Frequency of follow-up for patients with low-, intermediate- and high-risk colorectal adenomas

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

Datasets: + NDRS Cancer Registrations

Objective for processing

[3 paragraphs unchanged] The study has utilized this baseline investigation, plus subsequent colonoscopy and pathology [21 words unchanged] study cohort. The hospital data was combined with data received from NHS Digital England (NHSE) on colorectal cancer incidence and deaths, to ensure all incidences of colorectal cancer were reported for the study cohort. [3 paragraphs unchanged] To achieve these objectives the following NHS England Data (NHSE) sets have been disseminated previously The following National Disease Registration Service (NDRS) data was previously disseminated under Public Health England (PHE) under DARS-NIC-656814 -NDRS- Cancer Registrations The following NHSE data was previously disseminated under DARS-NIC-147827 -MRIS - Flagging Current Status Report -MRIS - Cohort Event Notification Report -MRIS - List Cleaning Report -MRIS - Cause of Death Report -MRIS - Members and Postings Report [11 paragraphs unchanged] Cancer staging data was required to complete the health economic analysis for [8 words unchanged] to obtain this data. In order for this data to be obtained NHS Digital NHSE needed to be able to share the study identifiers, NHS number and [58 words unchanged] PHE or one of its successors to be listed within this Agreement. The study has support under section 251 of the NHS Act 2006 to enable the common law duty of confidentiality to be temporarily lifted so that confidential patient information can be processed without consent. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

Processing activities

On receipt of the cancer and mortality data from NHS Digital on the All Adenomas study cohort, CSPRG formatted it in accordance with the existing All Adenomas study hospital database schema before uploading it to the All Adenomas study hospital study database. All CSPRG staff members who have access to the data are substantive employees of Imperial College London or PhD students. As PhD students at Imperial College London are not held to the same contractual clauses as staff, the CSPRG have implemented a ‘student data access agreement’ which they must complete to indicate their obligations for processing personal data. No further flows of data will occur under this data sharing agreement. Historically, on receipt of the cancer and mortality data from NHS England on the All Adenomas study cohort, CSPRG formatted it in accordance with the existing All Adenomas study hospital database schema before uploading it to the All Adenomas study hospital study database. All CSPRG staff members who have access to the data are substantive employees of Imperial College London or PhD students. As PhD students at Imperial College London are not held to the same contractual clauses as staff, the CSPRG have implemented a ‘student data access agreement’ which they must complete to indicate their obligations for processing personal data. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The Data will be accessed by authorised personnel via remote access and onsite at ICL. The Data will remain on the servers at ICL at all times. The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract. For remote access: - Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA; - Personnel are both prohibited and technically prevented from downloading or copying NHSE data to local devices; - Access controls granting users the minimum level of access required are in place; - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; - Multifactor authentication (MFA) is required for remote access; - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; - All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this agreement) and complies with the organisation’s remote access policy. The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose). [13 paragraphs unchanged] The Data will not leave: England/Wales at any time. Analysts/researchers from the CSPRG at ICL will only process the data for the purposes described above.

Expected output

The results of the All Adenomas study have been and will continue to be published in high-impact journals and at scientific conferences. The publication of the outcomes of this study in international journals will ensure that this data is available for future validation of the recommendations from the study and potential uptake into revised guidelines for surveillance. Update as provided from Imperial College London’s Annual Confirmation Report 8th January 2024 The All Adenomas study is a continuation and expansion of the 2006 Intermediate Adenomas (IA) study, funded by the National Institute for Health Research Health Technology Assessment (NIHR-HTA) following a commissioned call (reference 04/01/33) to investigate the most suitable frequency of follow-up for patients with intermediate-risk adenomas detected during colonoscopy. The CSPRG were awarded further funding by the NIHR-HTA in March 2017 (reference 15/80/13) to expand the remit of the IA study to investigate the same endpoints in all adenoma risk-groups, not just the intermediate-risk group, and the IA study protocol was amended to the 'All Adenomas study'. [1 paragraph unchanged] The IA study NIHR Final Report was published in May 2017: Atkin [15 words unchanged] effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade intermediategrade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations. Health Technol Assess 2017;21(25). [2 paragraphs unchanged] The results of the All Adenomas study have been and will continue to be published in high-impact journals and presented at scientific conferences and patient and public engagement events. The publication of the outcomes of this study in international journals will ensure that this data is available for future validation of the recommendations from the study and potential uptake into revised guidelines for surveillance. [1 paragraph unchanged] The NIHR Final Report is at pre-press for publication in the NIHR-Health Technology Assessment (HTA) Journals Library in early 2022. The All Adenomas study NIHR Final Report was published in the NIHR-Health Technology Assessment (HTA) Journals Library in May 2022: Cross AJ*, Robbins EC, Pack K, Stenson I, Kirby PL, Patel B, Rutter MD, Veitch AM, Saunders BP, Little M, Gray A, Duffy SW, Wooldrage K. Colonoscopy surveillance following adenoma removal to reduce the risk of colorectal cancer: a retrospective cohort study. Health Technol Assess 2022 May;26(26) doi: 10.3310/OLUE3796. The Chief Investigator presented results in a World Endoscopy Organization webinar talk on 2 December 2021, ‘PCCRC 2021 'PCCRC & Quality in Colonoscopy + Surveillance after Colorectal Neoplasia – - The evidence on the effectiveness of surveillance: What is known, evidence gaps, future research’ https://www.worldendo.org/resources/weo-video-library/crc-sc-expert-working-group-webinar-recordings/. research' (https://www.worldendo.org/resources/weo-video-library/crc-sc-expertworking-group-webinar-recordings/). [2 paragraphs unchanged] • - Cross AJ*, Robbins EC, Pack K, Stenson I, Patel B, Rutter MD, [13 words unchanged] in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy postpolypectomy surveillance guidelines. Gut. 2021 Mar 5:gutjnl-2020-323411. Doi: 10.1136/gutjnl-2020-323411. A visual abstract was also published on Gut website: https://gut.bmj.com/pages/wp-content/uploads/sites/25/2021/11/Kalfors-et-al-Visual-Abstract.png • - Harewood R*, Wooldrage K, Robbins EC, Kinross J, von Wagner C, Cross [8 words unchanged] cancer incidence: a retrospective cohort study. Br J Cancer. 2022 Feb 11. Doi: 10.1038/s41416-022-01719-4. Doi:10.1038/s41416-022-01719-4. Another paper, ‘Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicentre, retrospective cohort study’, has been accepted by Endoscopy and is due for publication in 2022 along with an accompanying video to appear on the Endoscopy website. - Cross AJ*, Robbins EC, Pack K, Stenson I, Rutter MD, Veitch AM, Saunders BP, Duffy SW, Wooldrage K. Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicenter, retrospective cohort study. Endoscopy. 2022 Oct;54(10):948-958. doi: 10.1055/a-1795-4673. In addition, an abstract was presented at the British Society for Gastroenterology Virtual Campus Conference in Jan 2021 and published online by Gut (https://gut.bmj.com/content/70/Suppl_1): Harewood R*, Wooldrage K, Kinross J, von Wagner C, Cross AJ. O56 (Oral presentation). Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk? Doi:10.1136/gutjnl-2020-bsgcampus.56 BSG Virtual campus conference Jan 2021. In addition: The University of Oxford produced a chapter report for the NIHR Final Report in the form of summary statistics. They have also submitted abstracts/manuscripts to cancer-specific and/or health economics conferences/journals in order to disseminate the results of the health economic research independently. - An abstract was presented at the British Society for Gastroenterology Virtual Campus Conference in Jan 2021 and published online by Gut (https://gut.bmj.com/content/70/Suppl_1): Harewood R*, Wooldrage K, Kinross J, von Wagner C, Cross AJ. O56 (Oral presentation). Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk? Doi:10.1136/gutjnl-2020-bsgcampus.56 BSG Virtual campus conference Jan 2021. - Emma Robbins, PhD student, gave an invited talk on 'Who deserves surveillance? Selection of patients at the highest risk after polyp removal' at the World Endoscopy Organization (WEO) Colorectal Cancer (CRC) Screening Committee (CRC) Expert Working Group Sessions and Plenary Meeting on 13 October 2023 in Copenhagen, Denmark (https://worldendo.org/events/weo-crc-sc-plenary-meeting-ewg-sessions). - The University of Oxford produced a chapter report for the NIHR Final Report on the results of their health economic research in the form of summary statistics. [1 paragraph unchanged] The study has a panel of four Public Patient Representatives (PPRs; 2 [30 words unchanged] Adenomas study (March 2018); and (2) a workshop to co-design the remaining PPI/E Patient and Public Involvement and Engagement (PPIE) activities for the study (April 2018). When the study results were available, [25 words unchanged] 2019); and (2) the All Adenomas PPI Dissemination Workshop (November 2019). There are were no further updates since as PPIE events possible during the study have not been able to convene further workshops with PPRs COVID-19 pandemic and other activities since the Coronavirus pandemic began. There are no PPRs lockdowns, and none planned at this current time but if further funding is obtained for a substantive period then there will be further Patient and Public Involvement and Engagement. time. Communication channels the CSPRG has utilised to proactively share study results directly with patients and the public include: • - Study website https://csprg.org.uk/ia/ • - Dissemination of study outcomes and results via official CSPRG Twitter X (formerly Twitter) account @CSPRG_Imperial • - Patient event 16 Jul 2020 – The Head of CSPRG when the Chief Investigator gave a virtual talk and Q&A session on ‘Colorectal 'Colorectal cancer surveillance’ surveillance' for Maggie’s Maggie's Centre, Imperial College London, to patient, public and research audiences.

Expected measurable benefits

[1 paragraph unchanged] • - those at sufficiently low risk of colorectal cancer after adenoma removal to render colonoscopy surveillance unnecessary; • - those most likely to benefit from colonoscopy surveillance; • - the minimum surveillance required to afford adequate protection from colorectal cancer, and when surveillance can be safely stopped. The number of follow-up colonoscopies carried out is stretching healthcare resources and [12 words unchanged] possible that too many follow-up colonoscopies are being carried out, putting patients and at risk and resulting in the NHS incurring potentially unnecessary costs. [1 paragraph unchanged] • - Research that will include looking at the ongoing need for surveillance beyond the first surveillance colonoscopy. • - Research that also includes on optimising surveillance strategies for patients with an increased risk of colorectal cancer. cancer

Benefits reported

Feb 22 update: Benefits of the All Adenomas study are yet to be fully realised; however, the generation of the IA study database enabled the CSPRG to obtain additional funding from the NIHR-HTA to extend the analysis to include all three risk groups (low-, intermediate- and high-risk) as the 'All Adenomas study'. Benefits are yet to be fully realised; however, the generation of the IA study database enabled the CSPRG to obtain additional funding from the NIHR-HTA to extend the analysis to include all three risk groups (low-, intermediate- and high-risk) as the 'All Adenomas study'. The study results contributed evidence to support the update of the post-polypectomy surveillance guidelines carried out in the UK for the British Society for Gastroenterology (BSG), The Association for Coloproctology of Great Britain and Ireland (ACPGBI) and PHE. These new guidelines were published in 2020 and were supported by high quality data from this study to make sure there is appropriate use of limited colonoscopy resources (Imperial College London anticipate 80% fewer surveillance colonoscopies required under new guidelines) that will limit risks to patients and reduce costs for the NHS. Additional analyses of this data are ongoing; for example, mortality within each of the risk groups is being investigated. The study results contributed evidence to support the update of the surveillance guidelines carried out in the UK for the British Society for Gastroenterology (BSG), The Association for Coloproctology of Great Britain and Ireland (ACPGBI) and PHE. These new guidelines were published in 2020 and were supported by high quality data from this study to make sure there is appropriate use of limited colonoscopy resources (Imperial College London anticipate 80% fewer surveillance colonoscopies required under new guidelines) that will limit risks to patients and reduce costs for the NHS. Additional analyses of this data are ongoing; for example, mortality within each of the risk groups is being investigated. This study determined that colorectal cancer risk was no higher in some low- and intermediate-risk patients than in the general population. These patients likely do not need follow-up colonoscopy and could be managed by screening. In the case of higher-risk patients, who even after adenoma removal have a higher colorectal cancer risk than the general population, follow-up colonoscopies are necessary and cost-effective. This study determined that colorectal cancer risk was no higher in some low- and intermediate-risk patients than in the general population. These patients may not need as many follow-up colonoscopies as recommended. In the case of higher-risk patients, who even after adenoma removal have a higher colorectal cancer risk than the general population, follow-up colonoscopies are necessary and cost-effective. This study is the first to use colorectal cancer incidence as an outcome to evaluate post-polypectomy surveillance requirements. This study provides new, high-quality data on long-term colorectal cancer risk following adenoma removal. The large size of the cohort, longevity of follow-up, and contemporary data mean that the results generated will have enduring value as a referent for future interventions for minimising colorectal cancer risks in adenoma patients. This study is the first to use colorectal cancer incidence as an outcome to evaluate adenoma surveillance requirements. This study provides new, high-quality data on long-term colorectal cancer risk following adenoma removal. The large size of the cohort, longevity of follow-up, and contemporary data mean that the results generated will have enduring value as a referent for future interventions for minimising colorectal cancer risks in adenoma patients.

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

Objective for processing

[11 paragraphs unchanged] 1. To extend the analysis to investigate the ideal frequency of follow-up [11 words unchanged] intermediate- or high- risk, as defined by the UK adenoma surveillance guidelines, 2002), 2002 & 2020), using the same study cohort. [3 paragraphs unchanged] The health economic analysis will would be conducted by the University of Oxford to determine the cost implications [20 words unchanged] high-risk adenoma groups (either an increase or decrease). The University of Oxford have been were asked by Imperial to do the economic analysis which will result in the provision of a chapter for the proposed report plus any associated publications. [1 paragraph unchanged] 2019 amendment to this agreement: Civil Registration Mortality Data was required to ensure all incidences of deaths were reported and whether this was due to colorectal cancer. Cancer staging data is was required to complete the health economic analysis for the All Adenomas study. CSPRG has been working worked with PHE to obtain this data. In order for this data to be obtained NHS Digital need needed to be able to share the study identifiers, NHS number and date [6 words unchanged] identify the subcohort of the All Adenomas study who had baseline adenomas. As such PHE, who are no longer a legal entity, were listed a data processor within the previous iteration of this Agreement, as all the necessary data has now been obtained PHE there is no longer a reason for PHE or one of its successors to be listed within this Agreement. The data to be provided by PHE on the subcohort includes the tumour staging and treatment received for those people reported to have a cancer of the digestive system, with minimal descriptive information on the cancer to ensure accurate linkage of the data to the All Adenomas study database.

Processing activities

[1 paragraph unchanged] Staff For information, processing by the University of Oxford is now finished as their task is complete and therefore the data that the University of Oxford held has now been destroyed. For historic purposes, staff accessing the data at the University of Oxford are were all substantive employees of the University of Oxford. [1 paragraph unchanged] The data will be was pseudonymised and given to CSPRG statisticians for analysis and to give the required outputs for reporting and publication in accordance with the NIHR-HTA terms and conditions. [1 paragraph unchanged] A sub-set of the pseudonymised data will be was shared with the University of Oxford for the purpose of conducting the health economic analysis. The sub set will be was minimised by the CSPRG study team before sharing with Oxford to ensure that only those fields that are essential for the analysis are were sent. [1 paragraph unchanged] The data received from the CSPRG will be was used to estimate resource use (for example, number of healthcare appointments), costs, and health outcomes (for example, number of adenomas and cancers detected). This will involve involved rearranging the data; applying unit cost estimates and resource use estimates from external sources; and producing summary statistics. Secondly, the University of Oxford will estimate estimated long-term economic outcomes by fitting statistical models to the data received. The statistical models will be combined with unit costs and quality of life estimates to estimate long-term [17 words unchanged] by the CSPRG, and cancer stage as provided in the linked data). The data will was not be further linked with other patient level datasets for the analysis by the University of Oxford beyond what is provided by the CSPRG. Under this Agreement, the University of Oxford have now completed their task and as such, the data that was provided to the University of Oxford is now destroyed. In order to receive cancer staging data from PHE. PHE, CSPRG will provide provided NHS Digital with the unique study identifiers for the 30,259 people who had adenomas detected at their baseline investigation. NHS Digital will then provide provided the unique study ID, NHS number and date of birth to PHE for this cohort. PHE will use used the information provided by NHS Digital to identify the participants with cancers and send CSPRG the corresponding staging information (without the NHS number or date of birth). PHE, who are no longer a legal entity, or its successors no longer have access to the identifying information provided by NHS Digital. [2 paragraphs unchanged] There will be not no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement.

Expected output

The primary outcomes of the Intermediate Adenoma study have been published in the Lancet Oncology on the 25th April 2017 (electronically); https://doi.org/10.1016/S1470-2045(17)30187-0. The results of the All Adenomas study have been and will continue to be published in high-impact journals and at scientific conferences. The publication of the outcomes of this study in international journals will ensure that this data is available for future validation of the recommendations from the study and potential uptake into revised guidelines for surveillance. The Intermediate Adenoma study NIHR Final Report was published in May 2017 [Atkin W, Brenner A, Martin J, Wooldrage K, Shah U, Lucas F, et al. The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations. Health Technol Assess 2017;21(25)]. The primary outcomes of the IA study were published in the Lancet Oncology on the 25th April 2017 (electronically): Atkin W*, Wooldrage K, Brenner A, Martin J, Shah U, Perera S, Lucas F, Brown JP, Kralj-Hans I, Greliak P, Pack K, Wood J, Thomson A, Veitch A, Duffy SW, Cross AJ. Adenoma surveillance and colorectal cancer incidence: a retrospective, multicentre, cohort study. Lancet Oncol. 2017 Jun;18(6):823-834. https://doi.org/10.1016/S1470-2045(17)30187-0. Secondary outcomes of the IA study will be submitted to journals such as the Lancet Oncology, Gut or Gastroenterology. The IA study NIHR Final Report was published in May 2017: Atkin W, Brenner A, Martin J, Wooldrage K, Shah U, Lucas F, et al. The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations. Health Technol Assess 2017;21(25). Secondary outcomes of the IA study have been published in Endoscopy: Robbins EC, Wooldrage K, Stenson I, Pack K, Duffy S, Weller D, Levin T, Conell C, Wright S, Nickerson C, Martin J, Cross AJ*. Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study. Endoscopy. 2021 Apr;53(4):402-410. doi: 10.1055/a-1217-0155. [1 paragraph unchanged] The All Adenomas study: The primary outcomes of the All Adenomas study were published in the journal Gut in 2020: Cross AJ*, Robbins EC, Pack K, Stenson I, Kirby PL, Patel B, Rutter MD, Veitch AM, Saunders BP, Duffy SW, Wooldrage K. Long-term colorectal cancer incidence after adenoma removal and the effects of surveillance on incidence: a multicentre, retrospective, cohort study. Gut 2020 Jan 17. pii: gutjnl-2019-320036. doi.org/10.1136/gutjnl-2019-320036. The results of the All Adenomas study will be written up for publication in similar high-impact, peer-reviewed journals and submitted for presentation at a scientific conference in 2019. The publication of the outcomes of this study in international journals and presentation at international conferences during 2019 will ensure that this data is available for future validation of the recommendations from the study and potential uptake into revised guidelines for surveillance. The NIHR Final Report is at pre-press for publication in the NIHR-Health Technology Assessment (HTA) Journals Library in early 2022. Of note, the CSPRG have been working with the British Society for Gatsroenterology surveillance guidelines group to ensure our data is used, when available, to inform the update of the adenomas surveillance guidelines for the UK. The Chief Investigator presented results in a World Endoscopy Organization webinar talk on 2 December 2021, ‘PCCRC & Quality in Colonoscopy + Surveillance after Colorectal Neoplasia – The evidence on the effectiveness of surveillance: What is known, evidence gaps, future research’ https://www.worldendo.org/resources/weo-video-library/crc-sc-expert-working-group-webinar-recordings/. The University of Oxford will produce reports in the form of summary statistics, and submit abstracts/manuscripts to cancer-specific and/or health economics conferences/journals in order to disseminate the results of the health economic research independently. The CSPRG worked with the British Society for Gastroenterology surveillance guidelines group to ensure our All Adenomas study data was used to inform the 2020 update of the post-polypectomy surveillance guidelines for the UK, published in Gut in 2020 (https://doi.org/10.1136/gutjnl-2019-319858) and endorsed by the British Society of Gastroenterology, the Association of Coloproctology of Great Britain and Ireland, and Public Health England. Secondary outcomes of the All Adenomas study have been published, including: • Cross AJ*, Robbins EC, Pack K, Stenson I, Patel B, Rutter MD, Veitch AM, Saunders BP, Duffy SW, Wooldrage K. Colorectal cancer risk following polypectomy in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy surveillance guidelines. Gut. 2021 Mar 5:gutjnl-2020-323411. Doi: 10.1136/gutjnl-2020-323411. A visual abstract was also published on Gut website: https://gut.bmj.com/pages/wp-content/uploads/sites/25/2021/11/Kalfors-et-al-Visual-Abstract.png • Harewood R*, Wooldrage K, Robbins EC, Kinross J, von Wagner C, Cross AJ. Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study. Br J Cancer. 2022 Feb 11. Doi: 10.1038/s41416-022-01719-4. Another paper, ‘Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicentre, retrospective cohort study’, has been accepted by Endoscopy and is due for publication in 2022 along with an accompanying video to appear on the Endoscopy website. In addition, an abstract was presented at the British Society for Gastroenterology Virtual Campus Conference in Jan 2021 and published online by Gut (https://gut.bmj.com/content/70/Suppl_1): Harewood R*, Wooldrage K, Kinross J, von Wagner C, Cross AJ. O56 (Oral presentation). Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk? Doi:10.1136/gutjnl-2020-bsgcampus.56 BSG Virtual campus conference Jan 2021. The University of Oxford produced a chapter report for the NIHR Final Report in the form of summary statistics. They have also submitted abstracts/manuscripts to cancer-specific and/or health economics conferences/journals in order to disseminate the results of the health economic research independently. [1 paragraph unchanged] The study now have has a confirmed panel of four Public Patient Representatives (PPRs; 2 men, 2 women) who have agreed to work worked with the CSPRG with the interpretation to interpret and communication of communicate the study results. Two meetings were held with the PPRs in 2018: (1) an Introduction to the All Adenomas study (16th March 2018) (March 2018); and (2) a workshop to co-design the remaining PPI/E activities for the study (April 2018). Once When the study results are available they will initiate were available, two meeting were held in 2019 to share the remaining PPI/E activities results and develop a dissemination plan: (1) All Adenomas Study Patient Public Involvement Results Meeting (June 2019); and (2) the dissemination plan All Adenomas PPI Dissemination Workshop (November 2019). There are no further updates since as the study have not been able to convene further workshops with them. PPRs and other activities since the Coronavirus pandemic began. There are no PPRs planned at this current time but if further funding is obtained for a substantive period then there will be further Patient and Public Involvement and Engagement. Communication channels the CSPRG has utilised to proactively share study results directly with the public include: • Study website https://csprg.org.uk/ia/ • Dissemination of study outcomes and results via official CSPRG Twitter account @CSPRG_Imperial • Patient event 16 Jul 2020 – The Head of CSPRG gave a virtual talk and Q&A on ‘Colorectal cancer surveillance’ for Maggie’s Centre, Imperial College London, to patient, public and research audiences.

Expected measurable benefits

The IA study was required to determine the extent to which the current UK adenoma surveillance guidelines gives rise to unnecessary colonoscopies in people with intermediate-risk adenomas; the elimination of which would minimise risks of complications associated with the procedure and worry to patients, plus ease the current unsustainable economic and workforce pressures on the NHS. The All Adenomas study estimates long-term colorectal cancer risk in patients following the removal of adenomas, in the presence and absence of surveillance; this has the potential to benefit patients and the NHS by identifying: For the All Adenomas study, by quantifying CRC risk in all adenoma patients with and without surveillance, the study will benefit patients and the NHS by identifying: • those at sufficiently low risk of colorectal cancer after adenoma removal to render colonoscopy surveillance unnecessary; • those at sufficiently low risk of CRC after adenoma diagnosis at colonoscopy to render surveillance unnecessary; • those most likely to benefit from colonoscopy surveillance; • those most likely to benefit from colonoscopic surveillance; • the minimum surveillance required to afford adequate protection from colorectal cancer, and when surveillance can be safely stopped. • the minimum surveillance required to afford adequate protection from CRC, and when it can be safely stopped. The number of follow-up colonoscopies carried out is stretching healthcare resources and each procedure carries a small risk of complications for patients. It is possible that too many follow-up colonoscopies are being carried out, putting patients and risk and resulting in the NHS incurring potentially unnecessary costs. This study will be the first to use CRC incidence as an outcome to evaluate adenoma surveillance requirements, and through its large size and longevity of follow-up, would provide new evidence of long-term CRC risk in all adenoma patients. Because the dataset is current, the results generated could have enduring value as a reference against which future interventions for minimising CRC risks in adenoma patients could be compared. CSPRG PhD research supported by the study includes: Further research is needed now because: • Research that will include looking at the ongoing need for surveillance beyond the first surveillance colonoscopy. 1. The increasing number of referrals for surveillance colonoscopy since the implementation of the Bowel Cancer Screening Programme (BCSP), is overwhelming NHS endoscopy resources (time, staff and costs); surveillance now constitutes ~20% of all colonoscopies performed (26). • Research that also includes optimising surveillance strategies for patients with an increased risk of colorectal cancer. 2. Surveillance colonoscopies may be too frequent or unnecessary in some subgroups: (a) The UK adenoma surveillance guideline (UK-ASG) has not changed since its implementation in 2002 due to lack of new evidence (15, 23, 24). Yet, the quality of colonoscopy has improved substantially since the introduction of national colonoscopy quality audits and modern high-definition endoscopes (26). As a result, interval cancer rates (those diagnosed within 3 years following colonoscopy) decreased by ~30% between 2001 and 2007 (32). Nowadays, more thorough baseline colonoscopies may be finding more adenomas (26) thereby increasing a patient’s risk classification according to existing UK-ASG definitions, whilst the more efficient removal of adenomas may be substantially lowering their colorectal cancer (CRC) risk. Hence, improved colonoscopy standards may significantly alter the population classified within each risk-group, providing strong justification for now reviewing risk-group definitions. (b) New evidence from our study of intermediate-risk (IR) patients has shown that adequate CRC protection can be achieved with less than the currently recommended surveillance. The study identified a subgroup (up to 50% of IR patients) in which CRC risk is so low that further surveillance after the first follow-up is not warranted. The study also justified using CRC risk as a more valid measure than advanced adenoma (AA) of the need for regular colonoscopy surveillance (HTA 04/033, report submitted (1)). As a result of increasing endoscopy demand, it is vital that risk groups are evaluated based on CRC outcome, rather than AA (which inevitably overestimates risk).

Benefits reported

Benefits are yet to be fully realised however the generation of the Intermediate Adenoma database has enabled the CSPRG to successfully receive additional funding from the National Institute for Health Research-Health Technology Assessment to extend the analysis to include both the low- and high-risk adenoma groups, as the 'All Adenomas study'. Feb 22 update: The outcomes of the All adenomas study will help to inform the update of the UK Adenoma Surveillance Guideline, which have not been updated since 2002. Benefits are yet to be fully realised; however, the generation of the IA study database enabled the CSPRG to obtain additional funding from the NIHR-HTA to extend the analysis to include all three risk groups (low-, intermediate- and high-risk) as the 'All Adenomas study'. The study results contributed evidence to support the update of the surveillance guidelines carried out in the UK for the British Society for Gastroenterology (BSG), The Association for Coloproctology of Great Britain and Ireland (ACPGBI) and PHE. These new guidelines were published in 2020 and were supported by high quality data from this study to make sure there is appropriate use of limited colonoscopy resources (Imperial College London anticipate 80% fewer surveillance colonoscopies required under new guidelines) that will limit risks to patients and reduce costs for the NHS. Additional analyses of this data are ongoing; for example, mortality within each of the risk groups is being investigated. This study determined that colorectal cancer risk was no higher in some low- and intermediate-risk patients than in the general population. These patients may not need as many follow-up colonoscopies as recommended. In the case of higher-risk patients, who even after adenoma removal have a higher colorectal cancer risk than the general population, follow-up colonoscopies are necessary and cost-effective. This study is the first to use colorectal cancer incidence as an outcome to evaluate adenoma surveillance requirements. This study provides new, high-quality data on long-term colorectal cancer risk following adenoma removal. The large size of the cohort, longevity of follow-up, and contemporary data mean that the results generated will have enduring value as a referent for future interventions for minimising colorectal cancer risks in adenoma patients.

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.