Plain English Summary
Background and study aims
Most bowel cancers develop from adenomas, a type of small growth that grows on the bowel wall. Removing adenomas can help to prevent the development of cancer. The NHS now offers screening for bowel cancer to all men and women aged between 60 and 69 years and from 2010, the age range will be extended to 74 years. The screening test, called FOBT, looks for traces of blood in the stool. People who have a positive FOBT are offered colonoscopy, an examination in which an endoscope is used to examine the lining of the bowel for cancers and polyps. Those who have large or multiple adenomas found at colonoscopy are known to have an increased risk of developing more adenomas and possibly bowel cancer. Therefore they are currently offered surveillance colonoscopy at 3 year intervals. There are a number of problems with this approach. Colonoscopy is a costly procedure requiring a skilled doctor, and it carries a small risk of serious complications. It can miss lesions - indeed most advanced lesions (large adenomas or cancers) found at follow-up examinations were present but missed at the previous colonoscopy. Surveillance colonoscopy is also wasteful of resources because significant lesions are found in only about 3% of examinations, so 97% of surveillance colonoscopies will find either nothing or only small harmless adenomas. This is reassuring to the patient but offers no real benefit. Because more adenomas are now being found as a result of the NHS Bowel Cancer Screening Programme (BCSP), the number of surveillance colonoscopies is increasing and threatens to overwhelm available resources. A more cost-effective way of protecting people with higher-risk adenomas is required. We propose that a new type of stool test (faecal immunological test, FIT) could offer effective protection for this higher-risk group at a fraction of the cost. Only patients who had a positive FIT result would need to be offered colonoscopy. This study is designed to estimate the benefit of this approach.
Who can participate?
People who have taken part in the Bowel Cancer Screening Programme (BCSP) and have been diagnosed with large or multiple adenomas
What does the study involve?
Participants are offered the FIT at 1, 2 and 3 years. The test is very simple, requiring participants to collect a tiny amount of stool on a probe and return to the laboratory (easier than the FOBT which requires 6 stool samples). Participants who have a positive FIT result are offered a colonoscopy immediately and their next colonoscopy will be three years later. Those who do not test positive to any of the three annual FITs have their colonoscopy at 3 years in the usual way. We compare the total number of bowel lesions found in people who test positive at the 1st, 2nd or 3rd FITs with the number of lesions found at 3-year colonoscopy in those who had a negative FIT result. If most important lesions are found in the group who have positive FIT results, this would suggests that this new approach could provide effective protection and ultimately mean that colonoscopy could be used only in cases with a positive FIT result.
What are the possible benefits and risks of participating?
Participants who have a positive FIT results at Years 1 or 2 will be offered a colonoscopy early and some of them will have no adenomas detected, so it will not benefit them, but some participants will have important lesions found that would otherwise not be detected until 3 years and therefore will derive benefit. The FIT test will be offered in addition to the 3-year colonoscopy which is the current procedure and we will not be replacing their colonoscopy, so the risk of missing lesions is not increased.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
January 2011 to December 2015
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)
Who is the main contact?
Current main contact as of 13/02/2019:
Dr Amanda Cross, amanda.cross@imperial.ac.uk
Previous main contact:
Prof Wendy S Atkin, w.atkin@imperial.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Amanda Cross
ORCID ID
http://orcid.org/0000-0002-0893-2377
Contact details
Imperial College London
St. Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom
+44 (0)20 7594 3401
amanda.cross@imperial.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 09/22/192
Study information
Scientific title
Faecal immunochemical testing for adenoma surveillance (FIT for Follow-up study)
Acronym
FIT for Follow-Up
Study hypothesis
The overall objective is to test the hypothesis that annual immunochemical faecal occult blood testing (iFOBT or FIT) is a feasible, safe, acceptable and cost-saving alternative to colonoscopy surveillance for the diagnosis of advanced adenomas (AA) and early stage colorectal cancer (CRC) in patients with intermediate risk colorectal adenomas.
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/0922192
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0016/54340/PRO-09-22-192.pdf
Ethics approval
Plan to submit to the Central London REC 1
Study design
Pragmatic accuracy and efficiency study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use contact details below to request a patient information sheet
Condition
Bowel cancer
Intervention
People who have taken part in the BCSP and been diagnosed with large or multiple adenomas will be offered the FIT annually at 1, 2 and 3 years. People participating in this study who have a positive FIT will be offered a colonoscopy immediately and their next colonoscopy will be three years later. Those who do not test positive to any of the three annual FITs will have their colonoscopy at 3 years in the usual way.
Patients will receive a Patient Acceptability and Mental Well Being Questionnaire in Years 1 and 2. In Year 3, remaining patients will receive an End of Study Questionnaire that will include an additional set of questions on preferences for annual FIT vs. 3-yearly colonoscopy.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
The cumulative yield of CRC/AA in those testing positive on any one of the 3 annual FITs, relative to the total CRC/AA (those testing positive on any of the FITs plus additional CRC/AA cases detected at the 3-year colonoscopy in those testing negative at all 3 FITs). From this we can calculate the proportion of cases which would go undetected if the FIT regimen was standard.
Secondary outcome measures
1. Completion and positivity rates for 1st, 2nd and 3rd annual FITs
2. Positive predictive values for detection of CRC/AA at the 1st, 2nd and 3rd FIT screenings in patients who undergo colonoscopic investigation
3. Detection rate of CRC/AA at the 3-year colonoscopy in patients who test negative at the 1st, 2nd and 3rd FIT screenings
4. Preference for annual FIT vs. 3-yearly colonoscopy for surveillance
5. Quality of life scores and subjective health status
6. Incremental costs and cost-effectiveness of the annual FIT vs. 3-yearly colonoscopy surveillance
Overall trial start date
01/01/2011
Overall trial end date
31/12/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Men and women aged 60-75 years
2. Tested positive in the NHS Bowel Cancer Screening Programme (BCSP)
3. Had colonoscopy at which intermediate risk adenomas were removed during the past year
4. Were told they required a colonoscopy at 3 years
We will invite eligible participants from the entire BCSP however recruitment will be coordinated by one centre.
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
8000
Participant exclusion criteria
Those who do not return a consent form
Recruitment start date
01/01/2011
Recruitment end date
31/12/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Imperial College London
London
W2 1PG
United Kingdom
Sponsor information
Organisation
Imperial College London (UK)
Sponsor details
Clinical Research Governance Office
G02
Sir Alexander Fleming Building
South Kensington campus
London
SW7 2AZ
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme (ref: 09/22/192)
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
A total of 8009 individuals were invited to participate in the study. Of those invited, 5938 (74%) returned a signed consent form and completed a FIT at year one; these individuals were included in our study. Participation in the study was similar amongst men and women, and across age groups.
We found that FIT was well-accepted with 97% of participants returning a completed FIT at years 2 and 3. Over the three years of the study, 786 (13%) participants tested FIT positive, at which point they were offered colonoscopy.
Participants who did not test FIT positive were offered colonoscopy at 3 years. Of the total 5938 participants, 5225 (88%) had a colonoscopy at some time during the study. Bowel cancer was diagnosed in 29 (0.6%) participants and advanced adenomas were diagnosed in 446 (8.5%).
In total, 725 (12%) participants underwent colonoscopy as a result of a positive FIT result. Among these individuals, bowel cancer was found in 17 (2.3%) and advanced adenomas in 151 (21%). Annual FIT therefore identified 17 of 29 (59%) participants with bowel cancer and 151 of 446 (34%) participants with advanced adenomas over the three years of the study.
In summary, the study demonstrated that annual FIT could identify 59 of every 100 bowel cancers and 34 of every 100 individuals with advanced adenomas if repeated over three years.
Publication list
2015 interim results in conference proceedings: http://gut.bmj.com/content/64/Suppl_1/A365.2
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30538097
2018 results in: https://gut.bmj.com/content/67/Suppl_1/A222.2
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/30618357
2019 results in: https://doi.org/10.3310/hta23010