Detect InSpect ChAracterise Resect and Discard 2 (DISCARD2)

May 22, 2012 updated by: South Tyneside and Sunderland NHS Foundation Trust

Bowel cancer is a common disorder in the UK. Most cancers happen when a type of polyp, called an adenoma, becomes cancerous. Polyps are growths in the large bowel that can be cancerous, non-cancerous, or pre-cancerous (adenoma). Polyps are most commonly detected during colonoscopy (camera test of the lower bowel). The removal of adenomas has been shown to reduce the subsequent risk of bowel cancer. Current practice is that all polyps are removed or biopsied to allow a laboratory diagnosis (histology). This is important as it influences if and when patients require follow-up colonoscopies, known as the surveillance interval. Patients with only non-cancerous polyps do not need surveillance.

A new blue light technology, called narrow band imaging (NBI), used during colonoscopy can help colonoscopists (doctor or nurse performing the procedure)differentiate between polyp types during colonoscopy. NBI is currently available in a large number of UK endoscopy units however is variably used. Studies from 'expert' centres have demonstrated that NBI allows accurate optical diagnosis of colonic polyps. Benefits of optical diagnosis include avoiding removal of non-cancerous polyps and an immediate (on the day) diagnosis for the patient including the surveillance interval.

The primary aim of this study is to evaluate the accuracy with which colonoscopists assess the required surveillance interval using optical diagnosis when compared with histology in non-expert centres. The investigators will invite 2500 patients, who have been referred for colonoscopy, to participate. Patients will undergo a routine colonoscopy the only addition being the use of NBI during the procedure. Colonoscopists will provide an optical diagnosis at the time of colonoscopy in addition to polyp removal or biopsy.

The investigators will compare surveillance intervals provided using optical diagnosis with the diagnosis from histology and thereby the accuracy with which colonoscopists can use the technology. The investigators will also calculate the cost savings to the NHS.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer (CRC) continues to be a major problem in the UK and is the second most common cause of cancer death. The annual incidence is approximately 30,000 cases with an annual mortality rate of in the region of 16,000 (1). Most sporadic non-hereditary CRCs arise from benign colorectal adenomas (2). The detection and resection of colorectal adenomas at colonoscopy has been shown to reduce the subsequent risk of CRC by as much as 80% (3).

The NHS Bowel Cancer Screening Programme (BCSP) began roll-out in 2006 in England and as of April 2010, was established across 99.4% of the country. The BCSP is based on a strategy of biennial faecal occult blood test (FOBt) screening for men and women aged 60-75, followed by colonoscopy for those who test positive. Among its aims is the detection and resection of potentially pre-malignant colorectal adenomas thereby potentially reducing the incidence of CRC. The introduction of the BCSP has resulted in a dramatically increased demand for colonoscopy. To date approximately 80,000 colonoscopies have been performed within the BCSP and at least one adenoma found in just under half of the procedures (4). In addition, from 2012, the BCSP will introduce flexible sigmoidoscopy screening for all individuals aged 55 yr olds. This extrapolates to approximately 500,000 flexible sigmoidoscopies per year, with at least one polyp expected to be found in 75,000 procedures.

Greater than 90% of polyps detected at colonoscopy are small (6-9mm) or diminutive (≤5mm), with the latter making up the majority (5-7). In addition, approximately 50% of small polyps are non-neoplastic (8), known as adenomas. The number of adenomas present strongly influences the future risk of the development of advance neoplasia for the individual patient and therefore determines decisions on future surveillance intervals. As a result even small polyps, with little risk of harbouring cancer, are currently sent for histological assessment in order to determine whether or not they are adenomatous (9-11).

The ability to correctly diagnose a small polyp (< 10mm) during colonoscopy as adenomatous or non-adenomatous from its endoscopic characteristics (optical diagnosis) would allow small adenomas to be resected and discarded without the need to retrieve the polyp for formal histological assessment. Additionally, hyperplastic rectosigmoid polyps can be left in situ thereby reducing the need for polypectomy and the associated risks. Optical diagnosis would also enable surveillance intervals to be determined immediately after colonoscopy thereby avoiding the need for out-patient follow up, potentially leading to significant time and cost savings. Notably, histological assessment is an imperfect current gold standard as polyps may be lost or be unable to be assessed due to diathermy artefact in 8-25% of cases. Furthermore, standard histological techniques may misclassify up to 15% of adenomas as benign lesions.

Narrow band imaging (NBI; Olympus, Japan (12, 13)) is a new 'blue light' optical imaging modality available at a push of a button on the colonoscope head. By enhancing mucosal detail and in particular vascular structures it allows assessment of microvascular density (vascular pattern intensity - VPI (14); meshed brown capillary network (15-17)). Neoplastic tissue is characterized by increased angiogenesis and, therefore, adenomas appear darker when viewed with NBI. The use of microvascular assessment appears to have a short learning curve, as short as 60 histologically verified polyps (18-20), making it a potentially attractive and practical option for optical diagnosis. There are no known adverse events associated with NBI.

Two studies to date have assessed clinical implications of endoscopic diagnosis of small polyps on surveillance intervals using white light in combination with NBI. A study of diminutive polyps (≤5 mm) performed by a single expert colonoscopist (21), 134 out of 136 (98.5%) of patients would have had the same surveillance intervals when recommendations based on optical and histological diagnoses were compared. Similar results were reported in a study performed by three of the co-applicants (AI, JEE, BPS)(22) where 82 out of 130 patients could be given a surveillance interval immediately after colonoscopy based on optical diagnosis alone and the same interval was found after formal histopathology in 80 patients (98%) using British Society of Gastroenterology guidelines (23). Optical diagnosis accurately diagnosed 186 of 198 adenomas (sensitivity 0.94; 95% CI 0.90-0.97) and 55 of 62 hyperplastic polyps (specificity 0.89; 0.78 -0.95) with an overall accuracy of 241 of 260 (0.93; 0.89-0.96) for small polyp characterisation. In this study, using simple cost analysis, the authors estimated that optical diagnosis would have resulted in 77% cost savings for polyp analysis and clinical follow up (£13343 for 130 patients examined). Using Markov modelling, Hassan et al modelled the cost-effectiveness of 'resect and discard policy' and found that using it for diminutive polyps (≤5mm) would result in annual saving of $33 million when applied to colonoscopy screening of the US population (corresponding to overall saving of $330 million, assuming cumulative period of 10 years to screen just under a quarter of US population) (24).

Optical diagnosis may therefore benefit:

  1. Patients: Shorter, more accurate examinations with fewer complications as a results of fewer polypectomies (less perforation and bleeding), reduced anxiety (awaiting histology results) and more appropriate use of endoscopic surveillance programmes.
  2. NHS and other Healthcare providers: Increased efficiency (shorter lists, more exams per endoscopy list, fewer out-patient appointments, avoids unnecessary use of histology capacity) and reduced risk (fewer complications and fewer polyp 'misses'). Since the need for histology is set to greatly increase with an expansion of screening, a move to the routine use of NBI may substantially reduce the need to expand histology services.

We foresee no significant constraints to adoption of optical diagnosis as financial costs should be easily offset by savings from the efficiency benefits described above as 90% of polyps detected at colonoscopy are <10mm in size and therefore suitable for optical biopsy.

Study Design DISCARD 2 is a blinded calibration diagnostic study which will compare NBI optical diagnosis with histological assessment (as a reference standard) for patients with small polyps (<10mm) identified at colonoscopy

Recruitment Patients who are due to attend for a routine colonoscopy will be identified during out-patient clinics, during colonoscopy booking, or on the day of colonoscopy at each of the participating sites. Patients will be sent or given an information pack containing an information sheet and consent form. There will be two phases of recruitment to the study. All consenting patients undergoing colonoscopy are included in phase 1 of the study. Those who undergo a complete colonoscopy and in whom one or polyp <10mm in diameter is found will enter phase 2 of the study.

More detail regarding inclusion and exclusion criteria and outcome measures are provided below.

Study Type

Observational

Enrollment (Anticipated)

2500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
    • County Durham
      • Darlington, County Durham, United Kingdom, DL3 6HX
        • County Durham and Darlington NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • John G Silcock, MBBS, FRCP
    • Cumbria
      • Carlisle, Cumbria, United Kingdom, CA2 7HY
        • North Cumbria University Hospitals NHS Trust
        • Contact:
        • Principal Investigator:
          • Chris E MacDonald, MBBS FRCP
    • Northumberland
    • Teeside
      • Middlesbrough, Teeside, United Kingdom, TS4 3BW
        • South Tees NHS Trust
        • Contact:
        • Principal Investigator:
          • Arvind Ramadas, MBBS, MRCP
      • Stockton-on-Tees, Teeside, United Kingdom, TS19 8PE
        • North Tees and Hartlepool NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Matthew D Rutter, MBChB MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients attending for routine diagnostic or screening colonoscopy.

Description

Inclusion Criteria:

Phase 1

  1. Patients able to provide valid informed consent.
  2. Patients over 18 years of age.
  3. Patients attending for routine colonoscopy.

Phase 2

  1. Patient fulfils inclusion criteria for phase 1.
  2. Patients with one or more polyps under 10mm detected at colonoscopy.
  3. Patients undergoing a complete colonoscopy confirmed by photo documentation of caecal landmarks.

Exclusion Criteria:

  1. Patients with known inflammatory bowel disease (ulcerative colitis of Crohns disease) or known polyposis syndromes.
  2. Patients who lack capacity to give informed consent as assessed by the clinical study team member taking consent.
  3. Patients who are known to be pregnant (self-reported).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Colonoscopy with Narrow band imaging (NBI)
All patients attending for routine colonoscopies performed for the diagnosis of symptoms or asymptomatic screening.
Device: Narrow band imaging for 'optical diagnosis' of colonic polyps (Olympus).
Colonoscopists will narrow band imaging to provide an 'optical diagnosis' for colonic polyps found during routine colonoscopies performed for the diagnosis of symptoms or asymptomatic screening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The sensitivity NBI optical diagnosis in determining colonoscopy surveillance intervals.
Time Frame: 12 months
The proportion of individuals requiring surveillance colonoscopy (according to British Society of Gastroenterology Guidelines)that are correctly identified by NBI optical diagnosis (test sensitivity).
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The sensitivity, specificity and accuracy of optical diagnosis on a per polyp basis.
Time Frame: 12 months
Sensitivity, specificity and accuracy of optical diagnosis on a per-polyp basis
12 months
The learning curve and maintenance of accuracy of optical diagnosis.
Time Frame: 12 months
Learning curve and maintenance of quality of optical diagnosis measured by proportion of polyps/patients diagnosed with high/low confidence.
12 months
The economic implications of replacing histological assessment with optical diagnosis.
Time Frame: 12 months
Potential cost saving of optical diagnosis
12 months
Description of the population undergoing routine colonoscopy and prevalence of polyps and polyp type.
Time Frame: 12 months
Proportion of patients with no polyps, small polyps, large polyps, categorised by age, gender and polyps type.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

South Tyneside and Sunderland NHS Foundation Trust

Collaborators

University of Durham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Anticipated)

June 1, 2013

Study Completion (Anticipated)

December 1, 2013

Study Registration Dates

First Submitted

May 17, 2012

First Submitted That Met QC Criteria

May 22, 2012

First Posted (Estimate)

May 23, 2012

Study Record Updates

Last Update Posted (Estimate)

May 23, 2012

Last Update Submitted That Met QC Criteria

May 22, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DISCARD2
  • PB-PG-1010-23222 (Other Grant/Funding Number: NHS National Institute for Health Research)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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