MR1240 - Evaluation of centralisation in head and neck cancer (Head and Neck 5000)

The aim of this renewal application is to request continued supply of data from NHS England (NHSE) to the Head

& Neck 5000 (H&N 5000) research study for the 10 year follow up study which is due to end 31/3/2026. H&N 5000 is a large United Kingdom (UK) cohort study in head and neck cancer.

The H&N 5000 study is sponsored by University Hospitals Bristol and Weston NHS Foundation Trust (University Hospitals Bristol and Weston) and is being conducted by researchers employed by University Hospitals Bristol and Weston and by the University of Bristol.

University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and the University of Bristol are joint data controllers who process data for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the Head and Neck 5000 10 year follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N 5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva, and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS England where consent was given for this.

Since 2012 the study has received data from NHS England's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. The data was last disseminated to the Head and Neck 5000 team around November 2019. Head and Neck 5000 now require the replacement data sets of Cancer Registration, Demographic and Civil Registration death data, annually until 31/03/2026.

The NHS England data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS England mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS England is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS England, so participants that survive remain in the study for at least 10 years and data will be required until 31st March 2026. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS England will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol and Weston NHS Foundation Trust or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol and Weston NHS Foundation Trust has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS England data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS England data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility, and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the H&N 5000 study have been, and will continue to be, disseminated to the funders of the study. Outputs are also disseminated at appropriate conferences (e.g. British Association of Head and Neck Oncologists, the British Association of Head & Neck Oncology Nurses, and the International Quality of Life Conference for Head and Neck Cancer.) as well as shared with interested charity organisations.

The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’. Results are also disseminated to patient groups and on the study website.

Links to published papers are published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public. To date 42 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pre-treatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumours arising across tissues share in part a common germline genetic basis)

• Patient-reported quality of life is similar following either radiotherapy or surgery for T1a glottic carcinoma. These data support current guidance recommended for this disease.

All outputs only contain aggregated data with small numbers suppressed.

There are currently over 30 ongoing projects that have approval to work on the study data and have been supplied with an anonymised dataset. They include the following projects:

• Using H&N 5000 data to analyse treatment outcome in laryngeal cancer

• Analysis of UK clinical practice and its impact on outcomes for non-surgically managed head and neck cancer patients

• Long term quality of life in people with head and neck cancer (BD4QoL study)

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project run by the World Health Organisation’s International Agency for Research on Cancer (IARC) bringing together a consortium of 15 partner institutions to study head and neck cancer.

• Epidemiology and Treatment for elderly Head and Neck Cancer patients in the UK

• Mapping the epigenetic landscape for sinonasal carcinoma

Future outputs may be aimed at policy makers, but they will also be aimed at other communities, i.e. not solely for policy makers.

The results of the planned 10 year follow up questionnaire will be disseminated though head and neck cancer patient and charity groups as well as in published papers.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/ Ongoing projects are listed at: http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/

UPDATED OUTPUTS 2024

As intended the Head and Neck 5000 study data and samples continue to be analysed in a variety of projects. Results of the study have been, and will continue to be, disseminated to the funders of the study and at appropriate conferences (e.g. British Association of Head and Neck Oncologists) as well as shared with interested charity organisations. The results are published in peer reviewed scientific journals and links to published papers are published on the study website.

To date 45 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• Cancer-related fatigue (CRF). (CRF is a common side-effect of cancer and its treatments, but few studies had investigated CRF in head and neck cancer. The likelihood of having CRF over 12 months was found to be significantly higher in patients who were female, current smokers, and had comorbid conditions or depression at baseline).

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pre-treatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying highrisk groups in nasal cavity cancer) • A comprehensive analysis of cross-cancer heritability (suggests that solid tumours arising across tissues share in part a common germline genetic basis)

• Patient-reported quality of life is similar following either radiotherapy or surgery for T1a glottic carcinoma. These data support current guidance recommended for this disease. There are currently 30 ongoing projects working on the study data, they include the following projects:

• The effect of smoking and alcohol cessation on prognosis from head and neck cancer

• Outcomes following definitive chemoradiotherapy for nasopharynx carcinoma

• Using H&N 5000 data to analyse treatment outcome in laryngeal cancer

• Pain fatigue and functional outcomes

• Analysis of UK clinical practice and its impact on outcomes for non-surgically managed head and neck cancer patients • Long term quality of life in people with head and neck cancer (BD4QoL study)

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project run by the World Health Organisation’s International Agency DARS Application Compliance Report version 1.6 05/02/2025 for Research on Cancer (IARC) bringing together a consortium of 15 partner institutions to study head and neck cancer.

A full list of publications can be found at: http://www.headandneck5000.org.uk/information-forresearchers/publications/ Ongoing projects are listed at: http://www.headandneck5000.org.uk/information-forresearchers/ongoingprojects/

Findings from the Head and Neck 5000 study have contributed to knowledge around lifestyle, aetiology, pathogenesis, management, and outcomes for people with head and neck cancer. Outputs also feed into an international consortia with a dedicated focus on head and neck patients. Whilst the work has not yet resulted in any direct changes to formal policy or guidance it is anticipated that the multidisciplinary outputs will provide evidence to inform future practice with an emphasis on predictive modelling, risk stratification and lifestyle modification.

Ultimately it is anticipated that the work will be important for improving outcomes and quality of life for people with head and neck cancer.

UPDATED YIELDED BENEFITS 2024

Benefits Head & Neck 5000 is one of the largest head and neck cancer studies in the world and continues to provide important information about social, lifestyle, clinical outcomes, and survival in head and neck cancer. Findings from the Head and Neck 5000 study have contributed to knowledge around lifestyle, aetiology, pathogenesis, management and outcomes for people with head and neck cancer. Outputs also feed into an international consortia with a dedicated focus on head and neck patients.

This Data Sharing Agreement permits the retention and processing 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 University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS England’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:

The Head and Neck 5000 study is sponsored by University Hospitals Bristol and Weston NHS Foundation Trust (University Hospitals Bristol and Weston) and is being conducted by researchers employed by University Hospitals Bristol and Weston and by the University of Bristol.

University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and the University of Bristol are joint data controllers who process data for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the H&N5000 Follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and also using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS Digital where consent was given for this.

Since 2012 the study has received Cohort Event Notifications and Cause of Death reports from NHS Digital's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. Ongoing reports will be required every 6 months until 31/12/2024. The study requires a one off Members and Posting report for cohort validation and reconciliation.

The NHS Digital data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS Digital mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors in order to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS Digital is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS Digital, so participants that survive remain in the study for at least 10 years and data will be required until 31st December 2024. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS Digital will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol and Weston NHS Foundation Trust or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol and Weston NHS Foundation Trust has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS Digital data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS Digital data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the study have been, and will continue to be disseminated to the funders of the study on an annual basis. Outputs are also disseminated at appropriate conferences (e.g. BAHNO) as well as shared with interested charity organisations on a regular, ongoing basis. The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’.

Links to published papers are also published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public. On average the study team have produced at least 6 publications a year.

To date 23 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pretreatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• How a head and neck cancer diagnosis affects smoking and drinking habits (a diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence, however, these changes are dynamic in the first year after diagnosis).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumors arising across tissues share in part a common germline genetic basis)

All Outputs contain only aggregated data with small numbers suppressed.

There are around 30 ongoing projects working on the study data. These include projects being undertaken by the Head and Neck 5000 study team exclusively or in collaboration with external researchers. They include the following projects:

• Gustatory function following treatment for head and neck cancer

• Looking at the tumour micro-environment of salivary gland malignancies to see if biomarkers predict clinical outcome

• Body mass index at diagnosis and its prognostic significance on head and neck cancer survival

• Functional outcomes and quality of life after radiotherapy or surgery for early/intermediate stage oropharyngeal carcinoma

• Appearance-related distress amongst head and neck cancer patients

• Quality of Life following treatment for oropharyngeal carcinoma; a comparison of surgery versus non-surgical therapy

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project bringing together a consortium of 15 partner institutions working across nine work-packages to study head and neck cancer.

• Using saliva to identify human papillomavirus driven oropharyngeal cancers

Future outputs may be aimed at policy makers but they will also be aimed at other communities, i.e. not solely for policy makers.

While the study collected the date of death from the medical notes up to one year and again at 3 – 5 years, mortality data has not always been available from the medical notes. The mortality data from NHS Digital is essential in assessing longer term survival.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/. Ongoing projects are listed at http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/.

To date, 23 peer reviewed papers arising from the study have been published, and these analyses have been presented at a number of scientific meetings. The study is currently supporting around 30 ongoing analysis projects and are part of the World Health Organisation’s International Agency for Research on Cancer (IARC) international consortia, exploring the role of germline and tumour genetics on Head and Neck cancer aetiology and prognosis.

As well as published papers findings have been presented at clinical conferences such as BAHNO (British Association of Head and Neck Oncologists) and BAHNON (British Association of Head & Neck Oncology Nurses) and the International Quality of Life Conference for Head and Neck Cancer.

To date the findings from Head and Neck 5000 have contributed to knowledge around aetiology and prognosis in people with head and neck cancer. To date these findings have not resulted in any formal changes to policy or guidance but it is anticipated that the work will provide evidence that will inform practice and improve the management of people with head and neck cancer in terms of risk stratification, lifestyle modification and prognostic prediction.

This Data Sharing Agreement permits the retention and processing 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 University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) 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:

The Head and Neck 5000 study is sponsored by University Hospitals Bristol and Weston NHS Foundation Trust (University Hospitals Bristol and Weston) and is being conducted by researchers employed by University Hospitals Bristol and Weston and by the University of Bristol.

University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and the University of Bristol are joint data controllers and joint data processors for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the H&N5000 Follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and also using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS Digital where consent was given for this.

Since 2012 the study has received Cohort Event Notifications and Cause of Death reports from NHS Digital's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. Ongoing reports will be required every 6 months until 31/12/2024. The study requires a one off Members and Posting report for cohort validation and reconciliation.

The NHS Digital data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS Digital mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors in order to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS Digital is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS Digital, so participants that survive remain in the study for at least 10 years and data will be required until 31st December 2024. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS Digital will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol and Weston NHS Foundation Trust or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol and Weston NHS Foundation Trust has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS Digital data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS Digital data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the study have been, and will continue to be disseminated to the funders of the study on an annual basis. Outputs are also disseminated at appropriate conferences (e.g. BAHNO) as well as shared with interested charity organisations on a regular, ongoing basis. The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’.

Links to published papers are also published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public. On average the study team have produced at least 6 publications a year.

To date 23 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pretreatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• How a head and neck cancer diagnosis affects smoking and drinking habits (a diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence, however, these changes are dynamic in the first year after diagnosis).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumors arising across tissues share in part a common germline genetic basis)

All Outputs contain only aggregated data with small numbers suppressed.

There are around 30 ongoing projects working on the study data. These include projects being undertaken by the Head and Neck 5000 study team exclusively or in collaboration with external researchers. They include the following projects:

• Gustatory function following treatment for head and neck cancer

• Looking at the tumour micro-environment of salivary gland malignancies to see if biomarkers predict clinical outcome

• Body mass index at diagnosis and its prognostic significance on head and neck cancer survival

• Functional outcomes and quality of life after radiotherapy or surgery for early/intermediate stage oropharyngeal carcinoma

• Appearance-related distress amongst head and neck cancer patients

• Quality of Life following treatment for oropharyngeal carcinoma; a comparison of surgery versus non-surgical therapy

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project bringing together a consortium of 15 partner institutions working across nine work-packages to study head and neck cancer.

• Using saliva to identify human papillomavirus driven oropharyngeal cancers

Future outputs may be aimed at policy makers but they will also be aimed at other communities, i.e. not solely for policy makers.

While the study collected the date of death from the medical notes up to one year and again at 3 – 5 years, mortality data has not always been available from the medical notes. The mortality data from NHS Digital is essential in assessing longer term survival.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/. Ongoing projects are listed at http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/.

To date, 23 peer reviewed papers arising from the study have been published, and these analyses have been presented at a number of scientific meetings. The study is currently supporting around 30 ongoing analysis projects and are part of the World Health Organisation’s International Agency for Research on Cancer (IARC) international consortia, exploring the role of germline and tumour genetics on Head and Neck cancer aetiology and prognosis.

As well as published papers findings have been presented at clinical conferences such as BAHNO (British Association of Head and Neck Oncologists) and BAHNON (British Association of Head & Neck Oncology Nurses) and the International Quality of Life Conference for Head and Neck Cancer.

To date the findings from Head and Neck 5000 have contributed to knowledge around aetiology and prognosis in people with head and neck cancer. To date these findings have not resulted in any formal changes to policy or guidance but it is anticipated that the work will provide evidence that will inform practice and improve the management of people with head and neck cancer in terms of risk stratification, lifestyle modification and prognostic prediction.

This Data Sharing Agreement permits the retention and processing 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 University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) 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:

The Head and Neck 5000 study is sponsored by University Hospitals Bristol and Weston NHS Foundation Trust (University Hospitals Bristol and Weston) and is being conducted by researchers employed by University Hospitals Bristol and Weston and by the University of Bristol.

University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and the University of Bristol are joint data controllers and joint data processors for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the H&N5000 Follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and also using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS Digital where consent was given for this.

Since 2012 the study has received Cohort Event Notifications and Cause of Death reports from NHS Digital's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. Ongoing reports will be required every 6 months until 31/12/2024. The study requires a one off Members and Posting report for cohort validation and reconciliation.

The NHS Digital data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS Digital mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors in order to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS Digital is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS Digital, so participants that survive remain in the study for at least 10 years and data will be required until 31st December 2024. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS Digital will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol and Weston NHS Foundation Trust or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol and Weston NHS Foundation Trust has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS Digital data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS Digital data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the study have been, and will continue to be disseminated to the funders of the study on an annual basis. Outputs are also disseminated at appropriate conferences (e.g. BAHNO) as well as shared with interested charity organisations on a regular, ongoing basis. The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’.

Links to published papers are also published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public. On average the study team have produced at least 6 publications a year.

To date 23 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pretreatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• How a head and neck cancer diagnosis affects smoking and drinking habits (a diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence, however, these changes are dynamic in the first year after diagnosis).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumors arising across tissues share in part a common germline genetic basis)

All Outputs contain only aggregated data with small numbers suppressed.

There are around 30 ongoing projects working on the study data. These include projects being undertaken by the Head and Neck 5000 study team exclusively or in collaboration with external researchers. They include the following projects:

• Gustatory function following treatment for head and neck cancer

• Looking at the tumour micro-environment of salivary gland malignancies to see if biomarkers predict clinical outcome

• Body mass index at diagnosis and its prognostic significance on head and neck cancer survival

• Functional outcomes and quality of life after radiotherapy or surgery for early/intermediate stage oropharyngeal carcinoma

• Appearance-related distress amongst head and neck cancer patients

• Quality of Life following treatment for oropharyngeal carcinoma; a comparison of surgery versus non-surgical therapy

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project bringing together a consortium of 15 partner institutions working across nine work-packages to study head and neck cancer.

• Using saliva to identify human papillomavirus driven oropharyngeal cancers

Future outputs may be aimed at policy makers but they will also be aimed at other communities, i.e. not solely for policy makers.

While the study collected the date of death from the medical notes up to one year and again at 3 – 5 years, mortality data has not always been available from the medical notes. The mortality data from NHS Digital is essential in assessing longer term survival.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/. Ongoing projects are listed at http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/.

To date, 23 peer reviewed papers arising from the study have been published, and these analyses have been presented at a number of scientific meetings. The study is currently supporting around 30 ongoing analysis projects and are part of the World Health Organisation’s International Agency for Research on Cancer (IARC) international consortia, exploring the role of germline and tumour genetics on Head and Neck cancer aetiology and prognosis.

As well as published papers findings have been presented at clinical conferences such as BAHNO (British Association of Head and Neck Oncologists) and BAHNON (British Association of Head & Neck Oncology Nurses) and the International Quality of Life Conference for Head and Neck Cancer.

To date the findings from Head and Neck 5000 have contributed to knowledge around aetiology and prognosis in people with head and neck cancer. To date these findings have not resulted in any formal changes to policy or guidance but it is anticipated that the work will provide evidence that will inform practice and improve the management of people with head and neck cancer in terms of risk stratification, lifestyle modification and prognostic prediction.

This Data Sharing Agreement permits the retention and processing 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 University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) 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:

The Head and Neck 5000 study is sponsored by University Hospitals Bristol NHS Foundation Trust (University Hospitals Bristol) and is being conducted by researchers employed by University Hospitals Bristol and by the University of Bristol.

University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) and the University of Bristol are joint data controllers and joint data processors for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the H&N5000 Follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and also using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS Digital where consent was given for this.

Since 2012 the study has received Cohort Event Notifications and Cause of Death reports from NHS Digital's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. Ongoing reports will be required every 6 months until 31/12/2024. The study requires a one off Members and Posting report for cohort validation and reconciliation.

The NHS Digital data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS Digital mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors in order to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS Digital is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS Digital, so participants that survive remain in the study for at least 10 years and data will be required until 31st December 2024. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS Digital will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol and Weston NHS Foundation Trust or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol and Weston NHS Foundation Trust has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS Digital data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS Digital data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the study have been, and will continue to be disseminated to the funders of the study on an annual basis. Outputs are also disseminated at appropriate conferences (e.g. BAHNO) as well as shared with interested charity organisations on a regular, ongoing basis. The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’.

Links to published papers are also published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public. On average the study team have produced at least 6 publications a year.

To date 23 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pretreatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• How a head and neck cancer diagnosis affects smoking and drinking habits (a diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence, however, these changes are dynamic in the first year after diagnosis).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumors arising across tissues share in part a common germline genetic basis)

All Outputs contain only aggregated data with small numbers suppressed.

There are around 30 ongoing projects working on the study data. These include projects being undertaken by the Head and Neck 5000 study team exclusively or in collaboration with external researchers. They include the following projects:

• Gustatory function following treatment for head and neck cancer

• Looking at the tumour micro-environment of salivary gland malignancies to see if biomarkers predict clinical outcome

• Body mass index at diagnosis and its prognostic significance on head and neck cancer survival

• Functional outcomes and quality of life after radiotherapy or surgery for early/intermediate stage oropharyngeal carcinoma

• Appearance-related distress amongst head and neck cancer patients

• Quality of Life following treatment for oropharyngeal carcinoma; a comparison of surgery versus non-surgical therapy

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project bringing together a consortium of 15 partner institutions working across nine work-packages to study head and neck cancer.

• Using saliva to identify human papillomavirus driven oropharyngeal cancers

Future outputs may be aimed at policy makers but they will also be aimed at other communities, i.e. not solely for policy makers.

While the study collected the date of death from the medical notes up to one year and again at 3 – 5 years, mortality data has not always been available from the medical notes. The mortality data from NHS Digital is essential in assessing longer term survival.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/. Ongoing projects are listed at http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/.

To date, 23 peer reviewed papers arising from the study have been published, and these analyses have been presented at a number of scientific meetings. The study is currently supporting around 30 ongoing analysis projects and are part of the World Health Organisation’s International Agency for Research on Cancer (IARC) international consortia, exploring the role of germline and tumour genetics on Head and Neck cancer aetiology and prognosis.

As well as published papers findings have been presented at clinical conferences such as BAHNO (British Association of Head and Neck Oncologists) and BAHNON (British Association of Head & Neck Oncology Nurses) and the International Quality of Life Conference for Head and Neck Cancer.

To date the findings from Head and Neck 5000 have contributed to knowledge around aetiology and prognosis in people with head and neck cancer. To date these findings have not resulted in any formal changes to policy or guidance but it is anticipated that the work will provide evidence that will inform practice and improve the management of people with head and neck cancer in terms of risk stratification, lifestyle modification and prognostic prediction.

The Head and Neck 5000 study is sponsored by University Hospitals Bristol NHS Foundation Trust (University Hospitals Bristol) and is being conducted by researchers employed by University Hospitals Bristol and by the University of Bristol.

University Hospitals Bristol and the University of Bristol are joint data controllers and joint data processors for this study. The University of Bristol is the primary employer for some of the staff involved in the study. Staff who handle identifying data are required to complete mandatory training on Information Governance and ICH-GCP.

The aims of the Head and Neck 5000 study were to evaluate the outcome of centralisation in Head and Neck cancer, identify prognostic indicators for head and neck cancer and to create a resource for translational and applied research in head and neck cancer.

The objectives are to:

i. compare morbidity and mortality outcomes across different centres,

ii. compare quality of life outcomes across different centres,

iii. describe the individual economic cost of head and neck cancer care, identify prognostic indicators for head and neck cancer,

iv. create a resource for translational and applied research in head and neck cancer.

In order to accomplish these aims and objectives, between 2011 and 2014 the study recruited a clinical cohort of 5,511 people with head and neck cancer from 76 hospitals across the UK.

The study has since been extended with further data collection in the H&N5000 Follow-up study. The aim of assessing centralisation has been completed but the remaining objectives are ongoing.

The study has established a resource for head and neck cancer research and the information gathered from the study is making an important contribution to research into the cause, development and outcome of head and neck cancer.

The Head and Neck 5000 Scientific Team is comprised of four highly experienced clinicians and academics who are employees of the University of Bristol. They determine how the data is used to deliver the aims above. For example, for the purpose of comparisons of outcomes across different centres, the Scientific Team determine which centres will be compared over what time periods and which specific outcomes will be in focus.

Personal data can be lawfully processed in line with Article 6(1)(e) –‘processing is necessary for the performance of a task carried out in the public interest’ and Article 9(2)(j) – ‘processing is necessary for archiving purposes in the public interest'.

The Head and Neck 5000 Study was initially funded by an NIHR programme grant and commenced recruitment in 2011.

The H&N5000 Follow-up Study was financed from three separate sources:

• Funding transferred to the study from a Cancer Research UK grant awarded to an employee of the University of Bristol who is working on some of the follow-up study data

• Funding awarded by the Research and Innovation Department at University Hospitals Bristol

• Funding from the Chief Investigator’s NIHR Senior Investigator Award

Ongoing work on the study is financed from a bequest administered by the Above and Beyond charity.

The study participants are adult men and women who at the time of recruitment had a newly diagnosed head and neck primary cancer. People who were considered to meet the criteria for mental incapacity or vulnerability set out in the Mental Capacity Act 2005, were not eligible to join the study. The youngest age at recruitment to the cohort was 18.

Study participants gave their consent to the study at hospital sites across England, Wales and Scotland. Data was collected on study participants from the medical notes and also using self-completed participant questionnaires. The study data is wide-ranging and has recorded information on age, gender, diagnosis, treatment, socioeconomic status, lifestyle (including smoking and alcohol intake), questions on psychological status and general and cancer specific quality of life questions. The data collection time points were at baseline, month 4, month 12 with a further follow up at 3-5 years. Blood, saliva and tissue samples were collected at baseline for use in translational studies. Longer follow-up is by survival data obtained from NHS Digital where consent was given for this.

Since 2012 the study has received Cohort Event Notifications and Cause of Death reports from NHS Digital's Medical Research Information Service (MRIS), providing the date of death and cause of death and details of cancer registrations. Ongoing reports will be required every 6 months until 31/12/2024. The study requires a one off Members and Posting report for cohort validation and reconciliation.

The NHS Digital data includes identifying data which is used to identify participants that have died to ensure that no further correspondence is sent out. The details of deaths allow the study to compare morbidity and mortality outcomes by participant characteristics and across centres. The researchers will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality.

The NHS Digital mortality data is important as it provides information about how long people live after their head and neck cancer diagnosis and how many people die from head and neck cancer or other causes. This information is analysed in relation to the type of cancer, stage of cancer, treatments given, data on quality of life and other factors in order to gain information that might help determine which treatment pathways are best and what factors influence how long patients survive after treatment. Cancer registration data from NHS Digital is necessary to study links between Head and Neck cancers and other cancers.

This study is large enough to compare groups by age, site and stage. Data are already collected on the care provided to patients with Head and Neck cancer as part of an ongoing National Head and neck cancer audit. It is intended that this research will complement these National audit data by investigating the role of patient characteristics not recorded as part of routine care and by examining a broader range of patient centred and clinical outcomes.

The study will also be able to analyse the broad range of patient centred outcomes collected in the study in relation to morbidity and mortality. The study will continue the follow up of participants through the mortality data provided by NHS Digital, so participants that survive remain in the study for at least 10 years and data will be required until 31st December 2024. Participants were recruited from England, Wales and Scotland so mortality data is required from these areas, although NHS Digital will only provide the mortality for patients in England and Wales.

The outcome of the study will allow clinicians and managers to design effective patient centred multidisciplinary centralised services for people with Head and Neck cancer.

The Head and Neck 5000 team collaborates with other researchers in the writing of papers for publication. In such instances, the individuals will only ever see the outputs of analyses undertaken by the Head and Neck 5000 team which will contain only aggregated data with small numbers suppressed as appropriate to comply with the HES Analysis Guide. The data under this Agreement will only be shared with substantive employees of University Hospitals Bristol or the University of Bristol and will not be shared with any other third parties.

One of the aims of the Head and Neck 5000 study was to create a resource for translational and applied research in head and neck cancer. University Hospitals Bristol has an Access Policy which allows them to share anonymised, aggregated and suppressed study data with other researchers working on approved projects. Sharing the data with other research projects enables the data gathered to have the widest possible benefit for patient care.

No NHS Digital data has been shared with any third parties and no data under this Agreement will be shared with any third parties.

For the purposes of other research studies, the Head and Neck 5000 team may produce aggregated outputs with appropriate small number suppression which include data derived from NHS Digital data. This Agreement permits the necessary processing of NHS Digital data for this purpose with the following conditions:

• Only data which complies with the definition of ‘Derived Data’ as documented in the Data Sharing Framework Contract may be shared with third parties;

• This derived data must not be combined with any other data which could potentially increase the risk of reidentification for individuals in the dataset.

Access to such data is only permitted for bone fide researchers and will not be permitted for commercial purposes. Controls are in place to ensure researchers complete a study proposal form. All submitted proposal forms are reviewed by the Head and Neck 5000 management team for relevance of project, feasibility and any overlap with existing projects. Data required must be relevant to the proposed project. If required, further information will be requested or an amendment to the project required before approval is given.

Where data are shared with researchers who are not part of the Head and Neck 5000 study team, a study contract, based on the NHS standard research contract, must be agreed and signed. Summaries of all approved projects are uploaded on to the study website.

All participants gave consent before taking part in the Head and Neck 5000 study. The study was set up so that participants could consent to take part in some sections of the study without taking part in others; so for example if consent was not given to data linkage the participant could still take part in other aspects of the study. The original study and the Follow-up study both received Research Ethics Committee approval.

Results of the study have been, and will continue to be disseminated to the funders of the study. Outputs are also disseminated at appropriate conferences (e.g. BAHNO) as well as shared with interested Charity organisations. The results are published in peer reviewed scientific journals; the majority of these will be ‘open access’.

Links to published papers are also published on the study website for the information of health care professionals, healthcare policy makers, study participants and the general public.

To date 15 peer reviewed papers have been published; a short summary of a selection of the papers is listed here:

• The prognostic role of smoking and alcohol intake at diagnosis (it was found that there was no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers, but smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality).

• Pretreatment depressive symptoms (it was found that persistent/recurrent/late depressive symptoms were associated with worse survival among people with head and neck cancer).

• How a head and neck cancer diagnosis affects smoking and drinking habits (a diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence, however, these changes are dynamic in the first year after diagnosis).

• Vegetable intake and head and neck cancer survival (they are modestly associated)

• A descriptive analysis of people with nasal cavity squamous cell carcinoma (identifying high-risk groups in nasal cavity cancer)

• A comprehensive analysis of cross-cancer heritability (suggests that solid tumors arising across tissues share in part a common germline genetic basis)

There are around 30 ongoing projects working on the study data. These include projects being undertaken by the Head and Neck 5000 study team exclusively or in collaboration with external researchers. They include the following projects:

• Gustatory function following treatment for head and neck cancer

• Looking at the tumour microenvironment of salivary gland malignancies to see if biomarkers predict clinical outcome

• Body mass index at diagnosis and its prognostic significance on head and neck cancer survival

• Functional outcomes and quality of life after radiotherapy or surgery for early/intermediate stage oropharyngeal carcinoma

• Appearance-related distress amongst head and neck cancer patients

• Quality of Life following treatment for oropharyngeal carcinoma; a comparison of surgery versus non-surgical therapy

• Translational Studies of Head and Neck Cancer in South America and Europe (HEADSpAcE). A European Union funded project bringing together a consortium of 15 partner institutions working across nine work-packages to study head and neck cancer.

• Using saliva to identify human papillomavirus driven oropharyngeal cancers

While the study collected the date of death from the medical notes up to one year and again at 3 – 5 years, mortality data has not always been available from the medical notes. The mortality data from NHS Digital is essential in assessing longer term survival.

Publications can be found at: http://www.headandneck5000.org.uk/information-for-researchers/publications/. Ongoing projects are listed at http://www.headandneck5000.org.uk/information-for-researchers/ongoingprojects/.

To date, 15 peer reviewed papers arising from the study have been published, and these analyses have been presented at a number of scientific meetings. The study is currently supporting around 30 ongoing analysis projects and are part of the World Health Organisation’s International Agency for Research on Cancer (IARC) international consortia, exploring the role of germline and tumour genetics on Head and Neck cancer aetiology and prognosis.

As well as published papers findings have been presented at clinical conferences such as BAHNO (British Association of Head & Neck Oncologists) and BAHNON (British Association of Head & Neck Oncology Nurses) and the International Quality of Life Conference for Head & Neck Cancer.

To date the findings from Head and Neck 5000 have contributed to knowledge around aetiology and prognosis in people with head and neck cancer. To date these findings have not resulted in any formal changes to policy or guidance but it is anticipated that the work will provide evidence that will inform practice and improve the management of people with head and neck cancer in terms of risk stratification, lifestyle modification and prognostic prediction.