Long term sequelae of radiation exposure due to computed tomography and fluoroscopic cardiology in childhood

Newcastle University requires access to NHS England Data for the following reasons:

1) the purpose of the following research project: Long term sequelae of radiation exposure due to computed tomography and fluoroscopic cardiology in childhood.

2) onward sharing to organisations via a sublicensing agreement (subject to Newcastle University’s governance approvals described in this data sharing agreement (DSA).

The following is a summary of the aims of the research project provided by Newcastle University:

"Computed Tomography (CT):

1. Assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from paediatric CT scans administered for purposes other than oncological investigation.

>To evaluate the risks of the defined subgroup of malignancies of radiation-sensitive organs/tissues (leukaemia, brain, thyroid, bone and breast), and of all cancers combined. Data on non-cancer deaths will also be captured.

>The study will construct a unique cohort which will form the basis for continued follow-up, allowing for assessment of cancer risk as the cohort members enter the age of increasing cancer risk, as well as evaluation of cancer and non-cancer mortality.

2. Spearhead an international effort to initiate collaborative studies on cancer risk after CT exposure and to later pool the results to increase statistical power for more detailed analyses of the dose-response and effect modification. This may also enable the study of rare outcomes.

3. Evaluate trends in CT use in the UK according to patient and health care characteristics

Paediatric Fluoroscopic Cardiology:

1. To establish a long-term register of individuals exposed to high levels of radiation during paediatric fluoroscopic cardiology interventions, estimate the radiation doses they received and, subsequently

2. Assess their cancer risk in relation to these doses.

A pilot study was conducted on the availability of information in electronic patient listings as well as individual CT film records for 333 patients who had CT scans in the four radiology departments within the Newcastle upon Tyne Hospitals NHS Trust. The pilot study showed there was adequate information available from electronic records alone for a cohort study.

Collection for the main study cohort (EPI CT) began in 2006 and participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2002 at large radiology departments in the UK. This study used data from NHS England.

A second phase of the study consisted of a nested case−control study on radiation exposures from paediatric CT scans and leukaemia risk, with other cancer outcomes considered should the number of cases suggest the additional case−control studies would have sufficient statistical power. The aim was to obtain further individual details on the CT scans and on confounders to that collected for the cohort study, to allow for more precise estimation of the radiation dose−response effects for leukaemia.

Collection for further data began in 2012 which increased the date range for scans to between 1985 and 2013.

The fluoroscopic cardiology study began in 2010 and collected data, for those particular procedures, with a date range of 1991 – 2014.

This was a national study of the potential long-term radiation-related risks associated with cardiology procedures. The study used records of children and young people with heart defects who were exposed to radiation from interventional cardiac (fluoroscopic) procedures. Exposed individuals were identified primarily from records of radiology and paediatric cardiology departments in Great Britain where interventional cardiology is performed in paediatric patients. The cohort was linked with the existing CT scan cohort of 250,000 patients to allow other medical diagnostic exposures to be included within analyses.

A further cardiology data collection process began in 2022 and is currently ongoing. This will expand the date range from 1991 – 2022.

From this a registry will be established, for long-term follow up, of children and young adults who underwent fluoroscopic cardiology procedures and assess their cancer risk in relation to the estimated radiation doses they received. Leukaemia will be the main outcome initially as it has a relatively short latency and tends to occur at younger ages.

Flagging the cohort for further cancer and mortality information will allow future analyses to consider rarer diseases thought to have aetiological components related to radiation exposure (such as brain, thyroid, skin and breast cancers).

The cohorts from the above studies are being combined with others throughout Europe to produce a pooled cohort. The advantage of this is that the increased study size will improve statistical power, resulting in a better ability to detect the risks at low doses."

Sublicensing:

The following is a summary of the onward sharing to organisations via a sublicensing agreement:

Identifiable data will not flow under the sublicense agreement.

Requests to use the linked NHS England Data come from researchers within the European Economic Area (EEA). All requests must follow the Application Governance process described below. With the exception of Newcastle University (as they are the Controller who also process data), all other approvals to access the linked NHS England Data must be via a sublicence agreement.

The following steps must be taken for a researcher to apply for a sublicensing agreement with Newcastle University :

• A collaboration agreement application must be completed for all requests for data.

• If linked NHS England Data is required, further actions are required. Any researcher who is undertaking analysis that includes NHS England Data must provide evidence of a completed Data Security and Protection Toolkit (DSPT) at their own institution. The external study must also be registered as part of the NHS England Sub-licensing Agreement, and will additionally fall under the terms of that agreement.

• Newcastle Radiation Epidemiology Data Advisory Group (NREDAG) will review the collaboration Agreement application within 4 weeks of receipt.

• Once the appropriate approvals are in place, data is shared with organisations under a sublicensing agreement.

Newcastle Radiation Epidemiology Data Advisory Group (NREDAG) provides oversight of all requests to access the linked NHS England Data.

NREDAG consider requests for access to data on the basis of the following considerations and criteria:

1) Are there any conflicts of interest in reviewing this application? If so, please give brief details.

2) Is the NREDAG able to easily understand what the researchers intend to do, why, and how? If not, the NREDAG can ask the researchers to revise the application to improve clarity before further review.

3) Is there a clear research question or hypothesis which is likely to lead to a generalisable finding, capable of publication in a peer reviewed medical journal?

4) Are the researchers likely to be able to conduct the study and analysis?

5) Is the appropriate data being used to conduct the research?

6) Are the methods appropriate to answer the question including the possibility of biases and confounding, and dealing with each missing data?

7) What patient and public involvement has there been, or will there be, in this research?

8) Are there any potential direct or indirect benefits for patients, or the public, or the health service?

9) Are there any potential risks to the ethical position of Newcastle Radiation Epidemiology in undertaking this research (including the potential identification of patients?)

10) All research is considered under the National Data Guardian’s Public Benefit Guidance

(https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1124013/NDG_public_benefit_guidance_v1.0_-_14.12.22.pdf). How does this research align with that guidance?

NREDAG will meet annually and when required. A register of data sharing will be maintained by NREDAG and will be publicly available on the Newcastle University website for the benefit of participants and other researchers, and will include a lay summary of studies/projects under that Agreement.

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary because this gives an indication of survival time and cause of death of participants who have received radiation exposure from the medical scans being studied (and may indicate if exposure leads to an increased risk).

• Cancer Registration – necessary because this gives an indication of if a participant developed a cancer after being exposed to radiation as part of the medical scans being studies, and how long after that exposure it was diagnosed (and may indicate if exposure leads to an increased risk).

The level of the Data will be identifiable – necessary to enable linkage of the data with data collected from other sources. In order to maintain data linkage for cancer, mortality and transplant outcomes the study team must maintain patient identifiable data. The study team need to be able to link together the radiology information for each patient to ensure that dose estimation is feasible. However, all dosimetric and statistical analysis is performed using pseudo-or fully anonymized data.

The Data will be minimised as follows:

• Limited to a study cohort (approx. 450,000) identified by Newcastle University – participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2013(cohort 1) and fluoroscopic cardiology procedures between 1991 and 2022 (cohort 2) at large radiology departments in the UK;

Newcastle University is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. Newcastle University is the sole Controller for the NHS England datasets (deaths, cancer) which are linked to the electronic patient listings data held by Newcastle University. The electronic patient listings data is distinct from the linked asset (the NHS England Data linked to the electronic patient listings data).

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by The European Union. The funding is specifically for the CT and fluoroscopic cardiology studies described via the HARMONIC project. Funding is in place until 30/11/2024.

The funder will have no ability to suppress or otherwise limit the publication of findings.

The Data will be stored on servers at Newcastle University, data and backup data are also located at Pulsant. Newcastle University rents secure rack space from Pulsant where the University hosts its servers. Pulsant only provides a secure managed location and does not have access to any hardware.

Newcastle University maintained a Patient Public Involvement (PPI) group. This included a specific representative for radiation epidemiology studies who met to discuss the research, including the CT scan study. As part of the Health Protection Research Units (HPRU) at least one public and patient involvement event was held each year, in which members of the public could learn about the research ask questions and raise concerns. No amendments to the study were made as part of this process, but the study has been used as a case study for a wider PPI group meeting and Newcastle University will work with the PPI group further when it comes to reporting results to the public.

PPIE is now being sought through Newcastle University’s Voice, a citizen involvement organisation, network and digital platform which harnesses the experience, ideas, and insights of citizens to ensure that research and innovation is focused on the real needs and priorities of real people.

The Voice platform will be used to contact and involve the public in the research, using it to disseminate information and receive feedback. It is also a platform that can be used for attempting to recruit lay members to advisory and steering groups. Voice also organises in person events to spread involvement and engagement to those who may be less inclined to use a website or digital platform. More information on Voice can be found here: https://voice-global.org/

The expected outputs of the processing will be:

• A report of findings to public and participants via website, and Voice PPIE platform, expected on completion of work with European partners (expected late 2024)

• Submissions to peer reviewed journals on completion of work with European partners (expected late 2024)

• Presentations at appropriate academic conventions or conferences.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Briefing documents provided to study sponsors

• Co-hosted events with other European partners in pooled data studies

• Public events [give details]

• Posters displayed at appropriate academic conventions and conferences

• Press/media engagement

• Public promotion of the research in association with European partners

• Reports aimed at both the public and academics

The next set of outputs have an expected target date of the end of 2024 and start of 2025.

Examples of outputs to date:

Harbron RW, Chapple CL, O'Sullivan JJ, Best KE, Berrington de González A, Pearce MS. Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children. Heart 2017; 103: 341-346.

Journy NM, McHugh K, Harbron RW, Pearce MS, Berrington De Gonzalez A. Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008. Br J Radiol 2016; 89: 20160532.

Journy NM, Lee C, Harbron RW, McHugh K, Pearce MS, Berrington de González A. Projected cancer risks potentially related to past, current, and future practices in paediatric CT in the United Kingdom, 1990-2020. Br J Cancer 2017; 116: 109-116.

Berrington de Gonzalez A, Journy N, Lee C, Morton LM, Harbron RW, Stewart DR, Parker L, Craft AW, McHugh K, Little MP, Pearce MS. No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma. Cancer Epidemiol Biomarkers Prev 2017; 26: 804-806.

Little MP, Wakeford R, Borrego D, French B, Zablotska LB, Adams MJ, Allodji R, de Vathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, Berrington de González A. Leukaemia and myeloid malignancy among people exposed to low doses ( <100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol 2018; 5: e346-e358.

There have been a number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505). It is not possible to quantify the direct benefits of the teams’ research to date, although results have led to some clinical groups changing practice to reduce the amount of radiation-related procedures in their patient groups. Most children’s hospitals now have dedicated paediatric CT protocols in place. Further efforts are needed to encourage community hospitals (where most paediatric patients are likely to undergo CT) to implement the same measures as opposed to using adult-calibrated CT protocols. It is hoped the studies will help inform this.

The findings from this study have led to increased awareness of potential side effects of CT scanning. Newcastle University believe that this research has contributed to the levelling off of CT usage in developing countries and driven research on new dose reduction technologies.

Papers and research where linked data has been used:

Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Sir Craft AW, Parker L, Berrington de González A. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012; 380: 499-505.

This was the first large-scale assessment of the cancer risks following CT scanning in childhood, and the first to utilise dose estimates to allow a dose response analysis. The results have led to increased awareness of potential side effects of CT scanning.

Berrington de Gonzalez A, Salotti JA, McHugh K, Little MP, Harbron RW, Lee C, Ntowe E, Braganza MZ, Parker L, Rajaraman P, Stiller C, Stewart DR, Craft AW, Pearce MS.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. Br J Cancer 2016; 114: 388-394

This study built on the earlier findings of Pearce et al (2012) and found that cancer pre-disposing conditions such as Down syndrome and Tuberous Sclerosis do not significantly confound the apparent relationship between CT scans and subsequent cancer risk. These findings reduce the uncertainty in risk estimates and have contributed to the design of subsequent research, including the European EPI-CT study.

Harbron RW, Chapple CL, O'Sullivan JJ, Lee C, McHugh K, Higueras M, Pearce MS. Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures. Eur J Epidemiol 2018; 33: 393-401

This study was the first analysis of the cancer risks from cardiac catheterizations that included dose response analysis and the first to account for the impact of transplantation. The study formed the groundwork for a much larger pan-European study of cancer risks following cardiac fluoroscopy in childhood (the HARMONIC study).

Newcastle University requires access to NHS England Data for the following reasons:

1) the purpose of the following research project: Long term sequelae of radiation exposure due to computed tomography and fluoroscopic cardiology in childhood.

2) onward sharing to organisations via a sublicensing agreement (subject to Newcastle University’s governance approvals described in this data sharing agreement (DSA).

The following is a summary of the aims of the research project provided by Newcastle University:

"Computed Tomography (CT):

1. Assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from paediatric CT scans administered for purposes other than oncological investigation.

>To evaluate the risks of the defined subgroup of malignancies of radiation-sensitive organs/tissues (leukaemia, brain, thyroid, bone and breast), and of all cancers combined. Data on non-cancer deaths will also be captured.

>The study will construct a unique cohort which will form the basis for continued follow-up, allowing for assessment of cancer risk as the cohort members enter the age of increasing cancer risk, as well as evaluation of cancer and non-cancer mortality.

2. Spearhead an international effort to initiate collaborative studies on cancer risk after CT exposure and to later pool the results to increase statistical power for more detailed analyses of the dose-response and effect modification. This may also enable the study of rare outcomes.

3. Evaluate trends in CT use in the UK according to patient and health care characteristics

Paediatric Fluoroscopic Cardiology:

1. To establish a long-term register of individuals exposed to high levels of radiation during paediatric fluoroscopic cardiology interventions, estimate the radiation doses they received and, subsequently

2. Assess their cancer risk in relation to these doses.

A pilot study was conducted on the availability of information in electronic patient listings as well as individual CT film records for 333 patients who had CT scans in the four radiology departments within the Newcastle upon Tyne Hospitals NHS Trust. The pilot study showed there was adequate information available from electronic records alone for a cohort study.

Collection for the main study cohort (EPI CT) began in 2006 and participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2002 at large radiology departments in the UK. This study used data from NHS England.

A second phase of the study consisted of a nested case−control study on radiation exposures from paediatric CT scans and leukaemia risk, with other cancer outcomes considered should the number of cases suggest the additional case−control studies would have sufficient statistical power. The aim was to obtain further individual details on the CT scans and on confounders to that collected for the cohort study, to allow for more precise estimation of the radiation dose−response effects for leukaemia.

Collection for further data began in 2012 which increased the date range for scans to between 1985 and 2013.

The fluoroscopic cardiology study began in 2010 and collected data, for those particular procedures, with a date range of 1991 – 2014.

This was a national study of the potential long-term radiation-related risks associated with cardiology procedures. The study used records of children and young people with heart defects who were exposed to radiation from interventional cardiac (fluoroscopic) procedures. Exposed individuals were identified primarily from records of radiology and paediatric cardiology departments in Great Britain where interventional cardiology is performed in paediatric patients. The cohort was linked with the existing CT scan cohort of 250,000 patients to allow other medical diagnostic exposures to be included within analyses.

A further cardiology data collection process began in 2022 and is currently ongoing. This will expand the date range from 1991 – 2022.

From this a registry will be established, for long-term follow up, of children and young adults who underwent fluoroscopic cardiology procedures and assess their cancer risk in relation to the estimated radiation doses they received. Leukaemia will be the main outcome initially as it has a relatively short latency and tends to occur at younger ages.

Flagging the cohort for further cancer and mortality information will allow future analyses to consider rarer diseases thought to have aetiological components related to radiation exposure (such as brain, thyroid, skin and breast cancers).

The cohorts from the above studies are being combined with others throughout Europe to produce a pooled cohort. The advantage of this is that the increased study size will improve statistical power, resulting in a better ability to detect the risks at low doses."

Sublicensing:

The following is a summary of the onward sharing to organisations via a sublicensing agreement:

Identifiable data will not flow under the sublicense agreement.

Requests to use the linked NHS England Data come from researchers within the European Economic Area (EEA). All requests must follow the Application Governance process described below. With the exception of Newcastle University (as they are the Controller who also process data), all other approvals to access the linked NHS England Data must be via a sublicence agreement.

The following steps must be taken for a researcher to apply for a sublicensing agreement with Newcastle University :

• A collaboration agreement application must be completed for all requests for data.

• If linked NHS England Data is required, further actions are required. Any researcher who is undertaking analysis that includes NHS England Data must provide evidence of a completed Data Security and Protection Toolkit (DSPT) at their own institution. The external study must also be registered as part of the NHS England Sub-licensing Agreement, and will additionally fall under the terms of that agreement.

• Newcastle Radiation Epidemiology Data Advisory Group (NREDAG) will review the collaboration Agreement application within 4 weeks of receipt.

• Once the appropriate approvals are in place, data is shared with organisations under a sublicensing agreement.

Newcastle Radiation Epidemiology Data Advisory Group (NREDAG) provides oversight of all requests to access the linked NHS England Data.

NREDAG consider requests for access to data on the basis of the following considerations and criteria:

1) Are there any conflicts of interest in reviewing this application? If so, please give brief details.

2) Is the NREDAG able to easily understand what the researchers intend to do, why, and how? If not, the NREDAG can ask the researchers to revise the application to improve clarity before further review.

3) Is there a clear research question or hypothesis which is likely to lead to a generalisable finding, capable of publication in a peer reviewed medical journal?

4) Are the researchers likely to be able to conduct the study and analysis?

5) Is the appropriate data being used to conduct the research?

6) Are the methods appropriate to answer the question including the possibility of biases and confounding, and dealing with each missing data?

7) What patient and public involvement has there been, or will there be, in this research?

8) Are there any potential direct or indirect benefits for patients, or the public, or the health service?

9) Are there any potential risks to the ethical position of Newcastle Radiation Epidemiology in undertaking this research (including the potential identification of patients?)

10) All research is considered under the National Data Guardian’s Public Benefit Guidance

(https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1124013/NDG_public_benefit_guidance_v1.0_-_14.12.22.pdf). How does this research align with that guidance?

NREDAG will meet annually and when required. A register of data sharing will be maintained by NREDAG and will be publicly available on the Newcastle University website for the benefit of participants and other researchers, and will include a lay summary of studies/projects under that Agreement.

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary because this gives an indication of survival time and cause of death of participants who have received radiation exposure from the medical scans being studied (and may indicate if exposure leads to an increased risk).

• Cancer Registration – necessary because this gives an indication of if a participant developed a cancer after being exposed to radiation as part of the medical scans being studies, and how long after that exposure it was diagnosed (and may indicate if exposure leads to an increased risk).

The level of the Data will be identifiable – necessary to enable linkage of the data with data collected from other sources. In order to maintain data linkage for cancer, mortality and transplant outcomes the study team must maintain patient identifiable data. The study team need to be able to link together the radiology information for each patient to ensure that dose estimation is feasible. However, all dosimetric and statistical analysis is performed using pseudo-or fully anonymized data.

The Data will be minimised as follows:

• Limited to a study cohort (approx. 450,000) identified by Newcastle University – participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2013(cohort 1) and fluoroscopic cardiology procedures between 1991 and 2022 (cohort 2) at large radiology departments in the UK;

Newcastle University is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. Newcastle University is the sole Controller for the NHS England datasets (deaths, cancer) which are linked to the electronic patient listings data held by Newcastle University. The electronic patient listings data is distinct from the linked asset (the NHS England Data linked to the electronic patient listings data).

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by The European Union. The funding is specifically for the CT and fluoroscopic cardiology studies described via the HARMONIC project. Funding is in place until 30/11/2024.

The funder will have no ability to suppress or otherwise limit the publication of findings.

The Data will be stored on servers at Newcastle University, data and backup data are also located at Pulsant. Newcastle University rents secure rack space from Pulsant where the University hosts its servers. Pulsant only provides a secure managed location and does not have access to any hardware.

Newcastle University maintained a Patient Public Involvement (PPI) group. This included a specific representative for radiation epidemiology studies who met to discuss the research, including the CT scan study. As part of the Health Protection Research Units (HPRU) at least one public and patient involvement event was held each year, in which members of the public could learn about the research ask questions and raise concerns. No amendments to the study were made as part of this process, but the study has been used as a case study for a wider PPI group meeting and Newcastle University will work with the PPI group further when it comes to reporting results to the public.

PPIE is now being sought through Newcastle University’s Voice, a citizen involvement organisation, network and digital platform which harnesses the experience, ideas, and insights of citizens to ensure that research and innovation is focused on the real needs and priorities of real people.

The Voice platform will be used to contact and involve the public in the research, using it to disseminate information and receive feedback. It is also a platform that can be used for attempting to recruit lay members to advisory and steering groups. Voice also organises in person events to spread involvement and engagement to those who may be less inclined to use a website or digital platform. More information on Voice can be found here: https://voice-global.org/

The expected outputs of the processing will be:

• A report of findings to public and participants via website, and Voice PPIE platform, expected on completion of work with European partners (expected late 2024)

• Submissions to peer reviewed journals on completion of work with European partners (expected late 2024)

• Presentations at appropriate academic conventions or conferences.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Briefing documents provided to study sponsors

• Co-hosted events with other European partners in pooled data studies

• Public events [give details]

• Posters displayed at appropriate academic conventions and conferences

• Press/media engagement

• Public promotion of the research in association with European partners

• Reports aimed at both the public and academics

The next set of outputs have an expected target date of the end of 2024 and start of 2025.

Examples of outputs to date:

Harbron RW, Chapple CL, O'Sullivan JJ, Best KE, Berrington de González A, Pearce MS. Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children. Heart 2017; 103: 341-346.

Journy NM, McHugh K, Harbron RW, Pearce MS, Berrington De Gonzalez A. Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008. Br J Radiol 2016; 89: 20160532.

Journy NM, Lee C, Harbron RW, McHugh K, Pearce MS, Berrington de González A. Projected cancer risks potentially related to past, current, and future practices in paediatric CT in the United Kingdom, 1990-2020. Br J Cancer 2017; 116: 109-116.

Berrington de Gonzalez A, Journy N, Lee C, Morton LM, Harbron RW, Stewart DR, Parker L, Craft AW, McHugh K, Little MP, Pearce MS. No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma. Cancer Epidemiol Biomarkers Prev 2017; 26: 804-806.

Little MP, Wakeford R, Borrego D, French B, Zablotska LB, Adams MJ, Allodji R, de Vathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, Berrington de González A. Leukaemia and myeloid malignancy among people exposed to low doses ( <100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol 2018; 5: e346-e358.

There have been a number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505). It is not possible to quantify the direct benefits of the teams’ research to date, although results have led to some clinical groups changing practice to reduce the amount of radiation-related procedures in their patient groups. Most children’s hospitals now have dedicated paediatric CT protocols in place. Further efforts are needed to encourage community hospitals (where most paediatric patients are likely to undergo CT) to implement the same measures as opposed to using adult-calibrated CT protocols. It is hoped the studies will help inform this.

The findings from this study have led to increased awareness of potential side effects of CT scanning. Newcastle University believe that this research has contributed to the levelling off of CT usage in developing countries and driven research on new dose reduction technologies.

Papers and research where linked data has been used:

Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Sir Craft AW, Parker L, Berrington de González A. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012; 380: 499-505.

This was the first large-scale assessment of the cancer risks following CT scanning in childhood, and the first to utilise dose estimates to allow a dose response analysis. The results have led to increased awareness of potential side effects of CT scanning.

Berrington de Gonzalez A, Salotti JA, McHugh K, Little MP, Harbron RW, Lee C, Ntowe E, Braganza MZ, Parker L, Rajaraman P, Stiller C, Stewart DR, Craft AW, Pearce MS.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. Br J Cancer 2016; 114: 388-394

This study built on the earlier findings of Pearce et al (2012) and found that cancer pre-disposing conditions such as Down syndrome and Tuberous Sclerosis do not significantly confound the apparent relationship between CT scans and subsequent cancer risk. These findings reduce the uncertainty in risk estimates and have contributed to the design of subsequent research, including the European EPI-CT study.

Harbron RW, Chapple CL, O'Sullivan JJ, Lee C, McHugh K, Higueras M, Pearce MS. Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures. Eur J Epidemiol 2018; 33: 393-401

This study was the first analysis of the cancer risks from cardiac catheterizations that included dose response analysis and the first to account for the impact of transplantation. The study formed the groundwork for a much larger pan-European study of cancer risks following cardiac fluoroscopy in childhood (the HARMONIC study).

Newcastle University requires access to NHS England Data for the purpose of the following research project: Long term sequelae of radiation exposure due to computed tomography and fluoroscopic cardiology in childhood.

The following is a summary of the aims of the research project provided by Newcastle University:

"Computed Tomography (CT):

1. Assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from paediatric CT scans administered for purposes other than oncological investigation.

>To evaluate the risks of the defined subgroup of malignancies of radiation-sensitive organs/tissues (leukaemia, brain, thyroid, bone and breast), and of all cancers combined. Data on non-cancer deaths will also be captured.

>The study will construct a unique cohort which will form the basis for continued follow-up, allowing for assessment of cancer risk as the cohort members enter the age of increasing cancer risk, as well as evaluation of cancer and non-cancer mortality.

2. Spearhead an international effort to initiate collaborative studies on cancer risk after CT exposure and to later pool the results to increase statistical power for more detailed analyses of the dose-response and effect modification. This may also enable the study of rare outcomes.

3. Evaluate trends in CT use in the UK according to patient and health care characteristics

Paediatric Fluoroscopic Cardiology:

1. To establish a long-term register of individuals exposed to high levels of radiation during paediatric fluoroscopic cardiology interventions, estimate the radiation doses they received and, subsequently

2. Assess their cancer risk in relation to these doses.

A pilot study was conducted on the availability of information in electronic patient listings as well as individual CT film records for 333 patients who had CT scans in the four radiology departments within the Newcastle upon Tyne Hospitals NHS Trust. The pilot study showed there was adequate information available from electronic records alone for a cohort study.

Collection for the main study cohort (EPI CT) began in 2006 and participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2002 at large radiology departments in the UK. This study used data from NHS England.

A second phase of the study consisted of a nested case−control study on radiation exposures from paediatric CT scans and leukaemia risk, with other cancer outcomes considered should the number of cases suggest the additional case−control studies would have sufficient statistical power. The aim was to obtain further individual details on the CT scans and on confounders to that collected for the cohort study, to allow for more precise estimation of the radiation dose−response effects for leukaemia.

Collection for further data began in 2012 which increased the date range for scans to between 1985 and 2013.

The fluoroscopic cardiology study began in 2010 and collected data, for those particular procedures, with a date range of 1991 – 2014.

This was a national study of the potential long-term radiation-related risks associated with cardiology procedures. The study used records of children and young people with heart defects who were exposed to radiation from interventional cardiac (fluoroscopic) procedures. Exposed individuals were identified primarily from records of radiology and paediatric cardiology departments in Great Britain where interventional cardiology is performed in paediatric patients. The cohort was linked with the existing CT scan cohort of 250,000 patients to allow other medical diagnostic exposures to be included within analyses.

A further cardiology data collection process began in 2022 and is currently ongoing. This will expand the date range from 1991 – 2022.

From this a registry will be established, for long-term follow up, of children and young adults who underwent fluoroscopic cardiology procedures and assess their cancer risk in relation to the estimated radiation doses they received. Leukaemia will be the main outcome initially as it has a relatively short latency and tends to occur at younger ages.

Flagging the cohort for further cancer and mortality information will allow future analyses to consider rarer diseases thought to have aetiological components related to radiation exposure (such as brain, thyroid, skin and breast cancers).

The cohorts from the above studies are being combined with others throughout Europe to produce a pooled cohort. The advantage of this is that the increased study size will improve statistical power, resulting in a better ability to detect the risks at low doses."

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary because this gives an indication of survival time and cause of death of participants who have received radiation exposure from the medical scans being studied (and may indicate if exposure leads to an increased risk).

• Cancer Registration – necessary because this gives an indication of if a participant developed a cancer after being exposed to radiation as part of the medical scans being studies, and how long after that exposure it was diagnosed (and may indicate if exposure leads to an increased risk).

The level of the Data will be identifiable – necessary to enable linkage of the data with data collected from other sources. In order to maintain data linkage for cancer, mortality and transplant outcomes the study team must maintain patient identifiable data. The study team need to be able to link together the radiology information for each patient to ensure that dose estimation is feasible. However, all dosimetric and statistical analysis is performed using pseudo-or fully anonymized data.

The Data will be minimised as follows:

• Limited to a study cohort (approx. 450,000) identified by Newcastle University – participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2013 (cohort 1) and fluoroscopic cardiology procedures between 1991 and 2022 (cohort 2) at large radiology departments in the UK;

Newcastle University is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. Newcastle University is the sole Controller for the NHS England datasets (deaths, cancer) which are linked to the electronic patient listings data held by Newcastle University. The electronic patient listings data is distinct from the linked asset (the NHS England Data linked to the electronic patient listings data).

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by The European Union. The funding is specifically for the CT and fluoroscopic cardiology studies described via the HARMONIC project. Funding is in place until 01/06/2024. Funding to continue the work described will be sought on an ongoing basis.

The funder will have no ability to suppress or otherwise limit the publication of findings.

In addition to servers located at Newcastle University, data and backup data are also located at Pulsant. Newcastle University rents secure rack space from Pulsant where the University hosts its servers. Pulsant only provides a secure managed location and does not have access to any hardware.

Newcastle University maintained a Patient Public Involvement (PPI) group. This included a specific representative for radiation epidemiology studies who met to discuss the research, including the CT scan study. As part of the Health Protection Research Units (HPRU) at least one public and patient involvement event was held each year, in which members of the public could learn about the research ask questions and raise concerns. No amendments to the study were made as part of this process, but the study has been used as a case study for a wider PPI group meeting and Newcastle University will work with the PPI group further when it comes to reporting results to the public.

PPIE is now being sought through Newcastle University’s Voice, a citizen involvement organisation, network and digital platform which harnesses the experience, ideas, and insights of citizens to ensure that research and innovation is focused on the real needs and priorities of real people.

The Voice platform will be used to contact and involve the public in the research, using it to disseminate information and receive feedback. It is also a platform that can be used for attempting to recruit lay members to advisory and steering groups. Voice also organises in person events to spread involvement and engagement to those who may be less inclined to use a website or digital platform. More information on Voice can be found here: https://voice-global.org/

The expected outputs of the processing will be:

• A report of findings to public and participants via website, and Voice PPIE platform, expected on completion of work with European partners (expected late 2024)

• Submissions to peer reviewed journals on completion of work with European partners (expected late 2024)

• Presentations at appropriate academic conventions or conferences.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Briefing documents provided to study sponsors

• Co-hosted events with other European partners in pooled data studies

• Public events [give details]

• Posters displayed at appropriate academic conventions and conferences

• Press/media engagement

• Public promotion of the research in association with European partners

• Reports aimed at both the public and academics

The next set of outputs have an expected target date of the end of 2024 and start of 2025.

Examples of outputs to date:

Harbron RW, Chapple CL, O'Sullivan JJ, Best KE, Berrington de González A, Pearce MS. Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children. Heart 2017; 103: 341-346.

Journy NM, McHugh K, Harbron RW, Pearce MS, Berrington De Gonzalez A. Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008. Br J Radiol 2016; 89: 20160532.

Journy NM, Lee C, Harbron RW, McHugh K, Pearce MS, Berrington de González A. Projected cancer risks potentially related to past, current, and future practices in paediatric CT in the United Kingdom, 1990-2020. Br J Cancer 2017; 116: 109-116.

Berrington de Gonzalez A, Journy N, Lee C, Morton LM, Harbron RW, Stewart DR, Parker L, Craft AW, McHugh K, Little MP, Pearce MS. No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma. Cancer Epidemiol Biomarkers Prev 2017; 26: 804-806.

Little MP, Wakeford R, Borrego D, French B, Zablotska LB, Adams MJ, Allodji R, de Vathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, Berrington de González A. Leukaemia and myeloid malignancy among people exposed to low doses ( <100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol 2018; 5: e346-e358.

There have been a number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505). It is not possible to quantify the direct benefits of the teams’ research to date, although results have led to some clinical groups changing practice to reduce the amount of radiation-related procedures in their patient groups. Most children’s hospitals now have dedicated paediatric CT protocols in place. Further efforts are needed to encourage community hospitals (where most paediatric patients are likely to undergo CT) to implement the same measures as opposed to using adult-calibrated CT protocols. It is hoped the studies will help inform this.

The findings from this study have led to increased awareness of potential side effects of CT scanning. Newcastle University believe that this research has contributed to the levelling off of CT usage in developing countries and driven research on new dose reduction technologies.

Papers and research where linked data has been used:

Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Sir Craft AW, Parker L, Berrington de González A. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012; 380: 499-505.

This was the first large-scale assessment of the cancer risks following CT scanning in childhood, and the first to utilise dose estimates to allow a dose response analysis. The results have led to increased awareness of potential side effects of CT scanning.

Berrington de Gonzalez A, Salotti JA, McHugh K, Little MP, Harbron RW, Lee C, Ntowe E, Braganza MZ, Parker L, Rajaraman P, Stiller C, Stewart DR, Craft AW, Pearce MS.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. Br J Cancer 2016; 114: 388-394

This study built on the earlier findings of Pearce et al (2012) and found that cancer pre-disposing conditions such as Down syndrome and Tuberous Sclerosis do not significantly confound the apparent relationship between CT scans and subsequent cancer risk. These findings reduce the uncertainty in risk estimates and have contributed to the design of subsequent research, including the European EPI-CT study.

Harbron RW, Chapple CL, O'Sullivan JJ, Lee C, McHugh K, Higueras M, Pearce MS. Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures. Eur J Epidemiol 2018; 33: 393-401

This study was the first analysis of the cancer risks from cardiac catheterizations that included dose response analysis and the first to account for the impact of transplantation. The study formed the groundwork for a much larger pan-European study of cancer risks following cardiac fluoroscopy in childhood (the HARMONIC study).

THIS DATA SHARING AGREEMENT PERMITS RETENTION OF THE DATA ONLY AND NO FURTHER PROCESSING.

Newcastle University requires access to NHS England Data for the purpose of the following research project: Long term sequelae of radiation exposure due to computed tomography and fluoroscopic cardiology in childhood.

The following is a summary of the aims of the research project provided by Newcastle University:

"Computed Tomography (CT):

1. Assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from paediatric CT scans administered for purposes other than oncological investigation.

>To evaluate the risks of the defined subgroup of malignancies of radiation-sensitive organs/tissues (leukaemia, brain, thyroid, bone and breast), and of all cancers combined. Data on non-cancer deaths will also be captured.

>The study will construct a unique cohort which will form the basis for continued follow-up, allowing for assessment of cancer risk as the cohort members enter the age of increasing cancer risk, as well as evaluation of cancer and non-cancer mortality.

2. Spearhead an international effort to initiate collaborative studies on cancer risk after CT exposure and to later pool the results to increase statistical power for more detailed analyses of the dose-response and effect modification. This may also enable the study of rare outcomes.

3. Evaluate trends in CT use in the UK according to patient and health care characteristics

Paediatric Fluoroscopic Cardiology:

1. To establish a long-term register of individuals exposed to high levels of radiation during paediatric fluoroscopic cardiology interventions, estimate the radiation doses they received and, subsequently

2. Assess their cancer risk in relation to these doses.

A pilot study was conducted on the availability of information in electronic patient listings as well as individual CT film records for 333 patients who had CT scans in the four radiology departments within the Newcastle upon Tyne Hospitals NHS Trust. The pilot study showed there was adequate information available from electronic records alone for a cohort study.

Collection for the main study cohort (EPI CT) began in 2006 and participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2002 at large radiology departments in the UK. This study used data from NHS England.

A second phase of the study consisted of a nested case−control study on radiation exposures from paediatric CT scans and leukaemia risk, with other cancer outcomes considered should the number of cases suggest the additional case−control studies would have sufficient statistical power. The aim was to obtain further individual details on the CT scans and on confounders to that collected for the cohort study, to allow for more precise estimation of the radiation dose−response effects for leukaemia.

Collection for further data began in 2012 which increased the date range for scans to between 1985 and 2013.

The fluoroscopic cardiology study began in 2010 and collected data, for those particular procedures, with a date range of 1991 – 2014.

This was a national study of the potential long-term radiation-related risks associated with cardiology procedures. The study used records of children and young people with heart defects who were exposed to radiation from interventional cardiac (fluoroscopic) procedures. Exposed individuals were identified primarily from records of radiology and paediatric cardiology departments in Great Britain where interventional cardiology is performed in paediatric patients. The cohort was linked with the existing CT scan cohort of 250,000 patients to allow other medical diagnostic exposures to be included within analyses.

A further cardiology data collection process began in 2022 and is currently ongoing. This will expand the date range from 1991 – 2022.

From this a registry will be established, for long-term follow up, of children and young adults who underwent fluoroscopic cardiology procedures and assess their cancer risk in relation to the estimated radiation doses they received. Leukaemia will be the main outcome initially as it has a relatively short latency and tends to occur at younger ages.

Flagging the cohort for further cancer and mortality information will allow future analyses to consider rarer diseases thought to have aetiological components related to radiation exposure (such as brain, thyroid, skin and breast cancers).

The cohorts from the above studies are being combined with others throughout Europe to produce a pooled cohort. The advantage of this is that the increased study size will improve statistical power, resulting in a better ability to detect the risks at low doses."

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary because this gives an indication of survival time and cause of death of participants who have received radiation exposure from the medical scans being studied (and may indicate if exposure leads to an increased risk).

• Cancer Registration – necessary because this gives an indication of if a participant developed a cancer after being exposed to radiation as part of the medical scans being studies, and how long after that exposure it was diagnosed (and may indicate if exposure leads to an increased risk).

The level of the Data will be identifiable – necessary to enable linkage of the data with data collected from other sources. In order to maintain data linkage for cancer, mortality and transplant outcomes the study team must maintain patient identifiable data. The study team need to be able to link together the radiology information for each patient to ensure that dose estimation is feasible. However, all dosimetric and statistical analysis is performed using pseudo-or fully anonymized data.

The Data will be minimised as follows:

• Limited to a study cohort (approx. 450,000) identified by Newcastle University – participants were identified from electronic radiology department listings of patients who had one or more CT scans between 1985 and 2013 (cohort 1) and fluoroscopic cardiology procedures between 1991 and 2022 (cohort 2) at large radiology departments in the UK;

Newcastle University is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. Newcastle University is the sole Controller for the NHS England datasets (deaths, cancer) which are linked to the electronic patient listings data held by Newcastle University. The electronic patient listings data is distinct from the linked asset (the NHS England Data linked to the electronic patient listings data).

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by The European Union. The funding is specifically for the CT and fluoroscopic cardiology studies described via the HARMONIC project. Funding is in place until 01/06/2024. Funding to continue the work described will be sought on an ongoing basis.

The funder will have no ability to suppress or otherwise limit the publication of findings.

In addition to servers located at Newcastle University, data and backup data are also located at Pulsant. Newcastle University rents secure rack space from Pulsant where the University hosts its servers. Pulsant only provides a secure managed location and does not have access to any hardware.

Newcastle University maintained a Patient Public Involvement (PPI) group. This included a specific representative for radiation epidemiology studies who met to discuss the research, including the CT scan study. As part of the Health Protection Research Units (HPRU) at least one public and patient involvement event was held each year, in which members of the public could learn about the research ask questions and raise concerns. No amendments to the study were made as part of this process, but the study has been used as a case study for a wider PPI group meeting and Newcastle University will work with the PPI group further when it comes to reporting results to the public.

PPIE is now being sought through Newcastle University’s Voice, a citizen involvement organisation, network and digital platform which harnesses the experience, ideas, and insights of citizens to ensure that research and innovation is focused on the real needs and priorities of real people.

The Voice platform will be used to contact and involve the public in the research, using it to disseminate information and receive feedback. It is also a platform that can be used for attempting to recruit lay members to advisory and steering groups. Voice also organises in person events to spread involvement and engagement to those who may be less inclined to use a website or digital platform. More information on Voice can be found here: https://voice-global.org/

THIS DATA SHARING AGREEMENT PERMITS RETENTION OF THE DATA ONLY AND NO FURTHER PROCESSING.

The expected outputs of the processing will be:

• A report of findings to public and participants via website, and Voice PPIE platform, expected on completion of work with European partners (expected late 2024)

• Submissions to peer reviewed journals on completion of work with European partners (expected late 2024)

• Presentations at appropriate academic conventions or conferences.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Briefing documents provided to study sponsors

• Co-hosted events with other European partners in pooled data studies

• Public events [give details]

• Posters displayed at appropriate academic conventions and conferences

• Press/media engagement

• Public promotion of the research in association with European partners

• Reports aimed at both the public and academics

The next set of outputs have an expected target date of the end of 2024 and start of 2025.

Examples of outputs to date:

Harbron RW, Chapple CL, O'Sullivan JJ, Best KE, Berrington de González A, Pearce MS. Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children. Heart 2017; 103: 341-346.

Journy NM, McHugh K, Harbron RW, Pearce MS, Berrington De Gonzalez A. Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008. Br J Radiol 2016; 89: 20160532.

Journy NM, Lee C, Harbron RW, McHugh K, Pearce MS, Berrington de González A. Projected cancer risks potentially related to past, current, and future practices in paediatric CT in the United Kingdom, 1990-2020. Br J Cancer 2017; 116: 109-116.

Berrington de Gonzalez A, Journy N, Lee C, Morton LM, Harbron RW, Stewart DR, Parker L, Craft AW, McHugh K, Little MP, Pearce MS. No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma. Cancer Epidemiol Biomarkers Prev 2017; 26: 804-806.

Little MP, Wakeford R, Borrego D, French B, Zablotska LB, Adams MJ, Allodji R, de Vathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, Berrington de González A. Leukaemia and myeloid malignancy among people exposed to low doses ( <100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol 2018; 5: e346-e358.

THIS DATA SHARING AGREEMENT PERMITS RETENTION OF THE DATA ONLY AND NO FURTHER PROCESSING.

There have been a number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505). It is not possible to quantify the direct benefits of the teams’ research to date, although results have led to some clinical groups changing practice to reduce the amount of radiation-related procedures in their patient groups. Most children’s hospitals now have dedicated paediatric CT protocols in place. Further efforts are needed to encourage community hospitals (where most paediatric patients are likely to undergo CT) to implement the same measures as opposed to using adult-calibrated CT protocols. It is hoped the studies will help inform this.

The findings from this study have led to increased awareness of potential side effects of CT scanning. Newcastle University believe that this research has contributed to the levelling off of CT usage in developing countries and driven research on new dose reduction technologies.

Papers and research where linked data has been used:

Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Sir Craft AW, Parker L, Berrington de González A. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012; 380: 499-505.

This was the first large-scale assessment of the cancer risks following CT scanning in childhood, and the first to utilise dose estimates to allow a dose response analysis. The results have led to increased awareness of potential side effects of CT scanning.

Berrington de Gonzalez A, Salotti JA, McHugh K, Little MP, Harbron RW, Lee C, Ntowe E, Braganza MZ, Parker L, Rajaraman P, Stiller C, Stewart DR, Craft AW, Pearce MS.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. Br J Cancer 2016; 114: 388-394

This study built on the earlier findings of Pearce et al (2012) and found that cancer pre-disposing conditions such as Down syndrome and Tuberous Sclerosis do not significantly confound the apparent relationship between CT scans and subsequent cancer risk. These findings reduce the uncertainty in risk estimates and have contributed to the design of subsequent research, including the European EPI-CT study.

Harbron RW, Chapple CL, O'Sullivan JJ, Lee C, McHugh K, Higueras M, Pearce MS. Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures. Eur J Epidemiol 2018; 33: 393-401

This study was the first analysis of the cancer risks from cardiac catheterizations that included dose response analysis and the first to account for the impact of transplantation. The study formed the groundwork for a much larger pan-European study of cancer risks following cardiac fluoroscopy in childhood (the HARMONIC study).

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The Institute of Cancer Research to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

Computed tomography (CT) scanning and interventional fluoroscopy play essential roles in the diagnosis and management of disease and injury. Use of CT scans has increased rapidly in the UK over the past 20 years and it is likely to become more widespread as advances in technology improve the imaging process. However, CT scans deliver significant radiation doses and are among the highest observed in diagnostic radiology, contributing over 40% of the total collective radiation dose to the UK population from all medical x-ray examinations. In particular, children scanned using CT may have received higher doses of radiation than adults due to failure to account for their smaller body size in scan settings. This is of concern as children are known to be at an increased susceptibility to the effects of radiation compared to adults.

Newcastle University requires cancer registration and civil registration mortality data for the purpose of following up a cohort of patients for the purpose of studying the ‘Long term sequelae of radiation exposure due to computed tomography in childhood’.

The main objective of the study is to assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from CT scans or fluoroscopy administered for purposes other than cancer investigation. The data used in Newcastle University's radiation research programme were obtained from hospital records of examinations performed in x-ray or cardiology departments at participating hospitals. Most, but not all hospitals in the UK, provided data for this study. Data were obtained electronically, as a download from the Radiology Information System (RIS). Study members are flagged at NHS Digital for cancer incidence and death.

The lawful basis for carrying out the research described in this Agreement under the General Data Protection Regulation (GDPR) is that the task is carried out in the public interest, Article 6(1)e, (processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller) as the research is cited as part of the University’s duties. Article 9(2)j (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes) also applies and the research has CAG approval under this basis. Regarding Article 9, paragraph 1 does not apply as processing is necessary for scientific research purposes

Numerous peer-reviewed scientific papers are planned. The main ones will be an update of Newcastle University's previous findings on the cancer risks associated with CT scans or fluoroscopy, with extended follow-up time and improved dosimetry, and as part of a wide international consortium to give increased sample size.

Published results will be anonymised and aggregated with small numbers suppressed where appropriate.

There has been a number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505).

Examples of planned specific outputs, as papers with target dates, are as follows:

- Radiation related risk of leukaemia following CT scans with extended follow-up (expected to be submitted in 2021, with a further paper in 2024 using more complete follow-up)

- Radiation related risk of solid tumours following CT scans (expected to be submitted in 2021, with a further paper in 2024 using more complete follow-up)

- Standardised cancer risks following radiation exposure from CT or fluoroscopy (expected in 2023)

- Radiation-related cancer risks following fluoroscopy, taking into account other medical exposures (expected in 2024)

It is impossible to quantify the direct benefits of the research to date, although Newcastle University are aware that some clinical groups have changed their practice to reduce the amount of radiation-related procedures in their patient groups.

The work has also resulted in further grant funding, from the European Union, Cancer Research UK and the British Heart Foundation demonstrating the wider agreement of the importance of this research.

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling Newcastle University to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

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

Patients undergoing scanning by computed tomography (CT) are a subset of the population exposed to higher levels of radiation than background. In particular, children scanned using CT may have received high doses when compared to those from other diagnostic procedures involving radiation, such as X-rays. This is of concern as children are known to be at an increased susceptibility to the effects of radiation compared to adults.

As yet, no studies have investigated the potential long-term risk from CT radiation exposure. Extrapolations have been used from the Japanese Atomic Bomb Survivor Study but this study will be the first to use empirical data.

This study of medically irradiated patients is very relevant to a policy of understanding the health effects of ionising radiation. In particular, the Department of Health announced last year that COMARE should look at the benefits and risks of using CT scanning in preventative healthcare. They subsequently agreed to co-fund this study. Very little is currently known about the potential risks of CT in any population, other than from extrapolation studies. This study of a subset of the population, which is likely to show the greatest effect of radiation from CT, should there be one, will provide the information urgently required to allow guidelines to be developed for safe and more effective use of CT scans in children and young adults.

The main objective of the study is to assess the risk of subsequent paediatric and young adult cancer after exposure to radiation from CT scans or fluoroscopy administered for purposes other than cancer investigation. Numerous peer-reviewed scientific papers are planned. The main one will be an update of our previous findings on the cancer risks associated with CT scans, with extended follow-up time.

A number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people (Pearce et al., Lancet 2012; 380: 499–505).

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling Newcastle University to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

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

Patients undergoing scanning by computed tomography (CT) are a subset of the population exposed to higher levels of radiation than background. In particular, children scanned using CT may have received high doses when compared to those from other diagnostic procedures involving radiation, such as X-rays. This is of concern as children are known to be at an increased susceptibility to the effects of radiation compared to adults.

As yet, no studies have investigated the potential long-term risk from CT radiation exposure. Extrapolations have been used from the Japanese Atomic Bomb Survivor Study but this study will be the first to use empirical data.

This study of medically irradiated patients is very relevant to a policy of understanding the health effects of ionising radiation. In particular, the Department of Health announced last year that COMARE should look at the benefits and risks of using CT scanning in preventative healthcare. They subsequently agreed to co-fund this study. Very little is currently known about the potential risks of CT in any population, other than from extrapolation studies. This study of a subset of the population, which is likely to show the greatest effect of radiation from CT, should there be one, will provide the information urgently required to allow guidelines to be developed for safe and more effective use of CT scans in children and young adults.

This Agreement permits the secure retention of the data only and no other processing.

No new outputs will be produced under this Data Sharing Agreement.

A number of publications to date, including the first empirical study of the cancer risks associated with CT scans in young people.

Due to an error by one of the GP computer system suppliers (TPP), NHS Digital did not receive updated details on patients who opted out after 1 April 2016 in GP practices running SystmOne (run by TPP). This means that information may have been incorrectly included when NHS Digital provided information to approved organisations, up until 27th May 2018.

This amendment is to re-supply the data between the following time period 01/04/2016 – 27/05/2018 under this agreement

Patients undergoing scanning by computed tomography (CT) are a subset of the population exposed to higher levels of radiation than background. In particular, children scanned using CT may have received high doses when compared to those from other diagnostic procedures involving radiation, such as X-rays. This is of concern as children are known to be at an increased susceptibility to the effects of radiation compared to adults.

As yet, no studies have investigated the potential long-term risk from CT radiation exposure. Extrapolations have been used from the Japanese Atomic Bomb Survivor Study but this study will be the first to use empirical data.

This study of medically irradiated patients is very relevant to a policy of understanding the health effects of ionising radiation. In particular, the Department of Health announced last year that COMARE should look at the benefits and risks of using CT scanning in preventative healthcare. They subsequently agreed to co-fund this study. Very little is currently known about the potential risks of CT in any population, other than from extrapolation studies. This study of a subset of the population, which is likely to show the greatest effect of radiation from CT, should there be one, will provide the information urgently required to allow guidelines to be developed for safe and more effective use of CT scans in children and young adults.

Patients undergoing scanning by computed tomography (CT) are a subset of the population exposed to higher levels of radiation than background. In particular, children scanned using CT may have received high doses when compared to those from other diagnostic procedures involving radiation, such as X-rays. This is of concern as children are known to be at an increased susceptibility to the effects of radiation compared to adults.

As yet, no studies have investigated the potential long-term risk from CT radiation exposure. Extrapolations have been used from the Japanese Atomic Bomb Survivor Study but this study will be the first to use empirical data.

This study of medically irradiated patients is very relevant to a policy of understanding the health effects of ionising radiation. In particular, the Department of Health announced last year that COMARE should look at the benefits and risks of using CT scanning in preventative healthcare. They subsequently agreed to co-fund this study. Very little is currently known about the potential risks of CT in any population, other than from extrapolation studies. This study of a subset of the population, which is likely to show the greatest effect of radiation from CT, should there be one, will provide the information urgently required to allow guidelines to be developed for safe and more effective use of CT scans in children and young adults.