Colonoscopic Surveillance for Familial Risk of Colorectal Cancer

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

Objective for processing

This Agreement relates to a long-running surveillance programme which has received data from the Medical Research Information Service (MRIS) and its predecessor since before that service transferred to what is now [19 words unchanged] surveillance of patients with a family history of colorectal and other cancers. [2 paragraphs unchanged] This program of work is carried out by The Family Cancer Clinic at St Mark’s Hospital (part of LNWUHNT). Hospital, London North West University Healthcare Trust (LNWUHNT). The clinic is referred patients who have a familial history of colorectal and other cancers, with the aim of assessing their risk of developing colorectal cancer. [2 paragraphs unchanged] The Bobby Moore Database is a dedicated clinical and research database that is maintained by the Family Cancer Clinic. This database is [13 words unchanged] Research UK Infrastructure Grant, but the funders are not involved in determining how the data is to be processed. purposes and means of processing. Previously, the Bobby Moore Database was previously hosted by Imperial College London (ICL). ICL have since destroyed all copies [8 words unchanged] and evidence of this data destruction has been sent to NHS Digital. [1 paragraph unchanged] The great majority of the surveillance that the team recommends is colonoscopic but the team may also recommend ultrasound, gastroscopy and breast screening in some cases. The vast majority Most of the surveillance is undertaken at St Mark's Hospital but some patients, if they [11 words unchanged] to have the results sent to the team at St Mark’s Hospital. When the cohort was originally flagged in 2003, the team discovered no [50 words unchanged] for cancer and mortality notifications to ensure that the team is not over estimating overestimating the benefits of surveillance. 2. Service Evaluation (Research) [8 paragraphs unchanged] LNWUHNT is planning for a patient information evening in October 2021 where it is anticipated that both family members and affected individuals will attend. Patients will be asked their opinion regarding the acceptability of using confidential patient information without consent for the purpose of the retrospective flagging and linkage with data from NHS Digital. Comments from a representative panel will be collated and provided to the Confidentiality Advisory Group and to NHS Digital. [3 paragraphs unchanged] The London North West University Healthcare NHS Trust (LNWUHNT) and King’s College [6 words unchanged] who also process the data for the purposes described in this Agreement. The principal applicant is a substantive employee of Imperial College London (ICL), but holds an honorary contract with LNWUHNT. Under previous iterations of this Agreement Queen Mary University of London (QMUL) were also listed as a data processor. All data held at QMUL has now been destroyed. Once this Agreement becomes active LNWUHNT will begin to flow pseudonymised extracts of the Bobby Moore Database to KCL.

Processing activities

[3 paragraphs unchanged] When LNWUHNT had verified and updated the Bobby Moore Database, all data received by NHS Digital was destroyed. destroyed with the exception of the data points that were used to update the Database. Evidence of data destruction has been provided to NHS Digital. The Bobby Moore Database is stored on the LNWUHNT servers and is only accessed by individuals who are substantively employed by LNWUHNT LNWUHNT, or those who hold honorary contracts with LNWUHNT. All individuals with access to the Database have received training in data protection and confidentiality. [1 paragraph unchanged] In the past LNWUHNT would send securely transfer a pseudonymised extracts from extract of the Bobby Moore Database to QMUL. However, under this Agreement LNWUHNT intend to flow this data to KCL. [2 paragraphs unchanged] The data is solely analysed to assess the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. Access to this pseudonymised data will be restricted to one individual a small number of individuals who is are substantively employed by KCL, and has have received sufficient training in data protection and confidentiality confidentiality. [4 paragraphs unchanged]

Expected output

Familial risk of colorectal cancer may be determined by constitutional genetic testing to see if patients carry specific genetic alterations or by an empiric risk assessment dependent on the number of relatives affected by colorectal cancer, the closeness of their relationship (eg parent or grandparent) and the age at which they were diagnosed. The team aims to analyse the data to look at the prospective outcome of colonoscopic surveillance in different genetic and familial risk groups and to continue groups. The team intends to submit new papers to prestigious peer reviewed journal journals (e.g. The British Medical Journal, Gastroenterology and The International Journal of Cancer). Several Journal articles have already been published; these are listed below: Dove-Edwin I, Adams J, Sasieni P, Thomas HJW. The prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: a sixteen year prospective follow-up study. Br Med J 2005; 331: 1047-9 Dove-Edwin et al. (Br Med J 2005; 331: 1047-9) - Published in the British Medical Journal (BMJ) with open access, this work demonstrated that colonoscopy reduces the risk of colorectal cancer in people with a strong family history. Those with the strongest family history require shorter intervals to prevent colorectal cancer. Those with a moderate family history may not need surveillance until aged 45 and thereafter less frequently if no significant polyp are found. Dove-Edwin I, de Jong A, Lipton L, Adams J, Mesher D, Lipton L, Sasieni P, Vasen HFA, Thomas, HJW. Prospective results of surveillance colonoscopy in autosomal dominant colorectal cancer families with and without Lynch syndrome. Gastroenterology 2006; 130: 1995-2000 Dove-Edwin et al. (Gastroenterology 2006; 130: 1995-2000) - Demonstrated that there was an increased prevalence of colorectal cancer and an increased incidence of high-risk adenomas (precursors of cancer) in the familial high-risk group that did not have Lynch syndrome. This indicated that there are other causes of familial risk apart from Lynch syndrome and this is now referred to as Familial Colorectal Cancer type x. It also demonstrated that interval cancers occur between colonoscopies in Lynch syndrome. This suggested that the cancers developed more rapidly, and shorter surveillance intervals might be required. This article was published in Gastroenterology, and has open access. Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Morak M, German HNPCC Consortium, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer. In J Cancer 2014; 134: 939-47 Mesher et al. (Int J Cancer 2014; 134: 939-47) - This was a multicentre study that demonstrated that in Familial Colorectal Cancer type x colorectal cancer is unusual below the age of 35 and that 5 yearly colonoscopic surveillance is effective in removing high-risk adenomas and preventing colorectal cancer. This article was published in the International Journal of Cancer and has open access. Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans DG, Eaden JA, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR; British Society of Gastroenterology: Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut 2010; 59: 666-689 Cairns et al. (Gut 2010; 59: 666-689) ; Monahan et al. (Gut 2020; 69: 441-44) - National Guidelines produced by the British Society of Gastroenterology that incorporate the findings of the above papers. Vasen HFA, Blanco I, Atkan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Sotormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jarvinen HJ, Moslein G. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-23 Vasen et al. (Gut 2013; 62: 812-232013) - European guidelines that incorporate the findings of the above papers. Monahan KJ, Dunlop M, Bradshaw N, Dolwani S, East J, Illyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, de Souza B, Tomlinson I, Thomas H, Hill J. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG) Association of Coloproctology of Great Britain and Ireland (ACPGBI) United Kingdom Cancer Genetics Group. Gut 2020; 69: 441-44 The team at LNWUHNT aim to present their findings at National and International meetings in 2021 or 2022, and will continue to publish results in high-impact journals. This will ensure that findings will reach international scientific and policy-making communities. The team at LNWUHNT aim to present their findings at National and International meetings in 2021 or 2022. This will ensure that findings will reach international scientific and policy-making communities. Further to this, the study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic write to each patient when they have undergone colonoscopy with a follow-up plan and send a questionnaire asking if there are any new developments in their family history. From time to time the Study team also send a family history questionnaire to patients who have not been seen recently. Patient information can be found on the study website and the study team also arranges patient information evenings for those with known genetic predispositions. The study team will include a section on the clinic website on the outcome of this research project. Further to this, the study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic write to each patient when they have undergone colonoscopy with a follow-up plan and also send a questionnaire asking if there are any new developments in their family history. From time to time the Study team also send a family history questionnaire to patients who have not been seen recently. Patient information can be found on the study website and the study team also arranges patient information evenings for those with known genetic predispositions. The study team will include a section on the clinic website on the outcome of this research project.

Expected measurable benefits

[4 paragraphs unchanged] The study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic will analyse the outcome of colonoscopic surveillance in the current cohort of patients. The study team will intend to publish the outcomes in various genetic and familial risk groups. This It is intended to use the data will be used to help develop updated National and European guidelines for the management of familial risk of colorectal cancer. This It is expected that this will allow surveillance to be targeted at those individuals in whom it is most appropriate with significant potential savings in cost to the NHS. [1 paragraph unchanged] The outcome of colonoscopic surveillance in different genetic / familial risk groups [28 words unchanged] clinical care and registered on the Bobby Moore Database. The study team will intend to publish the prospective outcomes of colonoscopic surveillance in different genetic / familial [5 words unchanged] may influence National and European guidelines when they are reviewed and updated. [1 paragraph unchanged] The intended benefit of this service evaluation is to prevent the development of familial colorectal cancer with colonoscopic surveillance that is tailored to an individual’s genetic testing results, family history of colorectal cancer and the outcome of previous colonoscopic examinations. Colorectal cancer may be prevented by the removal of pre-malignant colonic polyps at colonoscopy and, if interval cancers do occur during surveillance, they should be at a stage where they may be successfully treated with a colonic resection.

Benefits reported

[3 paragraphs unchanged] 1. Individuals with inherited genetic conditions such as Lynch syndrome may now [37 words unchanged] yearly surveillance is required (Dove-Edwin et al 2005 and Dove-Edwin et al 2006).. 2006). ). As a consequence of these studies colonoscopic surveillance is now undertaken more frequently in these high risk groups to prevent the development of interval cancers. 2. In contrast, individuals who used to be assessed as having a [50 words unchanged] years of age (Dove-Edwin et al 2006 and Mesher et al 2014). As a consequence of these studies colonoscopic surveillance is now started at a later age. 3. In the past individuals with a single first-degree relative who had [59 words unchanged] they would have been offered in the past (Dove-Edwin et al 2005). As a consequence of these studies these patients now undergo a single colonoscopy at the age of 55 whereas they would once have had five-yearly colonoscopy from the age of 25. [1 paragraph unchanged] Colonoscopy is a time-consuming invasive procedure requiring time off work to take [24 words unchanged] for it to be effective in preventing the development of colorectal cancer. As a consequence of the outcome of the prospective studies above colonoscopic surveillance is now tailored more appropriately to the genetic and empiric risk of the individual.

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

Objective for processing

[1 paragraph unchanged] Objective one – non-research purpose – direct clinical care management The project described in this Agreement serves two purposes: The Family Cancer Clinic at St Mark’s Hospital (part of LNWUHNT) is referred patients with a family history of colorectal and other cancers to assess their risk of developing colorectal cancer. The Family Cancer Clinic reviews the family history of each patient, constructs a pedigree (a basic tool of clinical genetics that is used to determine that a disease is genetic, track the transmission of the disease and estimate risks to the patient and other family members) and confirms cancers that have occurred in the family by obtaining death certificates and cancer registrations. Genetic testing is arranged if appropriate. The patient’s risk is then assessed and colonoscopic surveillance arranged if it is assessed as being appropriate. This data from the direct clinical care of these patients is maintained by the Family Cancer Clinic on a database (the "Bobby Moore Database") hosted solely on the LNWUHNT servers. Data sources which make up this database include Referral letters, Family History Questionnaires, Clinical History, Pathology and Endoscopy reports (including genetic testing of tumours and germline), Cancer Registries and Death Certificates, and results of colonoscopic surveillance. 1. Direct Clinical Care Management (Non-Research) The Family Cancer Clinic Bobby Moore Database is a dedicated clinical and research database that has been funded by a Cancer Research UK Infrastructure Grant but that organisation has no other involvement. This cohort of clinical patient data is controlled and processed solely by LNWUHNT. The previous database was hosted by Imperial College London (ICL). ICL have since destroyed that data. This program of work is carried out by The Family Cancer Clinic at St Mark’s Hospital (part of LNWUHNT). The clinic is referred patients who have a familial history of colorectal and other cancers, with the aim of assessing their risk of developing colorectal cancer. The Family Cancer Clinic at LNWUHNT have previously requested cancer registration and mortality data from NHS Digital about its patients who are undergoing colonoscopic surveillance for familial risk of colorectal cancer to ensure that there is complete ascertainment of cases of cancer. The data from NHS Digital has been used to verify the information already held on the Bobby Moore Database (a non-research purpose). The Clinic review the family history of each patient, constructs a pedigree (a basic tool of clinical genetics that is used to determine that a disease is genetic, track the transmission of the disease and estimate risks to the patient and other family members) and confirms cancers that have occurred in the family by obtaining death certificates and cancer registrations. The patient risk is then assessed and colonoscopic surveillance is arranged if it assessed to be appropriate. All data from the direct clinical care of these patients is maintained by the Family Cancer Clinic on a database (the "Bobby Moore Database"). Once verified, NHS Digital data provided by NHS Digital is destroyed. LNWUHNT previously received identifiable cancer registration and death data covering the period between October 2003 and July 2018. The data received from NHS Digital is used to verify and update the information already held on the Bobby Moore Database. This allows the Family Cancer Clinic to ensure that it has an accurate and complete data set of cancer registrations and deaths, allowing the Clinic to effectively monitor those individuals who have been identified for colonoscopic surveillance. Upon the receipt of the data there were 2110 individuals in the Bobby Moore Database, and LNWUHNT only received data relating to these individuals. The flagged data is to ensure that the Family Cancer Clinic at LNWUHNT has a complete data set of cancer registrations and deaths. The Bobby Moore Database is a dedicated clinical and research database that is maintained by the Family Cancer Clinic. This database is hosted solely on LNWUHNT servers. The database has been funded by a Cancer Research UK Infrastructure Grant, but the funders are not involved in determining how the data is to be processed. The great majority of the surveillance that the team recommends is colonoscopic but the team may also recommend ultrasound, gastroscopy and breast screening in some cases. The vast majority of surveillance is undertaken at St Mark's Hospital but some patients, if they live far away, elect to have their surveillance performed locally and to have the results sent to the team at St Mark’s Hospital. There are 3684 individuals resident in England and Wales who have had at least one colonoscopy. As of October 2019, there were 11,945 individuals in the database which continues to grow as more families are added. The database will continue indefinitely as it is used to organise the clinical care of patients. Previously, the Bobby Moore Database was hosted by Imperial College London (ICL). ICL have since destroyed all copies of the data that was in its possession and evidence of this data destruction has been sent to NHS Digital. The data sources which make up this database include Referral letters, Family History Questionnaires, Clinical History, Pathology and Endoscopy reports (including genetic testing of tumours and germline), Cancer Registries and Death Certificates, and results of colonoscopic surveillance. The great majority of the surveillance that the team recommends is colonoscopic but the team may also recommend ultrasound, gastroscopy and breast screening in some cases. The vast majority of surveillance is undertaken at St Mark's Hospital but some patients, if they live far away, elect to have their surveillance performed locally and to have the results sent to the team at St Mark’s Hospital. [1 paragraph unchanged] Objective two – research purpose – service evaluation 2. Service Evaluation (Research) In a second flow of data the direct clinical care data from the Bobby Moore Database will be pseudonymised by LNWUHNT and securely transferred to Queen Mary University of London (QMUL). At present time (v6.3) there has been no transfer of data between LNWUHNT and QMUL. QMUL currently hold the data previously transferred by Imperial College London. The service evaluation focuses on the cohort of patients who were selected for surveillance (as described above). The aim of this processing is to determine if surveillance is successful in preventing cases of colorectal and other cancers. It also allows an assessment of whether there are other causes of death that occur more frequently than expected in the cohort. The service evaluation focuses on a cohort of patients who have a family history of colorectal cancer and have been referred to the Family Cancer Clinic at St Mark’s Hospital (part of LNWUHNT) for assessment of their risk of developing colorectal cancer and for colonoscopic surveillance if this is felt to be appropriate. The service evaluation is undertaken to assess whether the colonoscopic surveillance is effective in preventing colorectal cancer and is undertaken by the Family Cancer Clinic team within St Mark’s Hospital with statistical support from a statistician at Queen Mary University of London (QMUL). To achieve this aim KCL receive a pseudonymised versions of the Bobby Moore Database, including items that may have been updated because of the receipt of NHS Digital Data. There will be no attempt to re-identify individuals using the pseudonymised data provided to QMUL. There will be no attempt to link the pseudonymised data to any other data set. This processing was formerly undertaken at QMUL, but under this Agreement it will take place at KCL. That data is stored on QMUL servers where the data is specifically and solely to analysed to assess the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. This data is mostly data collected from other sources but may include pseudonymised cancer or death data provided by NHS Digital where there were discrepancies between NHS Digital data and the Bobby Moore Database. The data supplied to QMUL contains no field indicating whether cancer or death information was provided by the clinical team at St Mark’s or by NHS Digital. At the present time the pseudonymised patient data for the purpose of service evaluation is sat at Queen Mary, University of London. This pseudonymised patient database is due to be moved to the School of Cancer Epidemiology and Population Health at Kings College London (following the employed specialist). It is proposed that after this amendment is approved (v6.3) a further amendment will be submitted to move the Data Processor from QMUL to KCL in order that the physical movement of data and processing of data can occur. The aim of the service evaluation is to see if surveillance is successful in preventing cases of colorectal and other cancers. It also allows an assessment of whether there are other causes of death that occur more frequently than expected in the cohort. [5 paragraphs unchanged] London North West University NHS Trust and Kings College London are joint data controllers. The legal basis for the processing described is the General Data Protection Regulation (GDPR) Article’s 6(1)(e) and 9(2)(j). The processing is deemed to be in the public interest as it will provide prospective evidence as to how to best manage familial risk of colorectal cancer, and therefore will benefit the provision of health and social care in England. London North West University Healthcare NHS trust and Queen Mary University of London are both data processors. To address the GDPR principle of data minimisation, LNWUHNT only requested data relating to a specific cohort of individuals (which at the time consisted of 2110 individuals). Further to this LNWUHNT will only transfer pseudonymised extracts of the Bobby Moore Database to KCL, identifiable data is not necessary for service evaluation. Currently, the pseudonymised data set stored on the QMUL server is the original data transferred from Imperial College London. The next amendment of this agreement will move the Data Processor to King's College London to allow the physical data to be moved to the school of Cancer Epidemiology and Population Health (KCL) Server and processing to commence again. QMUL will be removed as a data processor and a data destruction certificate provided. There is no alternative or less intrusive way of achieving the aims. LEGAL BASIS FOR PROCESSING The London North West University Healthcare NHS Trust (LNWUHNT) and King’s College London (KCL) are joint Data Controllers, who also process the data for the purposes described in this Agreement. The processing of patient data by both Kings College London and St Mark’s Hospital (part of LNWUHNT) is undertaken under General Data Protection Regulations Article 6(1) (e) and Article 9 (2) (j) as the information will provide prospective evidence as to how to best manage familial risk of colorectal cancer which is in the public interest for public health and scientific research. Under previous iterations of this Agreement Queen Mary University of London (QMUL) were also listed as a data processor. All data held at QMUL has now been destroyed. Once this Agreement becomes active LNWUHNT will begin to flow pseudonymised extracts of the Bobby Moore Database to KCL.

Processing activities

Data Flow one - NHS One (NHS Digital to LNWUHNT LNWUHNT): UNDER THIS AMENDMENT (V6.3) NO DATA HAS BEEN REQUESTED FROM NHS DIGITAL AND SO THE BELOW DESCRIPTION DEPICTS THE FUTURE DATA FLOW WHICH WILL BE SUBJECT TO AN AMENDMENT TO THIS AGREEMENT Under a previous iteration of this Agreement St Mark’s Hospital Family Cancer Clinic (part of LNWUHNT) provided NHS Digital with a set of patient identifiers: NHS Number, Name, and Date of Birth plus a Study ID. St Mark’s Hospital Family Cancer Clinic (part of LNWUHNT) will provide NHS Digital with a set of patient identifiers: NHS Number, Name, and Date of Birth plus a Study ID to NHS Digital who will then provide a ‘flagging’ / patient tracking service. NHS Digital will provide annual notifications of cancer registrations and deaths including cause of death to the Family Cancer Clinic team at St Mark’s Hospital under this Data Sharing Agreement. NHS Digital will replace the direct patient identifiers with the Study ID. In turn, NHS Digital provided a ‘flagging’/ patient tracking service, providing annual notification of cancer registrations and deaths, including cause of death. The team uses the data to ensure that its own data set on the Bobby Moore Database is accurate and complete. Where there are differences between the data provided by NHS Digital and the data in the Bobby Moore Database, the database is updated to include the latest data from NHS Digital. Where the data from NHS Digital matches the Database, no further action is taken. When LNWUHNT had verified and updated the Bobby Moore Database, all data received by NHS Digital was destroyed. Evidence of data destruction has been provided to NHS Digital. The data set received from NHS Digital is then destroyed by St Mark’s Hospital (LNWUHNT) Family Cancer Clinic. The Bobby Moore Database is stored on the LNWUHNT servers and is only accessed by individuals who are substantively employed by LNWUHNT or those who hold honorary contracts with LNWUHNT. All individuals with access to the Database have received training in data protection and confidentiality. This data is used for the non-research purpose of maintaining the most up to date data for the direct clinical care management of patients. Data Flow Two (LNWUHNT to KCL): The Bobby Moore Database is housed on the LNWUHNT servers. The Bobby Moore Database is only accessed by individuals within the Family Cancer Clinic team all of whom are substantive employees of the LNWUHNT or KCL or hold an honorary contract with LNWUHNT. In the past LNWUHNT would send pseudonymised extracts from the Bobby Moore Database to QMUL. However, under this Agreement LNWUHNT intend to flow this data to KCL. Data Flow two – LNWUHNT to QMUL The pseudonymised extracts from the Bobby Moore Database will be securely transferred to KCL on an occasional basis. The data received by KCL will mostly contain data collected from other sources but may include pseudonymised cancer or death data provided by NHS Digital where there were discrepancies between NHS Digital data and the Bobby Moore Database. UNDER THIS AMENDMENT (V6.3) NO DATA WILL FLOW BETWEEN LNWUHNT to QMUL AND DATA HELD BY QMUL WILL NOT BE PROCESSED BY QMUL OR KCL. This data will be stored on KCL servers and servers managed by AIMES Management Services. AIMES supply support to the system, but do not access data. Therefore, any access to the data held under this Agreement would be considered a breach of the Agreement. Pseudonymised The data is extracted from the Bobby Moore Database and securely transferred solely analysed to Queen Mary University of London (QMUL). That data is stored on QMUL servers with access restricted to one statistician who analyses the data specifically and solely to analyse assess the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. This Access to this data will be restricted to one individual who is mostly that collected from the direct care of the cohort of patients substantively employed by KCL, and their family but may include pseudonymised cancer or death has received sufficient training in data provided by NHS Digital where there were discrepancies between NHS Digital data protection and the Bobby Moore Database. confidentiality The data supplied to QMUL contains no field indicating whether cancer or death information was provided by the clinical team at St Mark’s Hospital or by NHS Digital. QMUL has no access to the identifiable data provided by NHS Digital to LNWUHNT. The data received from NHS Digital will not be linked to other data except as described above. The next amendment of this agreement will move the Data Processor to King's College London to allow the physical data to be moved to the school of Cancer Epidemiology and Population Health (KCL) Server and processing to commence again. There will be no attempt to re-identify individuals where pseudonymised data is being used. All organisations party to this agreement Agreement must comply with the Data Sharing Framework Contract requirements, including those regarding [5 words unchanged] that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e: - i.e. employees, agents and contractors of the Data Recipient who may have access to that data. data). [1 paragraph unchanged]

Expected output

The team aims to analyse this the data to look at the prospective outcome of colonoscopic surveillance in different genetic and familial risk groups and to continue to submit a new paper papers to a prestigious peer reviewed journal. As the study team journal (e.g. The British Medical Journal, Gastroenterology and The International Journal of Cancer). Several Journal articles have not already been able to analyse the data they do not yet know what the analysis may reveal and to which Journal it may be appropriate to submit a manuscript. The study team will publish a patient-orientated summary of their findings on their dedicated study website with links to any publications. published; these are listed below: The study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic keep in touch with the cohort of patients and families as, to be included in this study, individuals are having colonoscopic surveillance. The study team arrange the appointments and provide a written review of the results and a follow-up plan. From time to time the Study team also send a family history questionnaire for them to update. Patient information can be found on the study website and the study team also arranges patient information evenings for those with known genetic predispositions. Dove-Edwin I, Adams J, Sasieni P, Thomas HJW. The prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: a sixteen year prospective follow-up study. Br Med J 2005; 331: 1047-9 Dove-Edwin I, de Jong A, Lipton L, Adams J, Mesher D, Lipton L, Sasieni P, Vasen HFA, Thomas, HJW. Prospective results of surveillance colonoscopy in autosomal dominant colorectal cancer families with and without Lynch syndrome. Gastroenterology 2006; 130: 1995-2000 Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Morak M, German HNPCC Consortium, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer. In J Cancer 2014; 134: 939-47 Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans DG, Eaden JA, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR; British Society of Gastroenterology: Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut 2010; 59: 666-689 Vasen HFA, Blanco I, Atkan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Sotormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jarvinen HJ, Moslein G. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-23 Monahan KJ, Dunlop M, Bradshaw N, Dolwani S, East J, Illyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, de Souza B, Tomlinson I, Thomas H, Hill J. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG) Association of Coloproctology of Great Britain and Ireland (ACPGBI) United Kingdom Cancer Genetics Group. Gut 2020; 69: 441-44 The team at LNWUHNT aim to present their findings at National and International meetings in 2021 or 2022. This will ensure that findings will reach international scientific and policy-making communities. Further to this, the study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic write to each patient when they have undergone colonoscopy with a follow-up plan and also send a questionnaire asking if there are any new developments in their family history. From time to time the Study team also send a family history questionnaire to patients who have not been seen recently. Patient information can be found on the study website and the study team also arranges patient information evenings for those with known genetic predispositions. The study team will include a section on the clinic website on the outcome of this research project.

Expected measurable benefits

The assessment of familial risk of colorectal cancer has evolved over the [9 words unchanged] first established by the Imperial Cancer Research Fund at St Mark’s Hospital (LNWUHNT). (now at LNWUHNT). [5 paragraphs unchanged] The pseudonymised data is to be analysed in a collaboration between the clinicians in the St Mark’s Hospital (LNWUHNT) Family Cancer Clinic and the dedicated researcher at KCL. The outcome of colonoscopic surveillance in different genetic / familial risk groups [58 words unchanged] may influence National and European guidelines when they are reviewed and updated. LNWUHNT have targeted colonoscopic surveillance more appropriately with some individuals with Lynch syndrome requiring it more frequently to prevent interval cancers and others shown by genetic testing and empiric risk assessment to be at lower familial risk to require colonoscopy less frequently. Colonoscopy is a time-consuming invasive procedure requiring time off work to take the bowel preparation and for the procedure which itself has a small risk of complications. It should be performed as infrequently as is needed for it to be effective.

Benefits reported

[1 paragraph unchanged] In 1986 individuals with an empiric lifetime risk of developing colorectal cancer [30 words unchanged] in different empiric risk groups and the introduction of molecular genetic testing LNWUHNT St Mark's Hospital (LNWUHNT) have redefined risk groups and adapted surveillance protocols with some individuals requiring [8 words unchanged] This has led to a much more appropriate use of valuable NHS resources. resources and benefited patients by minimising the number of unnecessary invasive and inconvenient colonoscopies. As Below are examples of the developments that have been made: 1. Individuals with inherited genetic conditions such as Lynch syndrome may now [28 words unchanged] yearly surveillance and that more frequent colonoscopy with two yearly surveillance is required. required (Dove-Edwin et al 2005 and Dove-Edwin et al 2006).. 2. In contrast, individuals who used to be assessed as having a [40 words unchanged] started with five yearly colonoscopy at 35 instead of 25 years of age. age (Dove-Edwin et al 2006 and Mesher et al 2014). 3. In the past individuals with a single first-degree relative who had [54 words unchanged] the age of 25 which they would have been offered in the past. past (Dove-Edwin et al 2005). The team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic have previously published papers on the outcome of colonoscopic surveillance for familial risk of colorectal cancer: These changes have been included and referenced in National and European Guidelines (Cairns et al 2010, Monahan et al 2020, Vasen et al 2013). Dove-Edwin I, Adams J, Sasieni P, Thomas HJW. The prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: a sixteen year prospective follow-up study. Br Med J 2005; 331: 1047-9 Colonoscopy is a time-consuming invasive procedure requiring time off work to take the bowel preparation and for the procedure which itself has a small risk of complications. It should be performed as infrequently as is needed for it to be effective in preventing the development of colorectal cancer. Dove-Edwin I, de Jong A, Lipton L, Adams J, Mesher D, Lipton L, Sasieni P, Vasen HFA, Thomas, HJW. Prospective results of surveillance colonoscopy in autosomal dominant colorectal cancer families with and without Lynch syndrome. Gastroenterology 2006; 130: 1995-2000 Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Morak M, German HNPCC Consortium, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer. In J Cancer 2014; 134: 939-47 These papers have contributed to the development of National and European evidence-based guidelines on the management of familial risk of colorectal cancer: Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans DG, Eaden JA, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR; British Society of Gastroenterology: Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut 2010; 59: 666-689 Vasen HFA, Blanco I, Atkan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Sotormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jarvinen HJ, Moslein G. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-23

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

Data controllers: + KING'S COLLEGE LONDON

Objective for processing

This agreement relates to a long-running surveillance programme which has received data from the Medical Research Information Service and its predecessor since before that service transferred to what is now NHS Digital in 2008. The London North West University Healthcare NHS Trust (LNWUHNT) requires notifications overarching purpose for the use of cancer registrations and mortality data for use is in a service evaluation of its surveillance of patients with a family history of colorectal and other cancers. Objective one – non-research purpose – direct clinical care management The Family Cancer Clinic at St Mark’s Hospital (part of LNWUHNT) is referred patients with a family history of colorectal and other cancers to assess their risk of developing colorectal cancer. The Family Cancer Clinic reviews the family history of each patient, constructs a pedigree (a basic tool of clinical genetics that is used to determine that a disease is genetic, track the transmission of the disease and estimate risks to the patient and other family members) and confirms cancers that have occurred in the family by obtaining death certificates and cancer registrations. Genetic testing is arranged if appropriate. The patient’s risk is then assessed and colonoscopic surveillance arranged if it is assessed as being appropriate. This data from the direct clinical care of these patients is maintained by the Family Cancer Clinic on a database (the "Bobby Moore Database") hosted solely on the LNWUHNT servers. Data sources which make up this database include Referral letters, Family History Questionnaires, Clinical History, Pathology and Endoscopy reports (including genetic testing of tumours and germline), Cancer Registries and Death Certificates, and results of colonoscopic surveillance. The Family Cancer Clinic Bobby Moore Database is a dedicated clinical and research database that has been funded by a Cancer Research UK Infrastructure Grant but that organisation has no other involvement. This cohort of clinical patient data is controlled and processed solely by LNWUHNT. The previous database was hosted by Imperial College London (ICL). ICL have since destroyed that data. The Family Cancer Clinic at LNWUHNT have previously requested cancer registration and mortality data from NHS Digital about its patients who are undergoing colonoscopic surveillance for familial risk of colorectal cancer to ensure that there is complete ascertainment of cases of cancer. The data from NHS Digital has been used to verify the information already held on the Bobby Moore Database (a non-research purpose). Once verified, NHS Digital data provided by NHS Digital is destroyed. The flagged data is to ensure that the Family Cancer Clinic at LNWUHNT has a complete data set of cancer registrations and deaths. The great majority of the surveillance that the team recommends is colonoscopic but the team may also recommend ultrasound, gastroscopy and breast screening in some cases. The vast majority of surveillance is undertaken at St Mark's Hospital but some patients, if they live far away, elect to have their surveillance performed locally and to have the results sent to the team at St Mark’s Hospital. There are 3684 individuals resident in England and Wales who have had at least one colonoscopy. As of October 2019, there were 11,945 individuals in the database which continues to grow as more families are added. The database will continue indefinitely as it is used to organise the clinical care of patients. When the cohort was originally flagged in 2003, the team discovered no additional cases of colorectal cancer that it was not already aware of from the clinical care of their patients. However, when the team has previously submitted papers for publication on the outcome of surveillance for familial risk of cancer the journal’s reviewers have asked for the cohort to be flagged for cancer and mortality notifications to ensure that the team is not over estimating the benefits of surveillance. Objective two – research purpose – service evaluation In a second flow of data the direct clinical care data from the Bobby Moore Database will be pseudonymised by LNWUHNT and securely transferred to Queen Mary University of London (QMUL). At present time (v6.3) there has been no transfer of data between LNWUHNT and QMUL. QMUL currently hold the data previously transferred by Imperial College London. [1 paragraph unchanged] The Family Cancer Clinic Bobby Moore Database is a dedicated clinical and research database that has been funded by a Cancer Research UK Infrastructure Grant and is hosted on the servers of LNWUHNT. The previous database was hosted by Imperial College London (ICL). ICL have since destroyed that data. There will be no attempt to re-identify individuals using the pseudonymised data provided to QMUL. There will be no attempt to link the pseudonymised data to any other data set. Processing of private data is undertaken under General Data Protection Regulations Article 6 e and Article 9 (2) (j) as the information will provide prospective evidence as to how to best manage familial risk of colorectal cancer which is in the public interest for public health and scientific research. That data is stored on QMUL servers where the data is specifically and solely to analysed to assess the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. This data is mostly data collected from other sources but may include pseudonymised cancer or death data provided by NHS Digital where there were discrepancies between NHS Digital data and the Bobby Moore Database. The data supplied to QMUL contains no field indicating whether cancer or death information was provided by the clinical team at St Mark’s or by NHS Digital. The database was funded by Cancer Research UK but that organisation has no other involvement. At the present time the pseudonymised patient data for the purpose of service evaluation is sat at Queen Mary, University of London. This pseudonymised patient database is due to be moved to the School of Cancer Epidemiology and Population Health at Kings College London (following the employed specialist). The Family Cancer Clinic at St Mark’s Hospital is referred patients with a family history of colorectal and other cancers to assess their risk of developing colorectal cancer. The team in the Family Cancer Clinic reviews the family history of each patient, constructs a pedigree and confirms cancers that have occurred in the family by obtaining death certificates and cancer registrations. They arrange genetic testing, if appropriate. The patient’s risk is then assessed and colonoscopic surveillance arranged if it is assessed as being appropriate. It is proposed that after this amendment is approved (v6.3) a further amendment will be submitted to move the Data Processor from QMUL to KCL in order that the physical movement of data and processing of data can occur. The great majority of the surveillance that the team recommends is colonoscopic but they may also recommend ultrasound, gastroscopy and breast screening in some cases. The vast majority of surveillance is undertaken at St Mark's Hospital but some patients, if they live far away, elect to have their surveillance performed locally and to have the results are sent to the team at St Mark’s Hospital. There are 3684 individuals resident in England and Wales who have had at least one colonoscopy. As of October 2019, there are 11,945 individuals in the database which continues to grow as more families ß are added. The Family Cancer Clinic at LNWUHNT maintains the Bobby Moore Database with information on the outcome of surveillance and any cancer diagnoses. They require data from NHS Digital about its patients who are undergoing colonoscopic surveillance for familial risk of colorectal cancer to ensure that there is complete ascertainment of cases of cancer. The data from NHS Digital is used to verify the information already held on the Bobby Moore Database. [1 paragraph unchanged] When the cohort was originally flagged in 2003, the team discovered no additional cases of colorectal cancer that it was not already aware of from the clinical care of their patients. However, when the team has previously submitted papers for publication on the outcome of surveillance for familial risk of cancer the journal’s reviewers have asked for the cohort to be flagged for cancer and mortality notifications to ensure that the team is not over estimating the benefits of surveillance. [5 paragraphs unchanged] The flagged data is to ensure that the Family Cancer Clinic at LNWUHNT has a complete data set of cancer registrations and deaths. London North West University NHS Trust and Kings College London are joint data controllers. Under this Data Sharing Agreement, London North West University Healthcare NHS Trust is the sole data controller of this service evaluation and all associated research that takes place from it. Under this Data Sharing Agreement, no other organisation determines the purposes on how the data is processed. London North West University Healthcare NHS trust and Queen Mary University of London are both data processors. Currently, the pseudonymised data set stored on the QMUL server is the original data transferred from Imperial College London. The next amendment of this agreement will move the Data Processor to King's College London to allow the physical data to be moved to the school of Cancer Epidemiology and Population Health (KCL) Server and processing to commence again. QMUL will be removed as a data processor and a data destruction certificate provided. LEGAL BASIS FOR PROCESSING The processing of patient data by both Kings College London and St Mark’s Hospital (part of LNWUHNT) is undertaken under General Data Protection Regulations Article 6(1) (e) and Article 9 (2) (j) as the information will provide prospective evidence as to how to best manage familial risk of colorectal cancer which is in the public interest for public health and scientific research.

Processing activities

St Mark’s Hospital (part of LNWUHNT) will provide NHS Digital with the identifiers: NHS Number, Name, and Date of Birth to the Medical Research Information Service team at NHS Digital who will then provide a ‘flagging’ / patient tracking service. NHS Digital will provide annual notifications of cancer registrations and deaths including cause of death to the Family Cancer Clinic team at St Mark’s Hospital under this Data Sharing Agreement. Of the data that NHS Digital disseminate, identifying demographics will be replaced by the study’s pseudonymised study ID. Data Flow one - NHS Digital to LNWUHNT The team uses the data to ensure that its own data set on the Bobby Moore Database is accurate and complete. Where there are differences between the data provided by NHS Digital and the data in the Bobby Moore Database, the Database is updated to include the latest data from NHS Digital. Where the data from NHS Digital matches the Database, no further action is taken. The data set received from NHS Digital is then destroyed. UNDER THIS AMENDMENT (V6.3) NO DATA HAS BEEN REQUESTED FROM NHS DIGITAL AND SO THE BELOW DESCRIPTION DEPICTS THE FUTURE DATA FLOW WHICH WILL BE SUBJECT TO AN AMENDMENT TO THIS AGREEMENT The Bobby Moore Database is housed on the LNWUHNT servers. The Bobby Moore Database is only accessed by individuals within the Family Cancer Clinic team all of whom are substantive employees of the LNWUHNT or hold an honorary contract with the LNWUHNT. One such individual is employed by Imperial College London at St Mark’s Hospital and is an Honorary Consultant Physician at LNWUHNT. A copy of the Honorary Contract has been provided to NHS Digital. He is also an NHS Consultant Physician at Imperial College Healthcare NHS Trust. St Mark’s Hospital Family Cancer Clinic (part of LNWUHNT) will provide NHS Digital with a set of patient identifiers: NHS Number, Name, and Date of Birth plus a Study ID to NHS Digital who will then provide a ‘flagging’ / patient tracking service. NHS Digital will provide annual notifications of cancer registrations and deaths including cause of death to the Family Cancer Clinic team at St Mark’s Hospital under this Data Sharing Agreement. NHS Digital will replace the direct patient identifiers with the Study ID. Pseudonymised The team uses the data is extracted from to ensure that its own data set on the Bobby Moore Database is accurate and securely transferred to Queen Mary University of London (QMUL). That data is stored on QMUL servers with access restricted to one statistician who analyses complete. Where there are differences between the data specifically and solely to analyse the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. This data is mostly data collected from other sources but may include pseudonymised cancer or death data provided by NHS Digital where there were discrepancies between NHS Digital and the data and in the Bobby Moore Database. The Database, the database is updated to include the latest data supplied to QMUL contains no field indicating whether cancer or death information was provided by the clinical team at St Mark’s or by from NHS Digital. Where the data from NHS Digital matches the Database, no further action is taken. The data set received from NHS Digital is then destroyed by St Mark’s Hospital (LNWUHNT) Family Cancer Clinic. This data is used for the non-research purpose of maintaining the most up to date data for the direct clinical care management of patients. The Bobby Moore Database is housed on the LNWUHNT servers. The Bobby Moore Database is only accessed by individuals within the Family Cancer Clinic team all of whom are substantive employees of the LNWUHNT or KCL or hold an honorary contract with LNWUHNT. Data Flow two – LNWUHNT to QMUL UNDER THIS AMENDMENT (V6.3) NO DATA WILL FLOW BETWEEN LNWUHNT to QMUL AND DATA HELD BY QMUL WILL NOT BE PROCESSED BY QMUL OR KCL. Pseudonymised data is extracted from the Bobby Moore Database and securely transferred to Queen Mary University of London (QMUL). That data is stored on QMUL servers with access restricted to one statistician who analyses the data specifically and solely to analyse the outcome of colonoscopic surveillance in different familial risk groups and in different genetic conditions. This data is mostly that collected from the direct care of the cohort of patients and their family but may include pseudonymised cancer or death data provided by NHS Digital where there were discrepancies between NHS Digital data and the Bobby Moore Database. The data supplied to QMUL contains no field indicating whether cancer or death information was provided by the clinical team at St Mark’s Hospital or by NHS Digital. QMUL has no access to the identifiable data provided by NHS Digital to LNWUHNT. The next amendment of this agreement will move the Data Processor to King's College London to allow the physical data to be moved to the school of Cancer Epidemiology and Population Health (KCL) Server and processing to commence again. 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. No record level data provided under this agreement will be made available to any third parties not detailed in this data sharing agreement. The research outputs published will only present aggregate level data with small numbers suppressed in line with the HES Analysis Guidance.

Expected output

The team at St Mark’s has previously published papers on the outcome of colonoscopic surveillance for familial risk of colorectal cancer: The team aims to analyse this data to look at the prospective outcome of colonoscopic surveillance in different genetic and familial risk groups and to submit a new paper to a prestigious peer reviewed journal. As the study team have not been able to analyse the data they do not yet know what the analysis may reveal and to which Journal it may be appropriate to submit a manuscript. The study team will publish a patient-orientated summary of their findings on their dedicated study website with links to any publications. Dove-Edwin I, Adams J, Sasieni P, Thomas HJW. The prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: a sixteen year prospective follow-up study. Br Med J 2005; 331: 1047-9 The study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic keep in touch with the cohort of patients and families as, to be included in this study, individuals are having colonoscopic surveillance. The study team arrange the appointments and provide a written review of the results and a follow-up plan. From time to time the Study team also send a family history questionnaire for them to update. Patient information can be found on the study website and the study team also arranges patient information evenings for those with known genetic predispositions. Dove-Edwin I, de Jong A, Lipton L, Adams J, Mesher D, Lipton L, Sasieni P, Vasen HFA, Thomas HJW. Prospective results of surveillance colonoscopy in autosomal dominant colorectal cancer families with and without Lynch syndrome. Gastroenterology 2006; 130: 1995-2000 Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Morak M, German HNPCC Consortium, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer. In J Cancer 2014; 134: 939-47 These papers have contributed to the development of National and European evidence-based guidelines on the management of familial risk of colorectal cancer: Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans DG, Eaden JA, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR; British Society of Gastroenterology: Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut 2010; 59: 666-689 Vasen HFA, Blanco I, Atkan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Sotormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jarvinen HJ, Moslein G. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-23 The entire dataset has not been analysed since 2006 and it is anticipated that there are now over 30,000 patient-years of follow-up that is available for analysis. The team aims to analyse this data to look at the prospective outcome of colonoscopic surveillance in different genetic and familial risk groups and to submit a new paper to a prestigious peer reviewed journal.

Expected measurable benefits

The assessment of familial risk of colorectal cancer has evolved over the [8 words unchanged] was first established by the Imperial Cancer Research Fund at St Mark’s Hospital. Hospital (LNWUHNT). [1 paragraph unchanged] The team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic has shown that there is group of patients with a strong family [22 words unchanged] and less frequent colonoscopy from a later age of onset is required. Dissemination of the findings through publications and directly impacting NICE National Institute for Health and Care Excellence (NICE) and European guidelines is beneficial to health care and health care users. The prospective data on the outcomes of colonoscopy in different family risk groups published by the study team in the past, and hopefully in the future, has been used and referenced in surveillance guidelines produced by the British Society of Gastroenterology / NICE and European Guidelines. Primarily, identifying groups at higher risk of cancers enables effective and appropriate [26 words unchanged] not over-investigated leading to less inconvenience and less concern for such individuals. The study team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic will analyse the outcome of colonoscopic surveillance in the current cohort of patients. The study team will publish the outcomes in various genetic and familial risk groups. [35 words unchanged] is most appropriate with significant potential savings in cost to the NHS. The clinical data set is used to assess the familial risk of an individual within a family. For example, if a further family member is diagnosed with cancer or significant colonic polyps detected at colonoscopy that might lead to the age at which colonoscopic surveillance is commenced or the surveillance interval being altered. The pseudonymised data is to be analysed in a collaboration between the clinicians in the St Mark’s Hospital (LNWUHNT) Family Cancer Clinic and the dedicated researcher at KCL. The outcome of colonoscopic surveillance in different genetic / familial risk groups analysed using the pseudonymised data set may lead to alterations in the recommended surveillance protocols of individuals under the St Mark’s Hospital (LNWUHNT) Family Cancer Clinic study team’s clinical care and registered on the Bobby Moore Database. The study team will publish the prospective outcomes of colonoscopic surveillance in different genetic / familial risk groups and these outputs may influence National and European guidelines when they are reviewed and updated.

Benefits reported

[6 paragraphs unchanged] The team at St Mark’s Hospital (LNWUHNT) Family Cancer Clinic have previously published papers on the outcome of colonoscopic surveillance for familial risk of colorectal cancer: Dove-Edwin I, Adams J, Sasieni P, Thomas HJW. The prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: a sixteen year prospective follow-up study. Br Med J 2005; 331: 1047-9 Dove-Edwin I, de Jong A, Lipton L, Adams J, Mesher D, Lipton L, Sasieni P, Vasen HFA, Thomas, HJW. Prospective results of surveillance colonoscopy in autosomal dominant colorectal cancer families with and without Lynch syndrome. Gastroenterology 2006; 130: 1995-2000 Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Morak M, German HNPCC Consortium, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer. In J Cancer 2014; 134: 939-47 These papers have contributed to the development of National and European evidence-based guidelines on the management of familial risk of colorectal cancer: Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans DG, Eaden JA, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR; British Society of Gastroenterology: Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut 2010; 59: 666-689 Vasen HFA, Blanco I, Atkan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Sotormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jarvinen HJ, Moslein G. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62: 812-23

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

Objective for processing

[2 paragraphs unchanged] The Family Cancer Clinic Bobby Moore Database is a dedicated clinical and [20 words unchanged] LNWUHNT. The previous database was hosted by Imperial College London (ICL). ICL still has an embargoed data set to which no new data is being added. This will be have since destroyed once the applicant has obtained a new honorary contract from LNWHUNH. that data. [1 paragraph unchanged] . [12 paragraphs unchanged] Under this Data Sharing Agreement, London North West University Healthcare NHS Trust [10 words unchanged] all associated research that takes place from it. Under this Data Sharing Agreement Agreement, no other organisation determines the purposes on how the data is processed.

Processing activities

St Mark’s Hospital (part of LNWUHNT) will provide NHS Digital with the [16 words unchanged] NHS Digital who will then provide a ‘flagging’ / patient tracking service. . NHS Digital will provide annual notifications of cancer registrations and deaths including [24 words unchanged] disseminate, identifying demographics will be replaced by the study’s pseudonymised study ID. [1 paragraph unchanged] The Bobby Moore Database is housed on the LNWUHNT servers. The Bobby [38 words unchanged] London at St Mark’s Hospital and is an Honorary Consultant Physician at LNWUHNT . LNWUHNT. A copy of the Honorary Contract is not available and a new contract is being produced. has been provided to NHS Digital. He is also an NHS Consultant Physician at Imperial College Healthcare NHS Trust. [1 paragraph unchanged] The copy of the dataset at Imperial College London (ICL) is stored on ICL servers and will only be accessed if required to verify successful transfer of the database to LNWUHNT. Once a copy of the applicant’s Honorary Contract with LNWUHNT is available the copy at ICL will be securely destroyed.

Benefits reported

[3 paragraphs unchanged] 1. Individuals with inherited genetic conditions such as Lynch syndrome may now [28 words unchanged] yearly surveillance and that more frequent colonoscopy with two yearly surveillance is required . required. [2 paragraphs unchanged]

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

Unchanged: Expected measurable benefits.