MR461 - A long term follow-up study of Aperts Syndrome

Civil Registration mortality data and Cancer Registration data were supplied to the University of Oxford for the purpose of a long-term follow-up study of individuals with Apert Syndrome.

This study is now complete and closed. This study ran from 1994 to 2013. Data processing finished in 2015, when information on ages at event (death, cause of death, still living on 08/05/2013), with all identifiers removed, were provided to a statistical epidemiologist substantively employed by the University of Oxford. The findings (now in aggregated form) have been ready for publication since 2015 but this has been delayed pending clarification of the legal basis for retaining the data.

This Agreement permits the release of the publication, and the processing of the data for the purpose of secure storage and back up to ensure it is possible to verify the conclusions published from this study..

This Agreement does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this Agreement. Following publication of the study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with the University of Oxford, contact via the publishing journal or an open letter. In such circumstances, the University of Oxford may re-run the previously analyses undertaken to verify that the published results were accurate and may write a response to be issued directly to the challenger or published. The University of Oxford may not use the data to undertake different analyses to those undertaken during the original analysis.

This Agreement does not permit any onward sharing of the data. The data controller may process the data for the purpose of audit.

If any further data processing is required in addition to the above purposes or if the data needs to be moved to a different location/organisation the applicant must submit an amendment request to NHS Digital and receive formal approval in an amended Data Sharing Agreement before data is accessed.

Since 1960 there has been very little further research into Apert syndrome in this country until in 1994 a new study was created at the University of Oxford. The purpose of this new study at the University of Oxford was to try to find out what causes Apert syndrome. Apert syndrome is a rare malformation syndrome comprising two distinctive features, namely a characteristic appearance of the face and skull due to early closure of the skull bones (craniosynostosis) and bony fusions of the fingers and toes (syndactyly). This due to an alteration in one of the many thousands of genetic instructions which human beings carry from the time of conception. This study has already managed to identify which particular genetic instruction is altered, but much work needs to be done to try to understand why the alteration occurs in the first place, and how it causes the features of Apert syndrome.

In 1994 the University of Oxford sought permission from the head researcher of the 1959 study (who was based at the University of Sheffield) in order to obtain the names and dates of birth of the 24 participants in the 1959 study. These are the only data subjects.

The University of Oxford used these details to obtain data from the Medical Research service under the Office of Population Censuses and Surveys (OPCS). in January 1995. The service subsequently transferred to the Office for National Statistics (ONS) and then the Health and Social Care Information Centre (now known as NHS Digital). This detail was used to give the University of Oxford two options;

1 - Should the participant have passed away at time of flagging, the University of Oxford obtained the cause of death, and cancer registration data to understand whether there was an increased incidence of certain cancers.

2 - Should the participant be alive at time of flagging, the University of Oxford would invite them through their General Practitioner to take part in the study.

This study is considered to be in the public interest because it provides new (not previously available) information on the long-term survival of the medical disorder Apert syndrome. The retention of the data, which is now pseudonymised, is not expected to raise ethical issues because no individually identifying information on ages and causes of death is held.

It should be noted that this (currently unpublished) study provides very valuable information for people with Apert syndrome and their parents and carers, because it establishes for the first time that many individuals with the condition live into their 50s-70s. Moreover, although mortality is higher than average before this age, the causes are varied with no one frequent cause (for example a particular type of cancer), being revealed by the data. There is a strong public interest in making these findings widely known by publication in the medical literature.

Data collected were mortality and cancer data from 1994 until 2013. Initially data were supplied by OPCS/NHSCR on whether each individual was already deceased, and if so, the cause of death. In the case of individuals still alive, tracing of dates and causes of death, or cancers, continued (following necessary approvals after each administrative reorganisation) by ONS/NHSIC/HSCIC until 8 May 2013

Since then, actions have been taken to pseudonymise the Apert Syndrome data. These included converting date of birth to week and month of birth, deleting names, and deleting NHS Numbers. No identifying details are held by the University of Oxford in respect of this study.

The data controller is the University of Oxford which is also the only organisation which has processed this data. The analysis of the data completed in 2015, when information on ages at event (death, cause of death, still living on 8/5/2013), with all identifiers removed, were provided to a University of Oxford statistician who has completed a paper on this Apert syndrome. No external parties have been involved in this work. The findings have been ready for publication since 2015, but this has been delayed pending clarification of the legal basis for retaining the data. Following advice from NHS Digital, the University of Oxford has pseudonymised the data.

This study is now completed and closed.

On approval of this Data Sharing Agreement, a completed publication from 2015 will become publicly available. No new analyses will be undertaken using the data under this Agreement.

An online article would be prepared for Headlines, the UK Craniofacial Support Group, so that parents of children with Apert syndrome, and affected young adults, would be made aware of the findings. No new use of the data would be required for this. It would simply be targeting the already-existing information to a specific audience and in simple language.

A summary of the findings would be published in a peer-reviewed medical genetics journal, for example, American Journal of Medical Genetics.

Causes of death, or whether still alive at the end of the study, would be summarised in 5-year bins. As there are only 24 data subjects in the study, each 5-year bins contain fewer than 5 individuals and consequently if someone knew of a person who had Apert syndrome and was in the 1959 study and died within a specific 5-year age-range, they may be able to identify that person. However, the only additional information they may be able to determine about this individual from the summary data might be their primary cause of death which is a matter of public record. Death and cancer data would be summarised in the form of Kaplan-Meier survival curves or similar demonstrating the proportion of individuals still alive at a given age.

An Open Access charge would be paid to the publisher of the peer-reviewed article, to ensure that the article could be read by anybody wishing to do so.

The Headlines web-based article would ensure that the knowledge reached the relevant patient/parent group.

The Publication is expected to be made available for submission of manuscript for peer-review towards the end of 2019, with publication and associated Headlines article in 2020.

This is the sole planned data dissemination and therefore integral to the overall purpose of the work.

None, as the work has remained unpublished up to this point.

Civil Registration mortality data and Cancer Registration data were supplied to the University of Oxford for the purpose of a long-term follow-up study of individuals with Apert Syndrome.

This study is now complete and closed. This study ran from 1994 to 2013. Data processing finished in 2015, when information on ages at event (death, cause of death, still living on 08/05/2013), with all identifiers removed, were provided to a statistical epidemiologist substantively employed by the University of Oxford. The findings (now in aggregated form) have been ready for publication since 2015 but this has been delayed pending clarification of the legal basis for retaining the data.

This Agreement permits the release of the publication, and the processing of the data for the purpose of secure storage and back up to ensure it is possible to verify the conclusions published from this study..

This Agreement does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this Agreement. Following publication of the study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with the University of Oxford, contact via the publishing journal or an open letter. In such circumstances, the University of Oxford may re-run the previously analyses undertaken to verify that the published results were accurate and may write a response to be issued directly to the challenger or published. The University of Oxford may not use the data to undertake different analyses to those undertaken during the original analysis.

This Agreement does not permit any onward sharing of the data. The data controller may process the data for the purpose of audit.

If any further data processing is required in addition to the above purposes or if the data needs to be moved to a different location/organisation the applicant must submit an amendment request to NHS Digital and receive formal approval in an amended Data Sharing Agreement before data is accessed.

Since 1960 there has been very little further research into Apert syndrome in this country until in 1994 a new study was created at the University of Oxford. The purpose of this new study at the University of Oxford was to try to find out what causes Apert syndrome. Apert syndrome is a rare malformation syndrome comprising two distinctive features, namely a characteristic appearance of the face and skull due to early closure of the skull bones (craniosynostosis) and bony fusions of the fingers and toes (syndactyly). This due to an alteration in one of the many thousands of genetic instructions which human beings carry from the time of conception. This study has already managed to identify which particular genetic instruction is altered, but much work needs to be done to try to understand why the alteration occurs in the first place, and how it causes the features of Apert syndrome.

In 1994 the University of Oxford sought permission from the head researcher of the 1959 study (who was based at the University of Sheffield) in order to obtain the names and dates of birth of the 24 participants in the 1959 study. These are the only data subjects.

The University of Oxford used these details to obtain data from the Medical Research service under the Office of Population Censuses and Surveys (OPCS). in January 1995. The service subsequently transferred to the Office for National Statistics (ONS) and then the Health and Social Care Information Centre (now known as NHS Digital). This detail was used to give the University of Oxford two options;

1 - Should the participant have passed away at time of flagging, the University of Oxford obtained the cause of death, and cancer registration data to understand whether there was an increased incidence of certain cancers.

2 - Should the participant be alive at time of flagging, the University of Oxford would invite them through their General Practitioner to take part in the study.

This study is considered to be in the public interest because it provides new (not previously available) information on the long-term survival of the medical disorder Apert syndrome. The retention of the data, which is now pseudonymised, is not expected to raise ethical issues because no individually identifying information on ages and causes of death is held.

It should be noted that this (currently unpublished) study provides very valuable information for people with Apert syndrome and their parents and carers, because it establishes for the first time that many individuals with the condition live into their 50s-70s. Moreover, although mortality is higher than average before this age, the causes are varied with no one frequent cause (for example a particular type of cancer), being revealed by the data. There is a strong public interest in making these findings widely known by publication in the medical literature.

Data collected were mortality and cancer data from 1994 until 2013. Initially data were supplied by OPCS/NHSCR on whether each individual was already deceased, and if so, the cause of death. In the case of individuals still alive, tracing of dates and causes of death, or cancers, continued (following necessary approvals after each administrative reorganisation) by ONS/NHSIC/HSCIC until 8 May 2013

Since then, actions have been taken to pseudonymise the Apert Syndrome data. These included converting date of birth to week and month of birth, deleting names, and deleting NHS Numbers. No identifying details are held by the University of Oxford in respect of this study.

The data controller is the University of Oxford which is also the only organisation which has processed this data. The analysis of the data completed in 2015, when information on ages at event (death, cause of death, still living on 8/5/2013), with all identifiers removed, were provided to a University of Oxford statistician who has completed a paper on this Apert syndrome. No external parties have been involved in this work. The findings have been ready for publication since 2015, but this has been delayed pending clarification of the legal basis for retaining the data. Following advice from NHS Digital, the University of Oxford has pseudonymised the data.

This study is now completed and closed.

On approval of this Data Sharing Agreement, a completed publication from 2015 will become publicly available. No new analyses will be undertaken using the data under this Agreement.

An online article would be prepared for Headlines, the UK Craniofacial Support Group, so that parents of children with Apert syndrome, and affected young adults, would be made aware of the findings. No new use of the data would be required for this. It would simply be targeting the already-existing information to a specific audience and in simple language.

A summary of the findings would be published in a peer-reviewed medical genetics journal, for example, American Journal of Medical Genetics.

Causes of death, or whether still alive at the end of the study, would be summarised in 5-year bins. As there are only 24 data subjects in the study, each 5-year bins contain fewer than 5 individuals and consequently if someone knew of a person who had Apert syndrome and was in the 1959 study and died within a specific 5-year age-range, they may be able to identify that person. However, the only additional information they may be able to determine about this individual from the summary data might be their primary cause of death which is a matter of public record. Death and cancer data would be summarised in the form of Kaplan-Meier survival curves or similar demonstrating the proportion of individuals still alive at a given age.

An Open Access charge would be paid to the publisher of the peer-reviewed article, to ensure that the article could be read by anybody wishing to do so.

The Headlines web-based article would ensure that the knowledge reached the relevant patient/parent group.

The Publication is expected to be made available for submission of manuscript for peer-review towards the end of 2019, with publication and associated Headlines article in 2020.

This is the sole planned data dissemination and therefore integral to the overall purpose of the work.

None, as the work has remained unpublished up to this point.