Comprehensive Cancer Profiling in Myositis

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Expected output

[1 paragraph unchanged] - Analysis is anticipated to be completed in 2025. 2027. Findings will impact the 2028 2032 revision of the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening - [8 words unchanged] early cancer detection in adults with myositis, thus improving outcomes, including death. [2 paragraphs unchanged]

Unchanged: Objective for processing, Processing activities, Expected measurable benefits, Benefits reported.

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Objective for processing

***** This is a six month request for retention of NHSE data only and no further processing.***** This Data Sharing Agreement (DSA) permits the secure retention of the Data only. No other processing of the Data is permitted. Myositis is a longterm condition that causes inflammation in muscles, skin, and the lungs. For unknown reasons, one in four adults with myositis develop cancer within the three years before or after diseases onset. We want to carry out research with the aim to: The following information outlines the original purpose(s) for which the Data was provided: - Understand what cancers people with myositis develop Myositis is a long term condition that causes inflammation in muscles, skin, and the lungs. For unknown reasons, one in four adults with myositis develop cancer within the three years before or after diseases onset. The aim of the research is to understand: - What cancers people with myositis develop [2 paragraphs unchanged] Research into cancer and myositis will allow us to develop development of evidence-based personalised screening recommendations, leading to earlier detection and improved outcomes. The UKMYONET recruited UK-based adults with myositis. Demographic and clinical data were [12 words unchanged] participant. Recruitment began in 1999 and ended in 2020. A total of 1992 1,992 participants were recruited. 1503 1,503 participants consented for their UKMYONET data to be linked to NHS England for cancer and mortality data. [2 paragraphs unchanged] Regarding the Data Controller, Salford Royal Foundation Royal NHS Foundation Trust changed its legal entity on 1/10/2021 01/10/2021 to The Northern Care Alliance NHS Foundation Trust (NCA). It was created [6 words unchanged] Salford Royal NHS Foundation Trust and The Pennine Acute Hospitals NHS Trust. [2 paragraphs unchanged] We can confirm that there are no other alternatives to collating the required data. [2 paragraphs unchanged]

Processing activities

Northern Care Alliance NHS Foundation Trust will store received NHS England data the Data on a server in the Clinical Science Building on encrypted, password protected trust computers which can be only accessed at Northern Care Alliance NHS Foundation Trust. [2 paragraphs unchanged] This data is accessed only by the study coordinator. A pseudonymised (UKMYONET study ID only) version of received NHS England data will be created and linked to pseudonymised (study ID only) UKMYONET clinical and demographic data. This DSA permits the secure retention of the Data only. No other processing of the Data is permitted. Collated data will only be accessed by members of the University of Manchester Myositis Research Group who are also clinicians at Northern Care Alliance for the purpose of analysis. Participant level data will not be transferred to the University of Manchester, however aggregated summary data may be transferred for the purpose of result interpretation manuscript writing. Aggregated data accessed at the University of Manchester will be stored in secure, password-protected computer servers. All team members that will access data have been appropriately trained in data protection and confidentiality. Data will not be accessed or processed by any other third parties not mentioned in this agreement.

Benefits reported

[7 paragraphs unchanged] Publications have been included in the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening - due for publication published in early 2022. November 2023.

Changed only in punctuation, spacing or capitalisation: Expected output.

Unchanged: Expected measurable benefits.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

The University of Manchester requires mortality, cancer registration and NHS registration data for the purpose of the study ‘Identification of disease susceptibility genes associated with development and clinical characteristics of primary inflammatory muscle diseases, PM, DM and IBM’. ***** This is a six month request for retention of NHSE data only and no further processing.***** Regarding the Data Processor, Salford Royal Foundation Royal NHS Foundation Trust has changed its legal entity on 1/10/2021 to The Northern Care Alliance NHS Foundation Trust (NCA). It was created by bringing together two NHS Trusts, Salford Royal NHS Foundation Trust and The Pennine Acute Hospitals NHS Trust. Myositis is a longterm condition that causes inflammation in muscles, skin, and the lungs. For unknown reasons, one in four adults with myositis develop cancer within the three years before or after diseases onset. We want to carry out research with the aim to: Polymyositis (PM), Dermatomyositis (DM) and Inclusion Body Myositis (IBM) are a subset of inflammatory muscle disorders of unknown cause, currently classified under the umbrella term of idiopathic inflammatory myopathies (IIM). PM, DM and IBM are characterised by skeletal muscle inflammation and progressive muscle weakness, which can be debilitating and chronic in nature (occasionally fatal). Steroid and immuno-suppressive treatments are often only partially effective at reducing symptoms, and toxic side effects also limit their usefulness. - Understand what cancers people with myositis develop There is, however, increasing evidence that genetic factors, such as the polymorphisms around the complex human leukocyte antigen (HLA) molecules, as well as certain inflammatory cytokines, are intimately involved in both the development and expression (in terms of disease severity and organs targeted for damage) of these conditions. Many of the inflammatory mechanisms responsible for the pathological changes of PM, DM and IBM are similar to those mediating damage in other inflammatory diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), so it seems likely that genetic factors will similarly be involved in the development and expression of PM, DM and IBM. - Why people with myositis develop cancer This study is research in the public interest. Establishing the extent of involvement of these genetic mechanisms in PM, DM and IBM is of great importance, since understanding the aetiological mechanisms of any disease may eventually permit the development of specific and therefore more effective therapies. - What are the causes of death in people with myositis - those with and without cancer The Rheumatic Diseases Centre at and Northern Care Alliance NHS Foundation Trust in co-ordination with the Centre for Integrated Genomic Medical Research Unit (CIGMR) at the University of Manchester have come together in order to understand this disorder. The study started in 1999 under the joint controllership of individuals from Northern Care Alliance NHS Foundation Trust and the University of Manchester. Going forward, the study is now under the sole controllership of the University of Manchester. The data coordinator is substantively employed by the University of Manchester. Research into cancer and myositis will allow us to develop evidence-based personalised screening recommendations, leading to earlier detection and improved outcomes. Recruitment has now ended with 1992 patients recruited with the participants recruited as follows: The UKMYONET recruited UK-based adults with myositis. Demographic and clinical data were collected. Blood samples were also collected, which allowed genetic profiling of each participant. Recruitment began in 1999 and ended in 2020. A total of 1992 participants were recruited. 1503 participants consented for their UKMYONET data to be linked to NHS England for cancer and mortality data. This study will continue for the foreseeable future as it is a genetics study of a very rare condition and therefore needs large numbers. The data previously obtained from NHS Digital will enable the study to continue to investigate the causes of death and understand if any subgroups of patient are more likely to develop cancers and if so which type of cancers. In summary, proposed analysis will allow the research team to comprehensively characterise the cancer profile in the UKMYONET cohort, including type of cancer, location of cancer, number of deaths attributed to cancer, and, where available, tumour mutations. Patients have been recruited from over 70 recruiting centres. Recruitment commenced in 2000 and has now ceased. Patients were consented between 2004 and 2010 to be tracked with what was then the Office of National Statistics. These patients have been / are tracked for cancer and mortality with NHS Digital. UKMYONET data is held by Northern Care Alliance. A number of members of the Manchester Myositis Research Group, based within the University of Manchester, are also clinicians within Northern Care Alliance - data analysis will only be carried out by these members. Regarding the Data Controller, Salford Royal Foundation Royal NHS Foundation Trust changed its legal entity on 1/10/2021 to The Northern Care Alliance NHS Foundation Trust (NCA). It was created by bringing together two NHS Trusts, Salford Royal NHS Foundation Trust and The Pennine Acute Hospitals NHS Trust. This study is research in the public interest. Comprehensively profiling cancer and cancer-related death within the UKMYONET will inform cancer screening recommendations, thus directly impacting members of the public with new-onset myositis. Only NHS number and UKMYONET study ID will be submitted to NHS England for linkage - thus only pseudonymised data will be submitted. We can confirm that there are no other alternatives to collating the required data. Regarding minimising data, data access will be restricted only to participants that have explicitly consented to linkage of cancer and mortality data. Regarding the number of years of data requested, long term data is required to allow for identification of participants that have died and their cause of death.

Processing activities

Under previous iterations of this Data Sharing Agreement, Salford Royal NHS Foundation Trust (SRFT) provided files of identifiers (Patient’s forenames, surnames, date of birth, NHS Number) to the Health and Social Care Information Centre (now known as NHS Digital) for flagging. Northern Care Alliance NHS Foundation Trust will store received NHS England data on a server in the Clinical Science Building on encrypted, password protected trust computers which can be only accessed at Northern Care Alliance NHS Foundation Trust. Since 2008 NHS Digital has provided linked mortality and cancer data along with the associated participant's forename, surname, date of birth and NHS number to Northern Care Alliance NHS Foundation Trust . Identifiable data will not be stored alongside NHS England data. Northern Care Alliance NHS Foundation Trust stores the data on a server in the Clinical Science Building on encrypted, password protected Trust computers which can be only accessed at Northern Care Alliance NHS Foundation Trust . No attempt will be made to re-identify UKMYONET study participants. This data is accessed only by the study coordinator. A pseudonymised (UKMYONET study ID only) version of this dataset (i.e. containing no patient identifiers other than study received NHS England data will be created and linked to pseudonymised (study ID numbers) is transferred to the University of Manchester where it can be accessed by researchers working on study analysis. only) UKMYONET clinical and demographic data. The data received from NHS Digital can only be accessed by authorised individuals within the University of Manchester for the purposes described, all of whom are substantive employees. Collated data will only be accessed by members of the University of Manchester Myositis Research Group who are also clinicians at Northern Care Alliance for the purpose of analysis. Participant level data will not be transferred to the University of Manchester, however aggregated summary data may be transferred for the purpose of result interpretation manuscript writing. Aggregated data accessed at the University of Manchester will be stored in secure, password-protected computer servers. Blood samples from recruiting centres are posted to University of Manchester (UoM) where the samples are processed and stored. UoM carries out genetic analysis on the extracted DNA and then batch transfers the extracted plasma to University of Bath for the purpose of performing antibody analysis. No data from NHS Digital is transferred to the University of Bath. All team members that will access data have been appropriately trained in data protection and confidentiality. The data has been and will continue to be used to calculate mortality rate in myositis population and compared to norms. Cancer rates were studied in myositis population and compared to norms as well as comparison in between myositis sub groups in order to answer questions such as: ‘Do more people with dermatomyositis develop cancer as a result of cancer associated myositis (CAM) when compared with patients with polymyositis?’ and ’'Is cancer more common in patients with the TIF 1 antibody in blood sample when compared to absence of TIF 1 antibody?’ Therefore, cancer data from NHS Digital has been linked with antibody data from research blood analysis within the University of Manchester. Data will not be accessed or processed by any other third parties not mentioned in this agreement. All organisations party to this Agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract - i.e. employees, agents and contractors of the Data Recipient who may have access to that data). There will be no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement. Data will only be accessed and processed by substantive employees of The University of Manchester and will not be accessed or processed by any other third parties not mentioned in this agreement.

Expected output

A paper has been published in Rheumatology. This paper utilised cancer data generated from NHS Digital. Analysis will result in production of manuscripts for submission to high impact journals. Results will also be submitted for presentation at national and international rheumatology and oncology conferences. Only aggregate data will be published - no individual-level participant data will be published. -Oldroyd, A., Sergeant, J., New, P., McHugh, N. J., Betteridge, Z. E., Lamb, J., Ollier, W., Cooper, R. & Chinoy, H. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody positive dermatomyositis. Rheumatology, Volume 58, Issue 4, April 2019, Pages 650–655 Analysis is anticipated to be completed in 2025. Several conference abstracts, utilising data from NHS Digital, have been accepted, published and presented at international conferences: Findings will impact the 2028 revision of the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening - the intention of the guideline is to improve early cancer detection in adults with myositis, thus improving outcomes, including death. - American College of Rheumatology annual scientific meeting 2020 - “Earlier Cancer Diagnosis after Idiopathic Inflammatory Myopathy Onset is Associated with Improved Long Term Survival Results From Four European Cohorts” Findings will be disseminated to myositis patient organisations, such as Myositis UK. - British Society of Rheumatology annual conference 2016 – “The Risk of Premature Death of both Cancer Associated and Non-Cancer Associated Myositis in UK Adult-Onset Myositis Patients is Significantly Raised Compared to the General Population” 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. - Annual European Congress of Rheumatology 2015 – “The Standardised Mortality Rate in UK Adult-Onset Myositis Patients is Seven Times Higher than the UK General Population” Analysis utilising cancer and mortality data has resulted in a number of publications, thus increasing the understanding of risk factors for cancer and mortality for patients with an IIM. Publications have been included in guideline development for IIM management and cancer screening - each due to be published in early 2022. Further planned analysis will take place to delineate the risk of death premature death and cancer associated with myositis specific autoantibodies. Mortality data from NHS Digital will be utilised. Findings will be submitted for publication in high-impact open-access journals. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

Expected measurable benefits

Findings will be disseminated to clinicians through journal publication and presentation at specialist meetings (e.g. annual UKMYONET meeting). Clinician implementation of findings can lead to improved clinical outcomes for patients. Identification of clinical features associated with cancer and mortality in people with myositis will allow the research team to develop evidence-based recommendations on cancer screening - for use by clinicians to improve early cancer detection and outcomes, including survival; findings will be incorporated into the recommendation formation process of the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening review in 2028. Implementation of previously identified clinical association with myositis specific autoantibodies (e.g. Jo-1 association with interstitial ling disease) has led to improved patient outcomes. [2 paragraphs unchanged] All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Benefits reported

Details of yielded benefits will be provided in a subsequent Agreement. A paper has been published in Rheumatology. This paper utilised cancer data generated from NHS England. -Oldroyd, A., Sergeant, J., New, P., McHugh, N. J., Betteridge, Z. E., Lamb, J., Ollier, W., Cooper, R. & Chinoy, H. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody positive dermatomyositis. Rheumatology, Volume 58, Issue 4, April 2019, Pages 650–655 Several conference abstracts, utilising data from NHS England, have been accepted, published and presented at international conferences: - American College of Rheumatology annual scientific meeting 2020 - “Earlier Cancer Diagnosis after Idiopathic Inflammatory Myopathy Onset is Associated with Improved Long Term Survival Results From Four European Cohorts” - British Society of Rheumatology annual conference 2016 – “The Risk of Premature Death of both Cancer Associated and Non-Cancer Associated Myositis in UK Adult-Onset Myositis Patients is Significantly Raised Compared to the General Population” - Annual European Congress of Rheumatology 2015 – “The Standardised Mortality Rate in UK Adult-Onset Myositis Patients is Seven Times Higher than the UK General Population” Analysis utilising cancer and mortality data has resulted in a number of publications, thus increasing the understanding of risk factors for cancer and mortality for patients with myositis. Publications have been included in the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening - due for publication in early 2022.