this purpose. There are no funders or commissioners involved with the use of these data. The study was originally undertaken by a research grant from Cancer Research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, University of Bristol through staff time and support and infra-structure.

No new data will be supplied to the University of Bristol under this version of the Agreement.

The University of Bristol has plans to reuse the data in the future for biomedical research subject to the necessary approvals. Before using the data in future biomedical research, the University of Bristol must successfully apply to NHS Digital to amend this Agreement to permit processing for that purpose.

Researchers at the University of Bristol are currently exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval). In addition, the existing number of events that have already been provided are relatively few, so there is little statistical power to look at the existing growth data with cause specific mortality. The University of Bristol may therefore make a future application to NHS Digital to receive new events occurring since 2012 to enable a more rigorous analysis.

The University of Bristol require data on cause-specific mortality and cancer incidence so they can test whether pubertal growth patterns predict future diseases. By linking the existing detailed anthropometry (measurements and proportions of the human body) with these health outcomes, novel insights can be gained into disease aetiology (the cause, set of causes, or manner of causation of a disease or condition) which may help identify higher risk groups for stratification and potentially highlight interventions to prevent disease.

The data is minimised by:

-Limiting to a study cohort of ~2,700 former male students of CHS

-Destroying any identifiable information which is not required for analysis or linkage purposes

Processing of these data is in the public interest under UK GDPR Articles 6(1)(e) and 9(2)(j) as the processing may contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns, and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors.

The processing meets the conditions of Schedule 1 Part 1 paragraph 4 of the Data Protection Act 2018 as the processing:

(a)is necessary for archiving purposes, scientific or historical research purposes or statistical purposes,

(b)is carried out in accordance with Article 89(1) of the GDPR (as supplemented by section 19), and

(c)is in the public interest.

There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them.

CHS aims to examine whether timing of puberty is or is not associated with specific outcomes e.g. colorectal or prostate cancer. This has been examined with the existing data held, but because of the limited small number of events, it was decided that it was premature at this stage to interpret these results due to lack of statistical power and therefore the University of Bristol have not attempted to publish these data.

Subject to receiving further data under a subsequent version of this Agreement (an additional 10 years worth of follow-up), the Department of Population Health Sciences, University of Bristol hopes to undertake and complete further analyses in the following 2-3 years modelling the participants' growth and weight trajectories with future cancer and mortality events as well as enhancing the value of the research by adding new genetic data to look at analyses of genetic risk scores on outcomes. With this data, it is anticipated that the University of Bristol could undertake more substantive analyses to enable the below listed outputs. It is possible that for some events, there will still be too few events to enable valid analysis in which case further event updates would be requested over a longer period.

The University of Bristol have however been able to add to the scientific evidence base by showing how an earlier onset of puberty is associated with a raised hormone called IGF-I that may also increase future cancer risk. In addition, children who were heavier before puberty were more likely to have an earlier puberty with greater obesity in later adulthood as well as being shorter. These observations are important as they suggest the increasing rise of childhood obesity will in turn lead to greater adult obesity, diabetes and cardiovascular risk.

The University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification.

Abstracts will be submitted to relevant National and International conferences for oral presentation. If there is relevance to lay audiences then the University of Bristol would record podcasts or vlogs for dissemination through social media. Academic papers will be submitted to leading epidemiological and Public Health journals. If the findings have more specific policy relevance then the University of Bristol would aim to submit the evidence to the relevant bodies e.g. Royal Colleges.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest.

To advertise study findings to a wider audience where relevant, the University of Bristol would make use of the press release function of some academic journals which is sometimes picked up by newspapers and social media. In addition, if appropriate, the University of Bristol would aim to target the key charities, in this case Cancer Research UK to publicise the findings through their own website and newsletters.

The study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years.

This is the first study to document an association between timing of puberty and adult IGF-I levels. Higher levels of IGF-I has been implicated in an increased risk of certain cancers such as breast and prostate. A better understanding of the life course impact of obesity in childhood, adolescence and mid life on later life disease risk may provide new insights into disease aetiology and primary or secondary prevention. The University of Bristol anticipate future research outputs will be forthcoming over the next 5 years.

The University of Bristol believes that the knowledge gained from the analyses of this dataset will add to epidemiological understanding on life course influences on adult chronic diseases in relation to growth and development in childhood and adolescence. This is one of a few such cohorts in the world that have detailed data on childhood growth between the ages of 9 to 20. This has allowed the researchers to derive valuable measures such as peak height velocity and age at peak height velocity and relate this to risk markers of chronic disease risk such as IGF-I, a growth hormone associated with cancer risk.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital (CH) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long-term effect on chronic diseases such as cancer and heart disease. With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enabled the study to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease and diabetes.

The University of Bristol currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above.

No new data will be supplied to the University of Bristol under this Agreement.

The University of Bristol has plans to reuse the data in the future for biomedical research subject to the necessary approvals. Before using the data in future biomedical research, the University of Bristol must successfully apply to NHS Digital to amend this Agreement to permit processing for that purpose.

Researchers at the University of Bristol are currently exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval). In addition, the existing number of events that have already been provided are relatively few, so there is little statistical power to look at the existing growth data with cause specific mortality. The University of Bristol may therefore make a future application to NHS Digital to receive new events occurring since 2012 to enable a more rigorous analysis.

The University of Bristol require data on cause-specific mortality and cancer incidence so they can test whether pubertal growth patterns predict future diseases. By linking the existing detailed anthropometry with these health outcomes, we can gain novel insights into disease aetiology which may help identify higher risk groups for stratification and potentially highlight interventions to prevent disease.

Processing of these data is in the public interest under Articles 6(1)(e) and 9(2)(j) as the the processing may contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors.

There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them.

The University of Bristol is the sole data controller and also processes the data for this study. No other organisations process the data for this purpose.

The study was originally undertaken by a research grant from Cancer research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, University of Bristol through staff time and support and infra-structure.

CHS aims to examine whether timing of puberty is or is not associated with specific outcomes e.g. colorectal, prostate cancer. This has been examined with the existing data held, but because of the limited small number of events, it was decided that it was premature at this stage to interpret these results due to lack of statistical power and therefore we have not attempted to publish these data.

Under a subsequent version of this Agreement the University of Bristol wishes to request further data on this cohort. The updated event data (this will be an additional 10 years worth of follow-up) it is anticipated that researcher could undertake more substantive analyses.

The University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification.

Abstracts will be submitted to relevant National and International conferences for oral presentation. If there is relevance to lay audiences then we would record podcasts or vlogs for dissemination through social media. Academic papers will be submitted to leading epidemiological and Public Health journals. If the findings have more specific policy relevance then we would aim to submit our evidence to the relevant bodies e.g. Royal Colleges.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest.

If there is found to be a statistical relationship between growth and the risk of developing particular disease, and these results are replicated in other cohorts, the cumulative evidence could be used in future risk stratification algorithms with genetic and other risk factors.

The study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years.

This is the first study to document an association between timing of puberty and adult IGF-I levels. Higher levels of IGF-I has been implicated in an increased risk of certain cancers such as breast and prostate. A better understanding of the life course impact of obesity in childhood, adolescence and mid life on later life disease risk may provide new insights into disease aetiology and primary or secondary prevention. The University of Bristol anticipate future research outputs will be forthcoming over the next 5 years.

The University of Bristol believes that the knowledge gained from the analyses of this dataset will add to epidemiological understanding on life course influences on adult chronic diseases in relation to growth and development in childhood and adolescence. This is one of a few such cohorts in the world that have detailed data on childhood growth between the ages of 9 to 20. This has allowed the researchers to derive valuable measures such as peak height velocity and age at peak height velocity and relate this to risk markers of chronic disease risk such as IGF1 a growth hormone associated with cancer risk.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital (CH) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long term effect on chronic diseases such as cancer and heart disease.

With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enabled the study to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease and diabetes.

The University of Bristol currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above.

No new data will be supplied to the University of Bristol under this Agreement.

The University of Bristol has plans to reuse the data in the future for biomedical research subject to the necessary approvals. Before using the data in future biomedical research, the University of Bristol must successfully apply to NHS Digital to amend this Agreement to permit processing for that purpose.

Researchers at the University of Bristol are currently exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval). In addition, the existing number of events that have already been provided are relatively few, so there is little statistical power to look at the existing growth data with cause specific mortality. The University of Bristol may therefore make a future application to NHS Digital to receive new events occurring since 2012 to enable a more rigorous analysis.

The University of Bristol process these data in the public interest under Articles 6(1)(e) and 9(2)(j) as the data has previously been used and is being retained with the intention of future use to contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors. There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

The University of Bristol is the sole data controller and also processes the data for this study. No other organisations process the data for this purpose.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them. The University of Bristol intends to provide a new study member identifier to NHS Digital, as well as the original member ID, for the purpose of migrating the cohort onto the new NHS Digital platform. Once this is in place, the University of Bristol intend to request a further amendment to this Agreement to reflect that the data will be pseudononymised data with all personal identifying data removed other than a new unique identifier which will replace the old identifier so that data cannot be linked to existing paper records. A link file (old and new study identifier) will be stored by third parties who have do not access to any of the data. Having a link file will be necessary as there are blood samples stored in -80C freezers, that may be of great scientific value in the future and are labelled with the original identifier. In this way any future blood results could be sent to the third party who would add the new identifier and remove the original thereby allowing these new data to be added to the revised database. There would be no attempt to re-identify the individuals.

This Agreement permits the retention of data previously supplied by NHS Digital and ONS and processing for the purpose of pseudonymising the data as described above. No other processing is permitted.

The data is stored on a special secure audited server with access limited to the data processor. Individuals in this study could be located anywhere in the United Kingdom and some will have emigrated. The University of Bristol has decided there will be no requirement for further follow-up with the participants who completed the past questionnaire and are intending to pseudonymise the data under this Agreement.

There is no alternative way of obtaining outcome data on the full cohort other than through linkage to NHS Digital data due to difficulties in contacting participants either because of death or relocation. Merely following up survivors will introduce bias and under ascertain events.

The study was originally undertaken by a research grant from Cancer research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, University of Bristol through staff time and support and infra-structure.

The renewal is intended to examine whether timing of puberty is or is not associated with specific outcomes e.g. colorectal, prostate cancer. This has been examined with the existed data that we hold but because of the limited small number of events, it was decided that it was premature at this stage to interpret these results due to lack of statistical power and therefore we have not attempted to publish these data. However with future updated event data (this will be an additional 10 years worth of follow-up) we anticipate that we can now undertake more substantive analyses. In addition we hold stored blood samples and DNA from a subset of the cohort who were able to trace and who consented to a follow-up. We will undertake genomic assays to examine for genetic determinants of growth and relate these to the observed growth patterns as well as the new events provided by NHS digital to see if they predict disease risk.

The University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest. Given the historical nature of the data from over 50 years ago, the results may have some interest to populations in low middle income settings who are undergoing the epidemiological transition. In addition, findings may have some relevance to the health care providers and the National Health Service if it allows one to have a better estimate of future health needs using data on secular trends. For example, if earlier onset of puberty is associated with a greater risk of cancer then one could use data on the secular trends for pubertal timing to make predictions about future disease burden and hence related costs.

Any genetic findings help predict growth patterns and health-related outcomes may or may not have commercial value through the development of diagnostic or therapeutic agents that may help risk stratify individuals thereby enabling targeting of secondary or tertiary prevention interventions. The University of Bristol RED department would be actively involved in any opportunities for commercial exploitation.

Several publications have already resulted from this work to date. For example, the study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years. This is the first study to document an association between timing of puberty and adult IGF-I levels. Higher levels of IGF-I has been implicated in an increased risk of certain cancers such as breast and prostate. A better understanding of the life course impact of obesity in childhood, adolescence and mid life on later life disease risk may provide new insights into disease aetiology and primary or secondary prevention.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital (CH) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long term effect on chronic diseases such as cancer and heart disease.

With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enabled the study to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease and diabetes.

The University of Bristol currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above.

No new data will be supplied to the University of Bristol under this Agreement.

The University of Bristol has plans to reuse the data in the future for biomedical research subject to the necessary approvals. Before using the data in future biomedical research, the University of Bristol must successfully apply to NHS Digital to amend this Agreement to permit processing for that purpose.

Researchers at the University of Bristol are currently exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval). In addition, the existing number of events that have already been provided are relatively few, so there is little statistical power to look at the existing growth data with cause specific mortality. The University of Bristol may therefore make a future application to NHS Digital to receive new events occurring since 2012 to enable a more rigorous analysis.

The University of Bristol process these data in the public interest under Articles 6(1)(e) and 9(2)(j) as the data has previously been used and is being retained with the intention of future use to contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors. There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

The University of Bristol is the sole data controller and also processes the data for this study. No other organisations process the data for this purpose.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them. The University of Bristol intends to provide a new study member identifier to NHS Digital, as well as the original member ID, for the purpose of migrating the cohort onto the new NHS Digital platform. Once this is in place, the University of Bristol intend to request a further amendment to this Agreement to reflect that the data will be pseudononymised data with all personal identifying data removed other than a new unique identifier which will replace the old identifier so that data cannot be linked to existing paper records. A link file (old and new study identifier) will be stored by third parties who have do not access to any of the data. Having a link file will be necessary as there are blood samples stored in -80C freezers, that may be of great scientific value in the future and are labelled with the original identifier. In this way any future blood results could be sent to the third party who would add the new identifier and remove the original thereby allowing these new data to be added to the revised database. There would be no attempt to re-identify the individuals.

This Agreement permits the retention of data previously supplied by NHS Digital and ONS and processing for the purpose of pseudonymising the data as described above. No other processing is permitted.

The data is stored on a special secure audited server with access limited to the data processor. Individuals in this study could be located anywhere in the United Kingdom and some will have emigrated. The University of Bristol has decided there will be no requirement for further follow-up with the participants who completed the past questionnaire and are intending to pseudonymise the data under this Agreement.

There is no alternative way of obtaining outcome data on the full cohort other than through linkage to NHS Digital data due to difficulties in contacting participants either because of death or relocation. Merely following up survivors will introduce bias and under ascertain events.

The study was originally undertaken by a research grant from Cancer research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, University of Bristol through staff time and support and infra-structure.

The renewal is intended to examine whether timing of puberty is or is not associated with specific outcomes e.g. colorectal, prostate cancer. This has been examined with the existed data that we hold but because of the limited small number of events, it was decided that it was premature at this stage to interpret these results due to lack of statistical power and therefore we have not attempted to publish these data. However with future updated event data (this will be an additional 10 years worth of follow-up) we anticipate that we can now undertake more substantive analyses. In addition we hold stored blood samples and DNA from a subset of the cohort who were able to trace and who consented to a follow-up. We will undertake genomic assays to examine for genetic determinants of growth and relate these to the observed growth patterns as well as the new events provided by NHS digital to see if they predict disease risk.

The University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest. Given the historical nature of the data from over 50 years ago, the results may have some interest to populations in low middle income settings who are undergoing the epidemiological transition. In addition, findings may have some relevance to the health care providers and the National Health Service if it allows one to have a better estimate of future health needs using data on secular trends. For example, if earlier onset of puberty is associated with a greater risk of cancer then one could use data on the secular trends for pubertal timing to make predictions about future disease burden and hence related costs.

Any genetic findings help predict growth patterns and health-related outcomes may or may not have commercial value through the development of diagnostic or therapeutic agents that may help risk stratify individuals thereby enabling targeting of secondary or tertiary prevention interventions. The University of Bristol RED department would be actively involved in any opportunities for commercial exploitation.

Several publications have already resulted from this work to date. For example, the study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years. This is the first study to document an association between timing of puberty and adult IGF-I levels. Higher levels of IGF-I has been implicated in an increased risk of certain cancers such as breast and prostate. A better understanding of the life course impact of obesity in childhood, adolescence and mid life on later life disease risk may provide new insights into disease aetiology and primary or secondary prevention.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’Christ’s Hospital School (CHS) study'.

This data was linked to growth records from school records, subjects’ self-completed questionnaires and blood samples, all held by the University of Bristol.

The following provides background information on the purpose of the original study:

The CHS study is a retrospective cohort study that comprises former male students of Christ’s Hospital (CH) born between 1927 and 1956. During this period, students had regular measures of height and weight conducted by the School Medical Officer. Growth record cards with height and weight measures were found in the School archive and was the basis of testing the developmental origins hypothesis that growth patterns around puberty and young adulthood may have a long term effect on chronic diseases such as cancer and heart disease.

With the help of the School alumni office, former pupils for whom there was contact information were asked to complete a postal questionnaire to obtain data on life styles and chronic diseases and if willing, attend their local general practice to measure weight, blood pressure and have a blood sample taken.

The data collected for the CHS study enabled the study to look at whether growth and development during childhood and adolescence may be associated with risk factors for chronic diseases such as heart disease and diabetes.

The University of Bristol currently holds identifying record level data on the cohort on a secure auditable server. The data was received from November 1998 to September 2012. The purpose of retaining these data is to enable the empirical testing of the hypotheses stated above.

No new data will be supplied to the University of Bristol under this Agreement.

This Agreement permits the retention of data previously supplied by NHS Digital and ONS but no other processing is permitted.

The University of Bristol has plans to reuse the data in the future for biomedical research subject to the necessary approvals. Before using the data in future biomedical research, the University of Bristol must successfully apply to NHS Digital to amend this Agreement to permit processing for that purpose. That application must be supported with evidence of favourable REC approval and support for the processing under section 251 of the NHS Act 2006.

Researchers at the University of Bristol are currently exploring the possibility of using stored DNA to undertake genome wide analysis that can then be related to both the growth parameters and the health outcomes (with appropriate ethical approval). In addition, the existing number of events that have already been provided are relatively few, so there is little statistical power to look at the existing growth data with cause specific mortality. The University of Bristol may therefore make a future application to NHS Digital to receive new events occurring since 2012 to enable a more rigorous analysis.

The University of Bristol process these data in the public interest under Articles 6(1)(e) and 9(2)(j) as the data has previously been used and is being retained with the intention of future use to contribute to a greater understanding of health related risks, how secular changes in growth may impact on future disease patterns and how these may be tackled in terms of public health prevention and as such serve as public interest. Such research can identify new risk factors with the potential for developing new interventions to prevent disease or look at potential interactions between different risk factors. There are also stored biosamples that could be used to identify new biomarkers, including genetic markers, that may have value in risk prediction, earlier diagnosis and prognosis. In some cases, these findings may lead to the reuse of existing therapeutics or the development of new drug targets or diagnostics. There are very few cohorts with such detailed growth measurements during puberty so it is vital that where possible one replicates findings across cohorts. If this is the case then this adds to the generalisability of any findings on potential prevention strategies.

The University of Bristol is the sole data controller and also processes the data for this study. No other organisations process the data for this purpose.

Currently individuals are directly identifiable from the data held by the study as their personal details are held on the main study database and there are stored signed questionnaires from those who completed them. Personal details are held on the main study database and there are stored signed questionnaires from those who completed them. There are no moral or ethical reasons why the data cannot be retained or processed. However, in the future, under a subsequent Agreement, the University of Bristol intends to provide a new study member identifier to NHS Digital and request a second members and posting list including the new study member ID, as well as the original member ID, to ensure that linkage has been successful with the new identifier. Once this is in place, the University of Bristol intend to proceed to an amendment whereby they will move to a pseudononymised dataset where all personal identifying data are removed, other than a new unique identifier which will replace the old identifier so data cannot be linked to existing paper records. A link file (old and new study identifier) will be stored by third parties who have do not access to any of the data. This is essential as there are blood samples stored in -80C freezers, that may be of great scientific value in the future and are labelled with the original identifier. In this way any future anonymised blood results could be sent to the third party who would add the new identifier and remove the original thereby allowing these new data to be added to the revised database. There would be no attempt to re identify the individuals.

The data is stored on a special secure audited server with access limited to the data processor. Individuals in this study could be located anywhere in the United Kingdom and some will have emigrated. At this stage it is uncertain whether there will be any further follow-up with the participants who completed the past questionnaire. If the University of Bristol decides to undertake further follow-up, it will take advice from NHS Digital as to the appropriate explanation for the PIS and consent form to get permission for future follow-up of their health status.

There is no alternative way of obtaining outcome data on the full cohort other than through linkage to NHS Digital data due to difficulties in contacting participants either because of death or relocation. Merely following up survivors will introduce bias and under ascertain events.

The study was originally undertaken by a research grant from Cancer research UK though this has now ended. It does not currently receive any grant funding but is supported by the Population Health Sciences department, University of Bristol through staff time and support and infra-structure.

There will be no new outputs under this Agreement.

Under a future Agreement, the University of Bristol intend to undertake exploratory analyses looking at whether timing of puberty is or is not associated with specific outcomes e.g. colorectal, prostate cancer. Because of the limited number of events, it has not been decided whether to publish or not publish these findings at this stage due to lack of statistical power. However with future updated event data the University of Bristol would aim to disseminate findings through a variety of methods such as peer reviewed journals, reports, scientific presentations and conferences. All outputs will only contain summary data such as effect estimates but cell counts < 7 will be suppressed to minimise any potential for re-identification. It is likely there would be other research outputs using the non-NHS Digital data for example around statistical methods.

Beyond the research community, the University of Bristol will try to engage with policy makers and civil society more generally through websites and other social media channels to highlight what has been found. The University of Bristol has its own news website where it highlights research undertaken by staff that is thought to be of general interest. Given the historical nature of the data from over 50 years ago, the results may have some interest to populations in low middle income settings who are undergoing the epidemiological transition. In addition, findings may have some relevance to the health care providers and the National Health Service if it allows one to have a better estimate of future health needs using data on secular trends. For example, if earlier onset of puberty is associated with a greater risk of cancer then one could use data on the secular trends for pubertal timing to make predictions about future disease burden and hence related costs.

The stored blood samples may also identify genetic, epigenetic or other biomarkers that may predict growth patterns health-related outcomes. These findings may or may not have commercial value through the development of diagnostic or therapeutic agents that may help risk stratify individuals thereby enabling targeting of secondary or tertiary prevention interventions. The University of Bristol RED department would be actively involved in any opportunities for commercial exploitation.

Several publications have already resulted from this work to date. For example, the study has shown the impact of childhood obesity in the CHS cohort in terms of both timing of puberty, attainment of adult height and adult obesity. This is of particular relevance given the marked increase in childhood obesity seen in all high income countries over the last 20 years. This is the first study to document an association between timing of puberty and adult IGF-I levels. A better understanding of life course determinants of the IGF system may provide new insights into disease etiology and primary or secondary prevention.