MR1108: CT colonography, colonoscopy, or barium enema for diagnosis of colorectal cancer in older symptomatic patients: SIGGAR1 (Special Interest Group in Gastrointestinal and Abdominal radiology). Plus SOCCER (Symptoms of Colorectal Cancer Evaluation Research).

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

Objective for processing

The study sponsor for the Special Interest Group Gastrointestinal and Abdominal Radiology (SIGGAR) and Symptoms of Colorectal Cancer Evaluation Research (SOCCER) studies is Imperial College London (ICL). The research group responsible for the studies at ICL is the Cancer Screening and Prevention Research Group (CSPRG). ICL are the data controller and the data processor for the SIGGAR and SOCCER studies. Imperial College London requires access to NHS England data for the purpose of archiving only. When a person visits their doctor for symptoms that are suggestive of bowel cancer, the doctor might refer them to hospital for further investigations. Often people will be offered a test to examine the whole of the large bowel to look for abnormalities. Prior to the SIGGAR study, the tests that had proven most suitable for ‘whole colon’ examination were colonoscopy and barium enema. The following provides background: Colonoscopy is a procedure during which, usually under sedation, a tube (endoscope) with a small camera attached is inserted into the rectum and guided through the large bowel to examine its surface for abnormalities. The barium enema examination involves passing a white liquid containing barium into the bowel through the rectum and then taking x-rays of the bowel. Imperial College London (ICL) requires access to NHS England data for the purpose of the following research project: MR1108: CT colonography, colonoscopy, or barium enema for diagnosis of colorectal cancer in older symptomatic patients: SIGGAR1 (Special Interest Group in Gastrointestinal and Abdominal radiology). Plus SOCCER (Symptoms of Colorectal Cancer Evaluation Research). More recently, a new imaging test for examining the bowel has been developed. This test is called Computed Tomographic Colonography, which you might see abbreviated as CTC or called ‘virtual colonoscopy’. Virtual colonoscopy uses x-rays to take images of the bowel, and creates 3-dimensional pictures to aid diagnosis. It does not require barium. The following is a summary of the aims of the research project provided by ICL: Prior to the SIGGAR study it was thought likely that virtual colonoscopy was a useful test for examining people with bowel cancer symptoms, and might have some benefits over barium enema and colonoscopy. However, the strong evidence that was needed to adopt virtual colonoscopy more widely had not been collected. The SIGGAR study aimed to provide the robust evidence needed to support the use of virtual colonoscopy in bowel cancer diagnosis. To achieve this, ICL compared virtual colonoscopy with barium enema or colonoscopy in two randomised trials, to see how effective and safe virtual colonoscopy was compared with the other two tests. • Investigate the use of computed tomographic colonography (CTC) as an imaging technique for the diagnosis of colorectal cancer. The SIGGAR study recruited patients from 2004 to 2007. The aim of the study was to investigate the use of computed tomographic colonography (CTC) as an imaging technique for the diagnosis of colorectal cancer, compared against the then accepted alternatives of colonoscopy and barium enema. Patients within the SIGGAR cohort (n=8,484 in total) were divided into two categories: those who were randomised and consented in the trial (n=5,448), and those who were eligible to participate and were registered but were ultimately not randomised (n=3,036). • Compare virtual colonoscopy with barium enema or colonoscopy in two randomised trials, to see how effective and safe virtual colonoscopy was compared with the other two tests. Flexible sigmoidoscopy, which is an examination of the lower part of the bowel, has many potential benefits over tests that examine the whole of the large bowel, both for patients – who may find it more acceptable – and also for health services – that need to ensure resources are being used in the most effective way. • Provide robust evidence to support the use of virtual colonoscopy in bowel cancer diagnosis. Prior to the SOCCER study, scientists had carried out a study which showed that certain bowel cancer signs and symptoms are more common in people with bowel cancers in the lower part of the large bowel, and so within reach of the flexible sigmoidoscopy (a test to look inside the lower part of your large bowel), and that other symptoms are more common in people with cancer in parts of the bowel that are out of reach of the flexible sigmoidoscopy. This was a study at only one hospital, but it provided early evidence that specific signs and symptoms could be used to predict when flexible sigmoidoscopy could be a safe and effective test to diagnose bowel cancer, and when it is less likely to be effective. • Determine whether whole colon investigation (WCI) by colonoscopy, CTC, or barium enema was necessary for all patients with colorectal cancer symptoms, and for which patients a flexible sigmoidoscopy (FS) would suffice. The SOCCER study follows on from this SIGGAR work on bowel cancer symptoms. ICL are aiming to provide evidence that is needed to show whether flexible sigmoidoscopy is an effective and safe alternative to whole colon examinations for many people. If the results confirm the earlier study, ICL anticipate this will change how doctors diagnose bowel cancer in their patients based on their symptoms. The following NHS England data was accessed under previous iterations of this agreement: The SOCCER study was a retrospective analysis of data accrued from the SIGGAR study. The SOCCER study cohort (n = 7472) was made up of patients referred to hospital with symptoms suggestive of colorectal cancer and who were registered as potentially eligible for the SIGGAR study (whether they were subsequently randomised or not). Anyone who did not wish to take part in the SIGGAR trials, or withdrew their consent following randomisation, were excluded from the SOCCER study cohort. The aim of the SOCCER study was to determine whether whole colon investigation (WCI) by colonoscopy, CTC (computed tomographic colonography) or barium enema was necessary for all patients with colorectal cancer symptoms, and for which patients a flexible sigmoidoscopy (FS) would suffice. • MRIS - Members and Postings Report The CSPRG at ICL wish to extend this agreement to enable further analysis of the SOCCER data to conduct additional analyses included in the current SOCCER protocol and to be able to respond to questions from the scientific community post-publication. A review of the SOCCER protocol took place in 2020 and it was determined by the study Principal Investigator that the SOCCER protocol does not require any amendments. The CSPRG do not have any plans to conduct additional analyses on the SIGGAR trials; however, it is a requirement of ICL that the CSPRG hold data from all clinical trials for 10 years after the study is closed. • MRIS - Flagging Current Status Report Ethical approval for the SIGGAR study was obtained from Northern and Yorkshire Multi-Centre Research Ethics Committee in January 2004. The SIGGAR study was funded by an NIHR-HTA award (Project No: 02/02/01) from 2003 until June 2011. • MRIS - Cohort Event Notification Report Ethical approval for the SOCCER study as an add-on study using data from the SIGGAR cohort was obtained from Northern and Yorkshire Multi-Centre REC in April 2013. As per the latest progress report, submitted 31 March 2021, favourable ethical opinion continues to apply for the duration of the study. The SOCCER study was originally funded by the NIHR-HTA from January 2013 until the end of November 2015 (Project No: 11/136/120). The SOCCER study continues to be funded by the Cancer Research UK Population Research Committee programme grant until June 2023. No other funders are involved. The funders were not involved in the study design, data collection, data analysis, manuscript preparation, or publication decisions. • MRIS - Cause of Death Report Mortality and cancer information for the patients in the SIGGAR cohort was required to answer the objectives of the SOCCER study as detailed in the SOCCER Protocol v1.0. The primary objective of SOCCER was to investigate the link between patients’ symptoms at presentation and the risk of cancer in the proximal colon, to determine whether there were particular symptoms or symptom combinations which indicated that a patient could be adequately cared for by a distal colon exam (FS) rather than more extensive WCI. The SOCCER study was completed by 17/02/2022 and SIGGAR study was complete by 31/12/2022 as planned. ICL require retention of the data for archiving purposes only. The justification for obtaining and processing data for both the SIGGAR and SOCCER studies is covered by the General Data Protection Regulation Article 6 (1) e, Public task: the processing is necessary for you to perform a task in the public interest or for your official functions, and the task or function has a clear basis in law. ICL is a public research university whose legal status derives from a Royal Charter granted under Letters Patent in 1907. And Article 9 (2) j: processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data. The level of the data held is pseudonymised. The data was minimised as follows: • Limited to a study cohort identified by the CSPRG from ICL – The SIGGAR study cohort consists of 8,484 patients who consented to participate in the study between 2004 - 2007. • The SOCCER study is limited to a study cohort of 7,472 patients identified by the CSPRG from ICL as meeting the following criteria: i. Had received a referral to hospital with symptoms suggestive of colorectal cancer. ii. Were registered as potentially eligible for the SIGGAR study (whether they were subsequently randomised or not). • Limited to data between June 2008 - March 2014. • Identifiable data used for the study was securely destroyed in 2021. Only pseudonymised data has been stored for archiving purposes. Imperial College London is the research sponsor and the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above. The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; ICL is a public research university whose legal status derives from a Royal Charter granted under Letters Patent in 1907. The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. The SIGGAR and SOCCER studies were funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme. No other organisations are acting as a data processor, involved in an advisory capacity or as part of an oversight or steering committee.

Processing activities

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 new or further data will be provided under this version of the agreement. No data will flow to NHS England for the purposes of this Agreement. ICL is the sole data controller and processor for this agreement. Data was processed previously by colleagues at The University of Birmingham who were responsible for the health economic analysis for the SIGGAR studies. Their involvement in the SIGGAR studies ended in 2012. They have subsequently had no involvement in the SOCCER studies. The University of Birmingham therefore no longer have access to or process NHS Digital data. No data will flow of data out of NHS England for the purposes of this Agreement. Data historically requested and approved for the SIGGAR and SOCCER studies from NHS Digital include: The data will not be transferred to any other location. February 2009 The data will be stored on servers at Imperial College London only. -Follow-up of trial cohort with the Office for National Statistics (ONS) and local cancer registries (in addition to NHS Information Centre (NHSIC) to enable CSPRG to obtain cancer and death registrations. Imperial College London backup data on an encrypted portable drive kept in locked storage on premises owned by ICL. -Approval to allow cancer registries to match CSPRG data with the Hospital Episode Statistics (HES) database. There are no plans to access the data. The data will be held for archiving purposes only. Access may be required when interrogation of the data is required in instances where challenges to published outputs are raised. May 2009 The data will not leave England at any time. -Approval for data on randomised patients in SIGGAR (Approval under Section 251 of the NHS Act 2006 – formerly Section 60 of the Health and Social Care Act 2001. Access is restricted to individuals within the Cancer Screening and Prevention Research Group (CSPRG) of Imperial College London who have authorisation from the Principal Investigator. All such individuals are substantive employees of Imperial College London. -Approval to identify study population/control group for SIGGAR using death records and cancer registrations. All personnel accessing the data have been appropriately trained in data protection and confidentiality. -Variables to be supplied by NHS Central Register included; Patient ID variables (Patient’s name, DOB, sex and NHS No.), site of cancer (ICD codes), morphology of cancer (ICD codes), cancer registration no. (to include cancer registry codes), date of death (if applicable) ICD codes and description of causes of death (where applicable). The data was linked to the SOCCER Oracle database held by ICL using a unique patient study number. -Approval to flag records within the study population on the NHSCR (NHSCR – administered by NHSIC). The identifying details for the SOCCER study were stored in a separate database to the linked dataset used for analysis and the identifying details were securely destroyed in 2021. The identifiable data for the SIGGAR study were securely destroyed in May 2023.. All analyses used the pseudonymised dataset. There was no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. -Details to be flagged on the death records included; Date of death, cause of death. Analysis of the data was completed by analysts from Cancer Screening and Prevention Research Group (CSPRG) at Imperial College London for the purposes described above. Analysis is complete and no further processing of the data will occur. -Details to be flagged on the cancer registration records included; Date of cancer diagnosis, site of cancer (ICD codes), morphology of cancer (ICD codes), cancer registration number (to include cancer registry codes). -Approval to trace study population using date of death and cause of death. March 2011 - Received SIGGAR HES dataset May 2011 -Approval to receive data relating to registered but not randomised patients for use in SOCCER (Approval under Section 251 of the NHS Act 2006 – formerly Section 60 of the Health and Social Care Act 2001). -Approval to link data for approximately 4000 patients, who were eligible to take part in the SIGGAR trial but did not do so, with the national cancers and deaths databases held by the ONS and the NHSIC. -Approval to allow patient identifiers to be sent to the NHSIC (now NHS Digital) and ONS by participating hospitals and permit these organisations to match this data with their cancer and death databases. -Approval to use list cleaning service 2015 -CSPRG received data relating to registered but not randomised patients (approved in May 2011) in a pseudonymised form for the SOCCER study (MR1108A; DARS-NIC-291891-Y7J2F). The SIGGAR cohort used in SOCCER consists of two groups of patients: 1) Randomised patients (flagged as MR1108 by NHS Digital) - these patients consented to SIGGAR and did not subsequently withdraw consent (n=5,345 after exclusions). Identifiable data was sent from NHS Hospitals to NHS Digital only. All data sent from NHS Digital to the CSPRG was in a pseudonymised form but included the unique study number. Out of the original 5,448 and following exclusions the number reduced to n=5,345. 2) Registered but not randomised patients (flagged as MR1108A by NHS Digital) - these patients were registered for SIGGAR but were not randomised and were therefore not offered the opportunity to give consent (n=2,030 after exclusions). Identifiable data was sent from the NHS Hospitals to NHS Digital only. NHS Digital flagged these patients and sent only pseudonymised cancers/mortality data to the CSPRG. The legal basis for obtaining this data for SOCCER was Section 251 approval (14/CAG/1043). There was no requirement to minimise data when SIGGAR began (other than to request the right kind of data for the right people and the right time period). The studies covered the whole of England. The data dates as far back as 1971 and goes to at least 2014. The participating NHS hospitals were: • Royal United Hospital, Bath • Bradford Royal Infirmary • Queen Elizabeth Hospital, Birmingham • Charing Cross Hospital and Hammersmith Hospital • Leighton Hospital, Crewe • Royal Cornwall Hospital • Frimley Park Hospital • Royal Lancaster Infirmary/Furness General Hospital • Queen’s Medical Centre/Nottingham City Hospital • University Hospital of North Tees • The Royal Oldham Hospital • John Radcliffe Hospital, Oxford • St Mary’s Hospital, Paddington • Derriford Hospital, Plymouth • Queen Alexandra Hospital, Portsmouth • St Mark’s Hospital, Harrow • Withington Community Hospital/Wythenshawe Hospital, Manchester The data received to date has been analysed to support the NIHR Final Report and publications (see output section). Additional processing in 2019 – 2022 will be restricted to analyses relating to the existing SOCCER study objectives or analyses of the SOCCER database required to respond to questions from the scientific community following the CSPRG’s publication of the SOCCER study results and associated dissemination activities. No additional follow-up of the SOCCER study cohort is anticipated at this time. Explanation of the Data Flow Diagram: In 2015, the CSPRG did not request data on the 10% of patients who originally dissented to take part in the study (834 of the 3,036 registered but not randomised patients -> 2,202), nor the 64 patients who subsequently withdrew consent (5,448 randomised patients -> 5,384). In addition, a further 113 patients were excluded from the registered but not randomised patients as, after reviewing the study records, it was not clear whether these patients may have been approached to provide consent and dissented or may not have been capable of providing informed consent (2,202 -> 2,089). One further patient was excluded from the registered but not randomised patients as duplicate records were found (2,089 -> 2,088). Therefore, the cohort for the SOCCER study was reduced to a subset of 7,472 patients of the SIGGAR study on whom the CSPRG planned to base their analyses . The legal basis for obtaining this data was Section 251. NHS Digital sent pseudonymised cancers and mortality data (including causes of deaths) for the 7,472 patients. During the statistical analysis of the SOCCER study, additional exclusions were applied such that the final eligible numbers were reduced to 7,375 patients (5,345 randomised and 2,030 registered but not randomised patients). Reasons for exclusion were no signs or symptoms at baseline (n=32), duplicate records (n=9) and not being traced by NHS Digital (n=56). The data received in 2015 was uploaded to a secure SOCCER Oracle database and linked to the patients from the SOCCER cohort by the unique patient study number. No patient identifiers are held for any of these patients on this SOCCER database. The pseudonymised cancers and mortality data were not uploaded to the SIGGAR database, which contains the patient identifiable information and therefore any new pseudonymised cancers/mortality data received from NHS Digital were not linked back to the identifiable data on consented patients already held by the CSPRG. The data received in 2015 was combined with data on performed procedures and presenting signs/symptoms collected directly from the participating English NHS Hospitals as part of SOCCER. This data was analysed to determine if there was a correlation between cancer diagnoses/deaths occurring within three years of patients presenting at a clinic with specific symptom(s). For the SIGGAR study, patient identifiable data is stored in a dedicated and secure database server only accessible to specific CSPRG employees - data analyst/developer and the data clerk. Patient identifiers are removed before providing the data to any other employees for analysis. For the SOCCER study, all data is stored in a separate database to the SIGGAR trial data. All data on the SOCCER database is pseudonymised and is only accessible to a limited number of individuals (data analyst/developer and approved study researchers). Access to the database servers is tightly controlled and limited to specific IP client addresses in the CSPRG office. This access is granted only to specific individuals on a study-specific basis and passwords to access the database are changed every 90 days. All access to the system is logged and recorded. The identifiable patient data held by the CSPRG is only accessible by a limited number of staff (Data Analyst/Developer and data clerk) to enable them to manage the collection and secure storage of the data. The data is provided in anonymised or pseudonymised subsets and encrypted using the AES encryption standard, before transferring to other approved employees as required. Data is pseudonymised by replacing normal personal identifiers (such as names, addresses and NHS numbers) by a unique identifier. The key linking the pseudonymised data to the personal information is only accessible by the CSPRG Data Analyst/Developer. All individuals listed in the preceding paragraphs, who have had access to and processed NHS Digital data for the purposes of the SIGGAR and SOCCER studies, are substantive employees of ICL. All individuals handling the data are required to complete training courses in Good Clinical Practice, Information Security Awareness, Records Management, Freedom of Information and Data Protection and Research Data and Confidentiality. The CSPRG has its own Information Governance Policy which provides employees with extensive guidance on the legal obligations involved with sensitive data held within the CSPRG.

Expected output

CSPRG at ICL do not have any plans to conduct additional analyses on the SIGGAR trials at this time. The outputs of the processing are: The SOCCER study is an add-on study to the SIGGAR trials and additional processing is anticipated in the period to 31-Dec-2022 which will generate further publications. No data is being requested under v6. Additional processing will be outlined in a future iteration. Imperial College London have requested a 3-year Data Sharing Agreement in order to comply with their sponsor's 10-year retention policy for research data after study closure and as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines. • A report of findings to the National Institute for Health research (NIHR) in 2015 reporting findings of the SIGGAR study, and a report to NIHR in 2017 with findings of the SOCCER study: https://www.journalslibrary.nihr.ac.uk/hta/hta21660/#/abstract Publications for the SIGGAR and SOCCER studies using the data already received from NHS Digital are: • Reports to the National Library of Medicine in 2013 with findings of CTC vs Colonoscopy http://www.ncbi.nlm.nih.gov/pubmed/23414650 and CTC vs Barium Enema http://www.ncbi.nlm.nih.gov/pubmed/23414648 SIGGAR. • Publication in a peer reviewed journal in December 2018, the British Journal of Cancer: https://www.nature.com/articles/s41416-018-0335-z reporting findings of the SOCCER study. The National Institute for Health Research (NIHR) final report for SIGGAR in July 2015: Halligan S, Dadswell E, Wooldrage K, Wardle J, Von Wagner C, Lilford R, Yao GL, Zhu S, Atkin W. Computed tomographic colonography compared with colonoscopy or barium enema for diagnosis of colorectal cancer in older symptomatic patients: two multicentre randomised trials with economic evaluation (the SIGGAR trials). Health Technol Assess. 2015 Jul;19(54):1-134. doi: 10.3310/hta19540. The report is available online at: https://www.journalslibrary.nihr.ac.uk/hta/hta19540#/abstract. • Presentation of the SOCCER study at the Cancer Research UK Early Diagnosis conference in February 2017 and a presentation at the Saudi-International Colorectal Diseases forum in Riyadh on ‘Colorectal Cancer Surveillance and Early Detection’. The manuscript for the SIGGAR trial of CTC vs colonoscopy is available online at: http://www.ncbi.nlm.nih.gov/pubmed/23414650 (Atkin W, Dadswell E, Wooldrage K, Kralj-Hans I, von Wagner C, Edwards R, Yao G, Kay C, Burling D, Faiz O, Teare J, Lilford RJ, Morton D, Wardle J, Halligan S; SIGGAR investigators. Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial. Lancet. 2013 Apr 6;381(9873):1194-202. doi: 10.1016/S0140-6736(12)62186-2). • Promotion of the published SOCCER manuscript using scial media such as Twitter: @CSPRG_Imperial, https://twitter.com/CSPRG_Imperial The manuscript for the SIGGAR study of CTC vs BE is available online at: http://www.ncbi.nlm.nih.gov/pubmed/23414648 (Halligan S, Wooldrage K, Dadswell E, Kralj-Hans I, von Wagner C, Edwards R, Yao G, Kay C, Burling D, Faiz O, Teare J, Lilford RJ, Morton D, Wardle J, Atkin W; SIGGAR investigators. Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial. Lancet. 2013 Apr 6;381(9873):1185-93. doi: 10.1016/S0140-6736(12)62124-2). The outputs do not contain NHS England data and 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. The CSPRG were also involved in the preparation of a news article that was published on the ICL website in February 2013: http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_14-2-2013-12-20-5. The outputs were communicated to relevant recipients through the following dissemination channels: SOCCER. • Journals The NIHR final report for SOCCER in November 2017: Atkin W, Wooldrage K, Shah U, Skinner K, Brown JP, Hamilton W, Kralj-Hans I, Thompson MR, Flashman KG, Halligan S, Thomas-Gibson S, Vance M, Cross AJ. Is whole-colon investigation by colonoscopy, computerised tomography colonography or barium enema necessary for all patients with colorectal cancer symptoms, and for which patients would flexible sigmoidoscopy suffice? A retrospective cohort study. Health Technol Assess. 2017 Nov;21(66):1-80. doi:10.3310/hta21660. PMID: 29153075. The report can be viewed online at: https://www.journalslibrary.nihr.ac.uk/hta/hta21660/#/abstract. • Public reports In addition, CSPRG produced a manuscript describing the main findings from the SOCCER study for publication in a peer reviewed journal. The manuscript was published online in December 2018: Cross AJ, Wooldrage K, Robbins EC, Pack K, Brown JP, Hamilton W, Thompson MR, Flashman KG, Halligan S, Thomas-Gibson S, Vance M, Saunders BP, Atkin W. Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study. Br J Cancer. 2018 Dec 19. doi: 10.1038/s41416-018-0335-z. [Epub ahead of print]. The manuscript is available online at: https://www.nature.com/articles/s41416-018-0335-z. • Briefing documents provided to NIHR Presentations: • Co-hosted events such as Cancer Research UK Early Diagnosis conference and the Saudi-International Colorectal Diseases forum. In February 2017, a member of the CSPRG gave a presentation on the SOCCER study at the Cancer Research UK (CR-UK) Early Diagnosis conference, discussing the study rationale, methodology, and main findings. • Public promotion of the research using social media such as Twitter: @CSPRG_Imperial, https://twitter.com/CSPRG_Imperial In March 2018, a presentation was given at the Saudi-International Colorectal Diseases forum in Riyadh on ‘Colorectal Cancer Surveillance and Early Detection’. As part of this presentation, the presenter discussed the SOCCER study, to communicate the results with an audience of researchers, scientists, and clinicians. The SIGGAR and SOCCER studies are complete and no further dissemination of outputs will occur. Other: CSPRG have been using social media (i.e. Twitter - @CSPRG_Imperial https://twitter.com/CSPRG_Imperial) to promote the SOCCER manuscript following publication online in December 2018. This has helped to engage and share the findings with a wide audience, including researchers, clinicians, interested groups, and civil society. CSPRG also prepared a lay summary of the findings which was published as an online press release on ICL News in December 2018. This is available at: https://www.imperial.ac.uk/news/189612/quicker-safer-test-could-accurately-detect/. In addition, CSPRG have prepared a blog about the study results for the NIHR website as well as a summary of our findings for the Imperial BRC website, please see: NIHR blog: https://www.nihr.ac.uk/blog/reducing-pressures-on-the-nhs-using-flexible-sigmoidoscopy-to-investigate-bowel-cancer-symptoms/10988 Imperial BRC: https://imperialbrc.nihr.ac.uk/2019/01/10/csprg/ All outputs only contained aggregate level data with small numbers suppressed in line with the Hospital Episode Statistics (HES) Analysis Guide.

Expected measurable benefits

Both the SIGGAR and SOCCER studies were funded by the NIHR-Health Technology Assessment Programme. The study is complete and no further benefits are expected. The SIGGAR HTA Project No: 02/02/01 from January 2003 until June 2011. The SOCCER HTA Project No: 11/136/120 from January 2013 until November 2015. Imperial College London have confirmed that they have funding in place to cover the cost of this extension until at least 2025. The research for the SOCCER study utilised a significant amount of data collected within the SIGGAR trial to determine whether all patients with symptoms suggestive of colorectal cancer require a whole colon examination (i.e. colonoscopy or CTC), or whether flexible sigmoidoscopy, which examines just the rectum and distal colon, might suffice for some patients. The CSPRG found that the risk of cancer in the proximal colon was very low in patients without anaemia and/or abdominal mass, but who presented with rectal bleeding or solely a change in bowel habit to increased frequency. The CSPRG therefore concluded that flexible sigmoidoscopy would suffice for these patients. The SOCCER study also newly demonstrated that the probability of missing proximal cancers can be significantly reduced by adopting a broad definition of anaemia when deciding upon diagnostic investigation. The CSPRG found that 80% of proximal cancer cases could be identified using a broad definition of anaemia (Haemoglobin (Hb) <13 g/dL in men and <12 g/dL in women), compared to 39% using the narrow definition (Hb <11g/dL men; <10g/dL women) with requirement for iron deficiency anaemia. Given the importance of anaemia as a marker for proximal cancer, the SOCCER study concluded that all patients referred with suspected colorectal cancer should have a full blood count, unless an emergency investigation is required. In 2019, the CSPRG disseminated these findings to researchers, clinicians, policy makers, interested groups, and members of the public in order to inform policy and see that the recommendations are incorporated into future National Institute for Health and Care Excellence (NICE) referral guidelines for suspected colorectal cancer. In all dissemination channels, the CSPRG emphasised how the recommendations would benefit the provision of health care. Specifically, the CSPRG described how adoption of the criteria for flexible sigmoidoscopy would save the NHS time and money by minimising the number of unnecessary whole colon examinations. A reduction in demand for whole colon examinations would also mean that endoscopy and radiology resources could be utilised elsewhere; for example, in the NHS bowel cancer screening programme. Furthermore, the CSPRG outlined how the recommendations to take full blood counts and adopt a broad definition of anaemia would minimise the risk of missing proximal cancers.

Benefits reported

The SIGGAR trials showed that computed tomographic colonography (CTC), also known as virtual colonoscopy, was better than barium enema for the diagnosis of colorectal cancer and was significantly better value for money for the NHS. On the basis of preliminary results from the trial, the NHS Bowel Cancer Screening Programme recommended that only CTC should be offered as an alternative to colonoscopy. This is described in the Guidelines for the use of imaging in the NHS Bowel Cancer Screening Programme, Second Edition. NHSBCSP Publication No 5, Sheffield: NHS Cancer Screening Programmes, 2012, available at: https://www.gov.uk/government/collections/bowel-cancer-screening-commission-provide-inform. The findings of this research study contributed to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. Guidelines for the management of patients with symptoms suggestive of colorectal cancer were also updated in light of these findings, which now recommend CTC over barium enema as the first line alternative to colonoscopy: Colorectal cancer: diagnosis and management. NICE guideline (CG131). (Last updated 2014). London: NICE, 2011. https://www.nice.org.uk/guidance/cg131. The use of the data: • helped the system to better understand the health and care needs of populations. • led to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience. • informed planning health services and programmes by identifying the most effective cancer detection methods. • provided a mechanism for checking the quality of care. This includes identifying areas of good practice to learn from, or areas of poorer practice which needed to be addressed. The SIGGAR trials showed that computed tomographic colonography (CTC), also known as virtual colonoscopy, was better than barium enema for the diagnosis of colorectal cancer and was significantly better value for money for the NHS. On the basis of results from the trial, the NHS Bowel Cancer Screening Programme recommended that only CTC should be offered as an alternative to colonoscopy. Guidelines for the management of patients with symptoms suggestive of colorectal cancer were also updated in light of these findings, which now recommend CTC over barium enema as the first line alternative to colonoscopy. [2 paragraphs unchanged] If incorporated into guidelines, this strategy would greatly reduce significantly reduces the number of whole colon investigations (WCIs) performed in patients at low [6 words unchanged] alleviate the burden of WCIs on patients and endoscopy and radiology services. Through publication of findings in appropriate media, the findings of this research added to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients. Clients have taken action based on the information provided to them in order to realise the potential improvement opportunities. For example, on the basis of results from the SIGGAR trial, the NHS Bowel Cancer Screening Programme recommended that only CTC should be offered as an alternative to colonoscopy.

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Objective for processing

The study sponsor for the Special Interest Group Gastrointestinal and Abdominal Radiology (SIGGAR) and Symptoms of Colorectal Cancer Evaluation Research (SOCCER) studies is Imperial College London. London (ICL). The research group responsible for the studies at Imperial ICL is the Cancer Screening and Prevention Research Group (CSPRG). Imperial College London ICL are the data controller and the data processor for the SIGGAR and SOCCER studies. [3 paragraphs unchanged] Prior to the SIGGAR study it was thought likely that virtual colonoscopy [26 words unchanged] was needed to adopt virtual colonoscopy more widely had not been collected. The SIGGAR study aimed to provide the robust evidence needed to support the use of virtual colonoscopy in bowel cancer diagnosis. To achieve this, ICL compared virtual colonoscopy with barium enema or colonoscopy in two randomised trials, to see how effective and safe virtual colonoscopy was compared with the other two tests. The SIGGAR study aimed to provide the robust evidence needed to support the use of virtual colonoscopy in bowel cancer diagnosis. To achieve this, Imperial College London compared virtual colonoscopy with barium enema or colonoscopy in two randomised trials, to see how effective and safe virtual colonoscopy was compared with the other two tests. [2 paragraphs unchanged] Prior to the SOCCER study, scientists had carried out a study which [19 words unchanged] part of the large bowel, and so within reach of the flexible sigmoidoscopy, sigmoidoscopy (a test to look inside the lower part of your large bowel), and that other symptoms are more common in people with cancer in [47 words unchanged] diagnose bowel cancer, and when it is less likely to be effective. The SOCCER study follows on from this SIGGAR work on bowel cancer symptoms. Imperial College London ICL are aiming to provide evidence that is needed to show whether flexible [9 words unchanged] colon examinations for many people. If the results confirm the earlier study, Imperial College London ICL anticipate that this will change how doctors diagnose bowel cancer in their patients based on their symptoms. The SOCCER study was a retrospective analysis of data accrued from the SIGGAR study. The SOCCER study cohort (n = 7472) was made up of patients referred to hospital with symptoms suggestive of [50 words unchanged] study was to determine whether whole colon investigation (WCI) by colonoscopy, CTC (computed tomographic colonography) or barium enema was necessary for all patients with colorectal cancer symptoms, and for which patients a flexible sigmoidoscopy (FS) would suffice. The CSPRG at Imperial College London ICL wish to extend this agreement to enable further analysis of the SOCCER [12 words unchanged] to be able to respond to questions from the scientific community post-publication. A review of the SOCCER protocol took place in 2020 and it was determined by the study Principal Investigator that the SOCCER protocol does not require any amendments. The CSPRG do not have any plans to conduct additional analyses on the SIGGAR trials; however, it is a requirement of ICL that the CSPRG hold data from all clinical trials for 10 years after the study is closed. The CSPRG at Imperial College London would like to continue to keep the SIGGAR cohort flagged as they will be reviewing the SOCCER protocol in 2020 and, if an amendment is made, this may result in the need for additional follow-up data. Ethical approval for the SIGGAR study was obtained from Northern and Yorkshire Multi-Centre Research Ethics Committee in January 2004. The SIGGAR study was funded by an NIHR-HTA award (Project No: 02/02/01) from 2003 until June 2011. The CSPRG do not have any plans to conduct additional analyses on the SIGGAR trials; however, it is a requirement of Imperial College London that the CSPRG hold data from all clinical trials for 10 years after the study is closed. Ethical approval for the SOCCER study as an add-on study using data from the SIGGAR cohort was obtained from Northern and Yorkshire Multi-Centre REC in April 2013. As per the latest progress report, submitted 31 March 2021, favourable ethical opinion continues to apply for the duration of the study. The SOCCER study was originally funded by the NIHR-HTA from January 2013 until the end of November 2015 (Project No: 11/136/120). The SOCCER study continues to be funded by the Cancer Research UK Population Research Committee programme grant until June 2023. No other funders are involved. The funders were not involved in the study design, data collection, data analysis, manuscript preparation, or publication decisions. Ethical approval for the SIGGAR study was obtained from Northern and Yorkshire Multi-Centre REC in January 2004. The SIGGAR study was funded by an NIHR-HTA award (Project No: 02/02/01) from 2003 until June 2011. Ethical approval for the SOCCER study as an add-on study using data from the SIGGAR cohort was obtained from Northern and Yorkshire Multi-Centre REC in April 2013. The SOCCER study was originally funded by the NIHR-HTA from January 2013 until the end of November 2015 (Project No: 11/136/120). The SOCCER study continues to be funded by the Cancer Research UK Population Research Committee programme grant until December 2022. No other funders are involved. The funders were not involved in the study design, data collection, data analysis, manuscript preparation, or publication decisions. [1 paragraph unchanged] The justification for obtaining and processing data for both the SIGGAR and SOCCER studies is covered by the General Data Protection Regulation Article 6 (1e (1) e, Public task: the processing is necessary for you to perform a task [8 words unchanged] functions, and the task or function has a clear basis in law. and ICL is a public research university whose legal status derives from a Royal Charter granted under Letters Patent in 1907. And Article 9 (2j (2) j: processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

Processing activities

All organisations party to this agreement must comply with the Data Sharing [11 words unchanged] that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: i.e.: employees, agents and contractors of the Data Recipient who may have access [5 words unchanged] or further data will be provided under this version of the agreement. Imperial College London ICL is the data processor and sole data controller and processor for this study. agreement. Data was processed previusly previously by colleagues at The University of Birmingham who were responsible for the health economic analysis for the SIGGAR studies. Their involvement in the SIGGAR studies ended in 2012. They have subsequently had no involvement in the SOCCER studies. The University of Birmingham is not involved with the processing of the therefore no longer have access to or process NHS Digital data currently. data. [22 paragraphs unchanged] 1) Randomised patients (flagged as MR1108 by NHS Digital) - these patients [31 words unchanged] CSPRG was in a pseudonymised form but included the unique study number. Out of the original 5,448 and following exclusions the number reduced to n=5,345. [21 paragraphs unchanged] Additional processing in 2019 – 2022 will be restricted to analyses relating [34 words unchanged] No additional follow-up of the SOCCER study cohort is anticipated at this time; however, the CSPRG will be reviewing the SOCCER protocol in 2020 to determine if an amendment is required. If any additional secondary study objectives are identified, the protocol will be updated and submitted for approval to the Research Ethics Committee and the Health Research Authority - Confidentiality Advisory Group. time. [4 paragraphs unchanged] The data received in 2015 was combined with data on performed procedures and presenting signs/symptoms collected directly from the participating English NHS Hospitals as part of SOCCER. This data was analysed to determine if there was a correlation between cancer diagnoses/deaths occurring within three years of patients presenting at a clinic with specific symptom(s). This data was analysed to determine if there was a correlation between cancer diagnoses/deaths occurring within three years of patients presenting at a clinic with specific symptom(s). For the SIGGAR study, patient identifiable data is stored in a dedicated and secure database server only accessible to specific CSPRG employees - data analyst/developer and the data clerk. Patient identifiers are removed before providing the data to any other employees for analysis. The data controller must ensure that there are appropriate contracts and controls in place between the organisation and all persons accessing NHS Digital disseminated data. NHS Digital have the right to audit the controls in place under the data sharing agreement. There are currently no active contracts with third party data processers. For the SOCCER study, all data is stored in a separate database to the SIGGAR trial data. All data on the SOCCER database is pseudonymised and is only accessible to a limited number of individuals (data analyst/developer and approved study researchers). For the SIGGAR study, patient identifiable data is stored in a dedicated and secure database server only accessible to specific CSPRG employees - data analyst/developer and the data clerk. Patient identifiers are removed before providing the data to any other employees for analysis. For the SOCCER study, all data is stored in a separate database to the SIGGAR trial data. All data on the SOCCER database is pseudonymised and is only accessible to a limited number of individuals (data analyst/developer and approved study researchers). Access to the database servers is tightly controlled and limited to specific [27 words unchanged] every 90 days. All access to the system is logged and recorded. [1 paragraph unchanged] All individuals handling the data are required to complete training courses in Good Clinical Practice, Information Security Awareness, Records Management, Freedom of Information and Data Protection and Research Data and Confidentiality. The CSPRG has its own Information Governance Policy which provides employees extensive guidance on the legal obligations involved with sensitive data held within the CSPRG. All individuals listed in the preceding paragraphs, who have had access to and processed NHS Digital data for the purposes of the SIGGAR and SOCCER studies, are substantive employees of ICL. All individuals handling the data are required to complete training courses in Good Clinical Practice, Information Security Awareness, Records Management, Freedom of Information and Data Protection and Research Data and Confidentiality. The CSPRG has its own Information Governance Policy which provides employees with extensive guidance on the legal obligations involved with sensitive data held within the CSPRG.

Expected output

No new or further data will be provided under this version of the agreement. CSPRG at ICL do not have any plans to conduct additional analyses on the SIGGAR trials at this time. The Cancer Screening and Prevention Research Group (CSPRG) at Imperial College London do not have any plans to conduct additional analyses on the SIGGAR trials at this time. The SOCCER study is an add-on study to the SIGGAR trials and additional processing is anticipated in the period to 31-Dec-2022 which will generate further publications. No data is being requested under v6. Additional processing will be outlined in a future iteration. Imperial College London have requested a 3-year Data Sharing Agreement in order to comply with their sponsor's 10-year retention policy for research data after study closure and as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines. The SOCCER study is an add-on study to the SIGGAR trials and additional processing is anticipated in the period to 31-Dec-2022 which will generate further publications. [5 paragraphs unchanged] The CSPRG were also involved in the preparation of a news article that was published on the Imperial College London ICL website in February 2013: http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_14-2-2013-12-20-5. [4 paragraphs unchanged] In February 2017, a member of the CSPRG gave a presentation on [8 words unchanged] (CR-UK) Early Diagnosis conference, discussing the study rationale, methodology, and main findings. In March 2018, a presentation was given at the Saudi-International Colorectal Diseases forum in Riyadh on ‘Colorectal Cancer Surveillance and Early Detection’. As part of this presentation, the presenter discussed the SOCCER study, to communicate the results with an audience of researchers, scientists, and clinicians. In March 2018, a presentation was given at the Saudi-International Colorectal Diseases forum in Riyadh on ‘Colorectal Cancer Surveillance and Early Detection’. As part of this presentation, the presenter discussed the SOCCER study, to communicate the results with an audience of researchers, scientists, and clinicians. [1 paragraph unchanged] CSPRG have been using social media (i.e. Twitter) Twitter - @CSPRG_Imperial https://twitter.com/CSPRG_Imperial) to promote the SOCCER manuscript following publication online in December 2018. This [8 words unchanged] with a wide audience, including researchers, clinicians, interested groups, and civil society. CSPRG also prepared a lay summary of the findings which was published as an online press release on Imperial College London News in December 2018. This is available at: https://www.imperial.ac.uk/news/189612/quicker-safer-test-could-accurately-detect/. In addition, CSPRG have prepared a blog about the study results for the NIHR website as well as a summary of our findings for the Imperial BRC website. CSPRG also prepared a lay summary of the findings which was published as an online press release on ICL News in December 2018. This is available at: https://www.imperial.ac.uk/news/189612/quicker-safer-test-could-accurately-detect/. In addition, CSPRG have prepared a blog about the study results for the NIHR website as well as a summary of our findings for the Imperial BRC website, please see: NIHR blog: https://www.nihr.ac.uk/blog/reducing-pressures-on-the-nhs-using-flexible-sigmoidoscopy-to-investigate-bowel-cancer-symptoms/10988 Imperial BRC: https://imperialbrc.nihr.ac.uk/2019/01/10/csprg/ [1 paragraph unchanged]

Expected measurable benefits

No new or further data will be provided under this version of the agreement. [3 paragraphs unchanged] Currently SOCCER is funded through the Cancer Research UK Population Research Committee grant until December 2022. Imperial College London have confirmed that they have funding in place to cover the cost of this extension until at least 2025. [2 paragraphs unchanged] In 2019, the CSPRG disseminated these findings to researchers, clinicians, policy makers, interested groups, and members of the public in order to influence inform policy and see that the recommendations are incorporated into future National Institute for Health and Care Excellence (NICE) referral guidelines for suspected colorectal cancer. [1 paragraph unchanged] The SOCCER study dataset has the potential for use by a PhD student in the future - if any additional research questions are identified that are not already included in the current SOCCER study protocol, the CSPRG will go through the amendment process with REC / HRA-CAG / NHS Digital.

Unchanged: Benefits reported.

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

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