COBIx: Multi-site validation study of the COBIx reporting tool

ISRCTN ISRCTN96000018
DOI https://doi.org/10.1186/ISRCTN96000018
IRAS number 330776
Secondary identifying numbers DS631023, IRAS 330776, CPMS 59233
Submission date
30/11/2023
Registration date
20/02/2024
Last edited
02/05/2025
Recruitment status
Recruiting
Overall study status
Ongoing
Condition category
Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English Summary

Background and study aims
The diagnosis of serious large bowel diseases such as colitis, Crohn’s disease and cancer, is done by examining tissue samples (biopsies) taken by endoscopic camera examination of the intestine. Large bowel biopsies of this type create a large volume of laboratory workload, comprising approximately 10% of all tissue requests. A significant percentage of these samples are normal (between 30-40%) and contain no evidence of disease. The samples are currently examined manually by a pathologist (a doctor trained to examine tissue), using a microscope. Recent investment means that more laboratories can now scan the microscope slides into a computer as a digital image. The COBIx algorithm takes advantage of digitisation by using computers to analyse biopsy image pixel data to find any irregularities that indicate the presence of disease. This project will fully optimize the COBIx algorithm to a design freeze and then test it more widely across more sites and with a greater number of cases. This is important because different labs have slightly different equipment, stain characteristics and patient populations; thus this study will ensure that the COBIx algorithm works equally well across different sites, despite these variations. Eleven NHS Hospital Trusts from England and Scotland have been chosen. Over the next 3 years, 11,000 large bowel biopsies will be examined from these centres, comparing the pathologists’ reports with the results of the COBIx algorithm. The results will be compared and analysed statistically. The goal is to see if COBIx accurately separates normal large bowel biopsies from abnormal biopsies. This would enable normal biopsies to be solely reported by the computer program. Secondly, the study will see if the detection of serious disease by COBIx helps ensure cases containing diseases such as cancer or severe inflammation can be prioritised for urgent pathologist review.

Who can participate?
Identification will be done by NHS trust employees at each site who are part of the direct clinical care team. It will be done using a computer search (on each site's pathology reporting system) based on the tissue type (large bowel biopsy) and where specific diagnoses are required, using systemised nomenclature of medicine (SNOMED) codes apportioned to the cases. The cases will then be retrieved. The patient's NHS opt-in versus out status will be assessed by each site, and only those patients consenting to the use of their tissue in research will be included.

What does the study involve?
The study aims to recruit 10,000 patient samples from adults across 10 separate centres in the UK. All of the Haematoxylin and Eosin (H&E) stained slides (approximately 33,000 slides) from these samples will be scanned (or in some cases, have already been scanned) to digital whole slide images at the recruiting site using equipment used for routine diagnosis. Scanned images will be anonymised and transferred electronically to private cloud storage housed within the Tissue Image Analytics (TIA) Centre infrastructure. Once these digital slides have been transferred, they will be processed through the COBIx algorithm and classified into one of five categories. The results of the algorithm classification will be compared to the reference pathologist diagnosis.

What are the possible benefits and risks of participating?
There is no intervention which carries any risk physical or psychological to any patients or participants. As part of this study, there is a requirement to access patients' records to retrieve data on patient demographics, their clinical treatment and clinical outcomes. This will be carried out by staff at each NHS Trust who are part of the clinical care team who will access this data from the electronic records held on the trust's clinical results reporting system. This data will be uploaded to a secure web application with restricted access to protect patient confidentiality.

Where is the study run from?
University Hospitals Coventry and Warwickshire NHS Trust; Warwick Clinical Trials Unit, University of Warwick; TIA (Tissue Image Analytics) Centre, University of Warwick (UK)

When is the study starting and how long is it expected to run for?
April 2023 to November 2025

Who is funding the study?
NIHR, Accelerated Access Collaborative

Who is the main contact?
Professor David Snead (Chief Investigator), David.Snead@uhcw.nhs.uk, David.Snead@pathlake.org

Contact information

Prof David Snead
Scientific, Principal Investigator

University Hospital Coventry and Warwickshire NHS Trust
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

ORCiD logoORCID ID 0000-0002-0766-9650
Phone +44 (0)2476 968320
Email david.snead@uhcw.nhs.uk
Ms Rachel Flowers
Public

Research & Development
University Hospitals Coventry and Warwickshire NHS Trust
University Hospital
Coventry
CV2 2DX
United Kingdom

Phone +44 (0)2476 968650
Email cobix@uhcw.nhs.uk

Study information

Study designMulti-centre study
Primary study designObservational
Secondary study designCase series/case note review and laboratory study
Study setting(s)Hospital, University/medical school/dental school
Study typeDiagnostic, Screening, Efficacy
Participant information sheet No participant information sheet available
Scientific titleCOBIx: Multi-site validation study of the Colon and Rectal Endoscopic Biopsy (COBIx) reporting tool
Study acronymCOBIx
Study hypothesisThe diagnosis of serious large bowel diseases such as colitis, Crohn’s disease and cancer, is done by examining tissue samples (biopsies) taken by endoscopic camera examination of the intestine. Large bowel biopsies of this type create a large volume of laboratory workload, comprising approximately 10% of all tissue requests. A significant percentage of these samples are normal (between 30-40%) and contain no evidence of disease. The samples are currently examined manually by a pathologist (a doctor trained to examine tissue), using a microscope. Recent investment means that more laboratories can now scan the microscope slides into a computer as a digital image. The COBIx algorithm takes advantage of digitisation by using computers to analyse biopsy image pixel data to find any irregularities that indicate the presence of disease. This project will fully optimize the COBIx algorithm to a design freeze and then test it more widely across more sites and with a greater number of cases. This is important because different labs have slightly different equipment, stain characteristics and patient populations; we need to ensure that the COBIx algorithm works equally well across different sites, despite these variations. Eleven NHS Hospital Trusts from England and Scotland have been chosen. Over the next 3 years, we will examine 11,000 large bowel biopsies from these centres, comparing the pathologists’ reports with the results of the COBIx algorithm. The results will be compared and analysed statistically. The goal is to see if COBIx accurately separates normal large bowel biopsies from abnormal biopsies. This would enable normal biopsies to be solely reported by the computer program. Secondly, we wish to see if the detection of serious disease by COBIx helps ensure cases containing diseases such as cancer or severe inflammation can be prioritised for urgent pathologist review.
Ethics approval(s)

Approved 06/11/2023, Wales REC 5 (Health and Care Research Wales, Castlebridge 5, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922 940910; Wales.REC5@wales.nhs.uk), ref: 23/WA/0317

ConditionColon and rectal endoscopic biopsy
InterventionCurrent interventions as of 02/05/2025:

The study aims to recruit 10,000 patient samples from adults across 10 separate centres in the UK.
All of the Haematoxylin and Eosin (H&E) stained slides (approximately 33,000 slides) from these samples will be scanned (or in some cases, have already been scanned) to digital whole slide images at the recruiting site using equipment used for routine diagnosis.
Scanned images will be anonymised and transferred electronically to private cloud storage housed within the Tissue Image Analytics (TIA) Centre infrastructure.
Once these digital slides have been transferred, they will be processed through the COBIx algorithm and classified into one of five categories.
The results of the algorithm classification will be compared to the reference pathologist diagnosis.
Most cases (9000) will be from retrospective samples, while 1000 samples will be recruited prospectively. All except rare and unusual entities cases will be selected sequentially. Using retrospective cases is appropriate in this setting and ensures the volume of cases can be recruited and examined in the time available, it also ensures rare and unusual entities are included so we can explore how these are handled by the algorithm. Prospective cases allow the study to collect health economics data, including the time taken for pathologists to examine normal biopsy slides.

_____

Previous interventions:

The study aims to recruit 11,000 patient samples from adults across 10 separate centres in the UK.
All of the Haematoxylin and Eosin (H&E) stained slides (approximately 33,000 slides) from these samples will be scanned (or in some cases, have already been scanned) to digital whole slide images at the recruiting site using equipment used for routine diagnosis.
Scanned images will be anonymised and transferred electronically to private cloud storage housed within the Tissue Image Analytics (TIA) Centre infrastructure.
Once these digital slides have been transferred, they will be processed through the COBIx algorithm and classified into one of five categories.
The results of the algorithm classification will be compared to the reference pathologist diagnosis.
Most cases (9900) will be from retrospective samples, while 1100 samples will be recruited prospectively. All except rare and unusual entities cases will be selected sequentially. Using retrospective cases is appropriate in this setting and ensures the volume of cases can be recruited and examined in the time available, it also ensures rare and unusual entities are included so we can explore how these are handled by the algorithm. Prospective cases allow the study to collect health economics data, including the time taken for pathologists to examine normal biopsy slides.
Intervention typeOther
Primary outcome measureThe effectiveness of the COBIX algorithm compared with the original pathologist diagnosis (e.g. sensitivity, specificity, AUC-ROC, false negative rate, false positive rate, PPV, NPV) measured using a range of statistical measures at one timepoint
Secondary outcome measuresThe effectiveness of the COBIX algorithm at separating samples into different diagnostic categories compared with the original pathologist diagnosis measured using a range of statistical measures at one timepoint
Overall study start date04/04/2023
Overall study end date30/11/2025

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants10,000
Participant inclusion criteriaLarge bowel biopsies taken from adult patients at an endoscopic examination
Participant exclusion criteria1. All other types of GI biopsies e.g. small bowel
2. Other types of large bowel specimens e.g. resections
3. Biopsies from children and young persons (under 18 years)
Recruitment start date01/12/2023
Recruitment end date30/09/2025

Locations

Countries of recruitment

  • England
  • Scotland
  • United Kingdom

Study participating centres

University Hospital Southampton NHS Foundation Trust
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
The Royal Wolverhampton NHS Trust
New Cross Hospital
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Greater Glasgow and Clyde
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
North Tees and Hartlepool NHS Foundation Trust
University Hospital of Hartlepool
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom

Sponsor information

University Hospitals Coventry and Warwickshire NHS Trust
Hospital/treatment centre

Clifford Bridge Rd
Coventry
CV2 2DX
England
United Kingdom

Phone +44 (0)2476 966195
Email ResearchSponsorship@uhcw.nhs.uk
Website https://www.uhcw.nhs.uk/
ROR logo "ROR" https://ror.org/025n38288

Funders

Funder type

Government

National Institute for Health and Care Research
Government organisation / National government
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location
United Kingdom

Results and Publications

Intention to publish date30/09/2025
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal. All efforts will be made to ensure that the results arising from the study are published in a timely fashion, in established peer-reviewed journals. Results will be disseminated via internal and external conferences and seminars, newsletters, and via interested groups, including local healthcare commissioning groups.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol file version 1.0 12/10/2023 04/12/2023 No No

Additional files

44670_Protocol_v1.0_12Oct23.pdf

Editorial Notes

02/05/2025: The following changes were made to the trial record:
1. The interventions were changed.
2. The study participating centres The Newcastle upon Tyne Hospitals NHS Foundation Trust, Nottingham University Hospitals NHS Trust - Queen's Medical Centre Campus were removed and University Hospitals Birmingham NHS Foundation Trust was added.
3. The target number of participants was changed from 11,000 to 10,000.
04/12/2023: Study's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).