Will using a low-threshold faecal immunochemical test compared to the higher-threshold test used in the Bowel Cancer Screening Programme reduce the number of bowel cancer cases?

Plain English Summary

Background and study aims
The NHS Bowel Cancer Screening Programme (BCSP) offers a stool test every 2 years which checks for the presence of blood as this may indicate bowel cancer or something that may develop into cancer over time. From June 2019, the BCSP began using a new stool test called FIT, which quantifies how much blood, if any, is present. If the FIT result gives a level above a certain number or threshold, the patient is referred for a more invasive examination. This threshold can be set at any level, but in general, the lower the FIT threshold, the more sensitive the test, resulting in more bowel cancers being detected. Therefore, the optimal FIT threshold must balance the benefits of detecting potential cancers early versus the risk and costs of undergoing more invasive investigations.
The main aim of this study is to determine if using a low-threshold FIT compared to the higher-threshold FIT used in the BCSP will reduce the number of bowel cancer cases. This is important because if the study shows that low-threshold FIT reduces the number of bowel cancers and subsequent deaths, and is cost-effective, a strong case could be made to lower the FIT threshold used in the BCSP. This would mean that everyone taking part in screening would benefit from a more sensitive test.

Who can participate?
Men and women aged 60-66 who are eligible for FIT screening through the English BCSP

What does the study involve?
Participants will be recruited through the BCSP and randomly allocated to either a low- or the standard higher-threshold FIT used in the BCSP. Recruited participants will complete their bowel cancer screening as normal. Over a 10-year period, the researchers will examine data from up to five FITs per person to determine how much more effective low-threshold FIT is at reducing the number of bowel cancers and subsequent deaths from this disease.

What are the possible benefits and risks of participating?
For those participants allocated to a low-threshold FIT, there is the potential of detecting and treating a precancerous lesion or cancer at an earlier time due to the use of a more sensitive test. There are minimal risks for participants as they are not being exposed to novel or experimental products or procedures. Participants assigned to the low-threshold FIT are more likely to be referred for an invasive examination, such as a colonoscopy, as this threshold is more sensitive than the higher, usual-care, threshold. Colonoscopies are a safe examination performed routinely within the BCSP for a positive stool test by a registered screening specialist practitioner and the risks associated with colonoscopy are extremely low. Additionally, the low threshold for the FIT has been applied as standard in screening programmes in other countries. The Data Safety Monitoring Committee (DSMC) will regularly review and monitor reported adverse events throughout the duration of the study to assess and ensure the continued safety of participants.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
April 2020 to April 2038

Who is funding the study?
Cancer Research UK

Who is the main contact?
Prof. Amanda Cross
amanda.cross@imperial.ac.uk

Study website

Type

Scientific

Contact name

Prof 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

EudraCT/CTIS number

Nil known

IRAS number

279464

ClinicalTrials.gov number

Nil known

Protocol/serial number

20SM5904, IRAS 279464

Scientific title

Double-blind, population-based, randomized controlled trial of a low-threshold faecal immunochemical test versus the usual care test in reducing colorectal cancer incidence within the Bowel Cancer Screening Programme

Acronym

FIT for Screening

Study hypothesis

To determine whether screening with low threshold (20 µg/g) FIT can reduce incidence rates of colorectal cancer (CRC).

Ethics approval(s)

Approved 13/11/2020, London - Surrey REC (Nottingham Centre, The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)2071048088, (0)2071048102, (0)2071048388; surrey.rec@hra.nhs.uk), ref: 20/LO/1188

Study design

Double-blind population-based nationwide randomized controlled trial with a parallel-arm design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Other

Study type

Screening

Patient information sheet

Not applicable

Condition

Bowel cancer

Intervention

Assignment to either the intervention or control group will occur at the invitation to screening. The BCSS programming will be modified so that one in every 40 invitations within the eligible age range will be allocated to the intervention arm in order to spread out the additional colonoscopies that will be required. As the order of invitations are not affected by subject demographics, and the protocol for the intervention and control arms is the same until after the return of the FIT, allocation to either arm will not be influenced by age, sex, screening history or index of deprivation and will effectively be random. Participants, screening centres, and endoscopists will be blinded to allocation. Five invites in each block of 40 invitations will be allocated to the trial, four to the control arm and one to the intervention arm. Only individuals who return a valid FIT kit at the first round will be enrolled in the trial.

All participants will receive the same FIT device as is sent out through the BCSP. The device will be sent inside a box, which also contains the screening invitation letter and instructions for using the device. BCSP invitees are asked to collect a single faecal sample using the FIT device, record the sample collection date on the kit and post it immediately to their designated screening hub, in prepaid, addressed envelopes.

For the intervention group, a FIT threshold of 20 μg/g will indicate positivity at the first and up to five subsequent rounds of FIT screening. For the control group, the FIT threshold that will be used as standard practice in the BCSP, currently 120 μg/g, will be applied. Participants with a faecal Hb concentration above their assigned threshold will be referred to an SSP for endoscopy; the referral process will be identical for each trial arm and is the standard process for the NHS BCSP.

The trial will be conducted over a 10-year period, running over five biennial screening rounds. The study period of 10 years will allow the researchers to examine the effects of multiple FIT screening rounds. Trial follow-up will continue for an additional 5-year period, to permit sufficient cases to accrue to examine the effect on CRC mortality.

Intervention type

Other

Primary outcome measure

The number of new cases of CRC diagnosed in participants who underwent at least one round of FIT screening, measured using screening outcomes during 10 years of follow-up

Secondary outcome measures

1. The number of CRC deaths in participants who underwent at least one round of FIT screening, measured using screening outcomes during 15 years of follow-up
2. The number of participants who a) returned a valid FIT kit, b) tested FIT positive and c) attended a diagnostic endoscopy at five biennial screening rounds over a 10-year period
3. Faecal Hb concentration measured using FIT kit at five biennial screening rounds over a 10-year period
4. The number of lesions (polyps, all adenomas, AAs, CRC) detected and their diagnostic data including number, location, size, dysplasia, histology, and stage, measured using screening outcomes at five biennial screening rounds over a 10-year period
5. The cumulative number of endoscopies carried out, including follow-up surveillance, measured using screening outcomes at five biennial screening rounds over a 10-year period
6. The predictive power of faecal Hb concentrations measured using FIT kit at earlier rounds on faecal Hb concentrations and colonoscopy outcomes at five biennial screening rounds over a 10-year period
7. The number of adverse events reported by the BCSP at five biennial screening rounds over a 10-year period
8. Costs and cost-effectiveness of low- versus higher-threshold FIT, measured using surveillance cost, Quality-Adjusted Life Years (QALYs) and cost per QALY at 15 years of follow-up

Overall study start date

01/04/2020

Overall study end date

01/04/2038

Reason abandoned (if study stopped)

Participant inclusion criteria

Men and women aged 60-66 years at recruitment who are eligible for FIT screening through the English BCSP

Participant type(s)

All

Age group

Adult

Lower age limit

60 Years

Upper age limit

66 Years

Sex

Both

Target number of participants

190,566 (38,113 intervention: 152,453 control)

Participant exclusion criteria

1. Any individual who has opted-out of their data being used for research purposes. These individuals would be included in our initial invited population; however, we would not receive any of their data as NHS Digital removes all personal confidential information on national data opt-outs before datasets are shared
2. Individuals who were allocated to the intervention arm of the BCSP FIT pilot study
3. Individuals who are eligible to be screened but have opted-out of being invited to be screened

Recruitment start date

01/01/2025

Recruitment end date

01/03/2026

Countries of recruitment

England, United Kingdom

Study participating centre

Cancer Screening & Prevention Research Group
Imperial College London
St Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom

Organisation

Imperial College London

Sponsor details

Clinical Research Governance Office
G02
Sir Alexander Fleming Building
South Kensington campus
London
SW7 2AZ
England
United Kingdom
-
becky.ward@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk/

ROR

https://ror.org/041kmwe10

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal. The study protocol is not yet published or available.

Intention to publish date

01/04/2037

Individual participant data (IPD) sharing plan

The data-sharing plans for the current study are unknown and will be made available at a later date.

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs