NIHRDataInsights/HRCSData huggingface dataset:
Title: Can we prevent generation of pro-thrombotic and pro-coagulant extracellular vesicle populations in blood via a simple dietary intervention
Funder: Division for Social Care and Health Research (Wales)

Abstract: Microscopic vesicles are pinched off from cells in the blood and surrounding blood vessels. They carry components of the parent cell to other sites, and can perform damaging roles especially in cardiovascular disease. Our group aims to use state-of-art methods to assess the character of these vesicles and apply them to model systems mimicking disease conditions in the laboratory that will test their capacity to damage other cells and blood vessels. We will investigate whether inorganic nitrite influences the formation and/or action of damaging vesicles, and whether this could be applied as a dietary supplement of nitrate, as used by elite athletes and as a health supplement to promote cardiovascular well-being.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Positron Emission Tomography-Computerised Tomography scans (PET-CT) guided watch and wait policy versus planned neck dissection for the management of locally advanced (N2/N3) nodal metastases in patients with head and neck squamous cancer
Funder: Department of Health (England)

Abstract: The study has gained the support of the NCRI Head & Neck Clinical Studies Group (main HNC research committee in UK) the principal investigators local Arden Network Site Specific Group and most (20/34) of the major head and neck centres in the UK.DESIGN: PET-NECK is a pragmatic randomised controlled multi-centre phase III trial. Please see consort diagram (figure 1 p16) and schedule of assessments (table 2) in the proposal.All patients will receive chemoradiotherapy. Eligible patients are randomised to one of two arms: Experimental arm: CRT followed by PET-CT done at 3 months (range 9-13 weeks) after CRT completion: if neck -ve on PET-CT scan ----- watch and wait if neck +ve on PET-CT scan ---- neck dissection within 2 - 4 weeks Control arm: CRT + planned neck dissectionAll patients are assessed for response to CRT at 9-13 weeks after completion of CRT with the following below:1. CT scan of neck and primary 2. examination under anaesthetic (EUA) +/- biopsy; i.e. current gold standard staging If residual disease is detected at PRIMARY site ( i.e. does not show complete response after CRT) patient will be immediately withdrawn from trial to be considered by their treating team for salvage surgery. The incidence of this is expected to be equal in both arms due to randomisation.SETTING: Department of Health (DoH) designated head and neck cancer centres (tertiary referral centres) of which we have support to date from 20 out of 34 centres (covering a NHC catchment population of 34 million).TARGET POPULATION: patients with squamous cancer of head and neck (T1-4) with advanced (N2 or N3) neck nodal metastasis being treated with radical (curative) CRT.HEALTH TECHNOLOGIES BEING ASSESSED:a. Non-inferiority of PET-CT determined watch and wait (surveillance) policy in patients exhibiting complete response to CRT compared to the current practice of performing a planned neck dissection (before or after CRT) on all patients (whether or not there is evidence of residual disease). b. Accuracy of PET-CT compared to current gold standards (CT scan and EUA) in detecting residual disease at both primary site and neck after CRT.MEASUREMENT OF COSTS AND OUTCOMES:Primary endpoint:Overall survival with death from any cause defined as an event and survival times calculated as described in the proposal. Follow-up will be carried out on a monthly basis in the first year and two monthly in the second year and copies of all death certificates requested from the Office of National Statistics (ONS) to confirm the date of death.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: A pragmatic randomized controlled trial of physical activity as an aid to smoking cessation during pregnancy
Funder: Department of Health (England)

Abstract: Smoking during pregnancy is the most important cause of preventable harm to infants. Stopping smoking reduces this harm and also reduces womens risks of developing other harmful effects of smoking. Smoking cessation counselling can help pregnant smokers to stop but success rates are low few women attend such treatments and many pregnant women prefer not to use pharmaceutical aids to cessation. Moderate intensity activity (e.g. brisk walking) is recommended as part of antenatal care and there is some evidence that supervised exercise (e.g. treadmill walking) can help non-pregnant women to stop smoking. Pilot work has shown that many pregnant women would be happy to join a research study testing exercise for smoking cessation. The study will assess whether supervised exercise added to standard smoking cessation support can help pregnant smokers to quit. 866 pregnant smokers will attend six weekly sessions of smoking cessation counselling and half of them will be randomized to also receive 14 individual exercise sessions over eight weeks. The trial will primarily assess whether the exercise intervention increases the womens rates of biochemically validated smoking cessation up to the end of pregnancy. The women will also be asked about their smoking six months after the birth. In addition differences between the groups will be examined for the womens physical activity levels withdrawal symptoms urges to smoke depression weight perinatal outcomes (e.g. birth weight) and self-confidence to stop smoking. If the intervention was found to be effective it would provide a valuable blueprint for the construction of physical activity programmes for pregnant smokers and for smokers in general receiving smoking cessation treatment through the NHS.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: A randomised phase II trial in previously untreated patients with chronic lymphocytic leukaemia to compare fludarabine cyclophosphamide and rituximab with fludarabine and cyclophosphamide mitoxantrone and low dose rituximab. (CLL6)
Funder: Department of Health (England)

Abstract: The trial aims to establish whether the addition of mitoxantrone with a reduced dose of rituximab to fludarabine and cyclophosphamide (FCM-miniR) is at least as effective as FCR in terms of response in patients with previously untreated Chronic Lymphocytic Leukaemia (CLL). It is anticipated that full dose rituximab will be approved as standard therapy for patients with previously untreated CLL in 2009 and NICE approved in 2010. There is evidence that lower doses of rituximab are biologically active in CLL. However in order to justify studying a low dose of rituximab in a large Phase III trial evidence of the efficacy of low-dose rituximab in combination with chemotherapy is required. This trial aims to assess whether mini-R in combination with mitoxantrone is a reasonable alternative to full dose rituximab and is being timed to report at around the same time as NICE review rituximab for use in the treatment of CLL. If the results of this trial are positive a larger phase III trial will be pursued which is likely compare low-dose rituximab directly with the then licensed dose


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The impact of combined modality positron emission tomography with computerised tomography scanning (PET/CT) in the diagnosis and management of pancreatic cancer
Funder: Department of Health (England)

Abstract: Previous work has found that positron emission tomography (PET) has a similar accuracy to that of computerised tomography (CT) for imaging pancreatic cancer but does not provide additional benefit to that seen with CT alone. PET/CT provides an exactly fused anatomic and metabolic image which is significantly more accurate in staging solid tumours than PET alone. The additional value and role of PET/CT in the diagnosis and management of pancreatic cancer has yet to be determined in a large prospective series of patients. This multi-centre prospective diagnostic accuracy and clinical value study of PET/CT aims to investigate the incremental value of PET/CT in addition to standard practice in the diagnosis staging and treatment of these patients. Patients with suspected pancreatic malignancy will undergo standard CT staging and following informed consent eligible patients will undergo PET/CT scanning. A documented management decision will be made before and after PET/CT scan. Patients will be followed up for a minimum of 12 months. The impact of PET/CT in the diagnosis and management of these patients will then be assessed. Patients will be recruited from major pancreatic centres in the UK.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Faecal immunochemical testing (FIT) for adenoma surveillance. FIT for Follow-up
Funder: Department of Health (England)

Abstract: Around 1 in 4 people develop colorectal adenomas by age 60. Most of these are innocuous and only a minority will progress to cancer. However people with intermediate risk adenomas remain at a 3-4 fold increased risk of developing cancer. Colonoscopy surveillance is therefore recommended for this group. Although colonoscopy is considered the gold standard bowel examination it is not perfect. It can miss lesions and it is also a costly procedure with some risks to the patient. Furthermore the roll out of the BCSP to all people aged 60-74 years and the increased number of colonoscopies being undertaken for surveillance is already overwhelming the endoscopy service. Given all these shortcomings of colonoscopy as a method of surveillance it is important that an alternative method is investigated.A new type of occult blood test (faecal immunochemical test FIT) has become available that is more sensitive for the detection of colorectal cancer and advanced adenomas compared to the gFOBT used in the BCSP. FITs have features that make them more attractive option for protecting higher risk groups. For instance the threshold for positivity can be set at a low level to minimise the risk of missing significant lesions. If this approach was found to be successful only patients who had a positive FIT would need to be offered colonoscopy. We therefore propose that FIT may constitute a safer more acceptable and cost-effective method than colonoscopy for surveillance of people at increased risk of developing colorectal cancer.


Research activity codes: 4.3 INFLUENCES AND IMPACT;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: An evaluation of multi-functional magnetic resonance imaging in the diagnosis and characterisation of prostate cancer
Funder: Department of Health (England)

Abstract: At present men with raised serum prostate specific antigen (PSA) are advised to have a transrectal ultrasound (TRUS) guided biopsy. This study will investigate whether imaging prior to biopsy can be incorporated into the existing diagnostic pathway for prostate cancer. We will evaluate whether men with a raised PSA or other risk factors for harbouring prostate cancer should first undergo a MP-MRI in order to select a group that could safely forego prostate biopsy. In addition this study will evaluate the ability of MP-MRI to identify lesions for selective biopsy.In order to evaluate the diagnostic accuracy of MP-MRI (index test) against the TRUS guided biopsy (current standard test) both procedures need to be compared to a reference standard. This reference standard needs to be accurate at both detecting and ruling-out prostate cancer and amenable to application to all men at risk. Template Prostate Mapping (TPM) meets the necessary performance characteristics of such a reference test. It is performed under a general/spinal anaesthetic. By design PROMIS conforms to a validating paired cohort study (see Oxford Centre for Evidence-based Medicine Levels of Evidence 1b http://www.cebm.net/index.aspx?o=1025). All men in the study will have a MP-MRI (index test) followed by both a TPM biopsy (reference test) and a standard TRUS guided biopsy (current standard test). These 3 tests will be assessed and reported independently from each other. The main objectives of the trial are:To assess the ability of MP-MRI to identify men who can safely avoid unnecessary biopsy.To assess the ability of the MP-MRI based pathway to improve the rate of detection of clinically significant cancer as compared to TRUS biopsy.To estimate the cost-effectiveness of an MP-MRI based diagnostic pathway. Using data from the main study and the wider literature the study will consider the implications of alternative diagnostic strategies for NHS cost and mens quality-adjusted survival duration.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: OPTIMA prelim: Optimal Personalised Treatment of breast cancer usIng Multi-parameter Analysis: preliminary study
Funder: Department of Health (England)

Abstract: Multi-parameter prognostic tests such as Oncotype DX are increasingly used to identify women with ER +ve HER2 -ve early breast cancer treated with endocrine therapy who are unlikely to benefit meaningfully from chemotherapy. The supporting evidence for predictive testing is retrospective and is strongest for women without nodal involvement. More evidence is needed especially for patients with node positive disease. There is early evidence that other multi-parameter tests in development also have a predictive utility. OPTIMA will assess the value of multi-parameter tests in the NHS. OPTIMA prelim the feasibility phase will recruit 300 patients (with a 200 patient bridging extension to the main study). Eligible patients will have ER +ve HER2 -ve tumours with involved nodes (pN1-2). Patients will be randomised to standard treatment with chemotherapy or to have test-directed treatment with either the same chemotherapy or no chemotherapy assigned according to the result of an Oncotype DX test. All patients will receive endocrine therapy. OPTIMA prelim has 3 objectives. (1) To establish whether randomisation to test-directed treatment is acceptable to patients and clinicians. This will be done through qualitative research by recording and analysing consultations when the trial is discussed with potential participants and with in-depth interviews with OPTIMA researchers and participants. (2) Alternative multi-parameter tests will be evaluated on all patients’ tumours and their performance will be compared to Oncotype DX using statistical and cost-effectiveness analysis to select a candidate test(s) appropriate for NHS use to be evaluated in the main trial. (3) The success of the main trial depends on efficient tumour sample collection and analysis to avoid treatment delays. The obstacles to this will be analysed in detail using a sample tracking database. The main study is an efficacy trial of 2-3 arms It will compare 5-year relapse free survival of test-directed vs. conventional treatment with a non-inferiority hypothesis.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Is whole colon investigation (WCI) by colonoscopy CT colonography (CTC) or barium enema (BE) necessary for all patients with colorectal cancer (CRC) symptoms and for which patients would flexible sigmoidoscopy (FS) suffice?
Funder: Department of Health (England)

Abstract: DESIGN: This is a prospective study in a cohort of symptomatic patients to assess whether or not a whole colon investigation by colonoscopy CTC or BE is necessary for all patients with colorectal cancer symptoms and to determine for which patients FS might suffice. SETTING: 21 teaching and general NHS hospitals. TARGET POPULATION: Patients experiencing symptoms suggestive of colorectal cancer aged 55 years or above with no prior history of colon cancer ulcerative colitis or Crohns disease who are clinically judged to need a whole colon examination and have not had one in the preceding 6 months. HEALTH TECHNOLOGIES BEING ASSESSED: Colonoscopy CT colonography Barium Enema and flexible sigmoidoscopy.MEASUREMENT OF COST AND OUTCOMES: Primary outcome: Diagnostic yield of CRC (proximal or distal) within three years of presentation at clinic by symptom category at presentation.Secondary outcomes: (1) The number needed to screen to diagnose one cancer presented for various categories of symptoms at presentation. (2) Hypothetical proximal CRC miss rates if only patients with certain symptoms or combinations of symptoms were sent for WCI. (3) The actual miss rate of CRC at FS in the subgroup of patients given FS at baseline. (4) Prevalence of proximal and distal CRC in the study cohort. SAMPLE SIZE: The sample will consist of 8484 patients from 21 UK NHS hospitals comprising 5448 who were originally randomised as part of the SIGGAR study and 3036 who were considered eligible but not ultimately randomised.PROJECT TIMETABLE: Two years in total including 6 months to obtain R&D approvals and prepare the data for the NHS Information Centre 10 months to collect data on patient symptoms and 8 months to code clean and analyse the data and prepare the results for publication.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: What CEA level should trigger further investigation during follow up after curative treatment for colorectal cancer
Funder: Department of Health (England)

Abstract: Design: Secondary analysis of data collected in the FACS trialSetting: NHS general practices and hospitals from across the UKTarget Population: Patients randomised to undergo post-operative follow-up by CEA-testing in general practice following surgery for colorectal cancer with curative intent Health Technology Assessed: Serum CEA (carcino-embryonic antigen) as a diagnostic test for tumour recurrence or cureMeasurement of cost and outcome: This proposal seeks to define the conditions under which CEA monitoring will provide optimal diagnostic performance in detecting treatable recurrence (optimal interpretive strategy and cut-off point; optimal testing interval; optimal population to monitor). The primary outcome measure used to assess diagnostic performance is the area under the ROC (receiver operator characteristic) curve. The NHS and patient costs of CEA measurement are being assessed as part of the (already funded) cost-effectiveness analysis specified in the main trial protocol.Sample size: Of the 601 patients randomised to CEA testing 587 (97%) participated undergoing about 6000 CEA tests to date. At the time of the core analysis (after 3 year follow-up) we estimate there will have been approximately 110 recurrences in this group of patients 40 treated with curative intent and 70 treated with palliative therapy.Project Timetable: The main analysis will be undertaken between March 2013 and September 2013. A final analysis will be undertaken in August-September 2014 when the additional data on late recurrence has accrued.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Can the intra-tumoral immune signature of primary colorectal tumours identify a subset of patients who do not require follow up after resection?
Funder: Department of Health (England)

Abstract: Design This is a translational study undertaking immunophenotypic analysis of tissue blocks from 1260 patients randomised in the FACS trial.Setting FACS is a randomised trial performed in NHS hospitals and GP practices throughout the UK. The tissue analysis will be undertaken in Southampton and the statistical analysis in Oxford.Target population1260 patients randomised in the FACS trial who have had curative surgical treatment of colorectal cancer and followed up in a study determined schedule.Health technologies involvedImmunophenotyic and molecular analysis of formalin fixed paraffin embedded tissue from resected primary colorectal cancer.Measurement of cost and outcomeThe proposal seeks to determine whether immune scoring of the tissue blocks give prognostic information regarding patient outcome superior to TNM staging thereby identifying patients at very low risk of relapse who do not require follow up. This would have significant cost implications for the NHS. The NHS and patient costs are already being determined as part of the funded FACS cost effectiveness analysis. Sample size1260 patients are randomised in the study and to date 178 have developed recurrence. It is estimated that block retrieval will be in the region of 80%. The 138 blocks obtained already will be used as the learning set to develop hypotheses and the further blocks used for validation.Project timetableThe project will take 24 months. Tissue Transfer Agreements will be put into place between Nov 2012 and Mar 2013. From Apr 2013 to Oct 2013 blocks will be obtained from other centres and tissue microarrays manufacture and analysis DNA extraction and microsatellite instability analysis preformed on the learning set. Between Oct 2013 to Apr 2014 the analysis will be performed on the validation set. Full statistical analysis and write up will be completed between May 2014 to Dec 2014


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent (The FACS Trial)
Funder: Department of Health (England)

Abstract: Colorectal cancer is a major cause of morbidity and mortality. In the UK more than 40000 cases are diagnosed annually . Traditionally patients who have had curative treatment for colorectal cancer are subject to regular hospital follow-up for at least 5 years in order to detect recurrence. Although probably less than 5% of those with local recurrence are amenable to cure success in treating metastatic recurrence has been increasing. Approximately 40% of patients survive 5 years after complete resection of liver metastases and comparable results are being reported for lung metastases . There is also evidence of improved survival if metastatic disease is treated before it becomes symptomatic . Although seven trials have now been published comparing different follow-up regimes their methodological quality has been modest and the follow-up regimes assessed have varied substantially. The most recent Cochrane review of the existing trial evidence called for higher quality trials addressing the effectiveness of the individual components of follow-up.The FACS trial was commissioned by the UK NIHR Health Technology Assessment programme in late 1999 and begun in 2001-2 to assess the effectiveness of follow-up by blood CEA measurement and by CT-imaging of the chest abdomen and pelvis using a 2x2 factorial design. Follow-up is scheduled for 5 years - 3 monthly for 2 years and the 6 monthly for 3 years. The main trial outcome is treatment of recurrence with curative intent; deaths from colorectal cancer will also be reported. The cost of each follow-up method is being measured to allow an estimate of cost effectiveness (in terms of the cost per QALY saved). Over 1200 patients have been recruited and the interim results will be published in 2013 when all participants have completed a minimum of 3 years follow-up. The final results will be published in 2015.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS