Yorkshire and Humberside Haematology Network (YHHN) - Consented Cohort

This Agreement is for the purpose of maintaining and updating the Yorkshire and Humberside Haematology Network (YHHN).

Agreement DARS-NIC-346859-C9J6J covers a subset of the cohort for which support under section 251 NHS Act 2006 provides a lawful basis for processing confidential data without fully informed consent, whilst this Agreement (DARS-NIC-390749-C4P0X) covers the Data of a subset of the cohort who gave informed consent. DARS-NIC-06759-X5V7P provides a comparison cohort for the study.

The size of the subset of the cohort covered under Agreement DARS-NIC-346859-C9J6J is approximately 25,000. The size of the subset of the cohort covered under Agreement DARS-NIC-390749-C4P0X (this Agreement) is approximately 18,000. The comparison cohort consists of a population cohort totalling 181,263.

The University of York is the sole organisation processing the Data and is a joint Controller with Hull University Teaching Hospitals NHS Trust. YHHN is a collaboration with a clinical network, and the work is commissioned by Hull University Teaching Hospitals NHS Trust. All YHHN’s activities are agreed and monitored by the Haematology Network’s Audit Committee (the Yorkshire & Humberside Haematology Network Audit Committee). Blood Cancer UK (BCUK) and Cancer Research UK (CRUK) funds YHHN but are not involved in the conduct of the research. Only the University of York have access to Data under this Agreement.

Hull University Teaching Hospitals NHS Trust have been involved from the outset of the project as a member of the clinical network that comprises YHHN. Its involvement was formalised in 2009 in a previous approved version of the application to the Central Register for mortality Data, where the Trust confirmed that YHHN was being run on behalf of an NHS organisation for the purposes of “public health provision or the management of health services".

The YHHN is a collaboration with the local Clinical Haematology Network and researchers at University of York. All study activities fall under the auspices of the Network’s Clinical Audit Group, which includes senior academics from the University of York, and is chaired by the Consultant Haematologist and the Medical Director for the Cancer and Clinical Support Health Group at Hull University Teaching Hospitals NHS Trust (HUTH). HUTH acts a joint controller, along with the University of York, its responsibilities include overseeing what personal data are collected, and how these data are stored and used.

The legal basis for processing personal data under the UK GDPR is to perform a task in the public interest. This is covered under Article 6(1)(e); - University of York and Hull University Teaching Hospitals NHS Trust are both public bodies, and it is in the public interest that work is done into providing details on cancer treatments and mortality rates. The personal data requested under this Agreement includes information about a participants' health; these are considered as special category data, and therefore the legal basis for processing these data is processing required for scientific research purposes which is covered under Article 9(2)(j) of the UK GDPR.

This Agreement requests updates of death notifications and cancer registrations, and HES records up to the latest financial year available.

Population-based data on clinically meaningful haematological malignancy subtypes (>100 subtypes) are not available elsewhere (cancer registries have difficulty in accessing diagnostic information systematically and tend to group into four main categories that contain a mix of diseases). Furthermore, the YHHN area is representative of the United Kingdom in terms of both demography and clinical practice, meaning that results are highly generalizable and are of potential importance to the commissioning of cancer care services at a national level. YHHN is uniquely placed to utilise up-to-date diagnostic and treatment data to conduct research on these complex cancers. By linking the patient cohort to HES, the registry will extend its population-based data to include antecedent and post-diagnostic events in the healthcare setting. HES Data will be used to examine a number of questions along the patient pathway, including aetiological factors, routes to diagnosis, as well as healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

The overall aim is to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them. Examples of how this will be achieved are below:

In relation to policy development, mortality Data are required in order to identify whether the survival rates observed in clinical trials are replicated in the general patient population. This is particularly important for haematological cancers, where toxicity issues mean that clinical trials are often restricted to specific patient groups; for example, younger patients without existing co-morbidities. Hence population-based death Data on the general patient population (YHHN) are essential in order to identify the impact of new treatments on the service, and to assess the potential impact on the service, for example a change in mortality.

Haematological oncology is one of the fastest moving cancer fields, and treatments and clinical guidelines are subject to rapid change. In this context it is critically important to be able to monitor whether or not a change in policy is delivering the expected improvements in outcome (mortality/survival) across the patient population as a whole (YHHN).

To facilitate providers/clinicians understanding of whether their own activity falls within the expected range, “observed” practice and mortality frequencies need to be compared with those that are “expected” on the basis of general and/or best practice rates. Monitoring mortality and health activity is required in order to identify whether or not expected changes associated with alterations in service delivery actually occur; and to quantify such change(s) and their impact on the wider service.

YHHN provide a freephone number for patients to contact us if they have any queries regarding the study. The majority of calls are about the completion of paperwork (consent forms and questionnaires). However, occasional questions arise about data confidentiality, which are addressed by explaining the procedures in place. Where patients request that their data is not processed or sent to NHS England for linkage, these requests are implemented when they are received.

Background of study

YHHN’s cohort of patients with haematological cancers was established in 2004 to provide accurate population-based data on clinically meaningful cancer subtypes to inform aetiological hypotheses and plan health-care services, and also to monitor the impact of therapeutic changes in the general patient population. Patients enter the cohort when they are first diagnosed, and their molecular diagnostic/prognostic data are linked to clinical information in NHS medical records (paper and electronic).

Since September 2004, all patients resident in the study area newly diagnosed with a haematological neoplasm or precursor condition have been included (~2,200 per annum). To be included in YHHN, subjects have to be resident in the study area at the time of diagnosis. However, national linkage is required in order to comprehensively map hospital activity and cancer occurrence before and after diagnosis. Likewise, national linkage to deaths is required in order to examine survival. YHHN confirm there is no alternative, less intrusive way of achieving the purpose.

NHS England supply the University of York with linked Data on inpatient and outpatient Hospital Episode Statistics (HES), mortality Data and national cancer registrations. These Data complement the information collected from medical records. HES Admitted Patient Care (HES-APC) from 1997/98; Outpatients (HES-OP) from 2003/04; HES Accident and Emergency from 2007/08 until 2019/20 and the Emergency Care Data Set (ECDS) from 2020/21 are required in addition to mortality and cancer registrations from the earliest Data available for each YHHN participant. In order to examine aetiological factors and routes to diagnosis, YHHN require information prior to the date of diagnosis, and information up to the latest financial year are required to explore healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

It is not possible to reduce the number of years requested, as YHHN are looking at antecedent events prior to diagnosis and all post-diagnostic events to answer several important research questions, including the identification of potential aetiological factors and examination of health care utilization patterns along the whole length of the patient pathway.

In terms of identifying factors that may be causally associated with the subsequent development of a haematological cancer, contributing exposures and events may occur many years in the past – this holds true for the majority of cancers (e.g. smoking and lung cancer). For example, a YHHN publication examining the impact of previous rheumatological disorders on subsequent lymphoma and myeloma development, observed effects for diffuse large B-cell lymphoma 10-years prior to cancer diagnosis. Likewise, going forwards, many years may elapse before the adverse effects of cancer treatment (e.g. cardiac problems) become manifest.

This project is linked to the YHHN Comparison Cohort; within which each YHHN patient diagnosed between 01/01/2009 and 31/12/2015 had 10 sex and year of birth matched individuals selected from persons alive and registered with a general practice in the YHHN study region at the time of their diagnosis to compare against. Pseudonymised HES, mortality and cancer registration Data are supplied for these subjects from NHS England to the University of York.

Each individual in the comparison cohort has been assigned a unique identifier, allowing the University of York to identify the case in the patient cohort that they were matched to. All personal identifying data for the 181,270 individuals in the comparison cohort remain at NHS England and are not made available to the University of York. Data for the comparison cohort is pseudonymised and does not contain any personal or sensitive fields.

Haematological oncology is one of the most rapidly evolving areas of cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited - and YHHN’s linked register/NHS England Data provide a valuable UK resource for clinicians, patients and researchers.

Thus far, Data have been used to provide much needed information on mortality and survival for clinically meaningful cancer subtypes, and several peer reviewed papers and reports have been published. In addition to providing much needed baseline descriptive Data, linked Data have been used to tackle important topics relating to potential variations in survival with socio-economic status, mode of presentation, and age at diagnosis.

YHHN linked HES/Civil Registration (deaths) Data have also been used historically to examine health economic issues requiring “real-world” information that cannot be obtained from clinical trials; for example, the cost of treatment across the whole patient pathway has been scaled to estimate national figures for several haematological cancers (including acute myeloid leukaemia and diffuse large B-cell lymphoma).

All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (www.HMRN.org) – the umbrella Network under which YHHN sits. All peer reviewed articles are published under creative commons attribution 4.0 licence (CC BY) in well-respected journals; this far including the following:

• British Journal of Cancer,

• British Journal of Haematology,

• Blood, British Medical Journal Open,

• British Medical Journal Supportive & Palliative Care,

• Cancer Epidemiology,

• European Journal of Cancer,

• Journal of Clinical Oncology,

• PLoS One,

• Value in Health.

With respect to wider dissemination, the production and distribution of good quality descriptive information is a core YHHN objective and, in addition to feeding into reports and presentations, YHHN Data underpin the statistics section of the HMRN website (www.hmrn.org/statistics); providing scalable up-to-date information on incidence, prevalence and relative survival for researchers, clinicians and patients, selection tools allowing users to pick specific disorders, and stratify by age and sex.

In addition, findings are, and will continue to be, regularly disseminated at conferences including the Public Health for England meetings, British Society of Haematology (BSH), American Society of Haematology (ASH), European Haematology Association (EHA), National Awareness and Early Detection Initiative (NAEDI), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the Palliative Care Congress.

YHHN is also associated with an active patient partnership (https://yhhn.org/partnership), and findings are regularly presented and discussed at a wide range of patient forums.

YHHN benefits from an established Patient Partnership (https://yhhn.org/partnership), which was established by us in 2009. Patients and carers can join the Partnership at any time, provide feedback about their experiences and become involved in YHHN research activities. The partnership currently comprises over 800 patients, all of whom have agreed to various degrees of involvement including completing questionnaires, reviewing YHHN literature and taking part in focus group discussions.

The partnership has a Steering Group, comprised of YHHN patients and carers, local cancer user group leads, a clinical nurse specialist (and haematology user group lead), consultant haematologist and researchers. The Steering Group meets at regular intervals to tackle any arising matters and discuss new studies, as well as the dissemination of recent findings and future research directions; its members are fully involved in YHHN and in the development of further collaborations/research projects and are currently designing a newsletter to send to members of the partnership to update them of YHHN research activities.

One example of a project where user involvement has been instrumental is the National Institute for Health Research (NIHR) funded project “facilitating patient choice in haemato-oncology”, which is predicated on the YHHN Register. This project was developed following discussions at patient focus groups; where concern was repeatedly expressed about the paucity of information available to assist patients in making decisions about their disease management. The project commenced in 2016, and users have played an active role in steering the project, both as applicants and as independent members of the steering committee.

To ensure accessibility, all reports will be published under creative commons attribution 4.0 licence (CC BY); support for this is included in all of the grant applications and the study’s websites will provide links to these open access publications, conference proceedings and copies of reports summarizing the findings. These outputs may be promoted through the study’s Twitter account (@HMRN_UK (337 followers)) and via YHHN's funders @CR_UK (310,000 followers)). Lay summaries of the findings will be provided on the YHHN patient/public website (www.YHHN.org) and may be presented at the study’s local user groups and in the newsletter. YHHN also engages with national charities who publish study findings on websites and in their magazines, and regularly invite researchers to present findings from the study at their meetings.

YHHN currently receives support from a variety of peer-reviewed sources. Core funding comes from Cancer Research UK and Blood Cancer UK (formerly Bloodwise, Leukaemia, Lymphoma Research – LLR) programme grant (April 2016 - Mar 2021; ref 15037; the epidemiology of haematological malignancies: determinants, prognostics, treatment and survivorship and The Haematological Malignancy Research Network: a UK population-based programme of epidemiological research April 2020 - Mar 2025 ref 29685).

In addition, linked Data from YHHN also formed part of an NIHR program grant for applied research (Dec 2015-Nov 2019; ref RP-PG-0613-20002; facilitating informed decision-making in haemato-oncology) and a CRUK project grant (Oct 2015-Sept 2018); ref C9474/A18362; Quantification of antecedent events and outcomes in patients with haematological malignancies: analysis of a unique population-based matched patient cohort).

All funders receive annual interim reports, and final reports will be provided at the end of the funding periods Currently, several studies using HES/Civil Registration (deaths) Data are either in progress or are planned.

Outputs have so far included the:

1. Quantification of the relationship between rheumatological disorders and the non-Hodgkin lymphomas (https://doi.org/10.1016/j.canep.2019.02.014)

2. Risk of mature B-cell neoplasms and precursor conditions after joint replacement (https://doi.org/10.1002/ijc.32765)

3. Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) (http://dx.doi.org/10.1136/bmjopen-2020-041296)

YHHN expects to prepare reports on the following main topics in the next 12 months:

1. Examination of the relationship between haematological malignancies and other cancers

2. Risk of developing cardiac events after treatment with tyrosine kinase inhibitors in patients with chronic myeloid

leukaemia

3. The association of socio-economic status with the incidence of haematological cancers

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

A major aim of YHHN is to improve care and outcomes for patients, and data from the YHHN patient cohort has already impacted on the delivery of patient care across the 14 hospitals that serve the catchment population. Importantly, the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, meaning that results are generalizable and used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies.

These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS. Thus far YHHN data have been used in 15 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma.

Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits.

Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making. One example is approval of CAR-T therapy (axicabtagene ciloleucel) for relapsed diffuse large B-cell lymphoma (DLBCL). In this case, the NICE committee recommended: “NHS or UK standard of care data from the Haematological Malignancy Research Network should be explored to produce plausible estimates of survival for people having salvage chemotherapy.”

Haematological cancers are at the forefront of targeted-therapy development and use. Importantly, the granularity of YHHN data permit evaluation of outcomes in diagnoses with molecular characteristics. For example, in acute myeloid leukaemia (AML: a cancer only treatable with intensive chemotherapy, which most patients cannot tolerate), it is recognised that patients with an internal tandem duplication in the FLT3 gene (FLT3-ITD), rather than a mutation in the tyrosine kinase domain (TKD), have poorer outcomes. Midostaurin is a new therapy for patients with FLT3-ITD and was recently considered for approval in the NHS by NICE. However, the main evidence presented originated from a phase 3 trial, which only included patients aged 18-60 years, although the median age of AML diagnosis is 72 years. To facilitate decision-making, the NICE committee requested that YHHN’s real-world data was used to characterise the general AML patient population by FLT-3 status and examine associated outcomes.

YHHN was established to provide long-term, robust infrastructure, within which to generate evidence to inform and improve clinical practice, locally and national. This has undoubtedly been achieved; moreover, it has been accompanied by growing recognition of the study’s importance, relevance and uniqueness. Nationally, findings from YHHN-based work on routes-to-diagnosis of myeloma have been used by GatewayC (an online cancer education platform: https://www.gatewayc.org.uk/), in conjunction with CRUK, to develop training resources to promote early diagnosis among GPs and other primary care staff. YHHN’s published findings are also being used internationally, via online clinician education resources; for example: https://www.uptodate.com/contents/initial-treatment-of-mantle-cell-lymphoma. Furthermore, YHHN’s descriptive data are routinely incorporated into national cancer statistics and guidelines, as well as patient information leaflets and information produced by national charities (e.g. Cancer Research UK, Lymphoma Action, Blood Cancer UK).

The National Cancer Intelligence Network (NCIN), for example, commissioned YHHN to evaluate the quality of ascertainment of haematological cancers in English Cancer Registries. National rates were compared to those predicted from YHHN data. As a consequence of this report, information on incidence and outcome are now being presented by clinically meaningful groups. These data have been used by national organizations as a benchmark against which to evaluate the quality of their information gathering, and cancer commissioning services.

Whilst substantial improvements in national cancer registration data for haematological cancers has taken place over the last 5 years, data on incidence and survival for some diagnoses are still not available. Accordingly, YHHN data (website: www.hmrn.org; and peer-reviewed publications) were used in current NICE guidance (2015: Haematological Cancers: Improving Outcomes) to ensure accurate and clinically meaningful descriptions of cases newly diagnosed each year, and survival.

FEBRUARY 2024 ACR UPDATE:

Haematological oncology is one of the most rapidly evolving fields in cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited. Hence, linkage of YHHN data to NHS England data fills the evidence gap, providing a valuable UK resource for clinicians, patients and researchers. All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (HMRN) – the umbrella Network under which YHHN sits.

A major ongoing benefit of YHHN is the fact that data from the whole cohort is routinely used by clinicians, patients and cancer charities to provide much needed information on mortality and survival for clinically meaningful cancer subtypes. To support this, the study’s website statistics on incidence, prevalence, and survival are updated on an annual basis. Peer reviewed papers and reports are also published; the most recent one being on lymphoid malignancies, which account for around two-thirds of all blood cancers (Lamb et al; Lymphoid blood cancers, incidence and survival 2005-2023: a report from the UK’s Haematological Malignancy Research Network, https://doi.org/10.1016/j.canep.2023.102513). Providing information for commissioners, YHHN data are also used to examine health resource utilisation issues requiring “real-world” information that cannot be obtained from clinical trials; one recent example of such work is currently in press with NIHR’s (National Institute for Health Care Research) journal for Programme Grant’s for Applied Research (Roman et al; Pathways of patients with chronic haematological malignancies: a report from the UK’s population-based HMRN).

The underpinning purpose of YHHN is improvement of care and outcomes for patient, and it is used locally to monitor the delivery of patient care across the 14 hospitals that serve the catchment population. Furthermore, because the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, results are generalizable. Accordingly, they can be used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies. These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS.

Thus far YHHN data have been used in 49 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma. Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits. Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making.

This Agreement is for the purpose of maintaining and updating the Yorkshire and Humberside Haematology Network (YHHN).

Agreement DARS-NIC-346859-C9J6J covers a subset of the cohort for which support under section 251 NHS Act 2006 provides a lawful basis for processing confidential data without fully informed consent, whilst this Agreement (DARS-NIC-390749-C4P0X) covers the Data of a subset of the cohort who gave informed consent. DARS-NIC-06759-X5V7P provides a comparison cohort for the study.

The size of the subset of the cohort covered under Agreement DARS-NIC-346859-C9J6J is approximately 25,000. The size of the subset of the cohort covered under Agreement DARS-NIC-390749-C4P0X (this Agreement) is approximately 18,000. The comparison cohort consists of a population cohort totalling 181,263.

The University of York is the sole organisation processing the Data and is a joint Controller with Hull University Teaching Hospitals NHS Trust. YHHN is a collaboration with a clinical network, and the work is commissioned by Hull University Teaching Hospitals NHS Trust. All YHHN’s activities are agreed and monitored by the Haematology Network’s Audit Committee (the Yorkshire & Humberside Haematology Network Audit Committee). Blood Cancer UK (BCUK) and Cancer Research UK (CRUK) funds YHHN but are not involved in the conduct of the research. Only the University of York have access to Data under this Agreement.

Hull University Teaching Hospitals NHS Trust have been involved from the outset of the project as a member of the clinical network that comprises YHHN. Its involvement was formalised in 2009 in a previous approved version of the application to the Central Register for mortality Data, where the Trust confirmed that YHHN was being run on behalf of an NHS organisation for the purposes of “public health provision or the management of health services".

The YHHN is a collaboration with the local Clinical Haematology Network and researchers at University of York. All study activities fall under the auspices of the Network’s Clinical Audit Group, which includes senior academics from the University of York, and is chaired by the Consultant Haematologist and the Medical Director for the Cancer and Clinical Support Health Group at Hull University Teaching Hospitals NHS Trust (HUTH). HUTH acts a joint controller, along with the University of York, its responsibilities include overseeing what personal data are collected, and how these data are stored and used.

The legal basis for processing personal data under the UK GDPR is to perform a task in the public interest. This is covered under Article 6(1)(e); - University of York and Hull University Teaching Hospitals NHS Trust are both public bodies, and it is in the public interest that work is done into providing details on cancer treatments and mortality rates. The personal data requested under this Agreement includes information about a participants' health; these are considered as special category data, and therefore the legal basis for processing these data is processing required for scientific research purposes which is covered under Article 9(2)(j) of the UK GDPR.

This Agreement requests updates of death notifications and cancer registrations, and HES records up to the latest financial year available.

Population-based data on clinically meaningful haematological malignancy subtypes (>100 subtypes) are not available elsewhere (cancer registries have difficulty in accessing diagnostic information systematically and tend to group into four main categories that contain a mix of diseases). Furthermore, the YHHN area is representative of the United Kingdom in terms of both demography and clinical practice, meaning that results are highly generalizable and are of potential importance to the commissioning of cancer care services at a national level. YHHN is uniquely placed to utilise up-to-date diagnostic and treatment data to conduct research on these complex cancers. By linking the patient cohort to HES, the registry will extend its population-based data to include antecedent and post-diagnostic events in the healthcare setting. HES Data will be used to examine a number of questions along the patient pathway, including aetiological factors, routes to diagnosis, as well as healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

The overall aim is to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them. Examples of how this will be achieved are below:

In relation to policy development, mortality Data are required in order to identify whether the survival rates observed in clinical trials are replicated in the general patient population. This is particularly important for haematological cancers, where toxicity issues mean that clinical trials are often restricted to specific patient groups; for example, younger patients without existing co-morbidities. Hence population-based death Data on the general patient population (YHHN) are essential in order to identify the impact of new treatments on the service, and to assess the potential impact on the service, for example a change in mortality.

Haematological oncology is one of the fastest moving cancer fields, and treatments and clinical guidelines are subject to rapid change. In this context it is critically important to be able to monitor whether or not a change in policy is delivering the expected improvements in outcome (mortality/survival) across the patient population as a whole (YHHN).

To facilitate providers/clinicians understanding of whether their own activity falls within the expected range, “observed” practice and mortality frequencies need to be compared with those that are “expected” on the basis of general and/or best practice rates. Monitoring mortality and health activity is required in order to identify whether or not expected changes associated with alterations in service delivery actually occur; and to quantify such change(s) and their impact on the wider service.

YHHN provide a freephone number for patients to contact us if they have any queries regarding the study. The majority of calls are about the completion of paperwork (consent forms and questionnaires). However, occasional questions arise about data confidentiality, which are addressed by explaining the procedures in place. Where patients request that their data is not processed or sent to NHS England for linkage, these requests are implemented when they are received.

Background of study

YHHN’s cohort of patients with haematological cancers was established in 2004 to provide accurate population-based data on clinically meaningful cancer subtypes to inform aetiological hypotheses and plan health-care services, and also to monitor the impact of therapeutic changes in the general patient population. Patients enter the cohort when they are first diagnosed, and their molecular diagnostic/prognostic data are linked to clinical information in NHS medical records (paper and electronic).

Since September 2004, all patients resident in the study area newly diagnosed with a haematological neoplasm or precursor condition have been included (~2,200 per annum). To be included in YHHN, subjects have to be resident in the study area at the time of diagnosis. However, national linkage is required in order to comprehensively map hospital activity and cancer occurrence before and after diagnosis. Likewise, national linkage to deaths is required in order to examine survival. YHHN confirm there is no alternative, less intrusive way of achieving the purpose.

NHS England supply the University of York with linked Data on inpatient and outpatient Hospital Episode Statistics (HES), mortality Data and national cancer registrations. These Data complement the information collected from medical records. HES Admitted Patient Care (HES-APC) from 1997/98; Outpatients (HES-OP) from 2003/04; HES Accident and Emergency from 2007/08 until 2019/20 and the Emergency Care Data Set (ECDS) from 2020/21 are required in addition to mortality and cancer registrations from the earliest Data available for each YHHN participant. In order to examine aetiological factors and routes to diagnosis, YHHN require information prior to the date of diagnosis, and information up to the latest financial year are required to explore healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

It is not possible to reduce the number of years requested, as YHHN are looking at antecedent events prior to diagnosis and all post-diagnostic events to answer several important research questions, including the identification of potential aetiological factors and examination of health care utilization patterns along the whole length of the patient pathway.

In terms of identifying factors that may be causally associated with the subsequent development of a haematological cancer, contributing exposures and events may occur many years in the past – this holds true for the majority of cancers (e.g. smoking and lung cancer). For example, a YHHN publication examining the impact of previous rheumatological disorders on subsequent lymphoma and myeloma development, observed effects for diffuse large B-cell lymphoma 10-years prior to cancer diagnosis. Likewise, going forwards, many years may elapse before the adverse effects of cancer treatment (e.g. cardiac problems) become manifest.

This project is linked to the YHHN Comparison Cohort; within which each YHHN patient diagnosed between 01/01/2009 and 31/12/2015 had 10 sex and year of birth matched individuals selected from persons alive and registered with a general practice in the YHHN study region at the time of their diagnosis to compare against. Pseudonymised HES, mortality and cancer registration Data are supplied for these subjects from NHS England to the University of York.

Each individual in the comparison cohort has been assigned a unique identifier, allowing the University of York to identify the case in the patient cohort that they were matched to. All personal identifying data for the 181,270 individuals in the comparison cohort remain at NHS England and are not made available to the University of York. Data for the comparison cohort is pseudonymised and does not contain any personal or sensitive fields.

Haematological oncology is one of the most rapidly evolving areas of cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited - and YHHN’s linked register/NHS England Data provide a valuable UK resource for clinicians, patients and researchers.

Thus far, Data have been used to provide much needed information on mortality and survival for clinically meaningful cancer subtypes, and several peer reviewed papers and reports have been published. In addition to providing much needed baseline descriptive Data, linked Data have been used to tackle important topics relating to potential variations in survival with socio-economic status, mode of presentation, and age at diagnosis.

YHHN linked HES/Civil Registration (deaths) Data have also been used historically to examine health economic issues requiring “real-world” information that cannot be obtained from clinical trials; for example, the cost of treatment across the whole patient pathway has been scaled to estimate national figures for several haematological cancers (including acute myeloid leukaemia and diffuse large B-cell lymphoma).

All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (www.HMRN.org) – the umbrella Network under which YHHN sits. All peer reviewed articles are published under creative commons attribution 4.0 licence (CC BY) in well-respected journals; this far including the following:

• British Journal of Cancer,

• British Journal of Haematology,

• Blood, British Medical Journal Open,

• British Medical Journal Supportive & Palliative Care,

• Cancer Epidemiology,

• European Journal of Cancer,

• Journal of Clinical Oncology,

• PLoS One,

• Value in Health.

With respect to wider dissemination, the production and distribution of good quality descriptive information is a core YHHN objective and, in addition to feeding into reports and presentations, YHHN Data underpin the statistics section of the HMRN website (www.hmrn.org/statistics); providing scalable up-to-date information on incidence, prevalence and relative survival for researchers, clinicians and patients, selection tools allowing users to pick specific disorders, and stratify by age and sex.

In addition, findings are, and will continue to be, regularly disseminated at conferences including the Public Health for England meetings, British Society of Haematology (BSH), American Society of Haematology (ASH), European Haematology Association (EHA), National Awareness and Early Detection Initiative (NAEDI), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the Palliative Care Congress.

YHHN is also associated with an active patient partnership (https://yhhn.org/partnership), and findings are regularly presented and discussed at a wide range of patient forums.

YHHN benefits from an established Patient Partnership (https://yhhn.org/partnership), which was established by us in 2009. Patients and carers can join the Partnership at any time, provide feedback about their experiences and become involved in YHHN research activities. The partnership currently comprises over 800 patients, all of whom have agreed to various degrees of involvement including completing questionnaires, reviewing YHHN literature and taking part in focus group discussions.

The partnership has a Steering Group, comprised of YHHN patients and carers, local cancer user group leads, a clinical nurse specialist (and haematology user group lead), consultant haematologist and researchers. The Steering Group meets at regular intervals to tackle any arising matters and discuss new studies, as well as the dissemination of recent findings and future research directions; its members are fully involved in YHHN and in the development of further collaborations/research projects and are currently designing a newsletter to send to members of the partnership to update them of YHHN research activities.

One example of a project where user involvement has been instrumental is the National Institute for Health Research (NIHR) funded project “facilitating patient choice in haemato-oncology”, which is predicated on the YHHN Register. This project was developed following discussions at patient focus groups; where concern was repeatedly expressed about the paucity of information available to assist patients in making decisions about their disease management. The project commenced in 2016, and users have played an active role in steering the project, both as applicants and as independent members of the steering committee.

To ensure accessibility, all reports will be published under creative commons attribution 4.0 licence (CC BY); support for this is included in all of the grant applications and the study’s websites will provide links to these open access publications, conference proceedings and copies of reports summarizing the findings. These outputs may be promoted through the study’s Twitter account (@HMRN_UK (337 followers)) and via YHHN's funders @CR_UK (310,000 followers)). Lay summaries of the findings will be provided on the YHHN patient/public website (www.YHHN.org) and may be presented at the study’s local user groups and in the newsletter. YHHN also engages with national charities who publish study findings on websites and in their magazines, and regularly invite researchers to present findings from the study at their meetings.

YHHN currently receives support from a variety of peer-reviewed sources. Core funding comes from Cancer Research UK and Blood Cancer UK (formerly Bloodwise, Leukaemia, Lymphoma Research – LLR) programme grant (April 2016 - Mar 2021; ref 15037; the epidemiology of haematological malignancies: determinants, prognostics, treatment and survivorship and The Haematological Malignancy Research Network: a UK population-based programme of epidemiological research April 2020 - Mar 2025 ref 29685).

In addition, linked Data from YHHN also formed part of an NIHR program grant for applied research (Dec 2015-Nov 2019; ref RP-PG-0613-20002; facilitating informed decision-making in haemato-oncology) and a CRUK project grant (Oct 2015-Sept 2018); ref C9474/A18362; Quantification of antecedent events and outcomes in patients with haematological malignancies: analysis of a unique population-based matched patient cohort).

All funders receive annual interim reports, and final reports will be provided at the end of the funding periods Currently, several studies using HES/Civil Registration (deaths) Data are either in progress or are planned.

Outputs have so far included the:

1. Quantification of the relationship between rheumatological disorders and the non-Hodgkin lymphomas (https://doi.org/10.1016/j.canep.2019.02.014)

2. Risk of mature B-cell neoplasms and precursor conditions after joint replacement (https://doi.org/10.1002/ijc.32765)

3. Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) (http://dx.doi.org/10.1136/bmjopen-2020-041296)

YHHN expects to prepare reports on the following main topics in the next 12 months:

1. Examination of the relationship between haematological malignancies and other cancers

2. Risk of developing cardiac events after treatment with tyrosine kinase inhibitors in patients with chronic myeloid

leukaemia

3. The association of socio-economic status with the incidence of haematological cancers

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

A major aim of YHHN is to improve care and outcomes for patients, and data from the YHHN patient cohort has already impacted on the delivery of patient care across the 14 hospitals that serve the catchment population. Importantly, the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, meaning that results are generalizable and used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies.

These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS. Thus far YHHN data have been used in 15 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma.

Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits.

Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making. One example is approval of CAR-T therapy (axicabtagene ciloleucel) for relapsed diffuse large B-cell lymphoma (DLBCL). In this case, the NICE committee recommended: “NHS or UK standard of care data from the Haematological Malignancy Research Network should be explored to produce plausible estimates of survival for people having salvage chemotherapy.”

Haematological cancers are at the forefront of targeted-therapy development and use. Importantly, the granularity of YHHN data permit evaluation of outcomes in diagnoses with molecular characteristics. For example, in acute myeloid leukaemia (AML: a cancer only treatable with intensive chemotherapy, which most patients cannot tolerate), it is recognised that patients with an internal tandem duplication in the FLT3 gene (FLT3-ITD), rather than a mutation in the tyrosine kinase domain (TKD), have poorer outcomes. Midostaurin is a new therapy for patients with FLT3-ITD and was recently considered for approval in the NHS by NICE. However, the main evidence presented originated from a phase 3 trial, which only included patients aged 18-60 years, although the median age of AML diagnosis is 72 years. To facilitate decision-making, the NICE committee requested that YHHN’s real-world data was used to characterise the general AML patient population by FLT-3 status and examine associated outcomes.

YHHN was established to provide long-term, robust infrastructure, within which to generate evidence to inform and improve clinical practice, locally and national. This has undoubtedly been achieved; moreover, it has been accompanied by growing recognition of the study’s importance, relevance and uniqueness. Nationally, findings from YHHN-based work on routes-to-diagnosis of myeloma have been used by GatewayC (an online cancer education platform: https://www.gatewayc.org.uk/), in conjunction with CRUK, to develop training resources to promote early diagnosis among GPs and other primary care staff. YHHN’s published findings are also being used internationally, via online clinician education resources; for example: https://www.uptodate.com/contents/initial-treatment-of-mantle-cell-lymphoma. Furthermore, YHHN’s descriptive data are routinely incorporated into national cancer statistics and guidelines, as well as patient information leaflets and information produced by national charities (e.g. Cancer Research UK, Lymphoma Action, Blood Cancer UK).

The National Cancer Intelligence Network (NCIN), for example, commissioned YHHN to evaluate the quality of ascertainment of haematological cancers in English Cancer Registries. National rates were compared to those predicted from YHHN data. As a consequence of this report, information on incidence and outcome are now being presented by clinically meaningful groups. These data have been used by national organizations as a benchmark against which to evaluate the quality of their information gathering, and cancer commissioning services.

Whilst substantial improvements in national cancer registration data for haematological cancers has taken place over the last 5 years, data on incidence and survival for some diagnoses are still not available. Accordingly, YHHN data (website: www.hmrn.org; and peer-reviewed publications) were used in current NICE guidance (2015: Haematological Cancers: Improving Outcomes) to ensure accurate and clinically meaningful descriptions of cases newly diagnosed each year, and survival.

FEBRUARY 2024 ACR UPDATE:

Haematological oncology is one of the most rapidly evolving fields in cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited. Hence, linkage of YHHN data to NHS England data fills the evidence gap, providing a valuable UK resource for clinicians, patients and researchers. All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (HMRN) – the umbrella Network under which YHHN sits.

A major ongoing benefit of YHHN is the fact that data from the whole cohort is routinely used by clinicians, patients and cancer charities to provide much needed information on mortality and survival for clinically meaningful cancer subtypes. To support this, the study’s website statistics on incidence, prevalence, and survival are updated on an annual basis. Peer reviewed papers and reports are also published; the most recent one being on lymphoid malignancies, which account for around two-thirds of all blood cancers (Lamb et al; Lymphoid blood cancers, incidence and survival 2005-2023: a report from the UK’s Haematological Malignancy Research Network, https://doi.org/10.1016/j.canep.2023.102513). Providing information for commissioners, YHHN data are also used to examine health resource utilisation issues requiring “real-world” information that cannot be obtained from clinical trials; one recent example of such work is currently in press with NIHR’s (National Institute for Health Care Research) journal for Programme Grant’s for Applied Research (Roman et al; Pathways of patients with chronic haematological malignancies: a report from the UK’s population-based HMRN).

The underpinning purpose of YHHN is improvement of care and outcomes for patient, and it is used locally to monitor the delivery of patient care across the 14 hospitals that serve the catchment population. Furthermore, because the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, results are generalizable. Accordingly, they can be used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies. These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS.

Thus far YHHN data have been used in 49 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma. Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits. Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making.

This Agreement is for the purpose of maintaining and updating the Yorkshire and Humberside Haematology Network (YHHN).

Agreement ref DARS-NIC-346859-C9J6J covers a subset of the cohort for which support under section 251 NHS Act 2006 provides a lawful basis for processing confidential data without fully informed consent whilst this Agreement (DARS-NIC-390749-C4P0X) covers the data of a subset of the cohort who gave informed consent.

DARS-NIC-06759-X5V7P provides a comparison cohort for the study.

The size of the subset of the cohort covered under Agreement DARS-NIC-346859-C9J6J is approximately 25,000.

The size of the subset of the cohort covered under Agreement DARS-NIC-390749-C4P0X (this Agreement) is approximately 18,000.

The comparison cohort consists of a population cohort totalling 181,263

The University of York is the sole Data Processor and the joint Data Controller with Hull University Teaching Hospitals NHS Trust. YHHN is a collaboration with a clinical network, and the work is commissioned by Hull University Teaching Hospitals NHS Trust. All YHHN’s activities are agreed and monitored by the Haematology Network’s Audit Committee (the Yorkshire & Humberside Haematology Network Audit Committee). Bloodwise (a charity) and Cancer research UK funds YHHN but are not involved in the conduct of the research. Only the University of York have access to data under this agreement.

Hull University Teaching Hospitals NHS Trust have been involved from the outset of the project as a member of the clinical network that comprises YHHN. It's involvement was formalised in 2009 in a previous approved version of the application to the Central Register, for mortality data (MR1126), where the Trust confirmed that YHHN was being run on behalf of an NHS organisation for the purposes of “public health provision or the management of health services.

The Yorkshire & Humberside Haematology Network is a collaboration with the local Clinical Haematology Network and researchers at University of York. All study activities fall under the auspices of the Network’s Clinical Audit Group, which includes senior academics from the University of York, and is chaired by the Consultant Haematologist and the Medical Director for the Cancer and Clinical Support Health Group at Hull University Teaching Hospitals NHS Trust (HUTH).  HUTH acts a joint data controller, along with the University of York, its responsibilities include overseeing what personal data are collected, and how these data are stored and used.

The legal basis for processing personal data under GDPR, is to perform a task in the public interest. This is covered under Article 6(1)(e); - University of York and Hull University Teaching Hospitals NHS Trust are both public bodies, and it is in the public interest that work is done into providing details on cancer treatments and mortality rates. The personal data requested under this agreement includes information about a participants' health; these are considered as special category data, and therefore the legal basis for processing these data is processing required for scientific research purposes which is covered under Article 9(2)(j) of the GDPR.

YHHN is a collaboration between researchers at the University of York, specifically, the Joint Haematology Network Site Specific Group for the West Yorkshire and Humber, Coast & Vale Clinical Alliances (formerly known as the Cancer Networks of Yorkshire and Humber & Yorkshire Coast). The work is commissioned by Hull University Teaching Hospitals. This agreement requests updates of death notifications and cancer registrations, and HES records up to the latest financial year available. The objective of the project remains the same; namely to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them.

Population-based data on clinically meaningful haematological malignancy subtypes (>100 subtypes) are not available elsewhere (cancer registries have difficulty in accessing diagnostic information systematically and tend to group into four main categories that contain a mix of diseases). Furthermore, the YHHN area is representative of the United Kingdom in terms of both demography and clinical practice, meaning that results are highly generalizable and are of potential importance to the commissioning of cancer care services at a national level. YHHN is uniquely placed to utilise up-to-date diagnostic and treatment data to conduct research on these complex cancers. By linking the patient cohort to HES, the registry will extend its population-based data to include antecedent and post-diagnostic events in the healthcare setting. HES data will be used to examine a number of questions along the patient pathway, including aetiological factors, routes to diagnosis, as well as healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

Appropriate safeguards are in place including data minimisation comprising of pseudonymisation, and the use of anonymised data where possible. In terms of dissemination outputs will only contain aggregated data, with small numbers suppressed in line with the HES Analysis Guide.

The overall aim is to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them. Examples of how this will be achieved are below:

In relation to policy development, mortality data are required in order to identify whether the survival rates observed in clinical trials are replicated in the general patient population. This is particularly important for haematological cancers, where toxicity issues mean that clinical trials are often restricted to specific patient groups; for example, younger patients without existing co-morbidities. Hence population-based death data on the general patient population (YHHN) are essential in order to identify the impact of new treatments on the service, and to assess the potential impact on the service, for example a change in mortality.

Haematological oncology is one of the fastest moving cancer fields, and treatments and clinical guidelines are subject to rapid change. In this context it is critically important to be able to monitor whether or not a change in policy is delivering the expected improvements in outcome (mortality/survival) across the patient population as a whole (YHHN).

To facilitate providers/clinicians understanding of whether their own activity falls within the expected range, “observed” practice and mortality frequencies need to be compared with those that are “expected” on the basis of general and/or best practice rates.

Monitoring mortality and health activity is required in order to identify whether or not expected changes associated with alterations in service delivery actually occur; and to quantify such change(s) and their impact on the wider service.

YHHN provide a freephone number for patients to contact us if they have any queries regarding the study. The majority of calls are about the completion of paperwork (consent forms and questionnaires). However, occasional questions arise about data confidentiality, which are addressed by explaining the procedures in place. One patient in the last year requested that their data was not processed, and another two did not want their information to be sent to NHS Digital for linkage. The procedures required to ensure that this was implemented were carried out when the requests were received.

Background of study

YHHN’s cohort of patients with haematological cancers was established in 2004 to provide accurate population-based data on clinically meaningful cancer subtypes to inform aetiological hypotheses and plan health-care services, and also to monitor the impact of therapeutic changes in the general patient population. Patients enter the cohort when they are first diagnosed, and their molecular diagnostic/prognostic data are linked to clinical information in NHS medical records (paper and electronic).

NHS Digital supply the University of York with linked data on inpatient and outpatient Hospital Episode Statistics (HES) mortality data and national cancer registrations. These data complement the information collected from medical records. The present application requests an update to the latest death and cancer registrations, and HES records up to latest financial year. The objective of the project remains the same; namely to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them.

This project is linked to (Yorkshire and Humberside Haematology Network Register (YHHN) Comparison Cohort); within which each patient in MR1126 diagnosed between 01/01/2009 and 31/12/2015 had 10 sex and year of birth matched individuals selected from persons alive and registered with a general practice in the YHHN study region at the time of their diagnosis to compare against. Pseudinymised HES, mortality and cancer registration data are supplied for these subjects from NHS Digital to the University of York.

Each individual in the comparison cohort has been assigned a unique identifier, allowing the University to identify the case in the patient cohort that they were matched to. All personal identifying data for the 181,270 individuals in the comparison cohort remain at NHS Digital and are not made available to the University. Data for the comparison cohort is pseudonymised and does not contain any personal or sensitive fields.

Since September 2004, all patient's resident in the study area newly diagnosed with a haematological neoplasm or precursor condition have been included (~2,200 per annum). Yorkshire and Humberside Haematology Network (YHHN) cohort was initiated at a time when cancer care in England was co-ordinated through a series of area-based Cancer Networks. YHHN’s catchment covers two such adjacent Cancer Networks: the Yorkshire Cancer Network and the Humber & Yorkshire Coast Cancer Network. Health geography changed in April 2013 when Cancer Networks were incorporated into Strategic Clinical Networks, but YHHN’s boundaries were not affected.

The University of York requires data on Hospital Episode Statistics (HES) namely: HES Admitted Patient Care (HES-APC) from 1997/98; Outpatients (HES-OP) from 2003/04 until the latest financial year available. Accident and Emergency (HES-A&E) from 2007/08 until 19/20 M12. The Emergency Care Data Set data 20/21 annual refresh. In addition, mortality, and cancer registration. Data are returned from NHS Digital using unique YHHN study numbers; meaning the data are pseudonymised. In order to examine aetiological factors and routes to diagnosis YHHN require information prior to the date of diagnosis, and information up to the latest financial year are required to explore healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

It is not possible to reduce the number of years requested, as YHHN are looking at antecedent events prior to diagnosis and all post-diagnostic events to answer several important research questions, including the identification of potential aetiological factors and examination of health care utilization patterns along the whole length of the patient pathway.

In terms of identifying factors that may be causally associated with the subsequent development of a haematological cancer, contributing exposures and events may occur many years in the past – this holds true for the majority of cancers (e.g. smoking and lung cancer). For example, YHHN recent publication examining the impact of previous rheumatological disorders on subsequent lymphoma and myeloma development, observed effects for diffuse large B-cell lymphoma 10-years prior to cancer diagnosis. Likewise, going forwards, many years may elapse before the adverse effects of cancer treatment (e.g. cardiac problems) become manifest.

To be included in YHHN, subjects have to be resident in the study area at the time of diagnosis. However, national linkage is required in order to comprehensively map hospital activity and cancer occurrence before and after diagnosis. Likewise, national linkage to deaths is required in order to examine survival. YHHN confirm there is no alternative, less intrusive way of achieving the purpose.

Only the variables necessary to perform the analyses required to address the purpose are requested. The University of York upload patient’s surname, forename, gender, date of birth and NHS number, along with their YHHN unique study number to NHS Digital’s Data Exchange Service (DES) for matching and subsequent linkage. Data are returned using YHHN’s unique study number only, minimising the use of identifiable data.

The University of York is the sole Data Processor and the joint Data Controller with Hull University Teaching Hospitals NHS Trust. As outlined above, YHHN is a collaboration with the clinical network, and the work is commissioned by Hull University Teaching Hospitals NHS Trust. All YHHN’s activities are agreed and monitored by the Haematology Network’s Audit Committee (the Yorkshire & Humberside Haematology Network Audit Committee). Bloodwise funds YHHN but are not involved in the conduct of the research.

Haematological oncology is one of the most rapidly evolving areas of cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited - and YHHN’s linked register/NHS Digital data provide a valuable UK resource for clinicians, patients and researchers.

Thus far, data have been used to provide much needed information on mortality and survival for clinically meaningful cancer subtypes, and several peer reviewed papers and reports have been published. In addition to providing much needed baseline descriptive data, linked data have been used to tackle important topics relating to potential variations in survival with socio-economic status, mode of presentation, and age at diagnosis.

YHHN linked HES/Civil Registration (deaths) data have also been used historically to examine health economic issues requiring “real-world” information that cannot be obtained from clinical trials; for example, the cost of treatment across the whole patient pathway has been scaled to estimate national figures for several haematological cancers (including acute myeloid leukaemia and diffuse large B-cell lymphoma).

All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (www.HMRN.org) – the umbrella Network under which YHHN sits. All peer reviewed articles are published under creative commons attribution 4.0 licence (CC BY) in well-respected journals; this far including the following:

• British Journal of Cancer,

• British Journal of Haematology,

• Blood, British Medical Journal Open,

• British Medical Journal Supportive & Palliative Care,

• Cancer Epidemiology,

• European Journal of Cancer,

• Journal of Clinical Oncology,

• PLoS One,

• Value in Health.

With respect to wider dissemination, the production and distribution of good quality descriptive information is a core YHHN objective and, in addition to feeding into reports and presentations, YHHN data underpin the statistics section of the HMRN website (www.hmrn.org/statistics); providing scalable up-to-date information on incidence, prevalence and relative survival for researchers, clinicians and patients, selection tools allowing users to pick specific disorders, and stratify by age and sex.

In addition, findings are, and will continue to be, regularly disseminated at conferences including the Public Health for England meetings, British Society of Haematology (BSH), American Society of Haematology (ASH), European Haematology Association (EHA), National Awareness and Early Detection Initiative (NAEDI), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the Palliative Care Congress.

YHHN is also associated with an active patient partnership (https://yhhn.org/partnership ), and findings are regularly presented and discussed at a wide range of patient forums.

YHHN benefits from an established Patient Partnership (https://yhhn.org/partnership), which was established by us in 2009. Patients and carers can join the Partnership at any time, provide feedback about their experiences and become involved in YHHN research activities. The partnership currently comprises over 800 patients, all of whom have agreed to various degrees of involvement including completing questionnaires, reviewing YHHN literature and taking part in focus group discussions.

The partnership has a Steering Group, comprised of YHHN patients and carers, local cancer user group leads, a clinical nurse specialist (and haematology user group lead), consultant haematologist and researchers. The Steering Group meets at regular intervals to tackle any arising matters and discuss new studies, as well as the dissemination of recent findings and future research directions; its members are fully involved in YHHN and in the development of further collaborations/research projects and are currently designing a newsletter to send to members of the partnership to update them of YHHN research activities.

One example of a project where user involvement has been instrumental is the National Institute for Health Research (NIHR) funded project “facilitating patient choice in haemato-oncology”, which is predicated on the YHHN Register. This project was developed following discussions at patient focus groups; where concern was repeatedly expressed about the paucity of information available to assist patients in making decisions about their disease management. The project commenced in 2016, and users have played an active role in steering the project, both as applicants and as independent members of the steering committee.

To ensure accessibility, all reports will be published under creative commons attribution 4.0 licence (CC BY); support for this is included in all of the grant applications and the study’s websites will provide links to these open access publications, conference proceedings and copies of reports summarizing the findings. These outputs may be promoted through the study’s Twitter account (@HMRN_UK (190 followers)) and via YHHN's funders (@bloodwise_uk (28,800 followers), @CR_UK (310,000 followers)). Lay summaries of the findings will be provided on the YHHN patient/public website (www.YHHN.org) and may be presented at the study’s local user groups and in the newsletter. YHHN also engages with national charities who publish study findings on websites and in their magazines, and regularly invite researchers to present findings from the study at their meetings.

YHHN currently receives support from a variety of peer-reviewed sources. Core funding comes from a Bloodwise (formerly Leukaemia, Lymphoma Research – LLR) programme grant (April 2016 - Mar 2021; ref 15037; the epidemiology of haematological malignancies: determinants, prognostics, treatment and survivorship).

In addition, linked data from YHHN also form part of an NIHR program grant for applied research (Dec 2015-Nov 2019; ref RP-PG-0613-20002; facilitating informed decision-making in haemato-oncology) and a CRUK project grant (Oct 2015-Sept 2018); ref C9474/A18362; Quantification of antecedent events and outcomes in patients with haematological malignancies: analysis of a unique population-based matched patient cohort).

All funders receive annual interim reports, and final reports will be provided at the end of the funding periods Currently, several studies using HES/Civil Registration (deaths) data are either in progress or are planned.

With respect to the next 12 months, three specifics for examples are:

1. Investigate the impact of emergency admission on survival from a cancer that generally has good outcomes, Hodgkin lymphoma, to help explore why survival in a small proportion of patients is poor; this will involve linking HES/Civil Registration (deaths) data to YHHN’s diagnostic, prognostic and treatment data enabling a more thorough examination than is possible elsewhere.

2. Examine whether the mortality and healthcare utilisation return to that seen in the general population for patients who achieve remission with a potentially curable non-Hodgkin lymphoma - diffuse large B-cell lymphoma. This work will help support policies of when a patient no longer requires regular monitoring by haematology for disease re-occurrence.

3. Examine the relationship between previous joint replacement and subsequent diagnosis of specific haematological cancer. This work will help to identify whether joint replacements are a risk factor for developing certain subtypes of haematological cancers, or whether for certain subtypes (plasmacytoma/myeloma), the diseases could have been diagnosed at an earlier stage.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. No record level data will be published or shared with any of the funders.

A major aim of YHHN is to improve care and outcomes for patients, and data from the YHHN patient cohort has already impacted on the delivery of patient care across the 14 hospitals that serve the catchment population. Importantly, the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, meaning that results are generalizable and used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies.

These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS. Thus far YHHN data have been used in 10 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma.

Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits.

Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making. One example is approval of CAR-T therapy (axicabtagene ciloleucel) for relapsed diffuse large B-cell lymphoma (DLBCL). In this case, the NICE committee recommended: “NHS or UK standard of care data from the Haematological Malignancy Research Network should be explored to produce plausible estimates of survival for people having salvage chemotherapy.”

Haematological cancers are at the forefront of targeted-therapy development and use. Importantly, the granularity of YHHN data permit evaluation of outcomes in diagnoses with molecular characteristics. For example, in acute myeloid leukaemia (AML: a cancer only treatable with intensive chemotherapy, which most patients cannot tolerate), it is recognised that patients with an internal tandem duplication in the FLT3 gene (FLT3-ITD), rather than a mutation in the tyrosine kinase domain (TKD), have poorer outcomes. Midostaurin is a new therapy for patients with FLT3-ITD and was recently considered for approval in the NHS by NICE. However, the main evidence presented originated from a phase 3 trial, which only included patients aged 18-60 years, although the median age of AML diagnosis is 72 years. To facilitate decision-making, the NICE committee requested that YHHN’s real-world data was used to characterise the general AML patient population by FLT-3 status and examine associated outcomes.

YHHN was established to provide long-term, robust infrastructure, within which to generate evidence to inform and improve clinical practice, locally and national. This has undoubtedly been achieved; moreover, it has been accompanied by growing recognition of the study’s importance, relevance and uniqueness. Nationally, findings from YHHN-based work on routes-to-diagnosis of myeloma have been used by GatewayC (an online cancer education platform: https://www.gatewayc.org.uk/), in conjunction with CRUK, to develop training resources to promote early diagnosis among GPs and other primary care staff. YHHN’s published findings are also being used internationally, via online clinician education resources; for example: https://www.uptodate.com/contents/initial-treatment-of-mantle-cell-lymphoma. Furthermore, YHHN’s descriptive data are routinely incorporated into national cancer statistics and guidelines, as well as patient information leaflets and information produced by national charities (e.g. Cancer Research UK, Lymphoma Action, Bloodwise).

The National Cancer Intelligence Network (NCIN), for example, commissioned YHHN to evaluate the quality of ascertainment of haematological cancers in English Cancer Registries. National rates were compared to those predicted from YHHN data. As a consequence of this report, information on incidence and outcome are now being presented by clinically meaningful groups. These data have been used by national organizations as a benchmark against which to evaluate the quality of their information gathering, and cancer commissioning services.

Whilst substantial improvements in national cancer registration data for haematological cancers has taken place over the last 5 years, data on incidence and survival for some diagnoses are still not available. Accordingly, YHHN data (website: www.hmrn.org; and peer-reviewed publications) were used in current NICE guidance (2015: Haematological Cancers: Improving Outcomes) to ensure accurate and clinically meaningful descriptions of cases newly diagnosed each year, and survival.

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted.

Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated and destruction of the data will be required.

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

This Agreement is for the purpose of maintaining the Yorkshire and Humberside Haematology Network (YHHN).

Agreement ref DARS-NIC-346859-C9J6J covers a subset of the cohort for which support under section 251 NHS Act 2006 provides a lawful basis for processing confidential data without fully informed consent whilst this Agreement (DARS-NIC-390749-C4P0X) covers the data of a subset of the cohort who gave informed consent.

The Advisory Group has agreed to provide partial support under Section 251 to enable research nurses access to data in order to identify relevant patients from whom to seek consent. This approval also covers data extraction for deceased patients and for those too ill to provide consent, but the Group felt that consent should be sought from the ‘hard to reach’ groups and so your approval is limited in this respect.

DARS-NIC-06759-X5V7P provides a comparison cohort for the study.

The size of the subset of the cohort covered under Agreement DARS-NIC-346859-C9J6J is approximately 22,500.

The size of the subset of the cohort covered under Agreement DARS-NIC-390749-C4P0X (this Agreement) is approximately 15,000.

The University of York is the sole Data Processor and Data Controller. The work is commissioned by Hull & East Yorkshire Hospitals NHS Trust and funded by Cancer Research UK (CRUK grant number C9474/A18362). Data supplied by NHS Digital are only accessible to approved users within the Epidemiology & Cancer Statistics Group (ECSG) in the Department of Health Sciences at the University of York; no other organisations will have access to record level data obtained via NHS Digital.

Hull University Teaching Hospitals NHS Trust have been involved from the outset of the project as a member of the clinical network that comprises YHHN. it's involvement was formalised in 2009 in a previous approved version of the

application to the Central Register, for mortality data (MR1126), where the Trust confirmed that YHHN was being run on behalf of an NHS organisation for the purposes of “public health provision or the management of health services.

The legal basis for processing personal data under GDPR, is to perform a task in the public interest. This is covered under Article 6(1)(e); - University of York and Hull University Teaching Hospitals NHS Trust are both public bodies, and it is in the public interest that work is done into providing details on cancer treatments and mortality rates. The personal data requested under this agreement includes information about a participants' health; these are considered as special category data, and therefore the legal basis for processing these data is processing required for scientific research purposes which is covered under Article 9(2)(j) of the GDPR.

YHHN is a collaboration between researchers at the University of York, specifically, the Joint Haematology Network Site Specific Group for the West Yorkshire and Humber, Coast & Vale Clinical Alliances (formerly known as the Cancer Networks of Yorkshire and Humber & Yorkshire Coast). The work is commissioned by Hull University Teaching Hospitals. This agreement requests updates of death notifications and cancer registrations, and HES records up to the latest financial year available. The objective of the project remains the same; namely to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them.

Population-based data on clinically meaningful haematological malignancy subtypes (>100 subtypes) are not available elsewhere (cancer registries have difficulty in accessing diagnostic information systematically and tend to group into four main categories that contain a mix of diseases). Furthermore, the YHHN area is representative of the United Kingdom in terms of both demography and clinical practice, meaning that results are highly generalizable and are of potential importance to the commissioning of cancer care services at a national level. YHHN is uniquely placed to utilise up-to-date diagnostic and treatment data to conduct research on these complex cancers. By linking the patient cohort to HES, the registry will extend its population-based data to include antecedent and post-diagnostic events in the healthcare setting. HES data will be used to examine a number of questions along the patient pathway, including aetiological factors, routes to diagnosis, as well as healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

In terms of dissemination, YHHN do not envisage any moral or ethical issues. Appropriate safeguards are in place including data minimisation comprising of pseudonymisation, and the use of anonymised data where possible. In terms of dissemination outputs will only contain aggregated data, with small numbers suppressed in line with the HES Analysis Guide.

The overall aim is to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them. Examples of how this will be achieved are below:

In relation to policy development, mortality data are required in order to identify whether the survival rates observed in clinical trials are replicated in the general patient population. This is particularly important for haematological cancers, where toxicity issues mean that clinical trials are often restricted to specific patient groups; for example, younger patients without existing co-morbidities. Hence population-based death data on the general patient population (YHHN) are essential in order to identify the impact of new treatments on the service, and to assess the potential impact on the service, for example a change in mortality.

Haematological oncology is one of the fastest moving cancer fields, and treatments and clinical guidelines are subject to rapid change. In this context it is critically important to be able to monitor whether or not a change in policy is delivering the expected improvements in outcome (mortality/survival) across the patient population as a whole (YHHN).

To facilitate providers/clinicians understanding of whether their own activity falls within the expected range, “observed” practice and mortality frequencies need to be compared with those that are “expected” on the basis of general and/or best practice rates.

Monitoring mortality and health activity is required in order to identify whether or not expected changes associated with alterations in service delivery actually occur; and to quantify such change(s) and their impact on the wider service.

Background of study

YHHN’s cohort of patients with haematological cancers was established in 2004 to provide accurate population-based data on clinically meaningful cancer subtypes to inform aetiological hypotheses and plan health-care services, and also to monitor the impact of therapeutic changes in the general patient population. Patients enter the cohort when they are first diagnosed, and their molecular diagnostic/prognostic data are linked to clinical information in NHS medical records (paper and electronic).

NHS Digital supply the University of York with linked data on inpatient and outpatient Hospital Episode Statistics (HES) mortality data and national cancer registrations. These data complement the information collected from medical records. The present application requests an update to the latest death and cancer registrations, and HES records up to latest financial year. The objective of the project remains the same; namely to facilitate a greater understanding of the causes of haematological cancers, as well as their impact on the future health and healthcare needs of those who develop them.

This project is linked to (Yorkshire and Humberside Haematology Network Register (YHHN) Comparison Cohort); within which each patient in MR1126 diagnosed between 01/01/2009 and 31/12/2015 had 10 sex and year of birth matched individuals selected from persons alive and registered with a general practice in the YHHN study region at the time of their diagnosis to compare against. Pseudinymised HES, mortality and cancer registration data are supplied for these subjects from NHS Digital to the University of York.

Each individual in the comparison cohort has been assigned a unique identifier, allowing the University to identify the case in the patient cohort that they were matched to. All personal identifying data for the 181,270 individuals in the comparison cohort remain at NHS Digital and are not made available to the University. Data for the comparison cohort is pseudonymised and does not contain any personal or sensitive fields.

Since September 2004, all patient's resident in the study area newly diagnosed with a haematological neoplasm or precursor condition have been included (~2,200 per annum). Yorkshire and Humberside Haematology Network (YHHN) cohort was initiated at a time when cancer care in England was co-ordinated through a series of area-based Cancer Networks. YHHN’s catchment covers two such adjacent Cancer Networks: the Yorkshire Cancer Network and the Humber & Yorkshire Coast Cancer Network. Health geography changed in April 2013 when Cancer Networks were incorporated into Strategic Clinical Networks, but YHHN’s boundaries were not affected.

HES data, mortality and cancer registrations have already been supplied by NHS Digital. The data was returned from NHS Digital using unique YHHN study numbers; meaning the data was pseudonymised. In order to examine aetiological factors and routes to diagnosis YHHN require information prior to the date of diagnosis, and information up to the latest financial year are required to explore healthcare utilisation patterns & costings (before diagnosis, around the time of diagnosis, and onwards into the survivorship phase).

It is not possible to reduce the number of years requested, as YHHN are looking at antecedent events prior to diagnosis and all post-diagnostic events to answer several important research questions, including the identification of potential aetiological factors and examination of health care utilization patterns along the whole length of the patient pathway.

In terms of identifying factors that may be causally associated with the subsequent development of a haematological cancer, contributing exposures and events may occur many years in the past – this holds true for the majority of cancers (e.g. smoking and lung cancer). For example, YHHN recent publication examining the impact of previous rheumatological disorders on subsequent lymphoma and myeloma development, observed effects for diffuse large B-cell lymphoma 10-years prior to cancer diagnosis. Likewise, going forwards, many years may elapse before the adverse effects of cancer treatment (e.g. cardiac problems) become manifest.

To be included in YHHN, subjects have to be resident in the study area at the time of diagnosis. However, national linkage is required in order to comprehensively map hospital activity and cancer occurrence before and after diagnosis. Likewise, national linkage to deaths is required in order to examine survival. YHHN confirm there is no alternative, less intrusive way of achieving the purpose.

Only the variables necessary to perform the analyses required to address the purpose are requested. The University of York upload patient’s surname, forename, gender, date of birth and NHS number, along with their YHHN unique study number to NHS Digital’s Data Exchange Service (DES) for matching and subsequent linkage. Data are returned using YHHN’s unique study number only, minimising the use of identifiable data.

As outlined above, YHHN is a collaboration with the clinical network, and the work is commissioned by Hull University Teaching Hospitals NHS Trust. All YHHN’s activities are agreed and monitored by the Haematology Network’s Audit Committee (the Yorkshire & Humberside Haematology Network Audit Committee). Bloodwise funds YHHN but are not involved in the conduct of the research.

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted.

Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated, and destruction of the data will be required.

No further outputs of the data are permitted to be created under this version of the agreement. Outputs will only be permitted to be created once a new agreement that meets all of NHS Digital's legal, ethical and security requirements is in place.

The below provides background on to what has already been produced, and what will be produced once data flow and permission to process resumes.

Haematological oncology is one of the most rapidly evolving areas of cancer research; and more than 100 clinically meaningful diagnostic groups are currently recognized in the latest World Health Organization (WHO) classification. Comprehensive reliable population-based information about the underlying occurrence and survival of patients diagnosed with these cancers, and their associated healthcare usage is, however, limited - and YHHN’s linked register/NHS Digital data provide a valuable UK resource for clinicians, patients and researchers.

Thus far, data have been used to provide much needed information on mortality and survival for clinically meaningful cancer subtypes, and several peer reviewed papers and reports have been published. In addition to providing much needed baseline descriptive data, linked data have been used to tackle important topics relating to potential variations in survival with socio-economic status, mode of presentation, and age at diagnosis.

YHHN linked HES/Civil Registration (deaths) data have also been used historically to examine health economic issues requiring “real-world” information that cannot be obtained from clinical trials; for example, the cost of treatment across the whole patient pathway has been scaled to estimate national figures for several haematological cancers (including acute myeloid leukaemia and diffuse large B-cell lymphoma).

All published papers and reports, along with conference presentations, are available on the Haematological Malignancy Research Networks website (www.HMRN.org) – the umbrella Network under which YHHN sits. All peer reviewed articles are published under creative commons attribution 4.0 licence (CC BY) in well-respected journals; this far including the following:

• British Journal of Cancer,

• British Journal of Haematology,

• Blood, British Medical Journal Open,

• British Medical Journal Supportive & Palliative Care,

• Cancer Epidemiology,

• European Journal of Cancer,

• Journal of Clinical Oncology,

• PLoS One,

• Value in Health.

With respect to wider dissemination, the production and distribution of good quality descriptive information is a core YHHN objective and, in addition to feeding into reports and presentations, YHHN data underpin the statistics section of the HMRN website (www.hmrn.org/statistics); providing scalable up-to-date information on incidence, prevalence and relative survival for researchers, clinicians and patients, selection tools allowing users to pick specific disorders, and stratify by age and sex.

In addition, findings are, and will continue to be, regularly disseminated at conferences including the Public Health for England meetings, British Society of Haematology (BSH), American Society of Haematology (ASH), European Haematology Association (EHA), National Awareness and Early Detection Initiative (NAEDI), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the Palliative Care Congress.

YHHN is also associated with an active patient partnership (https://yhhn.org/partnership ), and findings are regularly presented and discussed at a wide range of patient forums.

YHHN benefits from an established Patient Partnership (https://yhhn.org/partnership), which was established by us in 2009. Patients and carers can join the Partnership at any time, provide feedback about their experiences and become involved in YHHN research activities. The partnership currently comprises over 800 patients, all of whom have agreed to various degrees of involvement including completing questionnaires, reviewing YHHN literature and taking part in focus group discussions.

The partnership has a Steering Group, comprised of YHHN patients and carers, local cancer user group leads, a clinical nurse specialist (and haematology user group lead), consultant haematologist and researchers. The Steering Group meets at regular intervals to tackle any arising matters and discuss new studies, as well as the dissemination of recent findings and future research directions; its members are fully involved in YHHN and in the development of further collaborations/research projects and are currently designing a newsletter to send to members of the partnership to update them of YHHN research activities.

One example of a project where user involvement has been instrumental is the National Institute for Health Research (NIHR) funded project “facilitating patient choice in haemato-oncology”, which is predicated on the YHHN Register. This project was developed following discussions at patient focus groups; where concern was repeatedly expressed about the paucity of information available to assist patients in making decisions about their disease management. The project commenced in 2016, and users have played an active role in steering the project, both as applicants and as independent members of the steering committee.

To ensure accessibility, all reports will be published under creative commons attribution 4.0 licence (CC BY); support for this is included in all of the grant applications and the study’s websites will provide links to these open access publications, conference proceedings and copies of reports summarizing the findings. These outputs may be promoted through the study’s Twitter account (@HMRN_UK (190 followers)) and via YHHN's funders (@bloodwise_uk (28,800 followers), @CR_UK (310,000 followers)). Lay summaries of the findings will be provided on the YHHN patient/public website (www.YHHN.org) and may be presented at the study’s local user groups and in the newsletter. YHHN also engages with national charities who publish study findings on websites and in their magazines, and regularly invite researchers to present findings from the study at their meetings.

YHHN provide a freephone number for patients to contact us if they have any queries regarding the study. The majority of calls are about the completion of paperwork (consent forms and questionnaires). However, occasional questions arise about data confidentiality, which are addressed by explaining the procedures in place. One patient in the last year requested that their data was not processed, and another two did not want their information to be sent to NHS Digital for linkage. The procedures required to ensure that this was implemented were carried out when the requests were received.

YHHN currently receives support from a variety of peer-reviewed sources. Core funding comes from a Bloodwise (formerly Leukaemia, Lymphoma Research – LLR) programme grant (April 2016 - Mar 2021; ref 15037; the epidemiology of haematological malignancies: determinants, prognostics, treatment and survivorship).

In addition, linked data from YHHN also form part of an NIHR program grant for applied research (Dec 2015-Nov 2019; ref RP-PG-0613-20002; facilitating informed decision-making in haemato-oncology) and a CRUK project grant (Oct 2015-Sept 2018); ref C9474/A18362; Quantification of antecedent events and outcomes in patients with haematological malignancies: analysis of a unique population-based matched patient cohort).

All funders receive annual interim reports, and final reports will be provided at the end of the funding periods Currently, several studies using HES/Civil Registration (deaths) data are either in progress or are planned.

With respect to the next 12 months, three specifics for examples are:

1. Investigate the impact of emergency admission on survival from a cancer that generally has good outcomes, Hodgkin lymphoma, to help explore why survival in a small proportion of patients is poor; this will involve linking HES/Civil Registration (deaths) data to YHHN’s diagnostic, prognostic and treatment data enabling a more thorough examination than is possible elsewhere.

2. Examine whether the mortality and healthcare utilisation return to that seen in the general population for patients who achieve remission with a potentially curable non-Hodgkin lymphoma - diffuse large B-cell lymphoma. This work will help support policies of when a patient no longer requires regular monitoring by haematology for disease re-occurrence.

3. Examine the relationship between previous joint replacement and subsequent diagnosis of specific haematological cancer. This work will help to identify whether joint replacements are a risk factor for developing certain subtypes of haematological cancers, or whether for certain subtypes (plasmacytoma/myeloma), the diseases could have been diagnosed at an earlier stage.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. No record level data will be published or shared with any of the funders.

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. No new data will be released under this version of the Agreement, and this Agreement allows the applicant to hold and not otherwise process any further data that has already been disseminated.

Permission to retain the data for the interim period is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated, and destruction of the data will be required.

A major aim of YHHN is to improve care and outcomes for patients, and data from the YHHN patient cohort has already impacted on the delivery of patient care across the 14 hospitals that serve the catchment population. Importantly, the YHHN area is representative of the UK as a whole in terms of both demography and clinical practice, meaning that results are generalizable and used in Health Technology Assessments; enabling organisations, including the National Institute for Health & Care Excellence (NICE) and the Scottish Medicines Consortium, to make decisions about the efficacy and cost-effectiveness of drugs for haematological malignancies.

These decisions impact directly on patients’ survival, quality of life, and wellbeing, as well as commissioning within the NHS. Thus far YHHN data have been used in 10 NICE submissions evaluating treatment options for myelofibrosis, myelodysplastic syndromes, acute myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma.

Evidence underpinning such assessment (i.e. clinical management and outcome by subtype) are usually extracted either from data derived from the website, peer-reviewed publications, or from clinical audits.

Indeed, NICE recognises that YHHN findings are representative of UK clinical practice and increasingly recommends that these data are used to underpin decision-making. One example is approval of CAR-T therapy (axicabtagene ciloleucel) for relapsed diffuse large B-cell lymphoma (DLBCL). In this case, the NICE committee recommended: “NHS or UK standard of care data from the Haematological Malignancy Research Network should be explored to produce plausible estimates of survival for people having salvage chemotherapy.”

Haematological cancers are at the forefront of targeted-therapy development and use. Importantly, the granularity of YHHN data permit evaluation of outcomes in diagnoses with molecular characteristics. For example, in acute myeloid leukaemia (AML: a cancer only treatable with intensive chemotherapy, which most patients cannot tolerate), it is recognised that patients with an internal tandem duplication in the FLT3 gene (FLT3-ITD), rather than a mutation in the tyrosine kinase domain (TKD), have poorer outcomes. Midostaurin is a new therapy for patients with FLT3-ITD and was recently considered for approval in the NHS by NICE. However, the main evidence presented originated from a phase 3 trial, which only included patients aged 18-60 years, although the median age of AML diagnosis is 72 years. To facilitate decision-making, the NICE committee requested that YHHN’s real-world data was used to characterise the general AML patient population by FLT-3 status and examine associated outcomes.

YHHN was established to provide long-term, robust infrastructure, within which to generate evidence to inform and improve clinical practice, locally and national. This has undoubtedly been achieved; moreover, it has been accompanied by growing recognition of the study’s importance, relevance and uniqueness. Nationally, findings from YHHN-based work on routes-to-diagnosis of myeloma have been used by GatewayC (an online cancer education platform: https://www.gatewayc.org.uk/), in conjunction with CRUK, to develop training resources to promote early diagnosis among GPs and other primary care staff. YHHN’s published findings are also being used internationally, via online clinician education resources; for example: https://www.uptodate.com/contents/initial-treatment-of-mantle-cell-lymphoma. Furthermore, YHHN’s descriptive data are routinely incorporated into national cancer statistics and guidelines, as well as patient information leaflets and information produced by national charities (e.g. Cancer Research UK, Lymphoma Action, Bloodwise).

The National Cancer Intelligence Network (NCIN), for example, commissioned YHHN to evaluate the quality of ascertainment of haematological cancers in English Cancer Registries. National rates were compared to those predicted from YHHN data. As a consequence of this report, information on incidence and outcome are now being presented by clinically meaningful groups. These data have been used by national organizations as a benchmark against which to evaluate the quality of their information gathering, and cancer commissioning services.

Whilst substantial improvements in national cancer registration data for haematological cancers has taken place over the last 5 years, data on incidence and survival for some diagnoses are still not available. Accordingly, YHHN data (website: www.hmrn.org; and peer-reviewed publications) were used in current NICE guidance (2015: Haematological Cancers: Improving Outcomes) to ensure accurate and clinically meaningful descriptions of cases newly diagnosed each year, and survival.