Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04402424 |
| Other study ID # |
19ONCN260384 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 16, 2019 |
| Est. completion date |
August 16, 2020 |
Study information
| Verified date |
March 2021 |
| Source |
Royal Surrey County Hospital NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Blood that can be detected in stool via faecal immunochemical testing is a recognised risk
factor for the presence of colorectal cancer.
There are a number of point of care faecal immunochemical testing devices available. This
study is to trial one of these machines into the clinical setting to see if the results are
safe and accurate as a 'rule out' test for colorectal cancer. We will be investigating
patients that present with symptoms or anaemia to their GP and are referred on the two-week
rule pathway to our hospital.
It has also been advocated that digital rectal examination (which is part of the routine
assessment for a patient presenting to colorectal clinic) provides an opportunity to use a
small sample of stool from a gloved finger to perform faecal immunochemical testing. We will
be comparing a patient provided sample with a DRE sample on a standard laboratory-based
machine.
Description:
Introduction
The demand for early diagnosis of bowel cancer
In the United Kingdom, there are an estimated 41,700 new cases of bowel cancer diagnosed each
year and it is the fourth most common cancer. Over 90% of patients that are diagnosed with
the earliest stage of bowel cancer will survive at least five years. In 2016 NHS England made
£200 million available to ensure we diagnose cancer earlier and faster.
Bowel cancer in symptomatic patients
Patients who present to their GPs that are anaemic or with symptoms of change in bowel habit,
rectal bleeding, abdominal pain, bloating or weight loss are often referred to a colorectal
clinic under the two-week rule (TWR) scheme. This is designed to enable patients to be seen
within two weeks from primary care referral by a specialist clinician to enable quicker
diagnosis of a cancer should it be present. Many of these patients will be referred by the
colorectal clinician to have a colonoscopy or other form of endoscopy as part of their
investigation and work up.
The National Institute for Health and Care Excellence (NICE) has set out guidelines for
patients to be referred via the TWR, these are known as NG12 criteria. The number of patients
referred for this service is increasing nationally and this in turn is creating significant
burden on endoscopy services. In 2015, 1.7 million endoscopies cases were estimated for that
year across England and this is expected to increase to over 2.4 million per year by 2020. Of
the TWR colorectal referrals, only 3-4% will end up with a diagnosis of colorectal cancer
(CRC) and only 27% of all colorectal cancers are picked up from these referrals nationally.
Once a patient is on the pathway, not only do they have to be seen within two weeks, but also
a diagnosis must be made by 28 days. This leaves no realistic opportunity for any reasonable
form of watch and wait approach for those that a clinician may have a low suspicion of CRC or
other significant colorectal disease.
Colonoscopy is currently seen as the gold standard for investigating symptomatic patients to
rule out bowel cancer. CT colonography is also widely used, yet both require bowel
preparation to be taken the day before. This is inconvenient for patients and can cause
dehydration and possible kidney injury to the frailer patients. In particular, colonoscopy is
unpleasant and can be painful. There is also a small risk of perforation (up to 1 in 500),
the consequences of which can be very serious. The cost of each diagnostic colonoscopy
procedure to the NHS is approximately £372.9
The Royal Surrey County Hospital (RSCH) has been particularly impacted by the increased
referrals of TWR patients to colorectal clinic. Recent analysis from our cancer database
shows that in the last financial year, we received 1414 referrals, of whom 51 patients were
found to have colorectal or anal cancer. The average for the years 2009-2015 was 709
referrals for 53 cancers per year. This shows that the number of referrals has doubled, yet
we do not pick up any extra cancers. Of these referrals it was noted that 80.6% were
primarily investigated by endoscopy, this has increased from 75% found in previous years. An
initial and less invasive "rule out" test with near instant results could enable a decision
to be made regarding triage and onward referral to endoscopy. Such a test with a high
sensitivity and high negative predictive value will safely reduce referrals to a more
manageable number without adverse risk.
2. Background to Faecal Immunochemical Testing (FIT)
Bowel Cancer and Screening
For some in the UK there is an opportunity for 'bowel scope screening' via flexible
sigmoidoscopy as a one-off test from the age of 55 to 60 depending on local availability.
Bowel cancer screening is uniformly available in the UK to all those aged 60-74.
Traditionally, a guaiac-based Faecal Occult Blood test (gFOBT) has been carried out, which
determines the presence of haemoglobin (Hb) in stool. A positive result warrants a
colonoscopy.
Screening is changing across the UK with the enrolment of Faecal Immunochemical Testing
(FIT). This is also a test from a stool sample, but offers a quantitative concentration
result as opposed to a qualitative positive/negative result. Concentration of haemoglobin in
stool has been showed to correlate with severity of colorectal neoplasia and other
significant colorectal disease (SCD) such as high risk adenomas and colitis. Unlike the
gFOBT, FIT is a more sensitive testing model and the quantitative cut off concentration can
be set to determine the number sent for colonoscopy according to resource availability and
likelihood of missing a cancer or SCD. It is only sensitive to human haemoglobin and
therefore it is not affected by diet. FIT also only requires one sample compared to two sets
of three that are required for gFOBT. It is therefore easier for the patient personally and
produces better compliance.
Use of FIT in Symptomatic Patients
FIT is a potential first line investigation for symptomatic patients as a "rule out" test,
thus reducing the demand for colonoscopy. The advantage of the quantitative result is that
the concentration (micrograms Hb/g faeces) has been shown to directly corelate with the
presence of significant colorectal disease including high risk adenomas and colitis, with
malignant neoplasia having the highest concentrations. In 2017, NICE published a diagnostic
guideline (DG30), which recommend the use of FIT for the detection of FOB in the NG12
criteria and a value of >10micrograms Hb/g faeces is seen as positive and warrants further
investigation. There are many forms of FIT analysis, but only four laboratory-based machines
are endorsed in the criteria. This can act as guidance for patients under investigation in
primary care with symptoms. However, once a patient is referred on the TWR pathway, the NG12
criteria state that patients be referred for further investigation without further recourse
to FIT12. The majority of FIT studies relate to those amongst the screening population and so
the evidence cannot be used in symptomatic patients. There are 10 small studies pertaining to
FIT in the symptomatic regarding the DG30 guidance, these total approximately 8,000 patients.
Other larger national studies are currently underway that aim to address this issue as well
as encourage its use further in primary care.
It seems that FIT may be valuable for all referrals to the TWR colorectal pathway. However,
the NG12 criteria also includes patients that may not have symptoms as it also incorporates
patients that are shown to be anaemic with or without iron deficiency. Patients that do not
have a recognised cause of anaemia come on to the pathway as the low serum Hb could be
related to a tumour that is bleeding in a subclinical fashion, particularly if the tumour is
on the right side of the colon. Extra caution for use of FIT should be given to these
patients as blood in the stool from the right side of the colon is older and the haemoglobin
may have been subjected to degradation and therefore not detectable using FIT.
Study Opportunity
Point of Care FIT
FIT has been developed as a point of care (POC) investigation by a number of manufacturers
and test kits are readily available for use by purchase online or over the counter. Some are
designed for home use and some for professional use in a clinical setting. Home FIT kits only
offer a qualitative result, which avoids the delay and cost of a laboratory test, however
generally have a higher cut off concentration than 10micrograms Hb/g faeces for positive or
negative and are also open to user interpretation errors. The cost ranges from £2.50 to
£34.99 (median £4.09), which is competitive with the average £9.42 for a laboratory-based
FIT. The POC professional kits differ, with some offering qualitative results and some work
to give a quantitative result via a portable machine or even mobile phone app.
Identified Requirement
An instant quantitative result in the clinical setting has the potential advantage over the
laboratory test in terms of triaging and referring patients for ongoing investigations
immediately. This is because the decision can be made in the one clinic setting rather than
the extra step of waiting a few days for the laboratory-based result to be determined.
Consequently, it is those machines that are designed for POC professional use that we are
interested in taking forward into trial. However, there is no scientific study that has been
done on these test kits to prove that they are accurate.
The POC FIT kits that are designed for professional use do not all detect the very low
haemoglobin concentrations that the laboratory-based machines can pick up, but the
manufacturers do report the ability to pick up positive results as low as 10microgram Hb/g.
This would be useful for primary care practitioners as that is in keeping with the DG30
guidance. Many of the available POC FIT kits have a "Conformite Europeene" (CE) approval but
have not had Food and Drug Administration (FDA) or other approval. The potential for harm is
high if either an inaccurate reading falsely indicates a high faecal Hb resulting in an
unnecessary colonoscopy, or more seriously a false negative result reassures the patient and
clinician that they do not have CRC.
The Southern Bowel Cancer Screening Hub (that is affiliated with RSCH) uses all the
laboratory-based machines that are recognised by NICE for FIT from the DG30 update and they
are internationally validated. The Hub has identified the need to assess the professional use
POC FIT kits against the standard set of baselines used by the laboratory machines. This will
help determine key criteria such as accuracy, effectiveness and safety for their use in the
decision-making process for onward investigation.
This protocol describes a study for a POC FIT machine that aligns with key criteria set out
by the Hub for use in the TWR colorectal clinic.
Digital Rectal Examination Sampling
Although FIT only requires a single sample, we recognise that not all patients will comply
with being able to perform this at home. It has been advocated that the digital rectal
examination (DRE), which is part of routine assessment in the TWR clinic provides enough
stool on the glove to wipe on to a sample stick. It would therefore be useful to assess which
of the two sampling methods provide the best compliance and most accurate results.
Rationale for study
- The referral rate to the TWR clinic via NG12 guidelines is dramatically increasing.
- This has not only increased our patients that are needed to be seen in clinic, but also
had a large effect on our endoscopy burden.
- If proven to be of value in secondary care clinic, then these results will be
transferable to the primary care clinic setting.
- This study needs to be performed in secondary care to obtain the colonoscopy result for
comparison.
- The NG12 criteria for these patients once referred into secondary care does not
currently advocate occult blood testing as an investigative tool due to lack of
evidence.
- POC testing over laboratory testing offers a one-stop investigation that can give the
clinician an instant result to help make a decision in the clinic regarding need for
endoscopic evaluation.
- A close correlation between POC FIT tests and endoscopy results for CRC will add to the
body of evidence regarding FIT as a triage and referral tool in symptomatic patients for
primary and secondary care.
- This will be safer and more convenient for patients in terms of reducing the need for
endoscopy.
- The burden on NHS funding and resources will be significantly reduced if the demand for
clinic time and colonoscopy is reduced.
