Stockton-on-tees, United Kingdom

Examining the Benefit of Graduated Compression Stockings in the Prevention of vEnous Thromboembolism in Low-risk Surgical Patients

Axillary Management in Breast Cancer Patients with Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease. Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. Methods: Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years. Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years. Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness. Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years. Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated. Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

It's Not JUST Idiopathic Pulmonary Fibrosis Study

The overall aims of this study are - Identify biomarkers and gene expression profiles that determine progressive fibrotic lung disease regardless of aetiology - To prospectively assess biomarkers which predict progressive fibrosis in patients with fibrosing lung disease of alternate aetiology, including RA-UIP, Asbestosis, Chronic Hypersensitivity Pneumonitis and Unclassifiable fibrotic lung disease - Investigate genetic associations and epigenetic modifications which affect fibrotic disease severity and progression - Prospectively evaluate longitudinal disease behaviour in patients with non IPF-fibrotic lung diseases with a view to developing composite clinical end-points for subsequent use in intervention studies in patients

PreOperative Endocrine Therapy for Individualised Care With Abemaciclib

In women with hormone sensitive early breast cancer, taking a hormone therapy (also known as endocrine therapy) for at least five years after surgery is very effective at reducing the risk of the cancer returning. However, for some women their cancer may eventually become resistant to these drugs. POETIC-A Registration part will identify those who have a higher risk of developing resistance to standard endocrine therapy (ET). At least 8000 women diagnosed with early stage breast cancer will enter the Registration stage from 80 centres. Study doctors will use aromatase inhibitors (AIs), a type of ET, to treat the cancer for between 2 weeks and 6 months before surgery. A sample will be taken from the cancer during surgery and the study laboratory will measure a biological marker called Ki67. If the level of Ki67 does not drop after 2 weeks of AI treatment, the patient is likely to be less sensitive to endocrine therapy, and the study doctor will explore additional treatments after surgery in the POETIC-A Treatment part. Everyone who agrees to join the Treatment stage (2032 patients) will be randomly put into one of the 2 treatment groups; Group1: ET only; or Group2: ET plus a new drug called abemaciclib. The first aim of the Treatment stage is to confirm whether abemaciclib given in combination with ET is more effective than giving ET alone in preventing the cancer coming back. The study laboratory will perform a second test on the cancer sample, called an AIR-CIS test. This test aims to find out if particular groups of patients based on their tumour biology are more suitable for treatment with abemaciclib. Patients in Group 2 will receive ET plus abemaciclib for 2 years. Patients in both groups will have regular study visits during this period.

EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection.

UK data suggests that current treatment for complicated intra-abdominal infections (cIAIs) results in unacceptably high rates of cIAI relapse and extra-abdominal infection. As a guiding rule, shorter antibiotic durations are important to combat antimicrobial resistance, but this is not true when these shorter courses need repeating and result in more days in hospital. Optimal care for patients should be our primary concern. The EXTEND trial aims to find out whether a fixed extended duration of 28 days of antibiotics is superior to the current standard duration (typically 7-18 days) based on clinical outcomes and quality of life assessed over 180 days of follow up. Cost effectiveness will also be determined. A target of 1166 patients will be recruited from ICUs and hospital in-patient wards across approximately 30 NHS trust hospitals. Only patients that are able provide consent (or those with a consultee able to confirm whether the patient would wish to be included in the study) can take part in the trial. They will receive antibiotics as prescribed by their treating clinician, but the duration of treatment will be determined by randomisation. Patients will have equal chance of randomisation to the standard care arm, in which the antibiotic duration will be determined by the treating clinician, or the intervention arm, a fixed duration of 28 days treatment. Patients (or a personal consultee) will complete a quality of life questionnaire at baseline and 30, 60 and 180 days after randomisation. At follow-up timepoints they will also complete questionnaires on antibiotic use and health care resource use. Hospital notes will be used to collect data on inpatient admissions, relapse and further infections. The study is Sponsored by the University of Leeds

Video Analysis of Errors and Technical Performance Within Minimally Invasive Surgery Short Title: Video Analysis in Minimally Invasive Surgery (VAMIS)

There are 2.5 million people who have cancer in the UK, projected to increase to 4M by 2030. Over the past three decades, there has been a rapid uptake of minimally invasive (keyhole) surgery i.e. laparoscopic and robotic techniques, to treat cancer across different specialties. Robotic surgery is a well-established modality; the most commonly used robot for surgery (da Vinci) has been used in more than 8.5 million procedures, 1.25 million of which were in 2020. Previous research from our group developed valid methods to accurately assess surgical skill and errors in laparoscopic procedures using video analysis of rectal cancer surgery. The methods and tools developed were able to link surgeons' technical skill, including errors made, to patient outcome i.e. those who scored better had better outcomes. Investigators hypothesise that understanding and optimising surgical processes and errors will reduce unwarranted variations and improve the performance of the entire surgical team that is ultimately hoped to enhance patient safety and outcomes. With an increasing use of robotic systems across different specialties, there is an need to standardize training, assessment, testing and sign-off as a competent robotic surgeon in order to improve patient safety. A study from the 1990s estimated that more than 250,000 people die in the USA every year from medical error. Another study from the USA reported between 2000-2013 10,624 adverse events relating to robotic procedures. Experts raised concerns over surgical curricula being random and insufficient to ensure patient safety, leading to the development of EAU Robotic Urology Section Curriculum (ERUS). In addition, an independent review by the Emergency Care Research Institute (ECRI) on health technology hazards identified a lack of robotic surgical training as one of the top 10 risks to patients. Comparisons are frequently made between the aviation industry and surgery in terms of adverse event analysis and non-technical skills. The aviation industry, however, has mandatory, recurrent, reassessment and requalification throughout the career pathway and an internationally agreed standard for training, which robotic surgery does not. Our research group has a track record in developing objecting assessment tools to aid training and accredit laparoscopic surgery and will utilise this expertise to enrichen assessment tools in robotic surgery. Given the link between surgical skill and error counts to patient outcome, this research team aims to analyse surgical video within robotic surgery in different procedures to further understand the surgical process and errors made. Further understanding of these processes could enhance our knowledge and ability to provide meaningful feedback and accurately assess surgeons. This in turn, it is hoped, will enhance performance and improve patient outcomes. Aim This research project aims to assess robotic techniques for surgical phases and error detection that would permit the objective assessment of surgical performance, allowing the assessment of surgeon and procedure specific proficiency gain curves (learning curves) and identifying training needs. 4.1 Objectives 1. Develop a standardised and agreed segmentation of the operations (Delphi system) 2. Video error analysis: Application of OCHRA into Robotic assisted radical prostatectomy 3. Video error analysis: Application of OCHRA into robotic rectal cancer surgery (anterior resection TME) 4. Validation of assessment tool scoring, video analysis to patient outcomes i.e., morbidity, histopathological data 5. Development of formative assessment tools for generic and specific-procedures 6. Video error analysis: Development, evaluation and application of automation and video error analysis (artificial intelligence and machine learning) in minimally-invasive surgery. 7. Qualitative data review of surgeons' perception of TSE after using the platform. 8. Qualitative data review of surgeons' perception of effect on learning curve. 9. Analyse kinematic data to further understand its role in errors and skill in minimally-invasive surgery 10. Development of summative assessment tools to aid certification and accreditation. . Study design: Observational study collecting anonymised video data and uploaded to Touch Surgery platform. Recruiting sites and Principal investigators: University College London Hospitals (Mr Ashwin Sridhar), Yeovil District Hospital NHS Foundation Trust (Professor Nader Francis), Queen Alexandra Hospital, Portsmouth (Professor Jim Khan), The Christie (Mr Chelliah Selvasekar) and Northwick Park & St Marks Hospitals (Mr Danilo Miskovic). Prospective data upload: Patient identification: The local team will identify patients in clinic/multi disciplinary team meetings based on adherence to inclusion criteria. The patient will be approached by a GCP trained member of the research team ideally at least 24 hours after they have been informed about the study and have had time to read the patient information sheet provided in clinic or posted to them. If the team is only able to provide information on the day of surgery, considering video recording is standard and it doesn't affect their care, this would be deemed acceptable. Consent and information sheets will be kept short in order to minimise disruption to patient care. Any surgeon willing to contribute their video data for analysis will be given access to the Touch Surgery Platform to review their own videos and annotate, these videos will also be added to a shared group with the clinical research team for analysis. The surgeon will be consented to allow their data to be analysed and results disseminated, which will be anonymised. If they wish, they can ask for analysis feedback. Surgeons will be recruited by their local Principal Investigator at each site, who will be working closely with the research team at The Griffin Institute. Data capture and analysis Surgical videos will be recorded via an encrypted hard drive or The Touch Surgery™ Enterprise DS1 Computer. The Touch Surgery™ Enterprise DS1 Computer is connected to the operating room's video imaging system with a HDMI cable (or other compatible wired connectivity). A member of the operating room staff uses the Touch Surgery™ Enterprise DS1 Wireless Controller to select the procedure and surgeon name. A custom file name and notes can also be added, and users are prompted with a reminder not to input any patient personal information. Throughout the case, and whilst the recording is in process, the video passes through our AI-powered safeguard, RedactOR™, before it is saved to the Touch Surgery™ Enterprise DS1 Computer. RedactOR™ works on the video in real-time to determine when the scope has exited the patient. The algorithm then pixelates the video frames, and will continue to do so, until the scope re-enters the patient. All videos will be uploaded to TSE and therefore be processed through RedactOR™. This redaction is irreversible, thereby giving additional confidence that visual information that could identify a patient is transmitted, processed or stored. Upon direction by the authorised user, the video is uploaded from the Touch Surgery™ Enterprise DS1 Computer to our secure cloud provided by Amazon Web Services (AWS). AWS complies with ISO 9001, ISO 27001, ISO 27017, and ISO 27018, and audited against HDS (France). Touch SurgeryTM Enterprise DS1 Computer will record, process and provide analytics on video recordings of minimal-access surgical procedures. These are recorded through the standard operating stack and require no additional steps or changes to standard care. Currently, procedures are routinely recorded in the operating room for training purposes to allow review and debrief after a procedure or to evaluate where improvements could be made. The dVLogger box additional records endoscope video in stereo and robotic movement data. No audio will be recorded. This data is collected by an encrypted hard drive and used by WEISS who will anonymise the data sent to Intuitive Surgical Inc. WEISS will have access to the study ID to link analysis to patient data, Intuitive will not. This research team does not anticipate that there will be any new material ethical issues associated with the recording system and surgical video feed. Operative steps will be closely analysed using this software, applying machine learning and OCHRA methodology techniques to identify phases and errors of minimally-invasive surgical operations. Researchers trained in these methodologies will be observing and analysing the data. Data upload to TSE will be anonymised with no patient identifiable data, but the clinical research team will pseudonymise patient data and outcomes including demography, identifiers to follow up outcome, surgeons' grade/level of expertise. Video editing software will be used to annotate and highlight surgical video data to categorise phases and errors. STUDY SETTING Data will be collected at multiple centres that have the capability to capture minimally-invasive surgery videos in the following procedures initially: patients undergoing a robotic-assisted cancer procedures including prostatectomy, cystectomy and anterior resection (rectal cancer operation). Patients will be approached during the consent process at participating research sites: University College London Hospitals, Queen Alexandra Hospital (Portsmouth), The Christie (Manchester) Northwick Park & St Mark's Hospitals and Yeovil District Hospital NHS Foundation Trust. However, it will expand to any NHS site performing minimally-invasive surgery and willing to participate. It is appropriate to have multiple sites, as this will provide the most data and ensure a richer data set to address the research objectives Site requirements; to perform minimally-invasive surgery and have video capturing devices installed. Data will be collected at each site and analysed by the clinical research team. Sampling including size of sample Sampling will be from a clinical setting during the consent process. Participant number: This project requires uploading a large number of video recorded cases in order to conduct the research and achieve all the primary and secondary end points. The type of cases will vary from generic laparoscopic procedures that will aid development initial phases of the project such as segmentation, to more advanced procedure segmentation e.g. Robotic prostatectomy and robotic rectal cancer surgery. Since OCHRA was applied extensively in laparoscopic rectal cancer surgery, a comparison will also be made with robotic, hence, video recording of laparoscopic colorectal cases will be required. In order to achieve this number investigators will partner with a number of hospitals including Yeovil District Hospital NHS Foundation Trusts, University College London Hospitals, Queen Alexandra Hospital (Portsmouth), The Christie (Manchester) and Northwick Park & St Marks Hospital. There is no formal power calculation in this study but investigators aim to record as many procedures as possible within the time frame of the project and with a maximum 250 from each centre. The researchers aim to conduct full OCHRA analysis including error annotation up to 50 videos per specialty. 7.3 Recruitment Patients at sites contributing to video analysis will be identified before surgery and consented using a standardised form and information leaflet. Patients will be identified and clinic or multidisciplinary team meetings and approached by the local research team by a GCP trained healthcare professional. They will explain the study and provide a patient information sheet which they can read at home. Over 24 hours after the first approach they will then be asked if they would consent to the study, this would be easily done on the day of the operation, using a separate consent form to the procedure consent form. There is minimal risk of coercion as it is a low risk, observational study, with no intervention or change to standard care. 7.3.1 Sample identification Healthcare professionals such as doctors, clinical nurse specialists or research nurses can identify patients who may be eligible for the study. Similarly, if trained appropriately, any of the above could take consent as it is low risk. If any healthcare professional not involved in the study is asked questions about it, they could let the research team know to contact the patient. Patients will be identified before surgery and will be provided with a patient information sheet and consented using a standardised form stating that the data will be anonymised and used for video analysis only. Clinical data and patient participants will be pseudonymized with a unique study identification number. Study ID numbers will be assigned with a local trust code e.g. UCL-001 and in order of upload to Touch Surgery, there is no need to randomise the numbers. There will be no advertisements or external recruitment, patients will only be approached if they are undergoing a minimally-invasive surgical procedure and have capacity and time to consent. A Participant Information Sheet will be provided to the identified patient to describe the study and what their involvement means explaining they can withdraw at any time, that it is anonymous and investigators believe ultimately through their involvement they will improve patient care through improving knowledge of surgical skill. 7.3.2 Consent Patient consent will be informed and at the same time of procedure consent, as all ethical concerns that could be associated with the study have been addressed, and due to the standard of routine recording surgeries in the participating sites. Participants will be allowed to ask questions, withdraw without reason at any time and it will not affect their care. Research entry and consent would take place at the same time as procedure consent. The use of translators (friends/relatives or professional services) would be at the discretion of the PI or co-investigator taking consent. Research entry is not possible without informed written consent. Where possible, translation for the PIS and consent form will be provided through the Trust translational services. If it is not available or there is not enough time pre-operatively, non-English speakers will be excluded from the study if they do not have the fluency to read & comprehend PIS and ICF. ETHICAL AND REGULATORY CONSIDERATIONS Patient confidentiality Patient confidentiality will be maintained. Surgical videos will be stored securely on Touch SurgeryTM Enterprise (TSE; https://www.touchsurgery.com/). No patient identifying information will be attached to the videos that are uploaded to the Touch SurgeryTM Enterprise platform, which will be monitored at the point of capture, using a real-time safeguarding algorithm, to ensure confidentiality. No audio is collected to maintain confidentiality. Clinical data will be collected and accessed by only the clinical research team, who all have employment or honorary contracts at the clinical sites. All clinical data will be kept on NHS password-protected computers, on a password-protected Microsoft Excel spreadsheet on Trust premises, accessible only by the clinical research team. Digital Surgery Ltd team cannot access clinical data and patient participants will be assigned with a unique study identification number, so the identity of the patient is not known to them, to preserve patient confidentiality. The data from dVLogger data sent to Intuitive is anonymised and sent on an encrypted hard drive. Data protection To capture the surgical videos, a video cable non-intrusively connects the standard video outputs of the surgical video monitor, surgical robotic device, or stack into the Touch SurgeryTM Enterprise encrypted computing equipment, the DS1. The DS1 is not a medical device. The DS1 runs Digital Surgery Limited's proprietary, in-situ AI safeguarding algorithm (RedactOR™), which redacts, via automatic pixelation, out-of-body surgical video footage, to remove identifiable personal data, in real-time. The encrypted computing equipment then transfers the anonymised videos to Touch SurgeryTM Enterprise platform; built upon a secure cloud server provided by Amazon Web Services in Europe, operated by Digital Surgery Limited. All anonymised data handling will be performed by designated, trained members of the clinical research team at TGI and technical research team at Digital Surgery Limited. All clinical data handling will be performed only by designated, trained members of the clinical team at The Griffin Institute. Digital Surgery Limited products and services (Touch Surgery ™ Enterprise) are compliant with the General Data Protection Regulation of 2018 (GDPR) and UK Data Protection Act of 2018 (UK GDPR). The data custodian will be the Chief Investigator Professor Nader Francis. Personal data will be stored in line with respective trust data retention standard procedures. This will remain for up to 5 years. Potential risks Investigators expect no difference between those patients in the trial or not. All patients require the operation as part of their routine care and this study does not alter the way the surgeon performs the case in any way, routinely surgeons will record operations, there is no change to standard care nor are additional patient visits required. Any potential risk to patient confidentiality has been addressed and sufficiently mitigated by the study protocol. There are no additional risks to the staff as part of this study. It will not impact surgical rotas; theatre lists or scheduled operations. The only possible potential risk with this study is identification of significant errors on the video analysis that are not detected by the operating team and therefore no corrective action taken. However, the nature of this project involves reviewing the videos a significant period of time after the operation. Any sequelae from this event would have been apparent in the post operative period well before video analysis is conducted. If there are any learning points, however, these will be communicated with the PI at each site. Potential benefits Researchers hypothesise that understanding and optimising surgical processes, and errors will reduce unwarranted variations and improve the performance of the entire surgical team that will ultimately enhance the patient's surgery and outcomes. It is noted that there is no direct benefit to the individual patient taking part other than potentially helping to improve the safety of standard routine surgical procedures in future operations. Researchers hope that this technology will be used to improve surgical training and preparation of the entire operating theatre team and optimise performance and standardisation. It is hypothesised that the implementation of this technology may benefit patients by reducing surgical variations and errors and may also enable monitoring and assessment of surgical competence based on reliable, actionable data. If patient loses capacity to consent during study If the patient loses capacity before consent then they will not be invited to participate (in accordance with inclusion criteria). If they are suspected of losing capacity afterwards then the participant will remain in the study at the clinician's discretion as this is an observational study will no unremediated risks. Physical security arrangements for storage of personal data Videos will be in electronic format and retained in encrypted storage. Procedural data will be directly uploaded from the device to a secure cloud server provided by AWS (Ireland, Europe), which is GDPR compliant. AWS will be used to store all media and data, which conforms to the ISO 27001 security management standard and is a member of the Cloud Security Alliance. Any transfer between the study sites would be in encrypted storage formats or through a secured internet connection. Data from the video recordings of surgery will be extracted, transferred and analysed using computerised software based at Digital Surgery Ltd. in London, UK. No patient data will be shared with Digital Surgery Limited in the duration of this study. Only Yeovil District Hospital NHS Foundation Trust/TGI (restricted to the clinical research team) will access and retain identifiable information such as study files. Yeovil District Hospital NHS Foundation Trust will only collect the minimum required information for the purposes of the study. Recruitment Arrangements and informed Consent Following informed consent to participate, the study patient participants will be assigned with a unique study identification number. This identifier is pseudo anonymised to the clinical research team. Patient consent forms will be securely stored in locked cupboards and password protected NHS equipment, NHS sites, with access restricted to the only authorised members of the clinical research team. How will researchers ensure the confidentiality of personal data? / Who will have access to participants' personal data during the study? The surgical video and associated metadata on Touch SurgeryTM Enterprise cannot identify the participant. Participant personal data (any data that may identify a participant) is not necessary for the service Touch SurgeryTM Enterprise provides to the study site. Only the clinical research team has access to identifiable information about the participant. Access restrictions are in place to mitigate any risk to confidentiality of participant personal data. Data will be used, stored and transferred in an encrypted format, and handled in accordance with the UK Data Protection Act of 2018 (UK GDPR). Where will the data generated by the study be analysed and by whom? Data generated will be analysed by the clinical research team. Only anonymised data will be transferred to Touch SurgeryTM Enterprise (UK) and analysed by authorised members of the Digital Surgery Limited team for the purpose of the study, to identify key markers such as surgical phases and associated variations. Intuitive Surgical Inc. will receive anonymised data from the dVLogger via an encrypted hard drive. Pseudonymised data will be analysed by the research team at TGI and WEISS. This will be stored on secure servers with access limited to the team. Based on previous similar uses of OCHRA errors in colonic surgery, error count results are expected to be normally distributed (however, this will be confirmed using detrended QQ statistical plots prior to analysis). Task and type specific error counts can be compared with Mann-Whitney U test. OCHRA as previously described is a validated methodology to manually, accurately and reliably assess errors in a minimally invasive procedure. Data from this can then be statistically analysed and linked to patient data including demography and outcome Digital Surgery data science team will be involved in video analysis through analytic reporting. Qualitative questionnaires will be used at the end of the study to evaluate surgeons' opinion and gain insights on the use of surgical video and novel analytics. This will be done using thematic analysis. SPSS will be used for all data analysis.

The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study

This is a major pragmatic multi-centre prospective parallel group open RCT. It will be conducted in the UK, Australia and New Zealand, funding is being sought in several countries to expand recruitment internationally. The study is in 2 phases: the vanguard and main phase. Therefore the study will run an internal pilot to prove recruitment of the relevant number of participants during the initial 2 years. The over-arching aim is to determine whether early AVR results in better clinical outcomes and cost-effectiveness than a strategy of expectant management in asymptomatic patients with severe AS. The primary hypothesis is that early AVR or TAVI in asymptomatic patients with severe AS will result in a reduction in the composite primary outcome of cardiovascular (CV) death and hospitalisation for heart failure (HHF) when compared to the conventional approach of expectant management. Potential participants will be identified by a member of the clinical care team following diagnosis with severe AS. Participants will be screened for eligibility using pre-specified inclusion/exclusion criteria. Eligible participants will be provided with a written version of the participant information sheet detailing the exact nature of the study, what it will involve for the participant and any risks involved with taking part. Participants will be given at least 24 hours to consider the information and decide whether or not to take part. The study will randomise up to 2844 patients with severe asymptomatic AS to either allocated expectant management OR aortic valve replacement. Participants randomised to AVR will be placed on a waiting list with the aim that surgery will be performed within 3 months, dependent on local hospitals' waiting lists. Participants randomised to AVR will undergo routine tests/procedures which may include coronary angiography. If the outcome of the coronary angiography reveals coronary heart disease, the decision to perform CABG or PCI will be made by the responsible cardiac surgeon and cardiologist, in consultation with the patient. All analyses will be undertaken using the principles of intention-to-treat with participants analysed in the group they were randomised regardless of treatment received. EASY-AS is collaborating with the EVoLVeD study (Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis, Clinical Trials.gov NCT03094143). In centres where both EASY-AS and EVoLVeD are running, participants in EASY-AS will be offered the opportunity to take part in EVoLVeD. Funding has been granted by the British Heart Foundation (UK), Medical Research Future Fund (Aus) and Heart Foundation (NZ). The UK sponsor is the University of Leicester. Additional support and resources for the study will be provided by the participating Trusts and their corresponding Clinical Research Networks in the UK. The central co-ordination centre is the University of Leicester Clinical Trials Unit.

COLO-COHORT (Colorectal Cancer Cohort) Study

Bowel cancer is the second commonest cause of cancer death in the UK with 16000 people dying per year. Although the NHS Bowel Cancer Screening Programme (BCSP) detects cancers at an earlier stage only 10% of all cancers are detected through screening. Currently, the only criteria for screening is age and no account is taken of other known risk factors such as smoking, alcohol, family history or obesity. Stool FIT (a new stool test which detects blood that can't be seen with the naked eye) will be introduced into the English BCSP, but there is poor evidence for its use in patients presenting with symptoms. There is also emerging data that there may be differences in the gut bacteria of people with and without cancer or pre cancerous bowel polyps (adenomas). This will be a national multi-centre study over 5-years. 10000 Patients undergoing colonoscopy as part of BCSP or due to symptoms will be recruited. Patients will be asked to fill in a health questionnaire, have their height, weight, waist circumference measured. Patients will also receive blood tests, stool tests or saliva tests depending on the indication for their colonoscopy. The results of the colonoscopy and any samples taken will be collated. Patients will receive a patient experience questionnaire or food frequency questionnaire. A further 10,000 patients from the North of England will be consented to be contacted for future studies with some of the information above collected. The aim of this study is to develop a risk prediction model to help determine which patients are at highest risk of having adenomas or bowel cancer. The investigators will also explore the significance of the gut bacteria composition in patients with adenomas or cancer to help inform this risk model. Additionally the investigators will develop a large platform of patients who consent to be contacted for future research.

Randomised Evaluation of Sodium Dialysate Levels on Vascular Events

RESOLVE is a pragmatic, cluster-randomised, open-label study designed to evaluate in real-world conditions the comparative effectiveness of two default dialysate sodium concentrations. Dialysis sites will be randomised in a 1:1 ratio to a default dialysate sodium concentration of 137mmol/l or 140mmol/l. 'Default' is defined as the use of the allocated dialysate sodium for ≥ 90% of delivered dialysis sessions in the unit. All other care will be according to standard local practices as determined by the site. Outcomes will be assessed on individual patients dialysing at those sites. Sites will be asked to consent to participation while waiver or opt-out consent will be sought for individual patients. It is anticipated that site accrual will occur over 5-7 years with average study duration expected to be approximately 2-5 years. The actual length of the study will be end-point determined.

Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker - Phase III Non CTIMP Trial

The only phase III clinical trial in the UK offering watch and wait, the TRIGGER trial aims to validate mrTRG as an imaging biomarker for the stratified management of patients with locally advanced rectal cancer. The 'good responders' (mrTRG1&2) often have no evidence of tumour and it may be possible to avoid surgery in this group and so maintaining QoL while not impacting survival rates. The 'poor responders' (mrTRG3-5) are at high risk of poor oncological outcomes and this knowledge is useful in planning ongoing treatment and surveillance. TRIGGER is now a non-cTIMP trial as the protocol does not specify chemotherapy or IMP treatments. Decisions about the use of chemotherapy will be based upon local MDT discussions as is normal practice and national policy and the trial CRFs will capture these decisions and whether more treatment is given to patients or not. TRIGGER does not mandate or recommend the use of any treatments: specifically it does not suggest the use of investigational medicinal products. If any centre wishes to use IMPs this would be in the context of separate trial protocols and would not preclude entry into TRIGGER.