Multi-Centre, Open-label, Randomised, Prospective Trial to Assess Efficacy and Safety of the CADDIE Artificial Intelligence System for Improving Endoscopic Detection of Colonic Polyps in Real-time.
Conditions: Polyps, Adenoma Colon, Colorectal Polyp, Colon Polyp
Sponsor: University College, London

   
Short Title: Computer Aided Diagnosis and Detection for Intelligent Endoscopy   
   
   
   
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Clinical Investigational Plan (CIP) summary for Medical Device Studies 
   
   
Full title of Investigation: 
 
Multi-Centre, open-label, randomised, prospective trial to assess 
efficacy and safety of the CADDIE artificial intelligence system 
for improving endoscopic quality 
Short title: 
 
 
CADDIE Trial - Computer Aided Diagnosis and 
Detection for Intelligent Endoscopy 
 
Sponsor: 
University College London 
Sponsor CIP number: 
126166 
NCT: 
NCT04325815 
Document Date: 
5th December 2022 
   
   
   
   
   
     
   
   
   
   
   
  
  
   
   
 

   
Short Title: Computer Aided Diagnosis and Detection for Intelligent Endoscopy   
   
   
   
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Title:   
Multi-Centre, open-label, randomised, prospective feasibility trial to assess 
efficacy and safety of the CADDIE artificial intelligence system for improving 
endoscopic quality.    
   
Short title:   
   
CADDIE Trial - Computer Aided Diagnosis and Detection for Intelligent
Endoscopy.   
   
Device:   
CADDIE  
Primary objectives:   
To determine whether the CADDIE artificial intelligence system improves
endoscopic detection of adenomas during colonoscopy.   
     
Secondary objectives:   
   
1. Evaluate the difference in number of adenomas detected per colonoscopy
between intervention and non-intervention arm.    
2. To determine whether the CADDIE artificial intelligence system improves
endoscopic detection of all polyps during colonoscopy.    
3. To determine whether the CADDIE system improves the accuracy of 
endoscopist optical diagnosis of diminutive polyps (≤5mm).   
4. To determine whether using the CADDIE system improves the accuracy in
assigning colonoscopy surveillance intervals.   
5. To determine whether using the CADDIE system improves the accuracy of 
endoscopist optical diagnosis of diminutive (≤5mm) rectal polyps.    
6. Evaluate the safety of the CADDIE in clinical application.     
7. Assess integration of CADDIE into normal colonoscopy clinical workflow.  
Type of Investigation:   
 
Multi-Centre, open-label, randomised, prospective study.   
Investigation design and 
methods:   
The CADDIE system comprises a computer attached to the output of the endoscopy 
stack which detects polyps using an AI software and a screen which shows the 
normal video output of the colon in real-time with an overlay highlighting the 
presence and location of the polyp.    
   
The CADDIE device is capable of recording the video output of the colon in real  
time irrespective of whether the CADDIE’s AI polyp detection system is active.    
   
In the run-in phase, we will verify individual endoscopists adenoma detection rates 
(ADR). We will then confirm their ADR by either extending the number of 
colonoscopies analysed to calculate their initial retrospective ADR or an additional 
prospective series of colonoscopies to calculate a confirmed ADR.   
 

   
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In the study phase of the trial, the endoscopists will be kept the same for the 
interventional and non-interventional arm. At the beginning of each procedure, patient 
information will be entered into an electronic system which will generate a random 
allocation into one of two arms (interventional and non-interventional arm). The 
intervention involves a colonoscopy assisted by the CADDIE system. The non-
intervention (control) is a colonoscopy without the CADDIE system (i.e. standard 
practice). Each endoscopist will have the CADDIE device present during all endoscopy 
lists for the purpose of recording the colonoscopy. The CADDIE system (i.e. AI polyp 
detection function) will only be active in the interventional arm.   
   
In both arms of the trial, for each polyp the endoscopist detects, they will:   
1. Measure polyp size, capture images, and optically diagnose polyp 
For polyps measured to be <10mm, the endoscopist will capture a still image of 
the polyp in both white light and NBI (in NBI-near focus, if available) or 
equivalent imaging modality to NBI. The endoscopist will proceed with optical 
diagnosis of the polyp (noting whether they have high or low confidence in the 
diagnosis).   
2. Resect diminutive polyps   
Management of rectal hyperplastic polyps will be standardised. Rectal polyps 
optically diagnosed by the endoscopist will be resected/biopsied. If multiple 
rectal hyperplastic polyps are optically diagnosed by the endoscopist, a 
minimum of 5 will be resected/biopsied for histopathology.       
3.    Label each polyp resected   
Each polyp resected (regardless of size) must be labelled according to 
instructions of the Specimen Handling SOP. Each unique polyp ID will need to 
be logged in chronological order on a per colonoscopy basis and sent for 
histopathology. Histopathology will be referenced as the gold standard for 
polyp diagnosis and characterisation.    
   
In the intervention arm, the endoscopist will use the normal endoscopy video system 
including the standard screen. When the CADDIE system detects a possible polyp, 
it will simultaneously sound an alarm and overlay the area of interest on the 
endoscopy screen with a bounding box. The endoscopist will then inspect the 
mucosal area. If it is deemed to be a polyp, the endoscopist will follow the steps 
documented above. When an image of the polyp is captured in NBI mode, the 
endoscopist will press on the foot pedal to reveal the CADDIE’s polyp 
characterisation. Using this information and the endoscopist own assessment, the 
endoscopist will log an optical diagnosis of the polyp and confidence in diagnosis 
(high or low) on a paper case report form (CRF). The optical diagnosis will be 
assessed against the polyp’s histopathology.    
   
On three occasions, the endoscopist will complete a brief questionnaire regarding 
their views on safety and efficacy of the system and how they feel it affected 
performance. The endoscopy nurses in the interventional arm will complete the 

   
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questionnaire once. Each patient will also complete a questionnaire to ascertain  their 
experience.   
   
The ADR for each endoscopist will be calculated in the run-in phase. Selected 
endoscopists will be invited to proceed with the study phase of the trial. In the study 
phase, we will compare endoscopist ADR between the non-intervention and 
intervention arms. This will allow us to evaluate whether the process of using AI 
software improves endoscopist ADR.    
   
   
Safety of the device will be assessed through monitoring of adverse events. 
Acceptability will be assessed through a qualitative questionnaire for the 
endoscopist, endoscopy nurse and patient in addition to measuring endoscopy 
markers such as caecal intubation time, procedural time, withdrawal time.   
  
Investigation duration 
per participant: 
 
From written consent to completion of questionnaire.   
Estimated total 
investigation duration:   
 
3 years 
Planned Investigation 
sites: 
University College London Hospitals NHS Foundation Trust 
Cambridge University Hospitals NHS Foundation Trust   
  
West Hertfordshire Hospitals NHS Trust   
Barts Health NHS Trust   
Surrey and Sussex Healthcare NHS Trust   
Imperial College Healthcare NHS Trust   
The Princess Alexandra Hospital NHS Trust    
Bradford Teaching Hospitals NHS Foundation Trust 
Sheffield Teaching Hospitals NHS Foundation Trust  
 
Total number of 
participants planned: 
654 subjects will be enrolled in the study-phase of the trial. As per the data 
monitoring committees (DMC) recommendation following the interim analysis, this 
has been increased to 766 subjects. 
Main disease/area: 
Main disease: Colorectal Polyps   
Main area: Colon and Rectum   
 
Main inclusion/exclusion 
criteria: 
Inclusion Criteria: 
- 
Participants scheduled to undergo a surveillance or symptomatic colonoscopy 
with an endoscopist participating in the study phase of the trial.   
- 
Male and female participants aged 18 years or older at the time of informed 
consent.   

   
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- 
Participants able to comprehend, sign and date the written informed consent 
document to participate in the study.  
 
Exclusion criteria:   
- 
Emergency and/or inpatient colonoscopies    
- 
Patients with inflammatory bowel disease (IBD)    
- 
Patients with current Colorectal Cancer (CRC)   
- 
Patients with previous CRC   
- 
Patients with previous colonic resections   
- 
Polyposis syndrome   
- 
Patients returning for a planned elective therapeutic colonoscopy.   
- 
Current or relevant history of a physical or psychiatric illness or any medication 
condition that in the opinion of the investigator could affect the patient’s safety 
or interfere with the study assessments.  
- 
Patients with a contraindication for biopsy or polypectomy. These include:  
o Patients who have not withheld medications pre-disposing to bleeding 
at time of colonoscopy as per local site /national guidelines.   
o Patients with a history of haemostasis disorders (Haemostasis 
disorders will include but will not be limited to: patients with 
haemophilia 
or other congenitally acquired 
clotting factor 
deficiencies, patients with cirrhosis with coagulopathy, patients 
known to have thrombocytopenia (<80,000 platelet/ul) and individuals 
with Von Willebrand’s disease or other known platelet malfunction 
disorders)   
- 
Patients is enrolled in another research study with an investigational 
medicinal product (IMP) or non-IMP that pre-disposes them to bleeding. 
 
Statistical methodology 
and analysis:   
We aim to recruit 327 subjects per arm to detect a 10% difference in ADR (from 
20% to 30%) between the two arms, using a two-group z-test with 80% power, a 
two-sided α level of 0.05, and accounting for an expected dropout rate of 10%. 
Thus, the total planned sample size consists of 654 patients in the study phase of 
the trial. As per the DMC recommendation following the interim analysis, the 
dropout rate has been increased to 15% and an additional 66 patients are to be 
recruited to account for local technical issues encountered during the initial 
recruitment of 66 patients across two sites. The total planned sample size therefore 
consists of 766 patients.  
 
The difference in the primary outcome measure between the intervention and control 
groups will be estimated using regression models. Significance will be considered 
at the 5% level and confidence intervals will be at the 95% level.  Secondary 
outcomes will also be assessed by means of appropriate regression models 
depending on the nature of the outcome.