MR1301: Prospective Study in the Lung Endpoints (PROFILE)

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Objective for processing

This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. Permission is granted under this version of the data sharing agreement to hold and not otherwise process data only. Mortality and cancer registration data was supplied to The University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study - MR1301: Prospective Study in the Lung Endpoints (PROFILE). [2 paragraphs unchanged] The University of Nottingham requires notifications of mortality,cancer registrations for a cohort of 550 consented individuals for use in the PROFILE study. ** Mortality data was supplied to the University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study. The University of Nottingham required notifications of mortality, cancer registrations for a cohort of 550 consented individuals for use in the PROFILE study. [1 paragraph unchanged] The PROFILE study aims aimed to use a prospective cohort study of IPF patients to validate a [55 words unchanged] design and the development of new therapies to treat idiopathic pulmonary fibrosis. [1 paragraph unchanged] For the data received from NHS Digital, the University of Nottingham is [9 words unchanged] the purpose(s) for and manner in which that data may be processed. GSK, McMaster University, The Royal Brompton Hospital, Imperial College and no other third party organisations are permitted to access the data in any form. The University of Nottingham will ensure that the data received from NHS Digital is used solely for the purpose and in the manner described within this Data Sharing Agreement. The University of Nottingham requires follow up data on the PROFILE study cohort’s health and mortality status. The data provided enables the analysis of mortality rates of idiopathic pulmonary fibrosis from initial diagnosis, linking survival rates in relation to identified biomarkers associated with IPF. GSK, McMaster University, The Royal Brompton Hospital, Imperial College and no other third party organisations are permitted to access the data in any form. The cancer data received from NHS Digital is needed because epidemiological studies in IPF have shown an association between IPF and increased risk of lung cancer. It is not clear whether there is a causal relationship between the two disease entities. Studying the disease pattern and behaviour may add new insights into the field. The University of Nottingham will ensure that the data received from NHS Digital is used solely for the purpose and in the manner described within this Data Sharing Agreement. These data are stored in a database in the University of Nottingham and no data will be shared with third parties except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. The data provided enabled the analysis of mortality rates of idiopathic pulmonary fibrosis from initial diagnosis, linking survival rates in relation to identified biomarkers associated with IPF. Recruitment started in September 2010 and last subject was recruited in September 2014. The study as a whole (including follow up visits) will be completed by Sept 2017. Final analysis of the entire quality controlled dataset will be completed by 2020. The cancer data received from NHS Digital was needed because epidemiological studies in IPF have shown an association between IPF and increased risk of lung cancer. It is not clear whether there is a causal relationship between the two disease entities. Studying the disease pattern and behaviour may add new insights into the field. These data were stored in a database in the University of Nottingham and no data was or will be shared with third parties not mentioned in this agreement except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. Recruitment started in September 2010 and last subject was recruited in September 2014. The study as a whole (including follow up visits) will be completed by Sept 2017. Final analysis of the entire quality controlled dataset will be completed by 2020.

Processing activities

Mortality data was supplied to the University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study. The University of Nottingham requires notifications of mortality,cancer registrations for a cohort of 550 consented individuals for use in the PROFILE study. 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 ie: employees, agents and contractors of the Data Recipient who may have access to that data). 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. Mortality data was supplied to The University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study - MR1301: Prospective Study in the Lung Endpoints (PROFILE). The University of Nottingham required notifications of mortality, cancer registrations for a cohort of 550 consented individuals for use in the PROFILE study. 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 or further data will be provided under this version of the agreement. 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. [1 paragraph unchanged] All data flowing from the University of Nottingham to the Health and Social Care Information Centre (which has since become NHS Digital) is encrypted. ** The University of Nottingham previously sent files of identifiers (NHS Number, Date of Birth and Postcode plus Unique Study ID) to the Health and Social Care Information Centre. The Health and Social Care Information Centre periodically provides reports of mortality and cancer notifications to the University of Nottingham. The University of Nottingham stores the data on a server in its Clinical Sciences Building. All data which flowed from the University of Nottingham to the Health and Social Care Information Centre (which has since become NHS Digital) is encrypted. Data received from the Health and Social Care Information Centre is entered into the PROFILE study database at the University of Nottingham. The University of Nottingham previously sent files of identifiers (NHS Number, Date of Birth and Postcode plus Unique Study ID) to the Health and Social Care Information Centre. The Health and Social Care Information Centre periodically provided reports of mortality and cancer notifications to the University of Nottingham. The University of Nottingham stored the data on a server in its Clinical Sciences Building. The data will only be accessed by the local University of Nottingham database manager and designated employees for the purpose described, all of whom are substantive employees of the University of Nottingham. The PROFILE study data (including data received from NHS Digital) will not be linked to other data sets. Data received from the Health and Social Care Information Centre was entered into the PROFILE study database at the University of Nottingham. The data provided is used was only accessed by authorised individuals the local University of Nottingham database manager and designated employees for the purpose described, all of whom are substantive employees of the University of Nottingham to analyse mortality rates of idiopathic pulmonary fibrosis from initial diagnosis. Nottingham. The PROFILE study data (including data received from NHS Digital) was and will not be linked to other data sets.

Expected output

No new outputs will be produced under this Data Sharing Agreement. Mortality data was supplied to The University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study - MR1301: Prospective Study in the Lung Endpoints (PROFILE). In any future application, the applicant will be required to provide details of the outputs that were produced and disseminated by the study as well as details of any future outputs planned. This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. The following information provides background information on the expected output activities of the original study and subsequent data sharing agreement with the Health and Social Care Information Centre (which has since become NHS Digital) 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 PROFILE study has published previous findings in the Lancet Respiratory Medicine in 2015, two studies in 2017 and a study in the European Respiratory Journal 2019. 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. ** 1. The results of the data processing have included written reports, grant applications, sharing of preliminary data as abstracts and presentation at conferences. Final peer reviewed outputs have been published in high impact peer reviewed journals and incorporated into quality standards and management dashboards. 2. All published outputs using the data has been aggregated with small numbers (<5) suppressed. No personally identifiable data has been published or presented including but not limited to dates of birth, death, names or addresses. 3. Dissemination will primarily include published manuscripts but as the data matures and is built upon in future studies it is anticipated that the data processing outputs will inform policy through incorporation into local and national guidelines to use genetic risk prediction models and biomarkers to guide treatment of patients with pulmonary fibrosis. The aim of the dissemination activities will be to enable the engagement with the scientific and policy-making communities / to ensure that knowledge developed by the research can benefit these communities. Communication of results to patients and carers will occur through media engagement activities, patient support groups and patient information and engagement days focusing on the diagnosis and management of pulmonary fibrosis. It is anticipated that the results will be disseminated and communicated for the next 5-10 years due to the rich nature of the dataset 4. The results of these studies will inform future implementation studies that are being undertaken as part of commercial and grant funded clinical trials. 5. The results from the PROFILE study has published previous findings in a number of peer review journals including the Allen et al Am J Respir Crit Care Med 2019, Hobbs et al Am J Resp Crit Care Med 2019, Organ et al Respir Res 2019, Dudbridge et al Nat Comms 2019, Stewart et al European Respiratory Journal 2019, Maher et al Lancet Respir Med 2017, Allen et al Lancet Respir Med 2017 and Jenkins et al Lancet Respir Med 2015. 6. These data have also been published on pre-print servers, presented in abstract form and disseminated through a range of meetings nationally and internationally and communicated to stake-holders through patient engagement events and the media. [1 paragraph unchanged] The University of Nottingham are currently working to understand the genetic risk factors that predict disease progression and mortality in IPF and to ensure the most reliable estimates of genetic risk to outcome we wish to explore the most up-to-date and complete data sets to ensure reliability of our genetic studies. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES The University of Nottingham anticipate generating further outputs related to our available physiological and biochemical data with outcome data that will be published in the next 12 months. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Expected measurable benefits

In any future application, the applicant will be required to provide details of the expected benefits resulting from the study. Mortality data was supplied to The University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study - MR1301: Prospective Study in the Lung Endpoints (PROFILE). The following information provides background information on the expected measurable benefits of the original study and subsequent data sharing agreement with the Health and Social care Information Centre (which has since become NHS Digital). 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 benefits of the original dissemination. 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. [5 paragraphs unchanged]

Benefits reported

In any future application, the applicant will be required to provide details of the actual benefits achieved as a result of the study. Mortality data was supplied to The University of Nottingham by the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research study - MR1301: Prospective Study in the Lung Endpoints (PROFILE). The following information provides background information on the yielded benefits of the original study and subsequent data sharing agreement with the Health and Social care Information Centre (which has since become NHS Digital). . This Data Sharing Agreement permits the retention of the data for an interim period but no other processing of the data is permitted. This study holds the largest longitudinal data set on patients with IPF in the world and three high impact papers published to date. Initial analysis of the PROFILE study data have already been published as high impact manuscripts (Jenkins et al Lancet Respiratory Medicine 2015, Allen et al Lancet Respiratory Medicine 2017, Maher et al Lancet Respiratory Medicine 2017, Stewart et al Eur Resp J 2019) and have been included as primary endpoints in a clinical trial being undertaken by Boehringer Ingelheim (NCT02788474). These papers have lead to re-design of clinical trials and some of the biomarkers are available in current clinical practice and implementation studies are planned imminently. Further PROFILE study analysis was a central theme of a successful application for an NIHR Research Professorship RP-2017-08-ST2-014 awarded in 2018 entitled Developing a biomarker guided strategy to treat patients with pulmonary fibrosis' 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 benefits of the original dissemination. 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. This study holds the largest longitudinal data set on patients with IPF in the world and three high impact papers have been published to date. Initial analysis of the PROFILE study data have already been published as high impact manuscripts (Allen et al Am J Respir Crit Care Med 2019, Hobbs et al Am J Resp Crit Care Med 2019, Organ et al Respir Res 2019, Dudbridge et al Nat Comms 2019, Stewart et al European Respiratory Journal 2019, Maher et al Lancet Respir Med 2017, Allen et al Lancet Respir Med 2017 and Jenkins et al Lancet Respir Med 2015.) and have been included as primary endpoints in a clinical trial being undertaken by Boehringer Ingelheim (NCT02788474). These papers have lead to re-design of clinical trials and some of the biomarkers are available in current clinical practice and implementation studies are planned imminently. Further PROFILE study analysis was a central theme of a successful application for an NIHR Research Professorship RP-2017-08-ST2-014 awarded in 2018 entitled "Developing a biomarker guided strategy to treat patients with pulmonary fibrosis". Initial outputs have identified a number of biomarkers which are now routinely used in clinical trials and are being assessed into clinical management protocols to help determine lung transplant prioritisation. Results from the trials by BI (NCT02788474) are expected to help identify patients who might benefit from antifibrotics and determine whether they are responding to therapy. Some of the biomarkers are being investigated as theranostic biomarkers with promising results. It is anticipated that biomarkers will become established in clinical management protocols for patients with pulmonary fibrosis in the next 5-10 years. Initial genetic analysis are being used to inform genetic risk scores.