ObeSity Related Colorectal Adenoma Risk
Conditions: Colorectal Adenoma, Colorectal Neoplasm, Colorectal Cancer, Obesity, Metabolic Syndrome, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis
Sponsor: South Tyneside and Sunderland NHS Foundation Trust

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The OSCAR Study 
ObeSity related Colorectal Adenoma Risk 
 
 
Protocol Version 1.1 
Date: 24/10/2017 
 
 
Sponsor: South Tyneside NHS Foundation Trust 
Funder: Norgine Pharmaceuticals 
 
 

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Signatures Page  
The OSCAR study, final version 1.1, dated 24/10/2017 has been written and approved by the 
following:  
 
 
Professor Colin Rees  
 
 
 
Date:   
Chief Investigator  
___________________________________________________________________________________ 
Principal Investigator Declaration  
I confirm I have read and understood this protocol and I agree to conduct the study in accordance with 
the protocol.  
Name of Principal Investigator 
: ___________________________________ 
 
 
Name of Centre 
 
 
: ___________________________________ 
 
 
Signature  
 
 
 
: ___________________________________ 
 
Date 
 
 
 
 
: ___________________________________ 
 
 

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Project Investigators 
 
Chief Investigator 
 
 
Professor Colin Rees 
 
 
 
 
 
Consultant Gastroenterologist 
 
 
 
 
 
South Tyneside District Hospital 
 
 
 
 
 
South Shields, England 
 
Co-Investigators 
 
 
Professor Mark Hull 
 
 
 
 
 
Professor of Molecular Gastroenterology 
 
 
 
 
 
University of Leeds 
 
 
 
 
 
Leeds, England 
 
 
 
 
 
 
Dr Stuart McPherson 
Consultant Hepatologist 
Freeman Hospital 
Newcastle, England 
 
Professor Steven Rushton 
Professor of Biological Modelling 
School of Biology 
Newcastle University, England 
 
Professor John Saxton 
Head of Department of Sport, Exercise and Rehabilitation 
Faculty of Health and Life Sciences 
Northumbria University, Newcastle, England 
 
Dr Laura Neilson 
Clinical Research Fellow  
South Tyneside District Hospital 
 
 
 
 
South Shields, England 
 
Northern Region Endoscopy Group 
Sponsor 
 
 
 
South Tyneside NHS Foundation Trust 
Funding 
 
 
 
Norgine Pharmaceuticals 
 
 
 

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Table of Contents 
 
Section 
Title 
Page 
1 
Background 
5 
2  
Study Objectives 
7 
2.1 
Primary Objective 
7 
2.2  
Secondary Objectives 
7 
3 
Study Design 
8 
3.1 
Patient Recruitment 
8 
3.2 
Inclusion Criteria 
9 
3.3 
Exclusion Criteria 
10 
3.4 
Withdrawal Criteria 
10 
3.5 
Data Collection 
10 
4 
Adverse Events 
13 
5 
Assessment and Follow Up 
13 
6 
Statistics and Data Analysis 
14 
7 
Regulatory Issues 
14 
7.1 
Ethics approval 
14 
7.2 
Consent 
15 
7.3 
Confidentiality 
15 
7.4 
Sponsor 
15 
7.5 
Funding 
16 
8 
Study Management 
16 
8.1 
Data Protection 
16 
8.2 
Records Retention 
16 
8.3 
Protocol Compliance 
16 
8.4 
Responsibilities 
17 
9 
Financing and Insurance 
17 
10 
Dissemination 
18 
11 
Publication Policy 
18 
12 
References 
18 
Appendix 1 
NCRI Endorsement 
22 
Appendix 2 
BSG Endorsement 
23 
Appendix 3 
BCSP Endorsement 
24 
Appendix 4 
Gaant chart 
25 
 
 
 

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1. Background 
Colorectal cancer (CRC) is the second most common cancer affecting both men and women in 
England.1 The adenoma-carcinoma sequence is established as the mechanism by which adenomatous 
polyps develop into CRC.2,3  Detection and removal of adenomas is important in reducing CRC risk. A 
study which undertook single screening flexible sigmoidoscopy and adenoma clearance in patients 
aged 55-64, with high risk features referred for colonoscopy, reduced CRC incidence by 23% and 
mortality by 31%.4 Several clinical risk and protective factors for sporadic colorectal neoplasia 
(including CRC and colorectal adenomas) are recognised. Age, gender and family history of CRC are 
non-modifiable risk factors for the detection of advanced colorectal neoplasia.5 Cigarette smoking and 
excess body weight (EBW) are modifiable risk factors.5,6 
Obesity is increasingly prevalent in the UK, with 24.4% of men and 25.2% of women classed as obese in 
England.7 In addition to type II diabetes mellitus and increased cardiovascular risk, obesity is 
independently linked with increased colorectal neoplasia and recurrence of colorectal adenomas.8–11 
One large European study found that up to 94% of obese individuals had non-alcoholic fatty liver 
disease (NAFLD), compared with 67% of overweight and 25% of normal weight patients.12  NAFLD is 
defined as fatty infiltration of the liver affecting more than 5% of hepatocytes, in the absence of 
alcohol excess or the consumption of steatogenic drugs. NAFLD encompasses various stages of fatty 
liver disease ranging from steatosis to steatohepatitis (fat + hepatocellular injury +/- fibrosis) through 
to cirrhosis and hepatocellular carcinoma.13–15  Obesity and type II diabetes are major risk factors for 
the progressive form of fatty liver, non-alcoholic steatohepatitis (NASH).15,16 At present there is no gold 
standard tool in screening for patients at risk of fatty liver disease, apart from identifying risk factors as 
mentioned above. The fatty liver index (FLI) is one such tool which incorporates height, weight, waist 
circumference, serum gamma-glutamyl transferase (GGT) and serum triglycerides, and if identified at 
high risk these patients be considered for further assessment for fatty liver with blood tests and 
ultrasonography.17 Approximately 40% of patients with NAFLD develop progressive fibrosis that can 
result in cirrhosis, putting patients at risk of hepatocellular carcinoma, liver failure and portal 
hypertension related complications.18–21  The development of advanced fibrosis (stage 3-4) in patients 
with NAFLD is clinically important as it is associated with a >3 fold increase risk of mortality (all-cause 
and liver-related) compared with a reference population.22  Non-invasive fibrosis scores, such as the 
FIB-4 score (comprising age, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and 
platelet count), are reliable in diagnosing or excluding advanced fibrosis in patients with NASH and are 

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now widely used to identify patients with advanced fibrosis who need specialist assessment.23 A recent 
study has reported that IgA is an independent predictor of advanced fibrosis.24 Transient elastography, 
more commonly known as Fibroscan is a non-invasive imaging based technique which measures liver 
stiffness, and it correlates well with the degree of liver fibrosis. It is commonly used in a wide range of 
liver conditions including NAFLD. However its use is of limited use in patients above the age of 50, who 
have central obesity, those who have a body mass index (BMI) of greater than 35 or type 2 diabetes as 
the results may be invalid.13 
Additionally patients with NAFLD are at higher risk of developing cardiovascular disease and the two 
are strongly associated.25The Qrisk 2 score is a validated tool in risk stratifying patients for 
cardiovascular disease.26 It is a score comprising of the past medical history, family history, smoking 
status, blood pressure, weight and height.  
A 2011 Hong Kong study demonstrated a high prevalence of colorectal adenomas and advanced 
neoplasia in patients with NAFLD. Adenomas were found more commonly in the right colon.27 A 
subsequent systematic review and meta-analysis investigating the link between NAFLD and colorectal 
neoplasia in screening patients found a significant association; however, this association was more 
prominent in the Asian population.28 These studies have not been repeated in a Western population, 
specifically the UK. Previous studies diagnosed NAFLD using ultrasound or liver biopsy, but have not 
determined whether there is an association between colonic adenomas and liver enzymes and / or 
non- invasive markers of fibrosis, such as the FIB4 or NAFLD fibrosis score.27,29–32 The advantage of 
using liver enzymes and non-invasive fibrosis scores to identify patients with NAFLD is that they can be 
readily assessed on large numbers of patients and could potentially be included in risk models to 
predict colonic adenomas. This negates the necessity for liver biopsy- an expensive, invasive procedure 
with significant risk.  
Approximately 400,000 colonoscopies are performed each year within the NHS for the investigation of 
gastrointestinal symptoms, including altered bowel habit, rectal bleeding and iron deficiency 
anaemia.33  Adenoma detection rate (ADR), defined as the number of procedures in which at least one 
adenoma is detected, is a widely accepted quality measure.34 A recent colonoscopy audit 
demonstrated an average polyp detection rate of 32.1%; however, ADR is variable between 
colonoscopists.35 A recent study estimated mean ADR of 15.9%.36 Patients found to have adenomas 
receive surveillance procedures, however these are currently based entirely upon number and size of 
adenomas with no patient factors considered.37 The NHS Bowel Cancer Screening Programme (BCSP) 

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invites all individuals aged 60-74 to undertake biennial faecal occult blood testing (FOBt). Screening is 
currently population based and non-targeted. Patients with a positive FOBt are invited for 
colonoscopy. The national Bowelscope screening programme is currently being rolled out in England 
and Wales, with the Lead applicants unit the first nationally to deliver this programme. All individuals 
aged 55 are invited for a single flexible sigmoidoscopy and adenoma clearance. Those deemed to be 
high risk undergo completion colonoscopy. 
The mean ADR per colonoscopist within the FOBt BCSP is 46.5%, which is much higher than the 
symptomatic population due to the targeted nature of the programme.38 The BCSP has demonstrated 
a significant stage shift in CRC diagnosed.39 At present, the FOBt based screening programme is not 
providing protection against right sided CRC.40,41 A trial within the Scottish screening programme 
demonstrated that screening was an effective environment for interventions to alter patient 
behaviour.42 
In summary, although a study in an Asian population suggested an association between NAFLD and 
colorectal neoplasia, this has not been repeated in a Western population. It is important that the 
association is explored in a Western population but using non-invasive markers of liver disease and a 
wider range of colorectal neoplasia risk factors. This will allow development of a model to predict 
colorectal adenoma risk guiding screening and surveillance. 
 
2. Study Objectives 
To measure the extent to which individuals with obesity and abnormal liver function are at increased 
risk of developing colorectal adenomas and CRC. This study aims to quantify that risk by developing a 
model of obesity-related and other known CRC risk factors. In addition the model will be refined using 
non-invasive measures of liver disease. 
2.1 Primary Objectives 
1. To explore the link between liver enzymes, NAFLD, obesity and colorectal neoplasia in terms of 
adenoma burden, site and histological features 
2. To assess whether the presence of liver fibrosis, measured using the FIB4 score, affects the risk of 
colorectal neoplasia 

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3. To identify which demographics contribute to increased predisposition to colorectal neoplasia 
 
3. Study Design 
A multi-centre observational study will identify colorectal neoplasia burden in patients undergoing 
index screening or diagnostic colonoscopy. Non-invasive markers of liver disease and obesity will be 
assessed and a multivariate model constructed. The primary outcome is to develop a risk model with 
emphasis on obesity-related factors, particularly in the population with abnormal liver enzymes, to 
inform colorectal screening. Secondary outcomes will support this model by identifying demographics 
which contribute to increased predisposition to colorectal neoplasia, additionally assessing whether 
the presence/degree of liver fibrosis affects this risk. The link between NAFLD, obesity and colorectal 
neoplasia in terms of adenoma burden, site and histological features will also be explored. 
3.1 Patient Recruitment 
Eight Northern Regional Endoscopy Group (NREG- with a strong track record in delivering large 
endoscopy trials) units and Kettering General Hospital NHS Trust will recruit patients. Sites from NREG 
include: South Tyneside District Hospital, Freeman Hospital, Northumbria NHS Trust, Sunderland Royal 
Hospital, James Cook University Hospital, County Durham and Darlington Foundation Trust, Leeds 
Teaching Hospitals NHS Trust and North Tees University Hospitals. 
Approximately 1430 patients undergoing colonoscopy as part of the BCSP or symptomatic service 
(most commonly patients with iron deficiency anaemia, altered bowel habit, weight loss and rectal 
bleeding) will be identified from endoscopy lists and recruited by a member of the research team.  The 
final target number of participants will be refined after the first 100 participants have been recruited 
however this is not expected to vary significantly. Methodology by Peduzzi et al is used to calculate the 
minimum number of cases required to measure all variables and develop the risk model.43 Sample size 
N=10*(k/p), where k is the number of covariates to be investigated in the model (n=15) and p the 
smallest of the proportions of positive or negative cases (=ADR=0.15). For non-BCSP population, ADR is 
around 15%; 1000 from this population are required. Minimum ADR within the BCSP is 35%; 430 cases 
are required to adequately power and build the model. This will allow resolution of small scale effects 
of covariates on risk prediction. Using Demidenko's method, the sample size needed for logistic 
regression with 80% power and 5% level of significance is N=8V/β2, where β is the natural log of the 

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odds ratio and V is logistic model variance due to covariates.44 This formula can be rearranged to 
determine the minimum odds ratio that can be detected at a sample size of 2000 with sufficient 
power. Assuming a moderate standard error in the regression (se=0.125), and calculating V from the 
standard error (V=(se*√N)2 ) the study will have sufficient statistical power to detect an effect with a 
small effect size with an odds ratio of 1.42.  The final sample size will be refined using data from the 
first 100 participants and observed effect size(s), however, the total number of recruits will not exceed 
2000.  
All potential participants will be sent or given a patient information leaflet about the study when their 
colonoscopy paperwork is sent or given to them, allowing adequate time to read the information 
leaflet (at least 24 hours) before consenting to the study. On attending the endoscopy unit for their 
procedure, they will be approached by a member of the research team and given the opportunity to 
discuss the study. Written consent will be obtained from those wishing to participate in the study. 
Specific consent to inform the participant’s General Practitioner (GP) of participation will be obtained. 
Both non-consenting and consenting patients will receive their colonoscopy according to standard 
routine practice. Study participants will also undergo a health questionnaire, height and weight 
measurements and blood tests. In addition, intra-procedure data will be collected by a member of the 
research team onto a case report form (CRF). Any polyps detected and removed will be followed up, 
and histological diagnosis recorded post procedure by the research team. No additional follow-up or 
alteration of subsequent care is required for this study. The study will not affect the timing of out-
patient appointments or results. Data will be collated and analysed by the research team. Adverse 
events will be classified by the chief investigators team.  
3.2 Inclusion criteria 
1. Aged 18 years and over 
2. Able to give informed consent 
3. Indications: 
a. Patients with positive faecal occult blood test (FOBt) referred for index colonoscopy as 
part of Bowel Cancer Screening Programme 
b. Colonoscopy conversion from Bowelscope 
c. Index diagnostic colonoscopy due to new gastrointestinal symptoms (including but not 
restricted to diarrhoea, change in bowel habit, abdominal pain, PR bleeding, weight 

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loss), iron deficiency anaemia, family history of CRC, abnormal findings on cross 
sectional imaging  
Recruitment materials will be produced in English; however, if language difficulties emerge in an 
interested patient, a professional translation service specialising in facilitating phone consultations will 
be used.  
3.3 Exclusion Criteria 
1. Absolute contraindication to colonoscopy 
2. Unable to give informed consent 
3. Known colorectal cancer 
4. Known polyposis syndrome 
5. Previous total/subtotal colectomy  
6. Known colonic stricture which would prevent completion of colonoscopy 
7. Attending for therapeutic procedure 
8. Attending for assessment of a known lesion  
9. Attending for assessment of known inflammatory bowel disease (IBD) 
10. Attending for surveillance colonoscopy (polyp surveillance, post colorectal cancer surveillance, 
IBD surveillance) 
11. Colonoscopy within the last 5 years 
3.4 Withdrawal Criteria 
1. New diagnosis of a polyposis syndrome 
2. Incomplete procedure due to any cause such as colonic stricture or obstructing lesion 
preventing completion of procedure, withdrawal of consent from patient  
3.5 Data Collection 
On attendance for colonoscopy and following completion of a written consent form, the participant 
will be asked to complete a health questionnaire. This can be done either by the participant alone or 
with help from a member of the research team. This questionnaire will include the following details: 
1. Age 
2. Ethnicity 
3. Gender 

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4. Smoking History- current and previous 
5. Alcohol consumption- current and previous 
6. Medication history  
7. Family history of colorectal cancer 
8. Family history of ischaemic heart disease 
9. History of liver disease 
10. Hypertension history 
11. Diabetic history 
12. History of chronic kidney disease (stage 4/5, eGFR <30ml/min) 
13. History of atrial fibrillation 
14. History of rheumatoid arthritis  
15. Previous anti-obesity surgery 
The clinical notes will be used to confirm the indication for the colonoscopy and to support the health 
questionnaire where participants are unsure of details. The research nurse will measure blood 
pressure, weight, height, waist circumference and calculate the body mass index (BMI in kg/m2). This 
information, including the health questionnaire, will be entered onto the case report form (CRF). 
Blood tests will be taken to identify patients with fatty liver defined as: 
- 
Definite if patients have raised ALT levels (above the upper limit of normal) and are overweight 
or obese (in the absence of excessive alcohol consumption) 
- 
Probable if the ALT >30 IU/ml for males and >19 IU/ml for females and they are overweight or 
obese (in the absence of excessive alcohol consumption) 
We will also determine stage of fibrosis defined by FIB-4 score ((age x AST)/(platelets x (√ALT)) as: 
- 
No / mild: FIB-4 score <1.3 
- 
Moderate: FIB-4 score 1.3 – 2.67 
- 
Advanced: FIB-4 score >2.67 
We will also determine the patient’s Qrisk 2 score and Fatty Liver Index (FLI) Score. 
Patients undergoing a colonoscopy usually have an intravenous cannula inserted to allow 
administration of sedative medication, analgesia and smooth muscle relaxants. Where possible the 
blood tests will be taken at the time of cannula insertion. To enable this, a size 18G (green) cannula will 

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be used. Where obtaining bloods from the cannula is not possible (failed attempt or poor venous 
access), this will be done using separate standard venepuncture methods. Blood samples will be 
collected in the appropriate containers and sent to the clinical laboratory at the site hospital. The 
blood tests will be requested and labelled according to individual site-specific usual practice.  The 
samples will not be anonymised, to enable the results to be later checked by a research nurse and 
entered onto the pseudonymised CRF.  The samples will be destroyed in line with individual site Trust 
policy (usually within 3-7 days).  Bloods will include: 
1. Bilirubin 
2. Alanine aminotransferase (ALT) 
3. Alkaline phosphatase (ALP) 
4. Aspartate aminotransferase (AST) 
5. Gamma-glutamyl transferase (GGT) 
6. Immunoglobulin A  
7. Full blood count (FBC) 
8. HbA1c 
9. Fasting blood glucose 
10. Lipids: Cholesterol, HDL and Triglycerides 
11. Albumin 
In the event that haemolysis of LFTs occurs, patients will still be included in the study to allow for 
analysis of other risk factors and their association with adenomas.  
Following colonoscopy to allow completion of the histological dataset, additional information will be 
collected either at the time of colonoscopy or from hospital reporting systems or from the patient 
record on the BCSP dataset. These will include: 
1. Site and number of cancers diagnosed 
2. Number of adenomas  
a. Site 
b. Morphology 
c. Size 
d. Villous component 
e. Degree of dysplasia 

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f. Presence of advanced neoplasia 
 
In a subset of patients attending for colonoscopy in the centres where  Fibroscan is available patients 
will have a liver stiffness measurement by Fibroscan using the M or XL probe as appropriate. 
The above data will be entered onto the CRF by a member of the research team. For patients who 
attend for a diagnostic colonoscopy but are taking warfarin or other anti-coagulation, polypectomy is 
contraindicated. If polyps are found, a further colonoscopy is usually organised as part of standard 
care. The polyp details will be recorded at this second colonoscopy to prevent confusion and 
unnecessary exclusion. 
4. Adverse Events 
As this is an observational study, there are no expected additional adverse events specifically 
associated with the study. Intravenous cannula insertion may cause some discomfort and bruising. 
 
5. Assessment and Follow Up 
Clinical follow up will be as per routine clinical practice.  Where colonoscopy is incomplete, the reason 
for this will be recorded. Eligible, consented patients will remain in the study for two weeks following 
discharge from the endoscopy day ward on the day of their procedure. This is to allow time to collect 
data from the blood and histology reporting systems. No additional visits are required for patients who 
enter the study. Any follow up appointments post-colonoscopy will be as per routine care for the unit. 
The timescale for the out-patient appointment and subsequent care will be unaltered by participation 
in the study. 
Checking liver function tests and HbA1c may pick up new diagnoses of fatty liver disease or diabetes. 
All abnormal blood tests will be communicated to the participant’s GP for further action by a member 
of the research team. 
 

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6. Statistics and Data Analysis 
Data from the CRFs will be transferred to a secure and encrypted electronic computer database. 
Statistical analysis will be undertaken by Professor Steven Rushton, Professor of Biological Modelling at 
Newcastle University.  
The relationship between adenoma incidence, NAFLD and blood markers will be investigated using 
logistic regression whilst adjusting for patient-related demographic variables including age and gender. 
This will assess the independent contribution of predictors to the odds of adenomas being found. 
Stepwise removal of non-significant covariates will then be used to identify variables best able to 
predict adenoma presence. ROC plot and AUC analyses of sensitivity and specificity will be used to 
characterise the ability of the model to discriminate between patients with and without adenomas and 
their potential as a predictive tool. These analyses assess the independent contribution of variables to 
the probability that adenomas will be found, but do not allow for confounding, interaction and 
associated indirect effects on detection. Structural Equation Modelling (SEM) will be used to 
investigate impact of indirect and direct effects of the predictors on adenoma incidence. Parsimonious 
models for logistic regression and SEM will be compared in terms of their ability to predict adenoma 
presence. 
As multiple adenomas may occur, the extent to which adenoma number is related to abnormal liver 
enzymes using Poisson regression models and SEM will be measured, following the same analytical 
framework. It is anticipated that the presence of multiple adenomas will be zero-inflated, with some 
patients having zero and others many. The extent to which zero-inflated models (eg allowing for 
aggregation) improve the prediction of adenomas will be assessed. Robustness and validation of all 
models will be validated using bootstrapping. The best model will be developed into a predictive tool.  
 
7. Regulatory Issues 
7.1 Ethics approval 
Ethical approval will be sought via the NHS Research Ethics Committee (REC) prior to study 
commencement. As the majority of patients undergoing colonoscopy have an intravenous cannula 
inserted for sedative medication or smooth muscle relaxants, the necessary blood tests can be 
obtained from this. To prevent haemolysis, a slightly larger cannula will be used (18G). In some cases, 

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the larger cannula may cause slightly more discomfort than the smaller cannulae commonly used for 
this procedure.  
Patients will be informed of the risks associated with standard colonoscopy and consented for the 
procedures according to standard practice, in addition to a study specific consent form which will be 
explained by the research team. 
The study will be conducted in accordance with the recommendations for physicians involved in 
research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later 
revisions. 
7.2 Consent 
Consent to enter the study will be sought from each participant only after a full explanation has been 
given, an information leaflet has been offered and time allowed for consideration. Signed participant 
consent will be obtained. The right of the participant to refuse to participate without giving reasons 
will be respected. All participants will be informed of their right to withdraw at any time from the 
study without giving reasons and without prejudicing further treatment. Potential participants will be 
assessed by a member of the study team, eligibility will be confirmed and baseline assessments 
performed.  
7.3 Confidentiality 
The Caldicott Principles and Data Protection Act will be fully adhered to when dealing with patient 
identifiable data. The Chief Investigators will preserve the confidentiality of participants taking part in 
the study. No staff beyond the usual care team will have access to identifiable data. No identifiable 
participant data will be passed outwith the participating Trusts. The data will be held at the site in 
accordance with local Trust policies and will be destroyed following the study close in accordance with 
local Research and Development protocols.  
7.4 Sponsor 
South Tyneside Foundation Trust will be the sponsor for this trial. 

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7.5 Funding 
This study will be conducted on existing NHS and BCSP lists, at no extra cost to the NHS. Funding for 
cannulation and blood collection equipment, blood test analysis and clinical trial unit costs will be 
provided by Norgine Pharmaceuticals. 
The chief investigator is a full-time dedicated clinical researcher and will be supported by a research 
team consisting of a research fellow and research nurses, who will invite, assess and consent 
participant, in addition to collecting data. No additional NHS resources will be required to conduct this 
study.  
 
8. Study Management 
8.1 Data Protection 
Patient data will be held on site at the Trust in accordance with local Trust policies. Patients will be 
assigned a unique study ID at study entry. All data passed to the trial team will have all patient 
identifiable data removed, aside from the unique study ID. Patients who withdraw will have all data 
collected up until the point of withdrawal included in the study. This data will be uploaded onto an 
electronic CRF and included in the analysis of the study. Data will be submitted either directly onto the 
electronic CRF or onto paper CRF before input into the electronic CRF. 
8.2 Records Retention 
The Principal Investigator will retain all study related records (CRFs, source documents, Investigator 
site file) for fifteen years after the end of the study. All study related records may be archived after the 
study has closed, the database has been locked and notification has been received from the trial team. 
The PI will be responsible for ensuring that these archived records are accessible, as required by 
current legislative regulations. Archiving will occur at each site according to local R+D protocols. 
8.3 Protocol Compliance 
A representative group of staff who will be part of the research team will attend a site initiation 
meeting to ensure compliance with the protocol and allow training in study procedures and data 
collection methods. The PI at each study site will apply for local R+D approval. The PI will sign a copy of 
the ethically approved protocol to confirm agreement to carry out all study related tasks in accordance 
with the protocol. 

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8.4 Responsibilities 
All staff involved in the study will undergo GCP training. Day to day delivery will be supported by a 
research nurse and a research fellow. The responsibilities of the trial team are as outlined below. 
Chief Investigator: 
1. Protocol development 
2. Coordination of trial 
3. Education of trial team 
4. Ensuring GCP training and governance 
5. Support application through approval processes and ethics 
6. Data interpretation 
7. Contribution to report and papers for publication 
8. Ensure uploading of accrual data 
 
Principal Investigators 
1. Protocol development 
2. Coordination of trial 
3. Education of trial team, hosting of trial 
4. Ensuring GCP training and governance 
5. Support application through approval processes and ethics 
6. Data interpretation (including timely assessment of seriousness of adverse events) 
7. Contribution to production of report and papers for publication 
8. Ensure uploading of accrual data 
9. Overall responsibility for conduct and running of the trial at site 
10. Ensuring local governance 
11. Applying for R&D approval at their site 
12. Recruitment and study conduct according to protocol 
9. Financing and Insurance 
This study will be funded by the Norgine Pharmaceuticals. Standard NHS indemnity arrangements are 
in place. 

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10. Dissemination  
OSCAR is supported by the British Society of Gastroenterology (BSG) Endoscopy Research Committee 
(Appendix 2). The study has been reviewed and endorsed by the Bowel Cancer Screening Research 
Committee (Appendix 3).  
Statistical analysis will be undertaken by Professor Steven Rushton, and the results will be written up in 
the form of a report by the research and academic team. Data from the study will be disseminated to 
participating patients within the study via the Trust’s websites. The results will then be submitted for 
publication in international peer reviewed journals and presented to the British Society of 
Gastroenterology Endoscopy Research Committee, BSG guideline groups and the Bowel Cancer 
Screening Programme. Feedback will be given to regional and national Endoscopy leads, maximising 
the exposure of findings to colonoscopists. Data will also be disseminated to local networks, and 
national and international symposia. 
11. Publication Policy 
The chief investigators will take responsibility to present and publish the outcomes of the study. The 
results will be disseminated through peer reviewed national/international journals and learned 
scientific societies. 
 
12. References 
1.  
Cancer registration statistics, England, 2012. Off Natl Stat. 
http://www.ons.gov.uk/ons/dcp171778_367563.pdf. 
2.  
Leslie A, Carey FA, Pratt NR, Steele RJC. The colorectal adenoma-carcinoma sequence. Br J Surg. 
2002;89(7):845-860. doi:10.1046/j.1365-2168.2002.02120.x. 
3.  
Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer. 
1975;36(6):2251-2270. doi:10.1002/cncr.2820360944. 
4.  
Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of 
colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010;375(9726):1624-1633. 
doi:10.1016/S0140-6736(10)60551-X. 
5.  
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Appendix 1- NCRI Endorsement 
 
 

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Appendix 2- BSG Endorsement 
 
 

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Appendix 3- BCSP Research Committee Approval 
 

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Appendix 4- OSCAR study Gaant chart